Podcast appearances and mentions of bill griffin

In this episode of Behind the Genes, we explore the hopes, concerns and complex questions raised by the idea of a lifetime genome — a single genomic record used across a person's life to guide healthcare decisions. Drawing on conversations from Genomics England's Public Standing Group on the lifetime genome, our guests explore what it might mean for individuals, families and society to have their genome stored from birth, and how it could transform healthcare. The discussion reflects on the potential for earlier diagnoses, better treatments and long-term prevention, alongside pressing ethical concerns such as data security, consent, and the impact on family dynamics. Participants share their views and discuss the future role of genomic data in medicine, with insights into how trust, equity and public dialogue must shape this evolving field. Our host for this episode, Dr Harriet Etheredge, is joined by Suzalee Blair-Gordon and Gordon Bedford, two members of the Genomics England's Public Standing Group on the lifetime genome, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that helped to facilitate this work. Together, they consider the broader societal implications of lifetime genomic data, and how public involvement can help guide policy and practice in the UK and beyond. This conversation is part of our ongoing work through the Generation Study, exploring how genomics can be used responsibly and meaningfully from birth onwards. You can listen to some of our Generation Study episodes by following the links below. What can we learn from the Generation Study? How has design research shaped the Generation Study? What do parents want to know about the Generation Study?   "This isn't just a science project, it's about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction."   You can download the transcript, or read it below. Harriet: Welcome to Behind the Genes. Suzalee: I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms.  Harriet: My name is Harriet Etheredge, and I am the Ethics Lead on the Newborn Genomes Programme here at Genomic England. On today's episode I'm joined by 3 really special guests, Suzalee Blair and Gordon Bedford, who are members of Genomics England's Public Standing Group on Lifetime Genomes, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that has helped us to facilitate this work.  Today we'll be discussing the concept of the lifetime genome. What do we mean when we say, ‘lifetime genome'? How can we realise the promise of the lifetime genome to benefit people's healthcare whilst at the same time really appreciating and understanding the very real risks associated? How do we collectively navigate ethical issues emerging at this genomic frontier? If you enjoy today's episode, we would really love your support. Please share, like and give us a 5-star rating wherever you listen to your podcasts. And if there's a guest that you'd love to hear on a future episode of Behind the Genes, please contact us on podcast@genomicsengland.co.uk. Let's get on with the show. I'll start off by asking our guests to please introduce yourselves.  Suzalee, over to you.  Suzalee: Thanks, Harriet. So I am a proud mum of two kids, teacher of computing at one of the best academic trusts in the UK, and I am also a sickler, and for those who don't know what that means, I am living with sickle cell disease.  Harriet: Thank you so much, Suzalee. Gordon, over to you.  Gordon: I'm Gordon Bedford, I'm a pharmacist based in The Midlands. I've worked in hospital and community pharmacy. I have a genetic condition, which I won't disclose on the podcast but that was my sort of position coming into this as I'm not a parent of children, but it was coming in from my perspective as a pharmacist professional and as a member of society as well.  Harriet: Thank you so much, Gordon. And, last but certainly not least, Suzannah.  Suzannah: So, yes, Suzannah Kinsella. I am a social researcher at Hopkins Van Mil, and I had the pleasure of facilitating all of the workshops where we gathered together the Public Standing Group and working on reporting the outcome from our discussions, so delighted to be coming in from South London. Harriet: Thank you so much, everyone, and it's such a pleasure to have you here today. So, many regular listeners to Behind the Genes will now that Genomics England is currently undertaking the Generation Study. I'm not going to speak about it in much detail because the Generation Study has already been the subject of several Behind the Genes podcasts and we'll put some links to these in the show notes for this episode. But briefly, the Generation Study aims to analyse whole genomes of 100,000 newborn babies across England, looking for 250 rare conditions. We have a view to getting these children onto treatments earlier and potentially enhancing their lives.  The Generation Study is a research project because we don't know if the application of this technology will work. And as a research project we can also answer other important questions, such as questions about a lifetime genome. When we invite parents to consent to the Generation Study on behalf of their newborn babies, we ask to store babies' genomic data and linked healthcare data in our trusted research environment.  This helps us to further research into genes and health. But a critical question is ‘what do we do with these data long term?' And one of the potential long-term uses of the data is to revisit it and re-analyse it over a person's lifetime.  We could do this at critical transition points in life, like adolescence, early adulthood or older age, with the aim of using the genomic data to really enhance people's health. But this is a very new concept. There's been little work on it internationally, however I am pleased to say that interest seems to be picking up. In the Generation Study, whilst we are at the present time doing no lifetime genomes work, we are looking to explore the benefits, risks and potential uses of the lifetime genome.  This Public Standing Group on lifetime genomes was our first foray into this area.  So, I'd like to start off by inviting Suzannah to please explain a bit more about what the Public Standing Group is, why it was created and how a group like this helps us to generate early deliberation and insight.  Suzannah: So, the first thing I should talk about is who were these 26 people that formed part of this group, and the first thing to say is that they were a wide range of ages and backgrounds from across England, so some from Newcastle, some from London and everywhere in between. And these 26 people all had one thing in common, which is they had all taken part in a previous Genomics England public dialogue, either the whole genome sequencing for newborn screening which took place in 2021, or in a more recent one in about 2022/23 which was looking at what should Genomics England think about in terms of research access to data that's drawn from the Generation Study. So, the great thing was that everybody had already some previous knowledge around genomics, but the concept of a lifetime genome was completely new. So these 26 people met on 5 occasions over the period of 2024, mostly meeting face to face, and really the task that they were given was to look at the lifetime genome and look at it from every angle; consent, use, information sharing and all sorts of other aspects as well. Harriet: Gordon and Suzalee, you were participants in our Public Standing Group, I'd love to hear from you what your roles in the Standing Group were and what you found most interesting, but also for you which bits were the most challenging. Suzalee, shall we start with you? Suzalee: For me the most interesting bits were being able to learn about one's genome and, through Genomics England and their possible use of pharmacogenetics, could determine the specific medication that could be prescribed for a new health condition instead of expensive and possibly tonnes of adverse side effects trial and error medications. Additionally, as a person living with sickle cell disease, I got the chance to share my story and to give voice to people living with the same condition or similar to myself, and how the potential of the genomics newborn programme could help our future generation. There were some tricky bits, and the most challenging bit was to initially discuss and think about the idea of whether or not a parent might choose to know or not to know the potential of their newborn developing or prone to develop a certain condition based on the data received from the programme. My thought went back to when I gave birth to my first child 16 years ago and I was adamant to know if my child would inherit the sickle cell disease, what type, if it would be the trait. In my mind I knew the result, as my haemoglobin is SC and their dad is normal, but I wanted to be sure of my child's specific trait. But then I asked myself, “What if my child was part of the Newborn Genomes Programme, then the possibility exists that other health conditions could be detected through the deep analysis of my child's genome. Would I really want to know then? What would be the psychological effect or, in some cases, the social impact of what I have to learn?” Harriet: Thank you so much, Suzalee. And I think it's just wonderful to hear about the personal impacts that this kind of work can have and thank you for bringing that to us.  Gordon, I'll hand over to you. I'd be really interested in your thoughts on this. Gordon: So my role in the Public Standing Group was to give my section of society my experiences in life to bring them together with other people, so experiences like Suzalee and the 24 other people that joined us on the study, to bring our opinions together, to bring our wide knowledge and group experiences of life. And it's important to have a wide group, because it forces us to wrestle with differences of opinion. Not everybody thinks like I do.  As a pharmacist, I can see the practical side of genomics, like pharmacogenomics, where we could use a baby's genome to predict how they'll respond to drugs over their lifetime. That's a game-changer for avoiding adverse reactions or ineffective treatments, but not everybody's sold on it. Some in our group worried about privacy, who gets this data, or ethics, like whether it's fair to sequence a baby who can't say yes or no. I get that. I don't have children, but I hear those things clearly. The most interesting bits for me, the pharmacogenomics discussion in meeting two stood out, everyone could see the tangible benefits of tailoring medicines to a person's genome, making treatments more effective, and in Meeting 5 designing our own lifetime genome resource was also fascinating. Ideas like it for public health research showed how far-reaching this could be. Some of the challenging sides of things that I came across, the toughest part was grappling with unknowns in Meeting 4, like how to share genetic info with your family without damaging relationships. Those risks felt real, and it was hard to balance them against the benefits, especially when trust from groups like minority ethnic communities is at stake. Harriet: Thank you so much, Gordon. I think from you and Suzalee it's so fascinating to hear how you were grappling, I think, with some of your personal and professional feelings about this and your deeply-held personal views and bringing those first of all out into the open, which is something that is very brave and we really respect and admire you doing that, and also then understanding that people do hold very different views about these issues. And that's why bring these issues to an engagement forum because it's important for us to hear those views and to really understand how people are considering these really tricky ethical issues. So, Suzalee, I'm wondering from your perspective how do you feel we can really be respectful towards other people's points of view? Suzalee: Yes, Harriet. In spite of the fact that we had different viewpoints on some topics discussed, every member, researcher, presenter and guests were respectful of each other's point of view. We all listened to each other with keen eyes, or sometime squinted eyes, with a hand on the chin which showed that what was being said was being processed or interpreted. All our views were recorded by our researchers for further discussion and analysis, therefore I felt heard, and I believe we all felt heard.  Harriet: Do you have any examples that you can recall from the groups where there were differing points of view and how we navigated those? Gordon: Where we had screening at age 5, but we agreed on an opt-out model, because it could help spot issues early. But some worried - psychological impacts, knowing too much too soon. But we looked at an opt-out model rather than an opt-in model because it's easier to say to somebody, “If you don't want to continue with this, opt out” rather than trying to get everybody opting in at every different age range. So, as we reach the age of 5, 10, 15, 20, whatever, it's easier to get people to opt out if they no longer want to be part of that rather than trying to get them to opt in at each stage throughout their life. Harriet: Suzannah, do you have anything to add there as a facilitator? How did you feel about bringing these different points of view together? Suzannah: Yeah, you asked about where are the tensions, where do people maybe agree a bit less or agree and hold different views, and I think what stands out is particularly…  There was an idea floated by one of the speakers about you could have your DNA data on an NHS app and then, let's say if you're in an emergency, a paramedic could have access to it or others. And that really I think brought out quite a wide range of perspectives of some in the group feeling, “You know what, anyone who has an interest, anyone that can help my health, let them have access to it as and when, completely fine,” and others took a more cautious approach saying, “This is my DNA, this is who I am, this is unique to me, my goodness, if someone, some rogue agent manages to crash the system and get hold if it goodness knows what nightmare scenario it could result in,” and so had a much more keep it locked down, keep it very limited approach to having access to your lifetime genome data and so on. So that was a really interesting example of people going, “Yep, make it free” and others going, “No, just for very specific NHS roles,” which I thought was fascinating. Harriet: Yeah, thank you so much, Suzannah. And I think it's a real tangible challenge that those of us working in this area are trying to grapple with, is finding the middle ground here with all of the challenges that this involves, for instance, our data infrastructure and the locations at which data are held. Advert: The Genomics England Research Summit is fast approaching and registration is now open! Join us for this one day in-person event on Tuesday 17 June 2025. This year's agenda dives into rare condition diagnosis, cancer genomics, pharmacogenomics, therapeutic trials, and the impact of emerging technologies. Hear from leading experts and inspirational speakers as we explore the present and future of genomics and the latest research and technology from the Genomics England research community. Keep an eye on the website, genomicsresearchsummit.co.uk for all the details and to secure your spot. Spaces are limited, so don't miss out. We'll see you at the summit! Harriet: I think this brings us really nicely onto looking at some of the ethical, legal and social issues that we need to think through when we're considering the lifetime genome.  I'm wondering if we can expand on some of these and the importance of addressing them. Gordon, would you like to give us your thoughts? Gordon: Sure, thank you. Our job was to dig into how a baby's genome could be used over the lifetime, think pharmacogenetics for better drugs, early childhood screening for conditions or carrier testing to inform family planning. We saw huge potential for individual health like catching diseases early, but also broader impacts like reducing NHS costs through prevention. Weighing the risks and benefits. The benefits like earlier diagnosis or research breakthroughs grew clearer over time with ratings rising from 4.1 to 4.7 - that's out of, I believe, a figure of 5, but risks like data breaches and family tensions over shared genetics stayed significant. We agreed the benefits could outweigh the risks but only with mitigations like transparent governance and strong security. And what are the global implications moving forward? What we discussed isn't just for the UK, it's feeding into the global conversation about newborns in genomic research. That responsibility made us think hard about equity, access, and how to build public trust. Harriet: Thank you, Gordon, I think there's so much there to unpack. And one point I think in particular that you've mentioned, and this came out really strongly as one of our main findings from these groups, was the way that a lifetime genome and the way that we might deliver that information could really impact family dynamics in ways that we might not have really thought of before or in ways that we really have to unpack further. And, Suzalee, I'd love to hear from you about this, how might diverse family dynamics need to be considered? Suzalee: Harriet, as it relates to diverse family dynamics a burning legal issue, which is then triangulated into being considered an ethical issue as well as a social issue, was the question can siblings of sperm donors be informed of life-threatening genomic discoveries? Whose responsibility is it? Will policies now have to be changed or implemented by donor banks to take into consideration the possibility of families being part of the new genomes programme? Harriet: Yeah, thank you, Suzalee. I think there's so much there that we have to unpack and in the Generation Study we're starting to look at some of those questions, but going forward into potential risks, benefits and uses of the lifetime genome, all of these new technologies around human reproduction are things that we're going to have to consider really, really carefully through an ethical and legal lens. Suzannah, I wondered if you have anything to add to these as major ethical issues that came out in these groups. Suzannah: I think, as you say, people were so fascinated by the idea of this information landing in a family, and where do you stop? Do you stop at your siblings, your direct family, the brothers and sisters of a child?  Do you go to the cousins?  Do you go to the second cousins?  It's this idea of where does family stop. And then people were really interested in thinking about who does the telling, whose job is it? And we had this fascinating conversation – I think it was in Workshop 3 – where this very stark fact was shared, which is the NHS doesn't know who your mother or your father or your siblings are; your NHS records are not linked in that way. And so that presented people with this challenge or concern that “Actually, if I get quite a serious genetic condition diagnosed in my family whose job is it to share that information, what support is there to do that and how far do we go?”  So, I think people were really fascinated and hopeful that Genomics England will really be at the vanguard of saying, “How do we as we move into an era of more genetic data being used in our healthcare, how's that managed and how's it shared?” Harriet: Yeah, thank you so much, Suzannah. So I think that what's coming out through everything that you're all saying is the huge breadth of issues that came up here. And of course we're seeing, very encouragingly, so many nods to the potential benefits, especially around things like pharmacogenomics, but we are seeing some risks.  Gordon, I wondered if you'd like to elaborate a bit further. Gordon: So, something that came up, and it divided the group quite considerably, carrier status divided us. Some saw it as reducing disease prevalence and others feared it could fuel anxiety or stigma amongst the family or other families. It showed how personal these choices are and why families need control over what they learn. Harriet: Yeah, it's a very good point, and carrier status is something that could be a conceivable use of our lifetime genome record. Suzannah? Suzannah: Just building off what Gordon was talking about, I remember there were also discussions around are we getting into a state where this is about eradication of so many different conditions, and actually how does that sit with a society that is more embracing, accommodating and supportive of people with different health needs. So, I think that was quite a big ethical discussion that was had, is, and particularly where we think about what we screen for in the future over time and so forth, people really being conscious that “Actually, where are we going with this? Are we risking demonising certain conditions and saying we don't want them on the planet anymore and what are the consequences of that?” Advert: If you're enjoying what you've heard today and you'd like to hear some more great tales from the genomics coalface, why don't you join us on the Road to Genome podcast, where our host, Helen Bethell, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests including the rapping consultant, clinical geneticist Professor Julian Barwell about Fragile X Syndrome, cancer genomics and the holistic approach to his practice. A genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts. Harriet: And I think came to a point in our final meeting where we were asking our participants, so Suzalee and Gordon and everybody else in the room, whether you might consider having a lifetime genome for yourself and what that would look like. We'd love to share your views about that, and Suzalee, I'm wondering if you can share your thoughts on that with us first. Suzalee: Definitely. I would wholeheartedly be interested in the lifetime genome programme if it was offered to me right now. I believe that the pros for me are phenomenal. I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms. Harriet: Thank you, Suzalee. And, Gordon, how did you feel about it? Gordon: Being part of the group showed me how genomics is both thrilling and daunting.  I'd lean towards ‘yes' for a lifetime genome resource for the chance to detect conditions early, but I get why some people may say ‘no' over the data fears or ethical lines. This isn't just a science project, it's about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction. Laws would have to be enacted regarding the storage, use and availability of genetic data. We haven't yet seen as well, how AI's complete benefits in medicine will develop over time. Harriet: Thank you so much, Gordon and Suzalee, for sharing that. And, Suzannah, I know that at the end of the Public Standing Group we generally asked all of our participants whether they would choose to have a lifetime genome, the same sort of question I've just asked Suzalee and Gordon. I wondered if you could just briefly give us an overall sense of how the Public Standing Group participants felt about that. Suzannah: Yes, so it's interesting to see that actually not everyone said, despite spending a year or almost a year discussing this, not everyone said, “Sign me up,” 6 said, “No” or “Maybe.” And the reasons they gave, this idea, “Well, all this data, could a government sell it off?  What guarantees have we got?”  So that was a reason. Somewhat of a concern also about breaches but also this idea of “What do I really want to know? Do I want to have a lifetime resource that can tell me what's going to happen next in my health?” and some say, “Let me deal with it when the symptoms start coming and that's the way I want to handle it.”  So, yeah, about 20 said, “I'd be really interested,” similar to Suzalee and Gordon, 6 on the fence or firmly, “No thanks.” Harriet: Thank you so much, Suzannah. I think your point about uncertainty there is so relevant and important to us. We see uncertainty across genomics and we're layering that here with uncertainty about futures, we're layering that with uncertainty about health. And I hope that this has served to really illustrate the magnitude of the challenge we're looking at here and I think also why for us as Genomics England this is just something we're exploring. There's so much to unpack, there's so much still to be done. In terms of our next steps for Genomics England, it feels like we could speak about this for a week but I'm going to have to wrap it up here. So, for us what are our next steps?  We hope really that as we publicise the findings of this Public Standing Group and when we start combining some of our work and looking at it in harmonisation with the work that others are doing across the world, we might be better positioned to understand the potential future directions that a lifetime genome could take. That's obviously very, very exciting because we expect to see this area of enquiry expanding significantly over the coming years.  And we're already hearing about a number of other countries who are also doing birth cohort studies like we are who might hope to use similar applications of the lifetime genome going forward. So, there's a real opportunity for us here to collaborate and it's really heart-warming that the voices of our participants in this Public Standing Group can be used to facilitate that level of engagement. For us at the Generation Study, we're already looking at the next iteration of our lifetime genomes work and we're being led by the findings of this Public Standing Group as we move forward, specifically in that we're going to be starting to take some of these emerging themes to the parents of our Generation Study babies to really find out how they would feel about them. Harriet: I'd like to extend my sincere gratitude to all for being my guests today, Suzannah Kinsella, Suzalee Blair and Gordon Bedford. Thank you so much for your time and joining me in this discussion of the lifetime genome. If you'd like to hear more content like this, which I am sure you would, please subscribe to Behind the Genes on your favourite podcast app. Thank you so much for listening. I've been your host, Dr Harriet Etheredge.  This podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac for Genomics England.

In this episode of Behind the Genes, we explore how ethical preparedness can offer a more compassionate and collaborative approach to genomic medicine. Drawing on insights from the EPPiGen Project, our guests discuss how creative storytelling methods, like poetry, have helped families and professionals navigate the complex emotional, ethical and practical realities of genomics. Our guests reflect on the power of involving patients and families as equal partners in research, and how this can lead to more inclusive, empathetic, and effective care. The conversation explores how ethics can be a tool for support, not just regulation, and how creating space for people to share their stories can have a lasting impact on healthcare delivery. Our host for this episode, Dr Natalie Banner, Director of Ethics at Genomics England is joined by Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics and Dr Richard Gorman, Senior Research Fellow, both at Brighton and Sussex Medical School, and Paul Arvidson, member of the Genomics England Participant Panel and the Dad's Representative for SWAN UK. Paul shares his poem 'Tap tap tap' from the Helix of Love poetry book and we also hear from Lisa Beaton and Jo Wright, both members of the Participant Panel. "The project gave us the tools to find a different way to get at all of those things inside of all of us who were going through that experience... It's almost like a different lens or a different filter to give us a way to look at all those things, almost like a magnifying lens; you can either hold it really close to your eye and it gives you like a blurry view of the world that goes on and you can relax behind that and find a way to explore things in a funny way or an interesting way, but you can also go really close into the subject and then you've got to deal with the things that are painful and the things that are difficult and the things that have had an impact." You can download the transcript, or read it below. Natalie: Welcome to Behind the Genes. Bobbie: In an earlier conversation with Paul, he used the word ‘extractive,' and he said that he's been involved in research before, and looking back on it he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it, and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants. Our participants now have a variety of ways in which they can transport their voices into spaces that they previously found maybe alienating, challenging, and not particularly welcoming. Natalie: My name is Natalie Banner, I'm the Director of Ethics at Genomics England and your host on today's episode of Behind the Genes. Today I'll be joined by Paul Arvidson, a member of the participant panel at Genomics England, Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School, and Dr Rich Gorman, Senior Research Fellow, also at Bright and Sussex Medical School.  Today, we'll be exploring the ethical preparedness in genomic medicine or EPPiGen Project. This project examined how the promise and challenges of genomic medicine are understood and experienced by the people at the heart of it, both the clinicians providing care and the patients and families involved.  A big part of the EPPiGen Project explored using creative methods of storytelling and poetry to explore the experiences of parents of children with rare genetic conditions.  We'll discuss why the idea of ethical preparedness is crucial in genomic medicine to acknowledge the challenges and uncertainties that often accompany the search for knowledge and treatment in genomic healthcare, and to help professionals develop the skills to navigate the complex ethical considerations.    If you enjoy today's episode we'd love your support. Please like, share and rate us wherever you listen to your podcasts. Is there a guest you'd really like to hear on a future episode?  Get in touch at podcast@genomicsengland.co.uk. So, I'm going to ask our fantastic guests to introduce themselves.  Paul, would you like to go first? Paul: Hi, I'm Paul Arvidson. As well as my Genomics England hat, I've got a SWAN hat as well, I'm the dads' rep for SWAN UK, and I'm on the poets from the EPPiGen Project.  Natalie: Brilliant to have you hear today. Thanks, Paul. Rich?  Rich: Hi, I'm Rich Gorman, I'm a Senior Research Fellow at Brighton and Sussex Medical School and I've been working on some of the research on the EPPiGen Project that looks at people's social and ethical experiences of genomic medicine, and particularly families' lived experiences of genomics.  Natalie: Brilliant. Really looking forward to hearing from you. And Bobbie?  Bobbie: Hello, I'm Bobbie Farsides, I'm Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School and co-PI with Professor Anneke Lucasson of the Wellcome Trust funded EPPiGen Project, and it's been my pleasure and privilege to be involved in the work that we're going to talk about today.  Natalie: Really fantastic to have the 3 of you here today. So, we're going to take a slightly unusual approach to starting the podcast today and we're going to begin with Paul who's going to read us a poem from the book Helix of Love. Paul, over to you.  Paul: This is called Tap, Tap, Tap.  ‘Tap, tap, tap, I hold the egg to my ear. There it is again, tap, tap, tap. Run to get a torch and light through the shell, to see who's tapping from within. Chicken's home from work these days just for fun and the odd egg. Market stalls swapped for medicines, cash boxes for cough machines. We kept the apron though. Profound learning disability is our life now, most of it, learning about it, learning from it, surviving with it, despite. It's a subtle egg though, this. The shell is there, invisible, but there's a person inside, tap, tap, tap.  What are you trying to tell us about what the world's like for you? Are you bored? Do you hurt? Is your sister a love or a pain? Tap, tap, tap. I wish I could set you free.'  Natalie: Thank you, Paul. Such beautiful and powerful words. I wonder if you wouldn't mind telling us a little bit about that poem and your journey and maybe touch on what the EPPiGen Project has meant for you.  Paul: Wow, that's a lot to unpack in one go. I suppose the oddness of the metaphor is probably worth a mention. The way the project worked is that Bobbie and Rich collected together a proper poet, Dawn Gorman, and she led us through the process of kind of, she basically taught us all to be poets from scratch, it was… When you say it like that it was a hugely audacious project really to just collect all these randoms together in a room and throw a poet at them and see what happened.   And they trusted us, I suppose, and trusted Dawn that there was going to be something came out of this. But one of Dawn's techniques was that like each week we did… I think we did… Did we do 6 weeks, chaps? Which felt like a huge amount of time, but it went in milliseconds. But what she did every week was that she gave us either a poetic form to work with, like, you know, “This week we're going to learn how to do a haiku, or a sonnet,” or whatever, or she'd gone away and thought of a particular poem that she thought might resonate with us and then she'd bring that to the session. And she'd read a poem out and then say, “Right, what did you make of this? Go away and write what it inspires you to write.”    So, the poem that I wrote was, the inspiration for that session was a poem called The Egg by Richard Skinner. His poem was more about the form of the object itself, so, although that sounds really abstract, it really, really helped. So, every week it would be like Dawn threw this object into the group and said, “Right, okay, here's your new prompt, bosh, off you go.” And although that sounds like the most obscure way to deal with anything, because you get a structure around which to organise your thoughts it was just this like hugely powerful thing for everybody.    And so, the thing that came to mind for me was the metaphor of the egg rather than the egg itself and it just kind of chimed with all of us. Like we used to run the egg stall in Minehead farmers' market and so, I married into a country girl and so she had like 200 laying hens at one point, and so we had this whole market stall antics but also it spoke to so many things in one hit. So we gave up that part of our lives as our daughter Nenah's condition became more and more complex.    She was always, once we knew what her genetic condition was one of the few things that we knew from the get-go was that it was progressive. So we knew in advance that that was the case, but we didn't know what that meant. And so slowly but surely one of the things we had to do was give up our working life, you know, one week and one hour at a time, it felt. So part of the poem's about that as well, the shift in the poem from the comedy bit to the beginning to the more serious bits at the end, and it kind of felt like we gave those things up day by day but the poem kind of got to speak to that.   And then there's also the metaphor. Once you've got a good metaphor it's always good to run with it, you know? And so the idea of the metaphor of somebody who's got profound learning disabilities and can't speak being inside this shell and as parents you're always kind of peeking in from the outside to see what's going on within or to try and find ways, the idea of when you're checking to see if you've got a chick inside your shell, and you do this thing called ‘candle' where you hold the light to it, that I describe in the poem, and you like hold it to your ear and hear if there's movement going on inside. And you kind of, I don't know, I felt with a profoundly learning-disabled child that you always feel like you're doing that as a parent as well to see if what you're doing is, you know, if you're still communicating while you're trying to be a parent.  Natalie: Fantastic. Thank you so much for sharing that with us, Paul, both the poem and also your exploration of how you got to that point in writing that poem.  Tremendously powerful to kind of understand and hear about that experience.  Bobbie, if I can come to you. Paul referred to that project as kind of audacious, can you tell us a little bit about the origins of the Helix of Love but also why storytelling, especially through poetry, was so important for the EPPiGen Project?  Bobbie: Yes, of course, Natalie. But can I start by saying I was so pleased that you got Paul to speak for a while after because I always have to compose myself after hearing these poems because they really do hit so powerfully, however many times you hear them. And I think that is part of what we wanted to achieve with this project, we wanted to use innovative research methods, we wanted to be…  I love the word ‘audacious'; I'm going to borrow that.  We wanted to be audacious; we wanted to be courageous, and let me tell you, our Ethics Committee were a little bit worried about the sorts of things we told them we wanted to do. But we knew because we live and work in Brighton that the world is full of creative people and we'd already had such wonderful partnerships with people over the years, we knew that we could draw people into this project who would help us to work with this fabulous group of parents ,in a way that would give them, as Paul says, an opportunity to explore their own feelings and their own experience and share it as they wished.    In an earlier conversation with Paul, which he might find surprising that it's stuck with me so much, he used the word ‘extractive' and he said that he'd been involved in research before and looking back on it he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants, and the poetry project probably wouldn't have come about if it hadn't been for the passion of one of our participants who was sort of finding a love for poetry herself and said, “Can we try this next?” So, you know, it means so much to Rich and I that we ended up with this amazing book, but it's not our book, it's our poets', as we like to refer to them, book.   So, one of the things that we are so pleased about in this project is that our participants now have a variety of ways in which they can transport their voices into spaces that they previously found maybe alienating, challenging, and not particularly welcoming. And I think another wonderful upshot from this project has been how receptive people have been to the work. And it's a sort of commonly held myth that your average philosophy article has a readership of 3.4 people. Rich created a wonderful map to show how Helix has travelled round the world and touched thousands of people – I don't think that's an exaggeration – and we couldn't be more grateful for that as researchers because we feel as passionately about these subjects as our participants and it is they who have really got this project on the map. Paul, you were going to come in, I hope.  Paul: I feel like the one thing that this project really did was, I know PPIE is a phrase that's bandied round but this project kind of stripped that theme apart and took the ‘I' bit, this project is like built around inclusion and because it felt like, if we'd have just been jumping in a room with Dawn and told to get on with it, I don't think it would've worked as well. The idea that it was kind of curated by Bobbie and Rich, we very much felt like our hands were held through the process, and after them having had to kick down doors in the Ethics Department to be able to get the project through at all, it's like “What are you going to do to these poor parents?” having gone through that process themselves behind the scenes, then to kind of feel like we were guided through this process. And we were guided and held, and they were super-aware of all of us. And the fact that every time you tell these stories as a parent who's gone through them there's a cost. And we've had this discussion with the panel before and the communication group, about the fact that every time you come to a parent and say, “Tell us your story” there's a cost.   And so, they were aware of that, and they held that in both of their hands and so it couldn't have been anything other than this collaborative project by the time we'd finished.  Advert: The Genomics England Research Summit is fast approaching and registration is now open! Join us for this one day in-person event on Tuesday 17 June 2025. This year's agenda dives into rare condition diagnosis, cancer genomics, pharmacogenomics, therapeutic trials, and the impact of emerging technologies. Hear from leading experts and inspirational speakers as we explore the present and future of genomics and the latest research and technology from the Genomics England research community. Keep an eye on the website, genomicsresearchsummit.co.uk for all the details and to secure your spot. Spaces are limited, so don't miss out. We'll see you at the summit! Natalie: We're going to hear a clip from Lisa Beaton, a member of the participant panel at Genomics England, who shares what it has meant for her to take part in the project.  Lisa: It was an amazing opportunity. I had a huge sense of imposter syndrome actually when I as invited to join, because I was aware of some of the people who'd already taken part in the project and although I can bring lived experience to the table I don't really consider myself as a creative writer or anything like that, although I do enjoy it. When I first started in the group, we were just doing free-flowing writing. It was really cathartic, and I didn't expect that in any way, shape or form. To put pen to paper without necessarily having any strategy in mind, just letting the thoughts come out and ramble away, I didn't really know what was going to come blurting out onto my notepad, and reading some of it back was moving but it was frustrating. It was moving, it was everything really, that opportunity just as a safe space, knowing I didn't have to share it with anybody if I didn't want to but I could, and I could just, I suppose I would call it almost like a brain fart, it just rambled away and maybe it was a way of downloading some of the emotions that I was carrying.   As the project went on and we explored different creative mediums I really enjoyed that and found different skills that I wouldn't have thought about. And it was very thought-provoking, being able to go back and think about some of our very early experiences, which is, not that I've buried them but it's just you move on to deal with the here and now, and it brought me back to some of those very raw emotions of the first days which I think are, I hope, helpful to certainly the medical community in terms of thinking about how they talk to new parents going through similar situations. I was very grateful.  Natalie: Rich, I'd like to come to you now. As Bobbie and Paul have both mentioned, the outputs for this project have really spread far and wide and maybe beyond the kind of academic circles that you might typically think. I'd really like to hear from you about how you think the project has helped healthcare professionals, particularly really enabling them to understand a little bit more about what it means to be part of a genomic healthcare service and the journey that patients and families go through. Would you share a little bit about your experience in the project, particularly for healthcare professionals?  Rich: Yeah, I mean, that was one of the things that when Bobbie and I set out to do this, that was one of the real aims, was to sort of help healthcare professionals have a bit more of an insight into what it means to access genomic medicine services from a patient or family perspective. And, as Bobbie said, there were 2 ways we could have gone and done this; we could've done some sort of conventional social science interviews, written that up in a lovely social science or philosophy journal article and no one would've probably read it, but instead we thought about the power of the arts to actually change in terms of how we were sort of collecting and collating people's stories and then how we were sharing and disseminating those stories as well. And I think the medium by which stories are told affect the kind of stories that get told, as Paul was sort of hinting at earlier.    When we ask patients to tell us their story, you know, there's a level of expectation there about what people are being asked to say in a form in a way, and certainly we didn't get people in a room and say, “You must write about genomics.” So many of the poems in the collection aren't really about sequencing or big data, they're about these kind of much wider themes of everyday life. And I think that's been really powerful in allowing healthcare professionals to sort of understand for patients obviously genomics is really important but it's not the be all and end all of everything that's going on in their lives, you know, there are so many other pressures, so many other hopes and desires, and people want an opportunity to express some of those positive aspects of their life with their loved ones and it not just be medicalised all of the time.    Again, as Bobbie said, it's also opened up our research travelling really well and just become something that's really accessible for people to pick up and read through, and I've had conversations with healthcare professionals that have said, “Oh I read through the book of poetry and it's made me realise all of these things.” Language particularly has been a really prominent theme that people have reported, telling us they've learnt a lot about it, and thinking about how they write their letters and how they communicate with people. And obviously this isn't new, you know, bioethicists for years have been talking about the need to communicate very carefully, very precisely and in a caring way, but I think there's something about communicating those messages through a really powerful art form like poetry through patients' own words that allows clinicians and healthcare professionals to sort of really get the impact of that in a very, very powerful way.  Natalie: Thanks, Rich, really helpful insights there. I really want to pick up on your point about language and come back to Paul on that because I know that's a topic area that can often be, you know, hugely sensitive to families that the medicalisation, the terminology that's used, especially, you know, complex areas like genomics, coming back to this term we mentioned earlier about being sort of alienating. How have you found that the work through the EpiGen project and Helix of Love, has it potentially helped the way that families can think about the right sorts of language and enable health professionals to sort of approach some of these questions in a slightly more human way? Paul: Difficult to say. It's a very, very live topic all the time. There's like a backchat communications channel with the Genomics England panel where, because we all go along and do this thing, but we all share that genomics common thread in our lives. One parent was breaking their heart about the fact that they'd had sight of genetic science reports that basically described their child, and children like them as ‘lumped together' in a project, and she was gutted about it. And we all were as well, and we were all open-mouthed about it. The whole idea of kind of separating the science and the science language out from the people who are involved, it is our job, isn't it, you know, our job as the panel members is to remind people that those are people, not statistics. But it's a really live subject and the more people, the more professionals who can be reminded of that on a daily basis and the more we can find kind and open ways to deliver that message to professionals, and every single day that we do that makes a difference, I think. If one parent has to get less of a letter like that or one professional thinks more carefully about how they phrase stuff before it goes out the door, then that's one less parent who's got to go through that.  Natalie: Absolutely. And I'm thinking about that insight. I suppose the anticipation and the realisation to healthcare professionals about the impact of the way they approach things, the language they use, the kind of mindset they might adopt with parents and families, one really important aspect of the project was to do sort of preparedness and the idea that you should be able to anticipate and plan for and acknowledge some of the ethical challenges that might come through when you're dealing with questions of genomic healthcare where there may be lots of uncertainty, there may be a long journey to go through.   Bobbie, can I come to you to help us unpack this notion of ethical preparedness as a core theme for EPPiGen? Help us understand what that means in kind of simple terms and why does it matter for those who are working in the genomic medicine and healthcare space.  Bobbie: I think the way in which most people will have heard of this concept of preparedness is in relation to disaster planning. We know that some of the good things we try and do in life are also potentially fraught with challenges and difficulties just because of their complexity and because of the wide range of people and organisations that will be involved. Can we take this idea of preparedness and almost say, “You have a moral responsibility to be ethically prepared when, for example, you embark upon a really dramatic change in healthcare delivery or an introduction of fantastic new healthcare innovation”?    And genomics seemed to be the perfect case study for this. We then had to say, “What does that actually mean in practice?” And I think here we wanted to move away from the idea that you can ethically prepare people by putting a small albeit very expert and clever group of people in a room to write guidance and regulations, those things are needed and they're useful. But it's actually much more important to almost recruit everybody, to bring everybody up to speed, so that the ethical challenges aren't a complete shock to those who are delivering the service in the frontline, so that those who plan systems actually think whilst doing so of the ethical challenges that can be posed by the tasks they're attempting to achieve.    And I was a sort of founder member of the Ethics Advisory Committee at Genomics England, and it was so interesting in those early days because there were no patients, there were no participants. We were sitting alongside people whilst they designed and put in place basic processes, strategies and ethics was a part of that. And a really important part of that to me, at those meetings, was hearing what the potential participants had to say about it because, again, the Participant Panel was involved. And I found that those were my people, those were the people who were worrying about, concerned about the same things as I was.  So, I think to be prepared we have to take on the responsibility of giving people who work in ethically challenging areas opportunities to come together to acknowledge the complexity of the task, to share strategies and tools, but also, very importantly, to not become divorced from the people that they are attempting to serve, because in fact we feel that this part of our project, and our project is much bigger than this and we've done some fantastic things working with healthcare professionals, medical scientists, etc, etc, but this part of the project is an attempt to say, “We can better prepare families as well by ensuring that we tell them that their voices are valuable, that they're important, and they help rather than hinder healthcare professionals in doing their jobs.”  Natalie: That's a really important point around the idea that this approach can help, can be positive. Because I think sometimes you think about preparedness and, and quite often with ethics it's about risk, it's about, you know, “How do we avoid the risks?” but there's a very positive story to tell about taking a more preparedness-type approach to thinking through ethical complexities, challenges and so on, both for health professionals and, as you say, for families. I wonder if you could just talk a little bit more about the kind of positive aspects that that can bring to everyone in that genomics healthcare journey, both the health professionals and the families.  Because I think sometimes it's easy just to think that it's mostly about sort of avoiding the risks and the pitfalls, and that might be harder to engage with people if you take that sort of risk-based approach.  Bobbie: Yeah, it's an interesting one. I think the ability to confront risk and uncertainty is a sign of maturity. And we find medical students, for example, hate any sense of uncertainty; they want to be told how to do something and they want to know that they'll be able to do that thing and get it right. And our job is often to say, “Well it's not going to be as easy as that, in fact it might be impossible, and here's what you have to do instead and here's how you allow yourself to fail or to not achieve in the way that you want but still do something really meaningful for the people that you're caring for.”  So, I think there's that aspect of saying, “It's part of medical education, it's part of how we should think in organisations that wherever you take risks, wherever you try to push frontiers, blur boundaries…”  I mean, genomic medicine has done something really interesting in terms of blurring the boundary between scientific research and clinical care. Wherever you do these things there are going to be challenges but those challenges, they're fascinating, they're interesting, they can bring us together. If we've got a shared will to get through them, you know, to make things work, then it's enlivens what you're doing; it's not a barrier.   I sort of began teaching and working in the space of bioethics right back in the ‘80s, which is a shock to you, I'm sure, but in those days I'm afraid that ethics was seen as a block, a barrier, a hurdle that people had to get over or through. And I think there's still a sensitivity, and certainly, I myself have been sort of challenged on critiques that I have offered to say, “Oh that's a bit harsh.” But I think what ethics attempts to do now, and certainly through really putting a positive spin on this idea of working together to establish ethical preparedness in important spaces, is to show that actually ethics can be very facilitative, it can be very supportive, and it can help people. It's not a surveillance mechanism, it's actually another clinical tool and something that, you know, people should seek support around.  Advert: If you're enjoying what you've heard today and you'd like to hear some more great tales from the genomics coalface, why don't you join us on the Road to Genome podcast, where our host, Helen Bethell, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests including the rapping consultant, clinical geneticist Professor Julian Barwell about Fragile X Syndrome, cancer genomics and the holistic approach to his practice. A genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts. Natalie: Rich, if I could come to you thinking about that reframing, I suppose, in your own research practice as an early career researcher, whether you're seeing that maturity in approach in thinking about some of these really complex, knotty ethical questions in genomics, are you seeing a greater appreciation for those?  And where do you think you're going to take your research as a result of this project in that space?  Rich: Yeah, thanks, that's a great question. Yeah, I think so, and I think one of the things that's really been revealing in this is the appetite for this kind of work in the sort of genomics sector, an appetite for thinking about the sort of complex ethical issues, for engaging with kind of arts-based research, for sort of finding new language and new spaces to involve patient and family perspectives and stories and think about how we can learn from them.    I think in the highly scientific, highly technical space of genomics we often assume that everyone wants numbers and hard data but actually I think the way that this work has travelled, the amount of invitations we've had to sort of exhibit this work and talk to healthcare professionals and scientists about this work shows that there's this really rich appetite for thinking about this complexity and doing that work of ethical preparedness, as Bobbie's talked about, and I think it's fascinating. And I know a lot of the participants who joined in our project have also sort of had opportunities from being involved in our work and found that there are people that want to listen to their voices and hear from them and learn from them as well. So that's been really exciting, and I hope it will continue and I hope there's opportunities for much more interdisciplinary collaboration in the genomics space with philosophers, with social scientists with ethicists, with artists and, importantly, with patients.    Paul: You mentioned the idea that certainly the poetry at the very least has allowed those voices to get into different spaces, and I think when those things first started happening it was when we at least as the people who'd written the poems felt that there was a huge big impact from this stuff. And I wasn't the first one to read one of these poems out loud, and in a way the collection of poetry became bigger than the sum of its parts in a funny kind of a way. And I can't remember but somebody read one of the poems at a conference somewhere and they said at the end of it that you could've heard a pin drop, and it was just that thought that actually with a big audience expecting kind of quite dry subject matter about genetics, to have felt that moment where the poem got launched off the stage and then it impacted on the audience and then, the way they described it, you could almost kind of feel them describing the ripples of the poem just like spreading out amongst this kind of silent audience and everyone kind of taking this kind of mental sigh of like “Oh that's what it feels like.” And the idea of that happening was when, for me anyway, when we knew that what we'd created was bigger than the sum of its parts and had its own legs, Bobbie and Rich had been the Dr Frankensteins of this kind of amazing, beautiful monster. Natalie: Obviously the poetry's got into your soul, Paul, the metaphors are fantastic. But just to make sure we bring in even more participant voices and perspectives into this we're just going to hear now from Jo Wright, who's another member of the participant panel, who's going to share what the project and the participant in it has meant for her.  Jo: So being part of the EPPiGen Project, it helped me to find my voice in an area that was relatively new to me, and also it was a way to take control of my own experiences rather than feel like I'm being swept along by a lot of systems.    And there were things that I really value that I thought contributed to making the project so successful. One was that they asked the question “What is this experience like for you, the experience of being part of a research project, the 100,000 Genomes experience of waiting, the experience of having your data in the library?” And no one had asked that before. You go to your appointments and you're in the system and, you know, it's kind of, everyone was finding their way to some extent because it was new for all the clinicians as well, but the fact that they asked, because no one asked that before, I don't have an outlet for that.     And then the other thing was that it was completely open so there was no research interview or questionnaire to answer, no expectation about what it was going to look like at the end. And I think working that way really strengthened the connection between us as parents of children with rare conditions and then also our relationships with Bobbie and Rich as the researchers and with the wider clinical community when they started to see our work and respond to it. So it was a way to understand people's individual experiences but it also made us feel connected and empowered through sort of like shared human experience, and that could be between us as the participants but also shared experiences between us and the researchers or us and clinicians and scientists that were looking at what we've done.  Natalie: So we've heard lots about the experience of participating in this fantastic EPPiGen Project, the kind of creative storytelling methods, the audacious methods that have been used, and some fantastic impacts beyond the kind of typical what could be quite dry sort of academic circles that this kind of work has spread out to.  I'd be really interested to hear from each of you about the takeaways, what you've learned, what's changed for you and what you'd like our listeners to really understand about this project and the work, and the sort of outputs from it and the ways it might continue to have resonance and impact going into the future, so whether people are patients, families, clinicians, researchers. What would you like people to remember and what's affected you most about the project?    Bobbie, I might start with you.  Bobbie: I think we have to always be very careful when we get excited about something - and the ‘we' here are the people in the health community, the education community, etc - to remember. As Rich said earlier, that this is only ever going to be quite a small part of other people's lives. You know, we've all devoted big parts of our careers, our enthusiasm, to thinking about genomics, to working in this space. I would really like people to pick up the book and work to understand a bit better about the everyday lives, the hopes, the expectations, the fears of the families who may or may not get a diagnosis, may or may not get on a good treatment path, all of whom want the best for themselves and everybody else from this venture.    But, as Paul knows better than most, it won't come to everybody, and we don't want anybody to be forgotten along the way. The people that signed up for Genomics England as participants were pioneers alongside medics and the scientists, and in these early years we want their experience to be recognised, and their experience goes much beyond their interaction with Genomics England and, unfortunately, all the work that we've produced shows how many challenges families have to face to secure a good life for their children, and I just want us all to just keep that in mind.    Natalie: Incredibly important to maintain that focus, that awareness. And, as you say, Bobbie, there's an interesting balance where there is a need for the drive and the innovation and the ambition to help ensure that we are pushing at the forefront of medical research but not leaving people behind and not ever forgetting, as you say, the experience of people who are actually at the forefront of this research and of genomic healthcare.   Paul, could I ask for your perspectives on this, and particularly how you see patient voices being involved in the future of genomic medicine, especially in light of your experience in the EPPiGen Project?  Paul: I think the biggest surprise and biggest takeaway for me was the project gave me, I mean, I can't speak necessarily for all the other poets, but you only need the evidence in the book itself. They gave us the tools, the project gave us the tools to find a different way to get at all of those things inside of all of us who were going through that experience. So it gave us a way to talk about all of those things and a way that was I suppose slightly removed to start with. It's almost like a different lens or a different filter to give us a way to look at all those things, almost like a magnifying lens; you can either hold it really close to your eye and it gives you like a blurry view of the world that goes on and you can relax behind that and find a way to explore things in a funny way or an interesting way, but you can also go really close into the subject and then you've got to deal with the things that are painful and the things that are difficult and the things that have had an impact.    But, because you've got that tool and you're used to using it or you're familiar with using it, it then gives you that safety. That's how I felt about it anyway, it was a massive tool to be able to get behind all of these things that I didn't even know I was feeling, or I knew they were making me uncomfortable, but I didn't know what they were or what name to give them. So the poetry gave us a chance to get behind all of that. Having read the poems, it feels like it's that for everybody but obviously you'd have to speak to them to know, but it certainly felt like that for me.  Natalie: And, Rich, your perspective.  What are you taking forward from the project, so what would your sort of key takeaway be?  Rich: I think it shows what is possible under that PPIE acronym. And there are many ways to do that involvement and engagement, it doesn't have to be a sort of dry tick-box exercise, there are much more creative ways to bring people's lived experiences and perspectives into conversations with genomics. So really, I suppose it's a call for other people to explore working in this way as well and think about what other kind of creative outputs could work here. I mean, we've had huge success, and I think a really interesting impact from working in this way.    And certainly as an early career researcher it's been really formative in my sort of academic journey, you know, reaffirmed that this is the kind of work that I want to do, working in this really co-productive way. And I think it's possible, it can be done, and, you know, ultimately it's just been a real privilege to do this kind of research, to sort of be trusted to sort of hold a space together for sharing people's stories and give people a platform to share some really powerful profound stories. And going back to what Paul was saying earlier, I think he hit the nail on the head, as he very often does, this is about evoking people's experiences, not just explaining people's experiences, and allowing those stories to travel.  And we don't know where stories will travel, we don't know how stories will travel, we don't know how stories will be received, but we know that they do sort of travel and they do have legacy and they stay memorable to people, they have emotional resonance. So, the impact of this work can often be hard to sort of pin down really specifically, but we know those stories are out there and people are listening and changing their practice as a result.  Natalie: We'll wrap up there. I'd like to thank our guests, Paul Arvidson, Professor Bobbie Farsides and Dr Rich Gorman, for joining me today as we discuss the EPPiGen Project. We heard some powerful insights from patients and families about their experiences, and why ethical preparedness is so important in the context of genomic medicine. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand. 

As of February 2025, the Generation Study has recruited over 3,000 participants. In this episode of Behind the Genes, we explore what we have learnt so far from running the study and how it continues to evolve in response to emerging challenges. The conversation delves into key lessons from early recruitment, the challenges of ensuring diverse representation, and the ethical considerations surrounding the storage of genomic data. Our guests discuss how ongoing dialogue with communities is helping to refine recruitment strategies, improve equity in access, and enhance the diversity of genomic data.  Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Alice Tuff-Lacey, Program Director for the Generation Study; Dalia Kasperaviciute, Scientific Director for Human Genomics at Genomics England; and Kerry Leeson Bevers, CEO of Alström Syndrome UK. For more information on the study, visit the Generation Study website, or see below for some of our top blogs and podcasts on the topic: Podcast: What do parents want to know about the Generation Study? Podcast: How has design research shaped the Generation Study? Blog: What is the Generation Study? "We always have to remember, don't we, that if people say no to these things, it's not a failure to on our part, or a failure on their part. It's just something they've thought about and they don't want to do, and for all sorts of different reasons. And the other reflection I have about different communities is the ‘different' bit, is that what approach works for one community may not work for another, and I think that that's something that's going to have to evolve over length of the study, is finding the things that are the right way, the most helpful way to approach people." You can download the transcript, or read it below.   Vivienne: Hello and welcome to Behind the Genes.    Alice: “And this is quite an exciting shift in how we use whole genome sequencing, because what we are talking about is using it in a much more preventative way. Traditionally, where we've been using it is diagnostically where we know someone is sick and they've got symptoms of a rare condition, and we're looking to see what they might have. What we're actually talking about is screening babies from birth using their genome, to see if they are at risk of a particular condition, and what this means is this raising quite a lot of complex ethical, operational, and scientific and clinical questions.”    Vivienne: My name's Vivienne Parry, and I'm Head of Public Engagement here at Genomics England, and I'm your host on this episode of Behind the Genes.      Now, if you are a fan of this podcast, and of course you're a fan of this podcast, you may have already heard us talking about the Generation Study, the very exciting Genomics England research project which aims to screen 100,000 newborn babies for over 200 genetic conditions using whole genome sequencing.      Well, we've got more on the study for you now. What we're doing to make it both accessible and equitable for all parents-to-be, and our plans to ensure that we continue to listen to parents, and perhaps in future, the babies as they grow up. We'll chat, too, about emerging challenges and how we might deal with them.    I'm joined in our studio by Alice Tuff-Lacey, the Programme Director for the Generation Study, and Dalia Kasperaviciute, Scientific Director for Human Genomics, both from Genomics England, and we're delighted to welcome Kerry Leeson-Bevers, Chief Executive of Alström Syndrome UK. And I'm just going to quickly ask Kerry, just tell us about Alström Syndrome and how you're involved.    Kerry: Yes, so Alström Syndrome is an ultra-rare genetic condition. My son has the condition and that's how I got involved. So, the charity has been around now since 1998, so quite a well-established charity, but as part of our work we developed Breaking Down Barriers, which is a network of organisations working to improving engagement and involvement from diverse, marginalised and under-served communities as well.    Vivienne: And you wear another hat as well?  Kerry: I do. So, I'm also a member of the research team working on the process and impact evaluation for the Generation Study. So, I'm Chair of the Patient and Public Involvement and Engagement Advisory Group there.    Vivienne: Well, the multiply hatted Kerry, we're delighted to welcome you. Thank you so much for being with us.      So, first of all, let's just have a sense from Alice Tuff-Lacey about this project. In a nutshell, what's it all about, Alice?  Alice: Thanks Viv. So, I think in the last few years we've seen some really big advances in the diagnoses of rare diseases through things the Genomic Medicine Service. But we know it takes about 5 years often to diagnose most of these rare conditions. What we also know is that there are several hundred of them that are treatable, and actually there can be massive benefits to the child's health from diagnosing and treating them earlier. I think a really good example of this which is often talked about is spinal muscular atrophy, which is a particular condition where there is a genetic treatment available and there is a really big difference in families from those babies where the condition was identified later on, versus their brothers and sisters where they were identified early because they knew there was a sibling that had it and they were given that treatment.     What we think there is a huge potential opportunity to identify these children from their genome before they get ill, and this is quite an exciting shift in how we use whole genome sequencing, because what we are talking about is using it in a much more preventative way.  But this is a really different approach to how we've been using it so far, because traditionally where we have been using it is diagnostically where we know someone is sick and they've got symptoms of a rare condition and we are looking to see what they might have, what we are actually talking about is screening babies from birth using their genome to see if they are at risk of a particular condition. And what this means is, this raises quite a lot of complex ethical, operational and scientific and clinical questions.      So the aim of the Generation Study is really to understand if we can and should use whole genome sequencing in this way to screen for rare conditions in newborn babies. We've been funded by the Department of Health and Social Care to do this over the following years, and the way we'll be doing this is by a national study across a network of trusts in England where we are aiming to recruit about 100,000 babies and screen them for rare treatable conditions that we know present in childhood. And really the aim of this is to understand if this will work and how it will work, and to generate the evidence to allow the NHS and the National Screening Committee to decide if this could become a clinical service, and that's very much the primary goal of the study.      Beyond that, however, there are some other aims of the study, and we also consent mothers to ask permission to retain their genomic data and to link it to the baby's clinical data over their childhood, and we'll be providing access to this to researchers in the de-identified way in our trusted research environment. And this is to really understand if that data can also be used to further generate information around other discovery research, but also critically understand that the motivations for parents involved will be very different, and we need to think very carefully about how we engage and work with the parents of the babies going forward about how we use their data.    Vivienne: And the super exciting thing is we've started recruiting. How many mothers have we recruited?  Alice: So, we've recruited over 3,000 to date, and it's building every day and every week really. And it's really exciting because we see more and more trusts coming online and the study building and really starting to learn from the experience. And every week and every month, we're learning much more about how this process works, what the impact it's having, and kind of what we need to do over the coming few months and years to deliver it.    Vivienne: And we did a huge about of work at Genomics England before the study even started, to try and find out what people wanted. So, we found out, for instance, that people didn't want to know about late onset conditions, they did want to know about conditions where there was a treatment, and they wanted things that could be done for their babies in childhood. So, we had a really clear steer from the public about this project before we even started. So, how are we continuing to learn from the people who are involved in the study and the public? I mean Kerry, you've been involved in this aspect. We need to listen, don't we, to find out what's going on?    Kerry: We do, we do, and I think it's really encouraging to see the public dialogue and the amount of engagement work that was done there to kind of identify what some of those areas were, but it's really important that we don't stop that engagement there. It's really important to continue that, and I know that we've got quite a diverse group for our Patient and Public Involvement Advisory Group and the Evaluation Team, and one of the things they're really interested in is how we're going out there to speak with communities. You know, we can't just be reliant on the media, and press releases about the study. We need to actually go to communities and have these conversations so that people can have a conversation within an environment that they feel safe and confident with the people that they feel supported by as well.    So I think it's really key that we continue to ask those questions but also learning from the evaluation and, as we go through the process, of speaking to the patient organisations as well who support families that suffer from some conditions that we plan to identify through this study, and learn what some of their challenges are as well. You know, do they feel equipped to be able to support parents that are getting a diagnosis? As well as obviously their participants and the general public, to make sure that we're aware of attitudes and perceptions as the study goes along.    Vivienne: Because there's always a danger with this kind of study that it's people who are health literate who end up being involved. Whereas some of the people on whom the burden of rare disease is greatest may not either feel that they can access, or would want to access, this study. So, what are we doing there? How are we listening to people?  Kerry: When we are looking at recruitment as well, like you say, you know this is a research study and when we look at history and when we look at participants in research studies, we very rarely do you get a diverse representation of people in these types of studies. So, it's really important that those extra efforts are made really in terms of recruitment to get the right sample of people involved. And I know at Genomics England, that they have invested their time and money in terms of interpreters and translating materials and things, but actually it's the sites and recruiting people that need to be well resourced in order to use recruitment strategies, because if we're just looking at posters in waiting rooms, for instance, you're going to get a particular demographic of people that will respond to those kind of posters, such as people who don't speak English as a first language, it would be really difficult sometimes to read those kinds of posters and then to ask questions about that.     We need skilled people within sites that are recruiting who have got cultural competence who can have those conversations, address some of those areas, some of those concerns so that we can get that diverse representation.    Vivienne: So, there's a whole piece about equity of access for everybody and Dalia, perhaps you can explain why this is so important, scientifically as well as ethically? There's another piece about making sure that we get a full diversity represented.    Dalia: We know that some of the conditions are more common in certain populations or certain communities. We also know that some of the conditions are caused by certain variants in one population but not in the others. And these genetic causes even of the same condition can vary between different communities and different genetic ancestors.  On the other hand, our knowledge about the conditions and the genes, and the variants which cause them, come a lot from what we've seen before. Where we've seen those variants in the patients with the disease, and importantly where we've seen those variants in control populations where these individuals which don't have conditions.      Therefore, if we lack the diversity in our datasets, we would not know about all the diverse reasons of why conditions can be caused, or how it progresses, or what it might mean for individuals. And we would not be able to have equitable testing, or we wouldn't know whether the test works for everyone. If that happened, we might be in the territory where we can't detect or don't detect as well all the conditions across different individuals. But also, we may be having more false positive results and create more anxiety for families as well as burden for healthcare system.    Vivienne: So, are you saying, Dalia, that actually sometimes we might get a false positive, or indeed a false negative, simply because in that person, the condition which we think is usually caused by a particular change, they've got a slightly different change and so therefore we're not picking it up.  Dalia: Indeed, but it's one of the possibilities. If, let's say, all our knowledge about certain genes came from a limited number of individuals, seeing a new variant in another individual might seem that it's something really rare and never seen before and it's potentially changes how the gene functions, we would say; “oh that's maybe something which causes the disease,” when actually it can be that it is a benign variant, just a normal variation which is very common in another part of the world, it's just that we don't have enough data to know about it. So, we need to be aware of those risks and take it into account when we interpret the variants.      And, we also need to be transparent when operating in the environment. There was historical and investment in the diversity in research and our data sets still are not as diverse as we would like to be. It's shifting, the balance is definitely shifting in the last few years. A lot of effort is being done but the only way to shift the balance forever and make that genomic medicine work for everyone is to really actively engage those individuals and involve them in the research, and taking all the effort that Kerry was talking about.    Advert: The Genomics England Research Summit is fast approaching and registration is now open! Join us for this one day in-person event on Tuesday 17 June 2025. This year's agenda dives into rare condition diagnosis, cancer genomics, pharmacogenomics, therapeutic trials, and the impact of emerging technologies. Hear from leading experts and inspirational speakers as we explore the present and future of genomics and the latest research and technology from the Genomics England research community. Keep an eye on the website, genomicsresearchsummit.co.uk for all the details and to secure your spot. Spaces are limited, so don't miss out. We'll see you at the summit!  Vivienne: Alice, that goes back to this thing about holding the genomic data, because you need to hold the genomic data because the thing about genomics as always, you need to know what happens next. So, for instance, if somebody had a negative result and then later developed a condition, you need to be able to go back that data in order to find out what the problem was.  Kerry: That's right. You know, as Dalia talked about, we know that there is a risk within the study and we try and be clear about that in our participant information that there are some babies where they may have a genetic condition that we will need not find it, and others where we might find something that doesn't go on to be the actual condition. And we need to kind of monitor those in different ways.      So in particular in the cases where, if we've returned a result where we don't think we suspect a condition and a baby goes on to develop a condition, it's quite complex how we monitor that, and we're trying to go for a multi-track approach, and I think a lot of the benefits is some of the infrastructure that Genomic England already has that we can utilise.  So, some of the foundational things we've put into the study to help support the approach are things like the ability to contact parents regularly so we can actually work with them to find out over time if their babies develop conditions.    As you say, ability and consent to access the clinical data about the baby so that we can then access national data sets, and then we can then potentially monitor to see if babies seem to be showing signs of developing a condition. And also, really continuing to work with a network of clinical specialists where we've work quite hard over the last couple of years to build that kind of network and engage with them about the study, because they'll be the ones who the babies will come to if they develop those conditions. So, they are a really good route to us finding out, whether or not there are babies who have been part of the study who then go on to develop a condition.     And I think the reality is that this is a really complex process and it's something that even traditional screening programmes really struggle with, and that's why this multi-pronged approach is really important, and why also we see that this approach will evolve over time, and at the moment, the important thing is we've worked hard to put the right foundations in to allow us to do this type of monitoring, and to really evolve that approach as things develop and as more things come along potentially where we can invest in.    Vivienne: So, it's interesting, isn't it, because I guess that some parents would think that if you get a false positive or false negative, that it means that the test is at fault. And actually the accuracy of the test is good, but what we may have an issue with is that there is something else causing the problem that we don't yet know about. So, a big part of this project is giving much, much more information about the causes of conditions.    Alice: Yes, and I think that's also why the discovery research aspect is really important, the fact that we consent for that ability to hold the baby's data. So not only will we want to use it for the evaluation, but as I mentioned at the beginning, we have asked for parents to be able to allow us to link it to clinical data which then allows us to track over time and find out more information, because it's always the quality of the information we know that will help us in the future to identify these conditions, so the more we can generate potential information, you know, the more we will learn as a society.    And so it's actually quite an altruistic thing we're asking of parents, and that's something we recognise and that's why it's also important we think about, how we continue to engage with the parents and the baby over their lifetime to remind them that we're holding this data, but also to understand what their concerns and feelings are about us holding that data and how we're using it for that broader research.  Vivienne: And that's very much what you're involved in, isn't it Kerry?  Kerry: Yes, and I think sometimes in some ways that may offer some reassurance to parents as well, to know that's there as a reference point if things do develop over time, but I know that one of the things we're looking at as part of the evaluation, and the PPI Group we're involved in, is looking at the experiences of patients through this journey because actually it will create quite a lot of uncertainty.      As a parent of a child with a genetic condition, that uncertainty really is one of the hardest things to learn to live with. So at that early stage, one of the things we're looking at is that experience, how much support people have received, whether that has an impact on the parent and their child and their on bonding and their experiences and things like that, and I think it is important that we do that, but I think also having those references, where you're able to go back and ask those questions, that's really important that the support is in place, and that pathway really for parents to know where to go to. Because sometimes, although we may arrange to have calls at regular intervals and things, sometimes the questions of parents don't necessarily come at the time when they are having a telephone call. They come really late at night when there's nobody to pick up the phone, so having as much information as we can available, and those support structures in place, is really key.    Vivienne: We all start off these projects thinking that they are going to go in a particular way, but actually there's a lot of flexibility in this study, isn't there, Alice?  For instance, we will be looking at all those false positives, false negatives because we need to learn from that. We will be, perhaps, changing our approach as we go on if there is something that isn't working out. Is that what we're doing?  Alice: Yes, I think what we have recognise is it is a study and therefore that involves learning by it's very nature, and that's why partly we're working with external evaluation partners that Kerry's involved with, but also why we invest in a lot of things internally. Like we do a lot of user research with our midwives and our participants, and also potential participants. Because, actually we don't know the answer to this. No one's done this before, and so this is about all of us really learning, and learning in the right way and continuing to do that throughout the study, but also more importantly capturing that information and making sure that at the end of it, we then have some understanding of if we were to see that it's right to deliver this as a clinical service, what that might actually involve.      But also, even if we get to that point, I think beyond that we will still continue to learn over time and that's again why that long enduring consent is quite important, because we can then continue to maintain that long term evaluation and continue to maintain that long term potential to help further further research. And so that's the thing where actually we'll be learning for the next 10-15 years, really what the Generational Study has learnt, and actually what we have achieved through it.  Vivienne: I just want to move back to something that you mentioned, Kerry, about conditions that we're looking for, and there were a lot of very specific things. I've said that what parents wanted, but there's also some scientific things, and Dalia might want to come in here, that these are conditions that we pretty sure that if you've got the particular genetic change, that you will get the condition – something called penetrance. So, you know, we're not leaving people with a lot of uncertainty. But, how will we go about assessing new conditions as part of this study, or are we just on the ones that we're on at the moment?  Dalia: So, we started from the things we understand the best and we know how to detect them and we know how to confirm them because the tests that we are doing in Genomics England is a screening test, it will not be a definitive answer whether you have or you don't have a condition. Anyone which will get a positive result will be referred to an NHS specialist clinician for further assessment. And some of those positive results turn out not to have the conditions and some of them will have, and they will have their treatment pathways. So, we're started to very cautiously, and that's what came from public dialogue, everyone was saying that; “you need to be really cautious, we need to see that it works for the conditions that we understand well”.     But as a starting point, as we learn more, we're learning of how could we expand that list.  What would be acceptable for public. Maybe some conditions will have an experimental treatment, which currently would not be included in screening but as treatments evolve, at some stages maybe there will be opportunities to include some conditions in the future.      As our science evolves, we keep assessing the new conditions and seeing can we include them, would it be acceptable to parents, would it be acceptable to the healthcare system, and one of the things about screening it's really important not to cause harm. There are a lot of benefits in screening but if we didn't do it cautiously, it also has some risks, and we need to be very careful about it.    Vivienne: Now Kerry, there are lots of parent groups who will come along to us and say; “oh you must include this condition,” but perhaps there isn't yet a treatment, or there isn't a pathway in the NHS that will help people get what they need. And I guess if we try to include too many conditions, we would actually undermine trust.    Kerry: So, the patient organisation, our condition, Alström Syndrome, isn't included in the list. For our condition, there is no specific treatment although we do have a highly specialised service, and it is very important to get early diagnosis because children can develop heart failure and there are symptom-specific treatments available there. But I get the reasoning why there needs to be a specific treatment and the need to include just a smaller group at the beginning, but our hope as with I'm sure a lot of other patient organisations, is that our condition will be added at a later time if it is found that this is something that would be acceptable in routine care.    Advert: If you're enjoying what you've heard today and you'd like to hear some more great tales from the genomics coalface, why don't you join us on the Road to Genome podcast, where our host, Helen Bethell, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests including the rapping consultant, clinical geneticist Professor Julian Barwell about Fragile X Syndrome, cancer genomics and the holistic approach to his practice. A genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts.  Vivienne: Let me move on to another aspect of this study. These are babies, and we are holding their genomic information but at 16, they will be able to decide whether they want us to continue holding their genomic information. Alice, is that very much part of this programme to think about what we're going to say and how we're going to engage those 16-year-olds?  Alice: Yes, it very much is. What I always say, because I get asked this question a lot, is that I don't think we can pre-judge what that looks like. Because I look at my children, and certainly their lives are very different from my childhood, and I don't think we can imagine exactly what our babies will look in 16 years and what that world looks like. I think the important thing is many of things we are trying to do is that we lay the right foundations in place, and part of that is ensuring that we continue to think about how we engage with young people as the study evolves and over time, so that we understand what the world is looking like from their perspective.      But also, how do we equip the parents to talk about the fact that these babies are part of the study to them? What does that look like? How can we support them? And that's very much something we want to be looking at in the next year, really working with parents from the Generation Study to understand how best we can do that so that they can have some of that conversation for themselves as well. I think we can't pre-judge exactly how we need to talk about them and also not think it's just one thing. We need to evolve and work with the children as they grow up, and work with their parents to equip them because, as I said, we don't really know how they're going to access information in the future. You know certainly TikTok didn't exist when I was a child, and so that's what we've got to think about is what's the best avenues or forums to really engage properly with them as they grow.  Vivienne: Kerry, what other concerns to parents have that we're learning now?    Kerry: I think the concern is that when treatments are being developed, that they are not necessarily being developed for the whole population. They're often being developed for sub-sets of population because we don't have a complete dataset. And when you think about people being involved in research, people feel that they are being left behind because their data is not necessarily represented within there, it doesn't reflect their community, and it's not being discussed within communities, the different research opportunities and things have been available, I think it's the fact that we're not investing enough in community engagement and dialogue to explain more about genetics.   I think technology has advanced at pace. As a parent of a child with a genetic condition, that is very encouraging to see that, but I think sometimes the support and the information is not necessarily keeping up, so we're not having those open conversations really about genetics and genomics, and I think that's one of the things I hope that this study will really lead to, that it will now become much more part of everyday conversation.   Because often, when you have a child with a genetic condition, you first hear about a condition, the way you take in that information and ask questions is very different than having a conversation with the general public about genetics. When you're concerned that your child may have a condition or you may have a condition yourself, you're in a completely different mindset. So, the hope is that that dialogue will open so that people will be able to ask questions to learn more about the projects and things that are out there and available so that people are included and can take part in research if they want to. But it's important to remember that not everybody will want to. It's about being given informed choices and to do that we need to make sure that the support and the information is appropriate, inclusive and accessible.    Vivienne: We always have to remember, don't we, that if people say no to these things, it's not a failure to on our part, or a failure on their part. It's just something they've thought about and they don't want to do, and for all sorts of different reasons. And the other reflection I have about different communities is the ‘different' bit, is that what approach works for one community may not work for another, and I think that that's something that's going to have to evolve over length of the study, is finding the things that are the right way, the most helpful way to approach people.   Kerry: I completely agree. I think it's like you say, if people say no, that is completely their right to do so as long as they're saying no when they've been given the information to be able to really take that on board, think through, consider it and then make an informed decision. I think often people say no because they've not been given the right information to be able to understand what is expected, so they've not necessarily been given the opportunity. And I think we all want good outcomes for everybody. That doesn't mean delivering the services in the same way. Sometimes we need to deliver services in different ways because often services aren't very accessible for some communities to be able to access. So sometimes we need to make changes, adapt, to make sure that everybody has the same opportunities to the same outcomes.  Vivienne: We are constantly re-evaluating, rethinking, re-engaging to try and make it the best we can. Whether it's with different communities and different approaches. Whether it's with constantly assessing people who've had false positives, false negatives and finding out why that is the case. And in the future, I think this will have some really major effect.  Dalia, you're the scientist amongst us today. Tell us what you're hoping for from this study in science terms.  Dalia: So, first of all, we want to find the babies which we can treat before we develop symptoms, before we get ill, so that we can have more fulfilling lives. That's the bottom line. But we're doing that, we also will learn about the conditions. We'll learn a lot about the natural history of the conditions. What happens when you detect it before baby gets ill, then you start treatment, and how does it work in the diverse communities and diverse populations that we've talked about. Are there are any differences based on people's ancestry, but not just ancestry, about their lifestyle, about anything else which can affect how disease develops, or how the care or treatment goes.      So, that's kind of the bottom line. The top line and now our ultimate aim, probably many years from now, would be that we can detect variants of genes or conditions before they develop, and we can create treatments for them before our children get their conditions.  That's something that the science community is very excited about. I think we're quite a few years from that, but that's where we hope all this will be heading in the future.    Vivienne: It's really becoming a possibility, but the science is only the first part of it. It's the human interaction. It's the how it lands with people. It's how they feel about it. It's how they trust it. And these are all the things that we're really working on at Genomics England to make this study not just a scientific success, not just a success for the NHS, but also something that is really meaningful and important and valuable and trusted for people having babies. Would you agree?  Alice: Yes, 100%. I think, just to come in there, Viv, I think we've talked a bit about the importance of public trust and being the foundations of what we do, and I think that's something that Genomics England's always held true to itself, but I think for the purpose of the Generation Study, it's been one of kind of the foundational principles from the beginning, and I think Kerry and you have touched upon some really important themes today about how it's not a ‘one size fits all' approach. And I think very much that piece that we touched on a bit about, kind of, how do we make this accessible to everybody, we see it very much as not a ‘one size fits all', and so we've been trying lots of different things to really tackle that, and evolving the approaches which, as you said, that's where the flexibility comes in.      My hope for the next 12 months is that we can really, now that we've got the study up and running, work a lot with the some of the regional networks, the Genomic Medicine Service alliances who are working at the regional level, and the recruiting trusts, to really explore different approaches and work out how we can support them to engage with the communities in their areas, because they're the ones who will understand who they are, and our role is to really try and provide, as Kerry highlighted, the tools of support to allow them to do that, and to try and make sure that we can make this as equitable as possible in terms of people being able to at least understand the studies here, get the information in the appropriate way, and then as we have also talked about, making their own minds up about whether this is the right thing for them to be part of.    Vivienne: So, the final question for you all is if I'm a mother-to-be, where can I find out more information. Let's start with you, Kerry.  Kerry: Well, from the Generation Study website, there's information there. Midwives, GP practices, obviously they're often going to be your first port of call, so I'm hoping that they feel equipped to be able to answer those questions and to signpost people to one of the trusts that are involved.    Vivienne: And we've also got a Genomics 101 episode where we answer some of the frequently asked questions, and I think there are at least 2 or if not 3 separate episodes from Behind the Genes, which people can look for which look at different aspects of the project. Anything else, Alice, that we need to know?  Alice: So, Kerry highlighted it, the Generation Study website is a really good starting point, but that's a good place to also find out what trusts are involved because it's also important to know that this is not available in all trusts in England at the moment. We have a network and it's growing, and it is all around England, but the first place to start is, kind of, is it in your local trust?  And then from there, it's then engaging with your trust and hospitals where there will be information, and the midwives are prepared to kind of talk to people.  So those are, kind of, the good first places to start.    Vivienne: Well, we're going to wrap up there. It's been so good talking to you all. So, thank you to our guests Alice Tuff-Lacey, Kerry Leeson-Bevers, and Dalia Kasperaviciute for joining me as we talked through how the Generation Study is continuing to evolve as it responds to emerging challenges. Now, if you would like to hear more about this, then please subscribe to Behind the Genes on your favourite podcast app and, of course, we hope that you would like to rate this.  Because, if you rate it, it allows more people to see it and more people to get enthused about Behind the Genes, which we love. It's available through your normal podcast apps. I've been your host, Vivienne Parry. The podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand at Genomics England. Thank you so much for listening. Bye for now.  

Multi-platinum singer-songwriter Christina Perri is best known for her hits A Thousand Years and Jar of Hearts, but behind her music lies a deeply personal story of resilience. From battling lifelong mental health challenges to navigating the heartbreak of miscarriage and stillbirth, Christina has endured unthinkable loss—including the tragic passing of her daughter Rosie in 2020. But through it all, she has transformed her grief into action, advocating for maternal healthcare reform and using her platform to inspire others. Here are Christina's Crisis Comforts This is a paid advertisement by BetterHelp. Give online therapy a try at betterhelp.com/CRISISPOD. Our listeners get 10% off their first month.Full episode: https://podcasts.apple.com/gb/podcast/christina-perri-on-fame-grief-and-turning-pain-into-purpose/id1517015748?i=1000697514142   Website: https://www.christinaperri.com/ X: https://x.com/christinaperri Facebook: https://www.facebook.com/ChristinaPerriMusic/ Instagram: https://www.instagram.com/christinaperri/ TikTok: https://www.tiktok.com/@christinaperri YouTube: https://www.youtube.com/christinaperri%20 Host: Andy Coulson  CWC team: Jane Sankey, Hana Walker-Brown, Bill Griffin, Louise Difford, and Mabel Pickering With special thanks to Ioana Barbu and the brilliant people at Global  For all PR and guest approaches please contact – podcast@coulsonpartners.com  

Multi-platinum singer-songwriter Christina Perri is best known for her hits A Thousand Years and Jar of Hearts, but behind her music lies a deeply personal story of resilience.From battling lifelong mental health challenges to navigating the heartbreak of miscarriage and stillbirth, Christina has endured unthinkable loss—including the tragic passing of her daughter Rosie in 2020. But through it all, she has transformed her grief into action, advocating for maternal healthcare reform and using her platform to inspire others.In this episode, Christina opens up about her struggles with addiction, the pressures of fame, and the lessons she's learned as a mother. She shares how she found the strength to keep moving forward, why she's fighting to change medical protocols for pregnancy loss, and how music continues to be her guiding force.This is a paid advertisement by BetterHelp. Give online therapy a try at betterhelp.com/CRISISPOD. Our listeners get 10% off their first month.Website: https://www.christinaperri.com/X: https://x.com/christinaperriFacebook: https://www.facebook.com/ChristinaPerriMusic/Instagram: https://www.instagram.com/christinaperri/TikTok: https://www.tiktok.com/@christinaperriYouTube: https://www.youtube.com/christinaperri%20Host: Andy Coulson CWC team: Jane Sankey, Hana Walker-Brown, Bill Griffin, Louise Difford, and Mabel PickeringWith special thanks to Ioana Barbu and the brilliant people at Global For all PR and guest approaches please contact – podcast@coulsonpartners.com

Rare condition research is evolving, and patient communities are driving the breakthrough. In this special Rare Disease Day episode, we explore the challenges and opportunities shaping the future of rare condition therapies. From groundbreaking gene therapy trials to the power of patient-driven research, our guests discuss how collaboration between families, clinicians, researchers, and regulators is paving the way for faster diagnoses, equitable access to treatments, and innovative approaches like nucleic acid therapies and CRISPR gene editing. With insights from Myotubular Trust, we follow the journey of family-led patient communities and their impact on advancing gene therapy for myotubular myopathy - showcasing how lived experience is shaping the future of medicine. However, while patient-driven initiatives have led to incredible progress, not every family has the time, resources, or networks to lead these research efforts. Our guests discuss initiatives like the UK Platform for Nucleic Acid Therapies (UPNAT), which aims to streamline the development of innovative treatments and ensure equitable access for everyone impacted by rare conditions. Our host Dr Ana Lisa Tavares, Clinical lead for rare disease at Genomics England, is joined by Meriel McEntagart, Clinical lead for rare disease technologies at Genomics England, Anne Lennox, Founder and CEO of Myotubular Trust and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at University of Oxford. "My dream is in 5 to 10 years time, an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested. And at that exact time, the day of the diagnosis becomes also a day of hope, in a way, where immediately the researcher that sent the genetics lab flags that specific variant or specific mutations. We know exactly which is the best genetic therapy to go after." You can download the transcript, or read it below. Ana Lisa: Welcome to Behind the Genes.    [Music plays]  Anne: What we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family, they would tell you, “Yes, my son has had the odd liver result.”  There were some very serious liver complications but everybody thought that was a minor issue, but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  [Music plays]  Ana Lisa: My name is Ana Lisa Tavares, I'm Clinical Lead for Rare Disease research at Genomics England and your host for this episode of Behind the Genes. Today I'm joined by Anne Lennox, Founder and CEO of the Myotubular Trust, Dr Meriel McEntagart, an NHS consultant and Clinical Lead for Rare Disease Technologies at Genomics England, and Dr Carlo Rinaldi, Professor of Molecular and Translational Neuroscience at the University of Oxford.    Today we'll be hearing about the importance of involving the patient community, particularly as new rare therapies are developed, and discussing the forward-facing work that's happening that could have potential to unlock novel treatments for many rare conditions.  If you enjoy today's episode we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you so much for joining me today.  Please could you introduce yourselves.   Anne: I'm Anne Lennox, I'm one of the founders of the Myotubular Trust, a charity that raises research funds for and supports families affected by the rare genetic neuromuscular disorder myotubular myopathy.  Meriel: I'm Meriel McEntagart, I'm a consultant in clinical genetics in the NHS and I have a special interest in neurogenic and neuromuscular conditions.  Carlo: Hi, I'm Carlo Rinaldi, I'm Professor of Molecular and Translational Neuroscience at the University of Oxford. I'm a clinician scientist juggling my time between the clinic and the lab where we try to understand mechanisms of diseases to develop treatments for these conditions.  And I'm also here as a representative of the UK Platform for Nucleic Acid Therapies, UPNAT. Thanks for your invitation, I'm very pleased to be here.  Ana Lisa: Thank you. Meriel, I'd love you to tell us a bit about your work and how you met Anne, how did this story start?  Meriel: Thank you. Well prior to being a consultant in clinical genetics, I spent 2 years as a clinical research fellow in neuromuscular conditions, and as part of that training I worked on a project where the gene for myotubular myopathy had just been identified, and so there was a big international effort to try and come up with sort of a registry of all the genetic variants that had been found as well as all the clinical symptoms that the affected patients had, and then do kind of a correlation of the particular variant mutation with symptoms.   I worked when I was training to be a clinical geneticist because of my interest in neuromuscular conditions so when I eventually became a consultant at St George's Hospital I was actually interviewed by the Professor of Paediatrics and he knew Anne and her son, when Anne was looking for more information about the condition he suggested that perhaps I might be a good person for Anne to talk to.  Ana Lisa: Thank you. Interesting connections. Anne, can you tell us your story and how this led you to found the Myotubular Trust?  Anne: Yes, thanks Ana-Lisa.  Well, as many families will tell you when they're newly diagnosed with a rare disease, you go from knowing nothing about a condition to being one of the few deep experts in that condition because there are so few deep experts. So this happened to us in 2003 when our son, Tom, was born, and when he was born he was floppy and his Apgar scores, the scores they do on new-born babies, were pretty poor, and before long we knew that it was more than just momentary issues at birth.  And, cutting a very long story short, 5 weeks later he was diagnosed with this very rare neuromuscular genetic disorder that we didn't know we had in the family.  We were told that this was a very serious diagnosis.    At that time – more than 20 years ago – over 80% of those boys didn't make it to their first birthday and the stark statistic we had in our head a lot was that only 1% made it past the age of 10. And that has changed due to better ventilator and breathing equipment, etc, but at the time we expected that he might not make it to his first birthday.    We were very lucky, we had Tom longer than one year, we had him for nearly 4 years, 4 very lovely years where it was tough, but he was a really lovely member of our family.  Despite being really weak he managed to be incredibly cheeky and bossy, and he was a great little brother for his big sister. We were also very lucky that he was being looked after by Professor Francesco Muntoni, who is Head of the Paediatric Neuromuscular Service at Great Ormond Street. And, like Carlo, he is a clinical researcher and actually that I found to be amazing as a family member because you knew what was happening out there and Professor Muntoni, other than living with the reality day to day you want to know where things are going.    We began to realise that back then 20 years ago the more common rare neuromuscular diseases were finally beginning to get some fundamental research funds, like Duchenne, spinal muscular atrophy, and Professor Muntoni was very good at explaining to lay non-scientific parents like us that one day the technologies that would lead to a cure, that would re-engage proteins for other conditions and would translate down eventually into the possibility of replacing myotubularin, which is the protein not being produced or not being produced enough in myotubular myopathy. And then we began to understand actually what the barriers to that would be, that translating developments in more common, or let's say more prevalent conditions, would be hard to do without some translation research being done; you could not just not lag years behind, you could lag decades behind if you haven't done some other work.    So, I met Wendy Hughes, another mother, of a boy called Zak who was a few years older than Tom, and these were the days before social media, and it was amazing to be in contact with another family going through something similar and we had great conversations. But then they were also looked after by Professor Muntoni and we particularly began to develop the idea as 2 families that we might be able to raise some research funds towards this concept of keeping pace with the scientific developments.  And then we discovered there was no charity we could channel those funds through. Even the umbrella body for neuromuscular diseases who were covering 30 to 40 conditions, frankly, they just couldn't trickle their funding down into investing in every neuromuscular disease, and slowly but surely it dawned on us that if we did want to make that difference we were going to have to set up our own charity.   So that's what we eventually did and back in 2006, we founded what was actually the first charity in Europe dedicated to myotubular myopathy – luckily, more have come along since – and we were dedicated to raising research funding. In fact, it wasn't our goal to set up another charity but around that time, about a year in, we happened to go to a meeting where the Head of the MRC, the Medical Research Council, was giving a talk and he said that in the last few years the MRC had begun to really realise that they couldn't cure everything, that they couldn't cure the diseases that would be cured in the next millennium from a top down perspective. There had to be a trick, there had to be a bottom up as well, because that was the only way this was going to happen. And I have to say that that was a really reassuring moment in time for us to realise that we weren't just chasing pipe dreams and trying to do something impossible, that there was a role for us.    Ana Lisa: I think it would be really interesting for people to hear your story and the amazing set-up and fundraising that you've done, and at the same time it would be really good for us to reflect on how this isn't feasible for every patient and every family and how we're going to need to work cooperatively to move forwards with rare therapies.  Anne: When we explored the idea with Professor Muntoni and Meriel and others about setting up a charity one of the really reassuring things that Professor Muntoni got across to us was that this wasn't about raising the millions and millions it would take to fund clinical trials but the issue in the rare disease space was funding the proof of principle work, the work where you take a scientist's hypothesis and take it over the line, and the rarer the disease, the less places there are for a scientist to take those ideas. And the example he gave us was a piece of research like that might cost a hundred to a couple of hundred thousand, if you fund a piece of work like that and if it is successful, if the scientist's principle gets proven, then behind you it's much easier for the bigger muscle disease charities to also invest in it. It's harder for them to spread their money across all the very rare diseases hypothesis out there, but if you've helped a scientist get over the line they'll come in behind you and then they won't be the ones who fund the tens of millions that it takes to run a clinical trial.    If it's got potential, then that's where the commercial world comes in, and that's where the biotechs come in. So he'd given the example of if you spent £ten0,000 on a piece of research and it actually is proven, in behind you will come the bigger charities that would put in the million that takes it to the next phase, and in behind them will come the bio-checks that'll provide biotechs that'll provide the tens of millions.    And then, you know, a lot of what happens relies on serendipity as well, we know that, and you could easily run away with the idea that you made everything happen but you don't, you stand on the shoulders of others. And our very first grant application in our first grant round, which received extraordinary peer review for how excellent the application was, was a £100,000 project for a 3-year project that had gene therapy at the core of it by a researcher called Dr Ana Buj Bello at Généthon in Paris. This piece of research was so promising that 18 months in she and another researcher were able to raise $780,000 and, as Professor Muntoni predicted, from the French muscle disease charity AFM and the American muscle diseases charity MDA.  And 18 months into that 3 years it was so promising that a biotech company was started up with $30 million funding, literally just on her work.    So that doesn't always happen but, as Professor Muntoni explained, our job was not that $30 million, our job was that first £100,000, and our job was also to make ourselves known to the people in the neuromuscular field.  If you have lab time, if you have research time and you have a choice where you're putting it there is a place you can go to for a myotubular myopathy related grant application, so it's not just that this will come to us out of the blue, people will have done prior work, and our existence makes it worth their while, hopefully, to have done that prior work.  Ana Lisa: That's an amazing story how you've set up this charity and how successful that first application for gene therapy was. I'd love to hear more about that gene therapy and did it get to the clinic and to hear that story from you.  Because I think there are a lot of learnings and it's really important that the first patients who are treated, the first families that are involved, the researchers who start researching in this area, the first treatments lead the way and we learn for all the other treatments for all the other rare conditions that we hope and that together as a community we can share these learnings.  Anne: Yeah. I sometimes describe it a bit like going out into space. When you see a rocket going off look at how many people are behind and the amount of work that's been done, the degree of detail that's managed, and then you go out into space and there are a whole load of unknowns, and you can't account for all of them.  Who knows what's out there in this sphere.  But the amount of preparation, it feels similar to me now, looking back.  We were so idealistic at the beginning.  Our grant to Dr Buj Bello was 2008 and actually it is a really fast time in, the first child was dosed in the gene therapy trial in September 2017.  Ana Lisa: So, we're talking less than 1 years.  Anne: Yeah. And in the meantime obviously as a charity we're also funding other proof of principle research. One of the founding principles of the charity was to have a really excellent peer review process and scientific advisory board so that we wouldn't get carried away with excitement about one lab, one research team, that everything would always come back to peer review and would be looked at coldly, objectively. I don't know how many times I've sat in a scientific advisory board meeting with my fingers crossed hoping that a certain application would get through because it looked wonderful to me, and then the peer review comes back and there are things you just don't know as a patient organisation. So, yes, in those 9 years we were also funding other work.  Ana Lisa: You've just given an interesting perspective on sharing the learnings between the scientists, clinicians, the experts in a particular condition, if you like, and the families, and I'd be really interested to hear your views on what's been learnt about how families and the patient community can also teach the clinical and scientific community.  Anne: So, the first child was dosed in September 2017 and by the World Muscle Society Conference 2 years later in October 2019 the biotech had some fantastic results to show. Children who had been 24-hour ventilated were now ventilator-free, which, unless you know what it's like to have somebody in front of you who's ventilator-dependent, the idea that they could become ventilator-free is just extraordinary.    However, one of the things we've learnt about gene therapy is that we are going out into space so there are extraordinary things to be found, and extraordinary results are possible, as is evidenced here, but there is so much that we don't know once we are dealing with gene therapy. So unfortunately, in May, June and August of 2020, 3 little boys died on the clinical trial. So we have a clinical trial where the most extraordinary results are possible, and the worst results are possible, and both of those things are down to the gene…  What we discovered and what is still being uncovered and discovered is that myotubular myopathy is not just a neuromuscular disorder, it is a disorder of the liver too, and these children didn't die of an immune response, which is what everybody assumes is going to happen in these trials, they died of liver complications.    And one of the things that has come out of that, well, 2 sides to that. Number one is that it is extraordinary that we have found a treatment that makes every single muscle cell in the body pick up the protein that was missing and produce that protein, but also what we've understood is that the knowledge and experience of families and patients is even more vital than we've all been going on about for a long time. Because the issue of there being a liver complication in myotubular myopathy has been hiding in plain sight all this time, because if you asked any family they would tell you, “Yes, my son has had the odd liver result, yes.”    We could see something that looked like it was not that relevant because it was outside the big picture of the disease, which was about breathing and walking and muscles, but actually there was this thing going on at the same time where the children had liver complications. There were some very serious liver complications but everybody thought that was a minor issue but if we are able to engage the people who live with the disease and the people who observe the disease at a much more fundamental level we may be able to see more about what these rare genes are doing.  Ana Lisa: Yeah, thank you very much for sharing such a moving story and with such powerful lessons for the whole community about how we listen to the expertise that families have about their condition, and also I think the really important point about how we tackle the research funding so that we're including and sharing learnings from the conditions that are initially studied in greater depth, and we hope that many more conditions will be better understood and more treatments found and that actually the learnings from these first gene therapy trials will really help inform future trials, not just for gene therapies but also for many other novel therapies that are being developed.  [Music plays] If you're enjoying what you've heard today, and you'd like to hear some more great tales from the genomics coalface, why don't you join us on The Road to Genome podcast. Where our host Helen Bethel, chats to the professionals, experts and patients involved in genomics today. In our new series, Helen talks to a fantastic array of guests, including the rapping consultant, clinical geneticist, Professor Julian Barwell, about Fragile X syndrome, cancer genomics and a holistic approach to his practice - a genuine mic-drop of an interview. The Road to Genome is available wherever you get your podcasts. [Music plays] Ana Lisa: Carlo, I would really like to come to you about some of the initiatives that are happening in the UK, and particularly it would be really interesting to hear about the UK Platform for Nucleic Acid Therapies as a sort of shining example of trying to do something at a national scale across potentially many different rare conditions.    Carlo: Thanks, Ana-Lisa. Thanks very much, Anne, for sharing your fantastic story. I mean, I just want to iterate that as clinician scientists we do constantly learn from experiences and constantly learn from you, from the patient community, and this is absolutely valuable to push the boundary. And I really liked your vision of a rocket being launched in space and I would imagine that this is a similar situation here. So, we are facing a major challenge. So, there is over 7,000 rare diseases in the world and with improvements of genetic diagnosis this is only increasing. So, in a way rare diseases is the ultimate frontier of personalised medicine and this poses incredible challenges.   So, you mentioned the bottom-up approach and the top-down approach and in a way, both are absolutely necessary. So your story is a fantastic story but also makes me think of all the other families where they don't share perhaps the same spirit, you know, they are in areas of the world that are not as well connected or informed, where patient community simply cannot be ‘nucleated', let's say, around the family. So, there is definitely an issue of inclusivity and fair access.    So, what we're trying to do at UPNAT, which is the UK Platform for Nucleic Acid Therapy, is to try to streamline the development both at preclinical and clinical level of nucleic acid therapies. So, we'll start with antisense oligonucleotides just because those are the molecules of the class of drugs that are most ‘mature', let's say, in clinic. So, there are several antisense oligonucleotides already approved in the clinic, we know that they are reasonably safe, we understand them quite well, but of course the aspiration is to then progress into other forms of gene therapy, including gene editing approaches, for example.   And one of the activities that I'm involved, together with Professor Muntoni, is to try to streamline the regulatory process of such therapies and in particular curate a registry of, for example, side effects associated with nucleic acid therapy in the real world, and you would be surprised that this is something that is not yet available.  And the point is exactly that, it's trying to understand and learn from previous mistakes perhaps or previous experiences more in general.    And this is very much in synergy with other activities in the UK in the rare disease domain.  I'm thinking of the Rare Disease Therapy Launchpad, I'm thinking of the Oxford Harrington Centre, I am thinking of the recently funded MRC CoRE in Therapeutic Genomics. These are all very synergistic. Our point is we want to try to amplify the voice of the patient, the voice of the clinicians working on rare disease, and we want to systematise. Because of course one of the risks of rare disease therapies is the fragmentation that we do all these things in isolation. And I would argue that the UK at the moment leveraging on the relatively flexible and independent regulatory agencies, such as the MHRA, on the enormous amount of genetics data available through Genomics England, and of course the centralised healthcare system, such as the NHS, is really probably the best place in the world to do research in the rare disease area, and probably I'm allowed to say it because I'm a non-UK native.       Ana Lisa: Thank you, that's a brilliant perspective, Carlo, and across all the different therapeutic initiatives that you're involved with. And, Carlo, presumably - we're all hoping - these different initiatives will actually lead to ultimately a bigger scaling as more and more novel therapies that target both our RNA and DNA and actually are working, I guess further upstream in the pathway.    So classically in the past it's been necessary to work out all the underlying biology, find a druggable target somewhere in that pathway and then get a larger enough clinical trial, which can be nearly impossible with many of the rare and ultra-rare conditions or even, as you've said, the sub-setting down of more common condition into rarer subtypes that perhaps can be treated in different ways.  And with the many new different treatments on the horizon, ASO therapies, as you've said, is a place that's rapidly expanding, and also crisper gene editing. I'd be really interested to hear your reflections on how this might scale and also how it might extend to other new treatments.  Carlo: Yeah, that's exactly the right word, ‘scaling up'. I mean, there will be of course very unique challenges to every single rare disease but I would argue that with genetic therapies, such as ASOs or crisper gene editing, the amount of functional work that you need to do in a lab to prove yourself and the scientific community that this is the right approach to go for can be certainly very important but can be less just because you're addressing very directly because of the disease.    And then there are commonalities to all these approaches and possibly, you know, a platform approach type of regulatory approval might serve in that regard. You know, if you are using the same chemistry of these antisense oligonucleotides and, you know, similar doses, in a way the amount of work that you need to produce to again make sure that the approach is indeed a safe approach and an effective approach might be also reduced.    I would say that there are also challenges on other aspects of course, as you were saying, Ana-Lisa. Certainly the typical or standard randomised placebo control trial that is the standard and ultimate trial that we use in a clinical setting to prove that a molecule is better than a placebo is many times in the context of rare diseases simply not possible, so we need to think of other ways to prove that a drug is safe and is effective.   This is something that we all collectively as a scientific community are trying to address, and the alliance with the regulatory agencies, such as the MHRA, and you said that you have found your interaction with the MHRA very positive, and I can tell you exactly the same. So we are all trying to go for the same goal, effectively, so trying to find a way to systematise, platformise these sort of approaches. And I guess starting with antisense oligonucleotides is really the right place to go because it's a class of drugs that we have known for a long time, and we know it can work.  Ana Lisa: Meriel, can you tell us a little about the National Genomic Research Library at Genomics England and how this could link with initiatives to find many more patients as new treatments become available for rare and ultra-rare conditions?  Meriel: Yes, I think what's wonderful now is actually that what we're really trying to do is give everybody the opportunity to have their rare condition specifically diagnosed at the molecular level, and the way in which that is being done is by offering whole genome sequencing in the NHS currently in England but to all patients with rare diseases.    And so, it's about trying to establish their diagnosis. And as well as that, even if the diagnosis isn't definitely made at the first pass when the clinical scientists look at the data, because the whole genome has been sequenced, actually all that information about their genome, if they consent, can then be put into the National Genomics Research Library.  And that is a fantastic resource for national and international researchers who get approved to work in this trusted research environment to make new disease gene discoveries and identify these diagnoses for patients.  What's also offered by Genomics England as well is when the National Genomics Library data results in a new publication, the discovery of a new gene or perhaps a new molecular mechanism that causes a disease we already know about, that feeds back into the diagnostic discovery pathway within Genomics England back onto the diagnostic side of all the data.    So, patients who may have had genetic testing previously using whole genome sequencing where they've, if you like, had their sequencing done before the diagnosis was sort of known about, will also be picked up. And so, what this is really doing is trying to kind of give this really equal platform for everybody having testing to all have the same opportunity to have their diagnosis made, either on the diagnostic side or with research.  Ana Lisa: So, sort of on a cohort-wide scale as new discoveries are made and published you can go back and find those patients that may actually have that diagnosis and get it back to them, which is brilliant.  Meriel: Exactly. And this speeds up the whole process of getting these diagnoses back to people. So on a regular basis in the NHS, we will get feedback from the Diagnostic Discovery Pathway about “Here's some patients who you requested whole genome sequencing from a number of years ago and actually now we think we know what the particular molecular condition is.”  And so, it's key of course for our patients with rare conditions to make that molecular diagnosis because then we're able to have them identified for our colleagues who are doing this ground-breaking research trying to bring therapies for these rare conditions.  Ana Lisa: Thank you. And I hope that, as currently, if a novel genetic mechanism, as you've just described, is identified that could explain a rare condition that those patients can be found and they can receive that diagnosis, even many years later, and hopefully as novel treatments become available and say there's a chance to individualise ASO therapies, for example, to start with, that one could also go and look for patients with particular variants that could be amenable potentially to that treatment. And that's really sort of exciting that one could look for those patients across England, irrespective of which clinic they're under, which specialist they're under, and I think that could be really powerful as new treatments develop. I suppose, Meriel, if somebody comes to see you now in clinic are things different?  Meriel: Well, I think one of the things for me when patients come to clinic now is we might have an idea about what we think their condition is, maybe even we think it's a specific gene. And we can offer whole genome sequencing and so it's not just the way we used to do things before by looking just at the coding regions of the gene, we can find more unusual ways in which the gene can be perturbed using whole genome sequencing.  But let's say we don't make the diagnosis. I encourage my patients, if they're comfortable with it, to join the National Genomics Research Library, because really it's been incredibly productive seeing the new genetic discoveries that are coming out of that, but as well I say to them, even if we don't get the diagnosis the first time round when we look at the data, actually this is a constant cycle of relooking at their data, either if they're in the NGRL or as well on the Diagnostic Discovery Pathway side of the service that's run by Genomics England. So yeah, I feel like it's a very big difference; they don't have to keep coming every year and saying, “Is there a new test?” because actually they've had an excellent test, it's just developing our skills to really analyse it well.  Ana Lisa: Yes, and our knowledge, the technology and the skills keep evolving, certainly.  And I think one of the things that I'm sort of hearing from this conversation is that balance of hope and realism, Carlo we were talking about earlier how you need all the pieces of the puzzle to be lined up - so the regulatory agency, the clinicians, all the preclinical work has to have been done, monitoring afterwards for side effects - every piece of the puzzle has to be lined up for a new treatment to make it to a patient.    And, Anne, I'd like to come back to you because we've talked about this before, how one balances these messages of optimism and hope which are needed for bringing everybody together as a community to crack some of these very difficult challenges highlighted by treatments for rare and ultra-rare conditions and at the same time the need for realism, a balance conversation.  Anne: Yeah, that was one of our big learnings through the gene therapy trial and other trials we've had in the condition. As a rare disease charity, you do everything. You know, my title is CEO, but I tell people that's Chief Everything Officer because there's only a few of you and you do everything. So, you go and you lead the London Hope Walk and you also are a layperson on the Scientific Advisory Board and you also send out the emails about grants... And so, you could easily as a small rare disease charity conflate different communication messages because you're in a certain mode.  And so we have been from the early days in the mode of raising hope for people to say, “Look, we can make a difference as a patient community, we could raise funds, we might be able to move things forward, you've got the power to make a difference if you want to.” That's one set of hope.  And it's not dreamlike hope, we're linked to the reality of there are great breakthroughs.  So, you know, in the world of spinal muscular atrophy these clinical trials have led somewhere very quickly, so we're not selling false hope, we're talking about the difference we can make.    But then as soon as you flip into “There's a clinical trial being run” that's a completely different type of communication and you cannot conflate that message with the previous message.  And we always say to everybody, “We're your team, we're a family, we're a team, we all help each other.  When you are considering joining a clinical trial your team is the clinical trial team.    The other team does other things for you but the people you need to work with and ask hard questions of and listen hard to, that's your clinical trial team led by the principal investigator because then you're in that with them. And, you know, the reality of the fact that many, many clinical trials don't work as we wish they would be and the decision you make for your child, your baby, your little one, to join a clinical trial… because that's what it comes down to in our disease, has to be made with that team, not the team that's selling you a fundraising event. It's worth reminding rare disease patient organisations we're wearing different hats and the hope and the realism are different tracks you have to go down.    But at the same time as being realistic you also have to keep remembering that there is still grounds for hope, we are moving forward. And 21 years ago, when Tom was born the idea that you would be able to get all of the muscles in the body to switch back on – putting it in lay terms – seemed like a bit dream. Well, that is what has happened in the gene therapy clinical trial, we just have to now make it safer and understand more about what we're dealing with. So, the 2 things, the hope and the realism, do exist side by side.  Ana Lisa: I think that perfectly encapsulates a lot of the messages around rare disease therapies where there's such hope that novel treatments will really target directly the DNA or RNA to potentially correct the problem across many different rare conditions and therefore actually making treatments one day suddenly available to a much, much bigger population of people with rare conditions than we could've dreamt of 20 years ago or perhaps now, and at the same time this massive need to work cooperatively to all make this as fair, as equitable. Not everybody is going to have the opportunity to fundraise massively to be an expert about their condition, and the importance of sharing these learnings and also really, really listening to the patient community and really, as Carlo was saying, keeping track of side effects, having registries/databases to share these is going to be incredibly important.  [Music plays]  Ana Lisa:  Anne, can you tell us a little about your reflections on equity from the patient community perspective?  Anne: Well I mentioned serendipity early and one of the aspects of serendipity that played into our favour for setting up the Myotubular Trust was that by hook or by crook Wendy Hughes, who set up the charity with me, and I were both able to devote time at that period of our lives to setting up a charity. When my husband, Andrew, and I were told that Tom would more than likely die before his first birthday, one of the decisions we made as a family was that he would never not be with a parent, we would always have someone around, and that kind of meant someone had to give up a full-time job and that was me.  We thought, “If Tom has a few scarce months on the planet, we'll be with him.” And then when Tom lived to be nearly 4, as a family we got used to living on one salary and we were very lucky that we could pay the mortgage that way and run our family that way and eventually that meant I had the time to run the charity.    That doesn't happen that easily, that's a tall order, particularly when you have somebody in the family who has such high needs. And one of the things that I have often thought about is that in the rare disease space we could do with a different funding model for rare disease charities, we could, in an ideal world I have this nirvana that I imagine where there's a fund that you can apply to that is contributed to by the people who make profits out of finding rare disease cures - so the pharmaceutical companies and the biotechs - and there's a fund that they contribute to and that if you have a rare disease and you are willing to set up an organisation that supports families, that raises research funds, that provides a way of hearing the patient voice, then you could apply to that for running cost funds and then you'd be able to run this charity. And then you wouldn't have to rely on whether you live in an area where people will raise money for you or…  We were very lucky that we came across a few great benefactors who would give us money for running the charity, which is actually how we fund it.    All the research money we raise goes 100% into research, not a penny of it goes towards running costs because we have serendipitously found people who will be benefactors for the charity, but we're relying on a lot of good luck for that kind of model to work. And when you look at how much profit is made from developing rare disease treatments and cures – which is fine because that's what puts the passion and that gets people working on it – then why not have an advance fund to run rare disease charities? One of my nirvana dreams.  Ana Lisa: It's good to dream. Indeed, my hope is that there will be some amazing shining examples that lead the way that open doors, make things possible, prove that something can work and how and that then that will enable many other treatments for many additional rare conditions to be added in so that if you've learnt how this particular treatment modality works for this rare condition and there was funding behind it and everything else that's needed that then you can, the learning from that, I'm going to use the word ‘tweak', which sounds minor and could be very major but actually the concept that you can then tweak all those learnings and findings so that that same type of treatment modality could be adapted to treat somebody else with a different rare condition in a different location would be absolutely incredible and really powerful, given that if something like 85% of rare conditions affect less than one in a million people it's not going to be feasible to use the same strategies that have been used in the past for very common conditions.    One of the other big barriers is the cost of developing treatment for ultra-rare conditions.  Where it's a small number of patients that you have and therefore all the challenges that come with monitoring, checking for efficacy, monitoring safety and ultimately funding the challenges are much greater, however if some of these treatment modalities are also going to be used to treat common conditions it might be that actually there's a lot more cross-talk between the nano-rare, ultra-rare, rare and common conditions and that we can share a lot of that learning. I'd love to hear from each of you where you hope we will be for rare disease and rare therapies.  Carlo: Well my dream is that in 5 to 10 years' time an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested, and at that exact time the day of the diagnosis becomes also a day of hope in a way where immediately the researcher, the centre, genetics lab, flags that there are the specific mutations, we know exactly which is the best genetic therapy to go after, antisense oligonucleotides as opposed to CRISPR editing, and a path forward, both at the preclinical and clinical level, to demonstrate and to cure these patients eventually is already laid out in front of the patient.  So, transforming the day of their diagnosis as a day of hope, this is my dream with the next ten years.  Ana Lisa: Thank you, that's a wonderful dream. Meriel, can I come to you?  Meriel: Yes, I think I just want to echo Carlo.  We've had great developments and progress with getting whole genome sequencing into the NHS for testing but what we really need is for it to be fast and efficient and getting those diagnoses established quickly. And we have had that set up now and we're really getting there in terms of speed, but then what we need is exactly what's the next step and actually structure like UPNAT that are developing these processes that we can then say to the patient, “And from there, now that we've established your diagnosis, this is what we have options to offer.”  Ana Lisa: Brilliant. And presumably that if the diagnosis isn't achieved now there is a hope that it will be achieved in the future as well. Anne...  Anne: Well, stepping one hundred per cent into the patient's shoes rather than the scientific side that we don't so much influence....  stepping in the patient's shoes, in 5 years' time I would absolutely love it if we were in a situation where all the parties that have come to the table looking at a therapy or in the earlier research genuinely want to bring the patient voice into the room. As Carlo talked about, there's even going to be more and more and more of these rare diseases, then those voices, those few people who have experience of it, they may be able to shed light on something. Maybe even sometimes don't even know it's a fact that they know but that were brought to the table as passionately as everything else is brought to the table.  [Music plays]  Ana Lisa: We'll wrap up there. Thank you so much to our guests, Anne Lennox, Carlo Rinaldi and Meriel McEntagart, for joining me today as we discuss the collaborative power of working together and look to the future of rare therapies that could have the potential to unlock treatments for many rare conditions. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I've been your host, Ana-Lisa Tavares. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.  

Dr. Bill Griffin and Dr. Mike Chupp sit down to have a conversation with well-known financial advisor and author David Bahnsen to talk about his new book, Full-Time: Work and the Meaning of Life. In this insightful offering, Mr. Bahnsen corrects some deeply held false assumptions that have become prevalent in our society's attitude regarding the work of our hands.

In this episode, our guests explore the impact of genetic discoveries on inherited retinal dystrophies, in particular retinitis pigmentosa (RP). The discussion highlights a recent study that identified two non-coding genetic variants linked to RP, predominantly in individuals of South Asian and African ancestry. The conversation highlights how advances in whole genome sequencing are uncovering previously hidden causes of genetic disease, improving diagnostic rates, and shaping the future of patient care. It also addresses the challenges faced by individuals from diverse backgrounds in accessing genetic testing, including cultural barriers, awareness gaps, and historical underrepresentation in genomic research. Our host Naimah Callachand is joined by researcher Dr Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, a patient representative diagnosed with retinitis pigmentosa and Founder and Chair of BAME Vision. We also hear from Martin Hills, an individual diagnosed with autosomal dominant retinitis pigmentosa. To access resources mentioned in this episode: Access the Unlock Genetics resource on the Retina UK website Visit the BAME vision website for more information and support Find out more about the groundbreaking discovery of the RNU4-2 genetic variant in the non-coding region which has been linked to neurodevelopmental conditions in our podcast episode   "Discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially, you know, we are all aiming towards being able to develop therapies for particular genes and particular diseases."   You can download the transcript or read it below. Naimah: Welcome to Behind the Genes.   Bhavini: The few common themes that always come out is that people don't really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing. There is already a taboo around the terminology. Then it is lack of understanding and awareness or where to get that information from, and also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with. So, they try and hide it. They try and keep that individual at home because they think they are going to have an outcast in the community, in the wider family, and it would be frowned upon).  Naimah: My name is Naimah Callachand and I am Head of Product Engagement and Growth at Genomics England.  I am also one of the hosts of Behind the Genes. On today's episode I am joined by Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, patient representative.  Today we will be discussing findings from a recently published study in the American Society of Human Genetics Journal which identified two non-coding variants as a cause of retinal dystrophy in people commonly of South Asian and African ancestry. If you enjoy today's episode, we'd love your support. Please like, share, and rate us on wherever you listen to your podcasts.  Okay, so first of all I would like to ask each of the three of you to introduce yourselves. Bhavini, maybe we'll start with you.  Bhavini: Hi, I'm Bhavini Makwana, patient representative, and also Chair of BAME Vision. I have other roles where I volunteer for Retina UK, and I work for Thomas Pocklington Trust.  Naimah: Thanks Bhavini. Gavin.  Gavin: Hi, my name is Gavin Arno, I am Associate Director for Research at the Greenwood Genetic Centre in South Carolina, and I am Honorary Associate Professor at the UCL Institute of Ophthalmology in London.  Naimah: Thanks Gavin. And Kate.   Kate: Hi, I'm Kate Arkell, Research Development Manager at Retina UK.   Naimah: Lovely to have you all today. So, let's get into the conversation then. So Gavin, let's come to you first. First of all, what is retinitis pigmentosa and what does it mean to have an inherited retinal dystrophy?  Gavin: So, retinitis pigmentosa is a disorder that affects the retina at the back of the eye. It is a disease that starts in the rod photoreceptor cells. So, these cells are dysfunctional and then degenerate causing loss of peripheral and night vision initially, and that progresses to include central vision and often patients will go completely blind with this disease. So, retinal dystrophies are diseases that affect the retina. There are over 300 genes known to cause retail dystrophy so far, and these affect different cells at the back of the eye, like retinitis pigmentosa that affects the rods. There are cone rod dystrophies, ones that start in the cone photoreceptors, macular dystrophies that start in the central retina, and other types of retinal dystrophies as well.  Naimah: Thanks Gavin. And Bhavini, just to come next to you. So, you received a diagnosis of retinitis pigmentosa at the age of 17 after a genetic change was found in the RP26 CERKL gene. At this time only ten other families in the UK had been identified with this type of genetic alteration. Would you mind sharing a bit more about your journey to your diagnosis?  Bhavini: Yeah. So, at the age of 17 is when I got officially diagnosed with retinitis pigmentosa, but leading up to that I was experiencing symptoms such as night blindness. So, I struggled really badly to see in the dark, or just in dim lighting, like this time of the year in winter when it gets dark quite easily, all my friends from college could easily walk across the pavement, but I struggled. I was bumping into a lot of things. Like things that I wouldn't really see now that I know my peripheral vision, I was losing that, so like lamp posts or trees or bollards, I would completely miss or bump into them. I was missing steps, and had a really, really bad gaze to the sun. Like, everything was really hazy. That continued and I just put it down to stress of exams. You know, just given that age and where I was at the time of my life. But then it kind of continued. So, I went to the see the optician who then referred me, and after months of testing I got diagnosed with retinitis pigmentosa. Back in the late 90s when I was diagnosed there wasn't really anything about genetic testing, or cures., or treatments. I was basically just told to get on with it, and that was it.   It was only until about 15/16 years later I came across Retina UK, started understanding what retinitis pigmentosa is, and what it means, and then when I was offered genetic testing and counselling at one of my annual Moorfields appointments, they explained to me what it involved, what it could mean, what kind of answers I would get, and I agreed to take part. It was a simple blood test that myself and both my parents took part in.      Naimah: Thanks for sharing that Bhavini. So, I know you were able to receive a diagnosis through whole genome sequencing in the 100,000 Genomes Project after the alteration in the gene was found, and this was found in the coding region of the genome. But in this study that we are talking about in this podcast, we know that the two genetic changes that were found, they were in the non-coding region of the genome. Gavin, could you tell me in simple terms what the difference is between the coding and non-coding region of the genomes and why these findings are significant in this case?   Gavin: Yes, sure. So, the human genome is made up of about 3 billion letters or nucleotides which are the instructions for life essentially. Now, within that human genome there are the instructions for roughly 20,000-25,000 proteins. This is what we call the coding genome. These are the bits of DNA that directly give the instructions to make a protein. Now, we know that that part of the genome is only roughly 2% of the entire genome, and the remaining 98% is called the non-coding genome. Now, we understand that far less well. We have a far poorer understanding of what the function of the non-coding genome is versus the coding genome. So, typically molecular diagnostic testing or genetic testing is focused on the coding genome, and historically that has been the fact. Now with advances in genome technologies like whole genome sequencing and the 100,000 Genomes Project, we are able to start to look at the non-coding genome and tease out the previously poorly understood causes of genetic diseases that may lie within those regions of the genes.   Naimah: Thanks Gavin, I think you have just really highlighted the possibilities available with looking at the non-coding region of the genome.  Kate, coming to you next. I wanted to talk about the importance of uncovering and understanding genetic causes of inherited retinal dystrophies, and how do discoveries like these change the landscape of care for patients with inherited retinal dystrophies?  Kate: So, getting a genetic diagnosis can really help families affected by inherited retinal dystrophy. It helps them and their ophthalmologists to better understand their condition, and in some cases gain some insight into possible prognosis, which helps people feel a lot more in control. It can also potentially inform family planning decisions and even open up options around access to reproductive technologies for example, not only for the individual, but sometimes also for their close relatives. Of course, researchers are making great strides towards therapies, some of which have reached clinical trials. But a lot of these approaches are gene specific, so for people who know their genetic diagnosis, they are more able to recognise research that is most relevant to them and quickly pick out potential opportunities to take part. At the moment it is still the case that around 30% of our community who have a genetic test will not receive a clear result, and that can feel very frustrating. So, the more discoveries like this that are made, the better.   Naimah: Thanks Kate.  So, now we are going to hear a clip from Martin Hills, our Retina UK patient representative who has been diagnosed with autosomal dominant retinitis pigmentosa. Martin has undergone genetic testing and shares more about his experience.  Martin: My name is Martin Hills, and I was officially diagnosed with autosomal dominant retinitis pigmentosa in 2001, and because of that I immediately had to stop driving which made a huge impact both on myself and my family.  My eyesight has slowly deteriorated over the years. It first started with difficulty seeing at night, and also playing some types of sport, which I think probably was in my 20s. My peripheral vision has been lost slowly and now has completely gone. Fortunately, I still have some reasonable central vision left which is a great help. I am registered as severely sight impaired, and I am also a symbol cane user. My father and aunt were both diagnosed with this condition, and my daughter has been relatively recently, as has altogether eight members of our wider family, and that also includes two younger generations. In 2015 I went for genetic counselling and testing and at that time it was for 176 genes known to be associated with retinal dystrophies. I believe that has now gone up to about 300, but at the time they couldn't recognise what my faulty gene was, and that has still been the case to my knowledge to date.   I have also been part of the 100,000 Genome Project along with several others of my wider family, and I am also a participant in the UK Inherited Retinal Dystrophy Consortium RP Genome Project, which has been sponsored by Retina UK. The impact of not having a positive genetic test result is quite interesting and has really been a rollercoaster. I guess it is all about hope, and to start with when I knew I was going to be genetically tested, I think my first reaction was optimism, and I think if you have a positive test result, that is a real hope for the future. I think that is quite exciting particularly as things seem to be progressing so rapidly. But because I didn't get a positive result, the next reaction I had really was disappointment because I felt one step behind people with a positive result. Of course the natural reactions are one of frustration, and then I guess followed by realisation of the situation, and heading towards trying to adjust and making coping strategies for the future.  I still feel that genetic testing for all forms of medical conditions is so important and has a huge future in understanding and then potential treatments for so many medical issues. I guess it might be a bit too late for me, but if I can contribute to finding a restorative treatment for the younger generations of my family, and for that matter other people, then I think that is good enough for me.   Naimah: So, we have just heard from Martin that although he has not been able to have a positive genetic test result, his involvement in various studies may have benefits in helping others find treatment. So, I guess on that point Bhavini, maybe you could comment, or ask you how you felt whenever you were about to get a diagnosis through whole genome sequencing?  Bhavini: Yes. When I got called in almost three and a half years after the testing that took place was a massive, massive relief because not only did I get genetic counselling before the testing period, but I got called in and I spoke to a genetic counsellor who explained what they had been able to find and what kind of RP it was, how it would progress, and just answer so many questions. I am the mother of two daughters and even having two children, I lost a lot of sight after my first daughter, but at that time there wasn't any evidence or there wasn't any … you know, there was nothing I even knew about what questions to ask or anything, so I did go on to have a second child and drastically lost more sight. I had always been told, because the lack of awareness and understanding of RP in my family, and I am one of four children, and I am the only one that has it, so there is no other family history. Now I know it could have skipped generations, but I was always told things like it was karma. I must have done something in my past life. I was told to kind of have these herbs or these remedies to cure my sight loss, you know my RP. I was even desperate enough to kind of …  all these bogues treatments that you find online. You know, anything. I was so desperate to find anything that would help me.   When I received that testing and the counselling, it explained so much about how my daughters may or may not be affected, how they are carriers, and that was explained to me, how it would progress. So many questions and worries that I had for almost a decade and a half, they were answered. And not only for me, for my family, and all those people that told me all these sorts of things that I used to worry about that could have caused my RP. I was able to explain it to them and they understood that it was nothing to do with me being bad in my past life. It was actually you know, there is something scientific about it. So, it kind of gave me lots and lots of answers, and actually I then created a private Facebook page just with my RP26 CERKL genetic that I have been diagnosed with, just to see if there is anybody else out there, because when I was diagnosed, I think at the time I was told there was only myself and nine other families in the UK diagnosed with this particular gene. Now, I haven't been that active on it, but you know there are people across the world who found my post and joined the group, and we share experiences about the age that we were kind of diagnosed, the kind of rate the symptoms have developed. It is so fascinating because we have got such similar experiences.   There is parents on there who are there on behalf of their children, and it is just so nice to see … I know it is RP, but the specific gene and the rate of which we have experienced all the symptoms, it is quite similar. So, it has been quite supportive and helpful and reassuring to my family including my daughters.  Naimah: That's incredible Bhavini and it's really nice that you have created that group and created kind of like a support network for all the other families that have been affected by the same genetic condition as well. Yeah, that's incredible. Gavin, I know the findings in the study show that the genetic changes in this study are more common in people of African and South Asian ancestry. So, so I want to understand why is this an impactful finding in the study?  Gavin: Yes, so Kate mentioned that around 30% of people with inherited retinal dystrophies who have genetic testing don't get a molecular diagnosis and we are working in my research lab and many other research labs to improve that. Now, that figure is very much higher in patients of for example African ancestry in the UK, and this is partly due to the fact that historically and even now genetic studies have been focused on European individuals and taken place in the US, and the UK, and Europe, and wealthy countries across the world. This means that people of African ancestry are poorly represented in genetic studies, not just genetic studies of genetic disease, but population studies as well. So, we have less of an understanding of the genetic variants found in the genomes of individuals of African ancestry. So, that means we solve less of the genetic cases, particularly at Moorfields we published a paper on this several years ago with the diagnostic rates in European patients versus those of African ancestry, and it was very, very much lower. So, we need to do better for those patients, and this study identified a cause of retinitis pigmentosa in 18 families of African ancestry who were recruited to the 100,000 Genomes Project.   This is a fairly large proportion of the patients with RP of African ancestry seen at Moorfields Eye Hospital, and when we contacted collaborators around the world many more families were identified, and I think we ended up publishing around about 40 families who were affected by this particular mutation. So, we can look at that variant, we can look at the DNA sequence around that variant, and we found there is a chunk of DNA around the mutation in the gene that was coinherited by all of those different individuals. So, this is what we call an ancestral haplotype. It's an ancient variant that goes back many, many generations and it has a fairly high carrier frequency in genomes of African ancestry. So, we think this will be a fairly significant cause of retinitis pigmentosa across the continent of Africa. And so, identifying it will enable us to provide a molecular diagnosis for those families. Potentially there will be many more families out there who don't know they have this cause of disease yet. They may be affected but they haven't yet received genetic testing.   But discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially you know we are all aiming towards being able to develop therapies for particular genes and particular diseases. As Kate mentioned many of the gene therapies are gene specific, so if we identify a cause of disease that is predominant like this and affects many, many people, then of course there is more interest from the pharmaceutical industry to develop a therapy for that specific gene.  Naimah: Thanks Gavin. I think that really does showcase how impactful these findings really are. Kate, can I come to you. So, Gavin touched on it there that people with African and Asian ancestry are significantly less likely to get diagnosed, but why is it important to ensure that these groups are represented in the genomic datasets?  Kate: So, we need to ensure that genetic testing and diagnostic accuracy works for everyone, and not just those of European ancestry. So, as Gavin said if the datasets don't reflect the genetic variations seen in African or Asian populations, then the tests based on those data are more likely to give incomplete results for those groups of people. We really need a diverse range of genetic information for researchers to work on. As it is clear from this study's results, populations from African backgrounds for example may have unique genetic mutations linked to retinal dystrophy. So, if those are really underrepresented in datasets based on European populations, that is obviously going to present a problem. Gavin mentioned access to treatment. We need to overcome some of these disparities in healthcare access, and   inclusion of broad spectrum of genetic data is actually a foundation for that.   Naimah: Thanks Kate.  So underrepresented groups are often less likely to know about genetic testing due to a combination of social economic and systemic factors that create barriers to access information. Cultural taboos can also play a significant role in shaping attitudes towards genetic testing, and I think Bhavini you kind of touched on this slightly with some of your experiences. I wonder, did you experience any of these cultural taboos?  Bhavini: Yes, some of them, but I think by the time I was informed about what genetic testing and counselling is I had come across Retina UK and I had already started having that background knowledge, so when that was offered to me, I actually had a basic understanding. But as Chair of BAME Vision I work with a lot of ethnic communities, and when I speak about my own personal experience about receiving genetic testing and counselling, I kind of break it down into my own language, and the few common themes that always come out is people don't really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing.  So, again there is already a taboo around the terminology. Then it is lack of understanding and awareness, or where to get that information from. Also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with, so they try and hide it. They try and keep that individual at home, because they think they are going to have an outcaste in the community and the wider family, and you will be frowned upon, people will talk really bad.   So, it is not really common knowledge, so they don't even talk about it. So, there is a lot of layers to unpick there. That is one of the priority areas in 2025 that we at BAME Vision are going to be working on to try and raise that awareness in different communities about what genetic testing is, what it could mean, how to get genetic testing if it is not offered to you at your own clinic. There is a lot of work I know Retina UK have done, so working with them, and how we can reach different communities to raise that awareness.  Naimah: That's great. You have touched on how important the education piece is. I wonder, do you have any other examples of how healthcare providers and genetic counsellors might better engage communities to ensure that they are receiving the care that they need?  Bhavini: Yeah, absolutely. So, I think having information in different languages is essential, and I don't expect to have lots and lots of leaflets in different languages. Whether it is audio form or whether there is different professionals within that setting that speak different languages that can communicate to those patients, or even their family or friends that could translate. I think language is definitely something. And having representation, so like different people who have accessed this and sharing their story and going out into community groups and sort of sharing those messages, is definitely what has been working for us, and we have been doing that on other topics that we have used.  Naimah: Yes, they all sound like really important ways to try and engage with different communities. You have already mentioned how amazing that Retina UK have been and the support that you have received from them. So, I wonder Kate, if you could tell us a bit more about the support that is available for those with inherited sight loss, and how these resources can support people from underrepresented groups as well.  Kate: So, we have a range of support services at Retina UK most of which involve our fantastic team of volunteers, one of whom is Bhavini, who are all personally affected by inherited retinal dystrophy themselves. So, they are all experts by experience so to speak. The team also does include members of the Asian community as well. So, if somebody makes a call to our helpline, they will be able to speak to somebody who genuinely understands what they are going through, which can be a lifeline for those who are feeling isolated and especially I think as Bhavini mentioned, if they feel unable to talk openly with their own family and certainly within their community. We have a talk and support service that offers ongoing more regular telephone support as well as in-person and online peer support groups where people can make social connections with others in similar situations. I think Bhavini has mentioned that she herself runs our London and Southeast local group.  We also have an information resource called Unlock Genetics. That explains genetics in understandable language and clearly explains how people can access testing and what that will involve. So, we have stories on there from people who have gone through the process and talk about that. So, that is available on our website, and we can provide it in audio format as well.  Naimah: So Gavin, looking to the future, what does this research mean for patients with sight loss and their families? What does this mean in the future?  Gavin: So, I think now that we have access to whole genome sequencing through projects like the 100,000 Genomes Project, we are able to start the process of understanding new causes of disease that are found outside of the coded region.  So, we can now look for non-coding variants that cause disease which was previously not possible because genetic testing was focused on 2% of the genome. As we make discoveries like this these will inform future studies. So, the more we identify this type of variant and are able to functionally test the effect on the gene or the protein, we are able to use that information to lead future tests. What this needs is large population datasets to be able to analyse these sorts of variants at scale. The more genomes we have the better our understanding will be of our population frequencies, and the key thing is here for inherited retinal dystrophies, all of these variants that we are identifying are very, very rare. So, we only find them in a very small number of individuals affected with disease, and an infinitely smaller number of individuals in the unaffected general population. So, the larger that population dataset is that we can study, the better we can understand the rarity of these variants and pick those out from the many, many millions of non-pathogenic or harmless variants that we find in the genomes of all the individuals.  Naimah: Do you think the paper will help lead the way for diagnosis of other conditions in African and South Asian communities?    Gavin: Yes. The better we understand causes like this, and we are now at the point where most of the genes that cause retinal dystrophy have been identified already, so the remaining causes to be identified will be these more difficult to find cases, non-coding variants, structural variants, which we haven't touched on today which are larger rearrangements of the genome. These things are harder to find, harder to interpret, so the more that we find like this, the better our ability will be to interpret those sorts of variants. There are many similar findings coming out of genome studies like 100,000 Genomes Project. For example, there was a significant finding recently published on a non-coding RNU gene which causes a significant proportion of neurological disorders in the 100,000 Genomes Project. You need these studies to be able to drive forward the research in areas like this.   Naimah: Thanks Gavin, and the discovery that you are mentioning is the RNU4-2 gene that was discovered earlier this year. You can hear more about that on our other podcast on our website which is ‘How has groundbreaking genome work discovery impacted thousands far and wide' to learn more about that as well. But yeah, I agree it is another really great example of how impactful these findings can be. Okay, we'll wrap up there. Thank you to our guests Gavin Arno, Kate Arkell, and Bhavini Makwana for joining me today as we discussed the findings from a recent study which has identified genetic changes responsible for retinal dystrophy, and people commonly of South Asian and African ancestry. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.

In this episode, our guests discuss the potential of large-scale health datasets to transform research and improve patient outcomes and healthcare systems. Our guests also delve into the ethical, logistical, and technical challenges that come with these programmes. We hear how organisations such as UK Biobank, Our Future Health, and All of Us are collecting rich, diverse datasets, collaborating and actively working to ensure that these resources are accessible to researchers worldwide. Hosting this episode is Dr Natalie Banner, Director of Ethics at Genomics England. She is joined by Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health, Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States. "There are areas where academia and the NHS are very strong, and areas where industry is very strong, and by working together as we saw very good examples during the pandemic with the vaccine and diagnostic tests etc, that collaboration between the NHS and academia industry leads to much more rapid and wider benefits for our patients and hopefully in the future for the population as a whole in terms of early detection and prevention of disease." You can download the transcript or read it below.  Natalie: Welcome to Behind the Genes   Naomi: So, we talked to each other quite regularly. We have tried to learn from each other about the efficiencies of what to do and what not to do in how to run these large-scale studies efficiently. When you are trying to recruit and engage hundreds of thousands of participants, you need to do things very cost effectively. How to send out web-based questionnaires to individuals, how to collect biological samples, how the make the data easily accessible to researchers so they know exactly what data they are using.   All of that we are learning from each other. You know, it is a work in progress all the time. In particular you know, how can we standardise our data so that researchers who are using all of us can then try and replicate their findings in a different population in the UK by using UK Biobank or Our Future Health.    Natalie: My name is Natalie Banner, and I am Director of Ethics at Genomics England. On today's episode we will be discussing how we can unlock the potential of large health datasets. By that I mean bringing together data on a massive scale, including for example genomic, clinical, biometric, imaging, and other health information from hundreds and thousands of participants, and making it available in a secure way for a wide range of research purposes over a long time period.   Through collaboration and industry partnerships, these programmes have the potential to transform research and deliver real world benefits for patients and health systems. But they also come with challenges ranging from issues in equity and ethics through to logistics, funding, and considerable technical complexities. If you enjoy today's episode, we would love your support. Please like, share, and rate us on wherever you listen to your podcasts.     I'm delighted to be joined today by 3 fantastic experts to explore this topic. Dr Raghib Ali, Chief Medical Officer and Chief Investigator at Our Future Health. Professor Naomi Allen, Professor of Epidemiology at the Nuffield Department of Population Health, University of Oxford, and Chief Scientist for UK Biobank, and Dr Andrea Ramírez, Chief Data Officer at the All of Us Research Program in the United States.   Andrea, if I could start with you. It would be really great to hear about All of Us, an incredibly ambitious programme in the US, and maybe some of the successes it has achieved so far.   Andrea: Absolutely. Wonderful to be here with you and thank for you for the invitation. The All of Us Research Program started in 2016 from the Precision Medicine Initiative and was funded with the goal of recruiting 1 million or more participants into a health database. That includes information not only from things like biospecimens including their whole genome sequence, but also surveys that participants provide, and importantly linking electronic health record information and other public data that is available, to create a large database that researchers that access and use to study precision health.   We have recruited over 830,000 participants to date and are currently sharing available data on over 600,000. So, we're excited to be with your audience, and I hope we can learn more and contribute to educating people listening about precision medicine.   Natalie: Thank you, Andrea. And not that this is competitive at all, but Raghib, as we are recording this, I understand the Our Future Health programme is marking quite a phenomenal milestone of 1 million participants. Would you mind telling us a little bit about the programme and something that you see as the benefits of working at scale for health research.   Raghib: Thank you very much. So, Our Future Health is a relatively new project. It was launched in 2020 with the aim of understanding better ways to detect disease as early as possible, predict disease, and intervene early to prevent common chronic diseases. Similar to All of Us, we are creating a very large database of participants who contribute their questionnaire data, physical data, genetic data, and linkage to healthcare records, with the aim as I said, to really improve our understanding of how best to prevent common chronic diseases.   So, we launched recruitment in October 2022. Our aim is to recruit 5 million participants altogether, and in the last 2 years about 1.85 million people have now consented to join the project. But you are right, as of last week we have what we call 1 million full participants, so people that have donated a blood sample, completed the questionnaire, and consented to link to their healthcare records. In our trusted research environment, we now have data on over 1million people available for researchers to use.   Of course, we have learnt a lot from the approach of UK Biobank, which we are going to hear about shortly, but the resource is open to researchers across the world, from academia, from the NHS, from industry, so that will hopefully maximise the benefits of that data to researchers, but as I say with a particular focus on early detection, early intervention, and prevention research.   Natalie: Thank you Raghib. Great to have you with us. Naomi, Raghib mentioned that UK Biobank has been running for a long time, since 2006.  It is a real success story in terms of driving a huge range of valuable research efforts.  Could you talk to us a little bit about the study and its history and what you have learned so far about the sort of benefits and some of the challenges of being able to bring lots of different datatypes together for research purposes?   Naomi: Yeah, sure. So, UK Biobank started recruiting 0.5 million participants in 2006 to 2010 from all across the UK with a view to generating a very deep dataset. So, we have collected information on their lifestyle, a whole range of physical measures. We collected biological samples, so we have data on their genomics and other biomarkers. Crucially because they recruited 15+ years ago, we have been able to follow up their health over time to find out what happens to their health by linkage to electronic healthcare records. So, we already have 8,000 women with breast cancer in the resource, cardiovascular disease, diabetes, and so on.   But perhaps most importantly, not only does it have great data depth, and data breadth, and the longitudinal aspect, is the data is easily accessible to researchers both from academia and industry, and we already have 18,000 researchers actively using the data as we speak, and over 12,000 publications already generating scientific discoveries from the resource.      Natalie: So, we have got 3 quite different approaches. Recruiting in different ways, different scale, different depth of data collection and analysis, but all very much around this ethos of bringing lots of different datatypes together for research purposes. I wonder if you could talk a little bit about how you might be sort of working together, even though you have got slightly different approaches. Are there things that you are learning from one another, from these different data infrastructures, or how might you be looking in the future to work together to address some of the challenges that might come up from working at scale?      Naomi: So, we talk to each other quite regularly. We have tried to learn from each other about the efficiencies of what to do and what not to do in how to run these large-scale studies efficiently. When you are trying to recruit and engage hundreds of thousands of participants, you need to do things very cost effectively. How to send out web-based questionnaires to individuals, how to collect biological samples, how to make the data easily accessible to researchers so they know exactly what data they are using.   All of that we are learning from each other, and you know it is a work in progress all the time. In particular, how can we standardise our data so that researchers who say are using All of Us can then try and replicate their findings in a different population in the UK by using UK Biobank or Our Future Health. So, can we come up with common standards so that researchers can better directly compare the data that they are using? So, we are in close contact with each other.   Natalie: Fantastic, thank you. And Andrea, from your perspective obviously you are collecting data in the US. Are you finding ways of working internationally and with other infrastructures like Biobank and Our Future Health around things like data standards? It sounds like something simple, but I can imagine it is quite complex in practice.   Andrea: Absolutely, and that dialogue and understanding and learning from each other both informally in meetings and talking as well through the published literature. So, all of these datasets are actively widely used, and seeing what is coming out in publications helps us know what researchers are doing with the data. And when you see different researchers either generating hypotheses from our datasets in a different way, or testing hypotheses differently, that helps us understand where some benefit might be added to our dataset or where we really may need to grow in a different direction to meet some other research needs.   I think that every study design always struggles with that balance between knowing exactly what we want to study and therefore building very specific questions and very specific protocols, but also allowing for the knowledge that we don't really know all of the discovery we need to make and bringing in datapoints that will really generate those new hypotheses for the future.     I think for our study in particular, UK Biobank has been so remarkable in this way, helping structure All of Us to be able to contact our participants like UK Biobank and say, “Hey, we didn't really know what we were going to get, but we have put all this wonderful data together and now we need to do a deeper dive.”   So, the engagement and long-term return of those UK Biobank participants has really enriched our data, and we have learnt from UK Biobank a lot there, and hope through growing our partnerships programme that we can continue to create partnered research opportunities to strengthen that data as well. That is a new thing coming out of our group. You may have heard of it previously as ancillary studies, but we recognise the partnership that is important for those research opportunities. So, we are reporting here that we are hoping to rebrand it to reach a larger audience, and that is led by Dr. Shelley, as partnered research opportunities that will allow us to re-contact, bring our participants back, and really deepen that dataset.   Natalie: Thank you. And Raghib, I know that it is a really important part of the Our Future Health model about going back to participants, but you are in quite early stages of working out what those opportunities might look like.   Raghib: Yes, very much early stages. Just to reiterate the point for me personally, having started my research in the UK about 20 years ago, I have certainly learnt a lot personally, but we have all learnt a lot from the model that UK Biobank established in terms of collecting data and providing it to researchers, and I see these 3 studies as very much complimentary.   All of Us again have done a lot more work in terms of providing feedback to participants about their risk of disease and genetic information, and as you say Our Future Health was set up deliberately to not just be a purely observational study, but to give participants feedback about their risk of different chronic diseases as well as the opportunity to take part in not just studies to collect data, but also interventional studies to see if we can change the natural history of disease and prevent diseases in our participants.   So, that has never really been done at scale before, and that is certainly a big challenge for us to do, not just in the UK, but anywhere, including the US and working with health systems as to how best to do that. So, you know we have spent the last 2 years really trying to understand how best to recruit participants and to provide data to researchers for the next couple of years, and long beyond that we will be looking really as to how we can maximise the benefits of providing feedback to participants and taking part in interventional studies.   Naomi: I think one way in which we can all learn from each other actually, is we know how to recruit hundreds of thousands of people, the general population, into research study, and the next challenge is how do you keep engaging them, telling them what you are doing. You can't collect everything when they first join the study, or they would be with you for days. So, what UK Biobank has been doing is sending out web-based questionnaires, a couple a year, to find out extra information about health outcomes, lifestyle factors. Inviting them back to specific assessment centres.   So, we are inviting 100,000 participants back for imaging, and then again over the next few years for a second scan. So, I think the real challenge here is once you have recruited them, how to find that right cadence of engaging those participants to keep contributing their data and their biological samples to really maximise the value of the dataset for research. That is an ongoing challenge for all of us. But I have to say, the UK Biobank participants, they are an amazing group of individuals, very altruistic.   Our Future Health and All of Us, we don't give feedback, so there is nothing in it for our participants other than knowing that their data may help the future health of their children, and their grandchildren, and the rest of the world. So, that is very humbling, to know that the data that they have generated, and we have collected on them, is being used in that way.   Natalie: That's a really interesting point, Naomi, about the difference between a research study that is designed for answering a particular question. You gather specific data for a specific purpose, and when it comes to recruiting participants into that you can be very clear about what it is you are trying to do.   But of course, for all of these programmes, the whole nature of them is that you are collecting a lot of data over a long period of time, and it could be used for all sorts of different purposes. You can't say at the outset exactly what those purposes might be and what those outcomes might be. So, there is a really interesting question, and of course I would say this with my ethics hat on, a really interesting question around sort of participant trust and confidence in those programmes.   Naomi, you spoke just then about one way of retaining engagement and retaining people's interest, but I wonder Raghib and Andrea, if you have got thoughts on those sort of questions of how you can create that environment where participants can trust what you are doing with data over a long period of time, when you can't at the point at which they consent, say exactly how that data might be used? You have got a sense of the kinds of purposes, but you can't be too specific         Andrea: Sure. We know, and I have learnt from my own peers in this role, that enrolment in the study isn't the end point of engagement. All of Us's approach on engagement has been communicating with the entire community and really being there in the community, and that has been very powerful.   One effort over the last year we are proud of has been what we are dubbing participant driven enquiry, and that is where we say, “Thank you participants. We have gotten a ton of data out there for use, and funded researchers to use it all the time, but what do you, the participants, really want?” We were able to then take papers that researchers write and help tell participants and explain it in lay language, so the participants can say, “Hey, I have a question. Could you answer that for me?” Maybe we can, maybe we can't, but it has been very interesting to hear what participants want to know, and that participant driven enquiry project has turned out to be a big opportunity there.    The question they came to was not easy. Certainly, we didn't expect an easy question, but they came to us asking, “Why is my diabetes worse than someone else's? Is it the environment? Is it my genome? Is it my access to care? Why can't my diabetes be as well controlled as someone else's?”  So, that has been huge, to interact directly with our participants and help really close the loop by answering questions in the language of research and show them how their data is contributing back.    Natalie: Thank you. And Raghib, how are you sort of grappling with these questions, particularly because you are recruiting so very heavily at the moment?   Raghib: So, as you say it is a challenge, and people do join the programme primarily based on trust that we will use their data for public health benefit and for the benefit of the whole population, but they also join on the basis that they will get back information about their own health and their risk of disease. To do both of those is not straightforward. I mean, the first of those, it has been well established by UK Biobank, and about 80% of our participants also say they are doing it primarily for to altruistic reasons, which is great. But 80% also said they would like to receive feedback about their own health, which is also understandable, and so we need to find ways to provide that in a timely way, but also in a way that the health service can manage. That is going to be one of our key challenges going forward.    But to echo what Naomi and Andrea have said, I mean to maintain participant's engagement with the programme is not easy. We need to make sure that they are receiving information regularly, are kept up to date with what we are doing with their data, with the work that we are doing with academia, with the NHS, with industry etc. It is easier now than it was before because Our Future Health has been set up as a digital cohort, so we have means of communicating much more easily with our participants. But yeah, as you say we are at early stages. Over time that does get harder, to maintain that engagement. So, we know in the next one to 2 years we need to step up our work on feedback and recontact.   Natalie: Fantastic. I really love the idea of like the participant-led enquiry. That is something that I think our participant panel at Genomics England would really like to hear more about.   So, speaking about sort of ongoing engagement with participants, one of the challenges we know around recruiting into large-scale studies like this is that many research datasets don't have equal representation from all communities. That might have an impact on the quality, the representativeness of the scientific outputs that you can generate, and potentially the benefits back to patients and participants.   How are you addressing this challenge in recruitment where you may have some communities that are not as engaged with scientific research. You may have elements of distrust or people being marginalised, having difficulty accessing research and these sorts of opportunities. Do you have any examples of what has worked really well? Raghib, if I could come to you first.   Raghib: Sure. So, I mentioned I worked on UK Biobank about 20 years ago. One of the things I was looking at then was how we could maximise participation, particularly of people from ethnic minorities into the project. Because of the age group that was chosen by UK Biobank for very good reasons, age 40 to 69, the proportion of people from ethnic minorities was relatively small. So, although it was representative for that age group, I think it was about 6%, or 34,000 out of the 500,000, that were from non-white ethnic minorities.   So, when Our Future Health was set up, we knew that the population has changed anyway. You know, the UK has become a much more ethnically diverse society. But also, because it is a cohort from 18+ and I think minorities tend to be younger on average than the white population, we knew we had an opportunity to really have a big step change in the number of people that could take part in a study like this. So, our aim is actually to get 10% of the whole cohort from ethnic minorities, so 500,000 out of the 5 million from ethnic minorities. Actually, so far we are pretty much on track. So, of the 1.8 million that have consented, about 180,000 are from non-white ethnic minorities.   That is extremely important, particularly for genetic research where non-European populations are very much underrepresented in nearly all genetic databases. Secondly, from a UK context, although it applies of course in all countries, is that people from more deprived backgrounds are also less likely to take part in this type of research. So again, we have made a very deliberate attempt to try and ensure we have adequate numbers from the most deprived quintile. Again, about 10% of the cohort so far, nearly 200,000 are from that most deprived quintile who both are underrepresented in research, but also have the worst outcomes. So, this is really our first study that has been big enough in the UK to look at that group properly and understand some of the factors at an individual level that we haven't been able to in the past.   Finally, geographically, so the first time again because it is a digital cohort, we were able to recruit people from all over the UK. So, every single part of the UK is now represented in Our Future Health, particularly coastal communities and rural areas that haven't been able to take part in this type of study before, as well as Northern Ireland. You know, for the first time we have got that full geographical coverage.   Natalie: Fantastic. I suppose a lot of that recruitment approach has very much been about going to where people are, rather than expecting them to come to you. Is that right?     Raghib: That is right and thank you for reminding me. So yeah, we have had a different approach. So, we have opened up many, many more clinics than previous studies through a combination of mobile units, shopping centres, community pharmacy. Community pharmacy in particular has been very important. So, to date we have had about 400 different venues that we have been able to recruit. That is over 1 million people that have given blood samples, and that has really enabled people from every part of the country to take part. Secondly, we have kept clinics open in areas of greater deprivation and ethnic diversity much longer than in other areas, to maximise the opportunity for them to join. Thirdly, we do provide reimbursement for people with expenses to ensure they aren't excluded because of financial reasons, and again that has helped.    Natalie: So, really making those efforts is evidently paying off. Andrea, have you had similar experiences as All of Us? What has your approach been to try and ensure that you are getting a wider representation from different communities?    Andrea: It has really been a focus on the programme from the start to engage those who have not been included in research in the past and make sure the opportunity is there to participate. Our Engagement Division, led by Dr. Corrine Watson has really pioneered reaching those communities here in the US.   I think one other thing I will mention that we think about when we think about how to engage participants and reach people to return value back to those communities, is to make sure the people who are accessing the data also represent them, and we can build diversity within that researcher workforce. So, since our data was first released in 2020, we have recognised that the biomedical workforce also has a huge group of underrepresented individuals, and a lot of our researcher engagement and researcher outreach has focused on reaching those of diverse backgrounds and career paths.   To that end we have reached out and engaged historically black colleges as well as other minority serving institutions, really looking to make sure that their students and researchers can have the same access as more traditional research-based institutions in the US system.    That has been important because our system is built on cloud-based architecture and shared data that doesn't require a huge cluster on campus, and that helps remove a barrier that some of those institutions and researchers may have had. We also know they haven't been able to participate in the past, and we think that cloud architecture again can make the data much more feasible and be a huge support to diversifying the researcher workforce as we go forward. That circling back, helping them be the voices speaking to their community, helps build out that diverse participant community base as well.    Natalie: That's such an important point, because it is not just about the participants and the data you can collect, but also who is able to look at it? Who is actually able to undertake the research?    Naomi, can I bring you in here? I know that UK Biobank has been thinking a lot about researcher access to data and trying to ensure that the data that you hold, the really rich datasets you hold in UK Biobank, are more accessible to researchers from different backgrounds who may not have the same level of resources. Can you tell us a little bit about the work you have been doing on that?   Naomi: Yeah. So, just following on from what Andrea said, it is really important to get as diverse ideas as possible from across the global research community to really move public health forward.   So, what UK Biobank has done is we are putting mechanisms in place so that early career students, and career researchers, and researchers at all levels of their career from lower income countries, can access the data at a much lower fee. So, currently for most researchers it costs about £9,000 to access all of the data. So, that is 40 petabytes of genomic data, biomarkers, clinical outcomes, lifestyle factors and so on. So, early career researchers and those in lower income countries, it is about £500.   On top of that a group of big pharmaceutical companies have got together to create a global researcher access fund, which essentially covers this reduced fee so that all researchers no matter where they are from have exactly the same opportunity to access the data to advanced scientific discoveries. So, on top of that all our researchers now use our online secure research analysis platform. While there is no charge to access the platform, there are costs associated with compute needed to analyse and store the results.    So, AWS have donated research credits for early career researchers and those from lower income countries up to a total of about $500,000 per year, to use the research platform. So, researchers can apply to use these research credits to offset the costs of compute and storage. So, that means that we are trying to democratise access to researchers from all around the world.   I think actually our biggest challenge is not so much … we have largely dealt with you know subsidising the cost. It is actually making researchers from lower income countries aware that these resources exist, and that are applicable to them.   So, sometimes we hear from say researchers in Africa or South America, “Well, there is no point accessing UK Biobank because it is not relevant to our population.” You know, a third of our researchers are from China. So, even if UK Biobank hasn't got coverage of those racial ethnic populations, that doesn't mean that the associations that you find between risk factors and disease risk are not applicable to other different populations. And that is also why having different resources like UK Biobank, like Our Future Health, like All of Us, in different populations around the world, is so important in order to replicate those findings.    Natalie: Absolutely, and fantastic just to hear the attention that is being paid to trying to ensure that diversity of different types of researchers who will just bring different questions to the table, different perspectives on the data, different priorities, different types of questions.    So, speaking about that diversity of researchers, one really important part of his ecosystem that we haven't really touched on so far is around the role of industry. There are a lot of really important research questions being addressed by industry. Some that can only really come from, maybe it is pharmaceuticals, maybe it is tech.   From your perspectives, what kind of role can and should industry and commercial partners play in supporting the kinds of long-term research studies that you have set up, and ultimately trying to get to that point of sort of generating benefits back to patients and health systems. Naomi, can I start with you, for that sort of longer-term perspective for Biobank?   Naomi: So, industry are great partners for long-term studies like ours because they can bring additional funding, expertise, and technology. So, for UK Biobank, because it is so easily accessible to industry and academics alike on exactly the same terms, what it has meant is that industry, particularly big pharma and also now big tech, they can access the data, they see the value of the data for their own research purposes, and then they have invested into UK Biobank to do whole-exome sequencing, whole genome sequencing, proteomics at scale to increase the value of the dataset for their own drug discovery pipelines.   But of course, it means that the data that they have generated, which cost millions of dollars to generate, when you need deep pockets to do these kinds of study enhancements, then become available to all researchers. So, having access to these large-scale resources that have deep data on genomics, physical measures, other biomarkers, and clinical outcomes enables pharma to rapidly increase their drug discovery pipelines in generating new drugs and treatments for patients, and also those data are then shared with the rest of the global research community.     So, we found it to be a really exciting win/win in which industry get what they need to help move forward new drug targets and discovery, but also other researchers get what they need in order to make other scientific discoveries in different fields of research.        Natalie: Thank you. And Raghib, I know that for Our Future Health, that industry relationship is a really important part of the founding model. Will you tell us a little bit about how you are engaging and working with industry partners?   Raghib: Sure. So, as you said Our Future Health was set up in a different way, as a very public private partnership. Although the largest funder is the UK Government, more than half of our funding has come from a combination of life science companies, so pharmaceutical, diagnostic companies, as well as the medical charities, so the larger medical charities in the UK. That partnership is deliberate for all the reasons that Naomi has outlined. There are areas where academia and the NHS are very strong, and areas where industry is very strong, and by working together as we saw very good examples during the pandemic with the vaccine and diagnostic tests etc, that collaboration between the NHS and academia industry leads to much more rapid and wider benefits for our patients and hopefully in the future for the population as a whole in terms of early detection and prevention of disease. So, we have 16 life sciences companies that have joined as founding partners with Our Future Health who have contributed financially to the programme.    Equally importantly they have also contributed scientifically, so there is a huge amount of scientific expertise in industry, and they work with us with our Scientific Advisory Board with our scientists internally to think about the best use of the resource for drug discovery, diagnostics, new medical technologies, and new targets etc.    So, that is the vision, and so far, it is working well. It is a relatively new model to have set up a project like this in this way, but it has been a very collaborative approach, and we all recognise, all have similar aims, so recognise what we are working towards. You know, we meet regularly. We have a Joint Founders Board where as I say academia, NHS, industry, and the charities come together to decide on the priorities for the coming years.   Natalie: Fantastic. And Andrea, I suppose in the US it might be slightly different culturally from the UK, but the role of industry with All of Us, how are you engaging with those pharmaceutical, technology bodies, and partners as well?     Andrea: Absolutely, and maybe this goes back a bit to your first question. We at All of Us love learning from UK Biobank and have really seen them forge a lot of wonderful partnerships that have enriched and developed their dataset. We at All of Us have started with academia and working through partnership opportunities really intramurally at intramural centres that make up parts of the National Institute of Health. We believe that building on those close friends and family relationships we have both in the government and academia get us through our first step to be able to interface with commercial organisations. That really started with taking the first step this year to ensure broad availability of data that can maximise both use of the data available, as well as look forward to our partnership opportunities in the future.   So, commercial organisations as of 2024 have also been able to access the All of Us dataset that is that first step in thinking about what a partnership would be, and we are glad to build on the access that international organisations and academic organisations already have.   Natalie: A lot to look forward to here. We are going to have to wrap up in a moment, so I'd just like to leave you all with a final question before we have to end the podcast. There is huge ambition in all of the research programmes that you are leading and involved in, but what are you most excited about coming down the line in the next few years? What do you think is going to be feasible? What really gets you excited about the work that you are doing and where you see the potential benefits really landing in the next few years? Andrea, would you like to start?   Andrea: Thanks. There is a lot we are really excited about. I haven't had a chance yet to mention our paediatric cohort, and that in addition to expanding access for international research, in 2024 we were able to enrol our first paediatric participants. That really sets up the potential to observe participants across the lifespan. That is a huge advance for All of Us and we are excited about the paediatric work going forward.    Natalie: I love that, how do you come into the future with us? That is fantastic. Naomi.   Naomi: Yeah, if I had to choose one would be the possibility of being able to measure circulating proteins on all half a million participants. We have done this on about 55,000 participants, and just that subset alone is already generating fascinating insights for early biomarkers for disease through protein profiles and risk prediction of disease. I think having that on all half a million coupled with their genomics data and health outcomes, will bring a sea change in how we diagnose disease earlier. So, I think that is a really exciting avenue for us to go into over the next couple of years.   Natalie: Really enriching. That data sounds like a very exciting set of possibilities. Raghib.   Raghib: Thank you. There are so many opportunities here, but I will just maybe mention 3. So, the first, in terms of being able to combine the genetic data that we are collecting and all the other information about risk factors, and particularly the fact that we have this on a lot of young people, will enable us to identify people at high risk of diseases in the presymptomatic phase and then to be able to offer them both feedback about their risk of disease but also interventions that can change their natural incidences. That has never really been possible before. That is extremely important for all diseases for people, but also it is very important for our healthcare system.   So, those of you listening in the UK, I know the NHS is under a huge amount of pressure, and the current model of healthcare which has been in place really since the inception of the NHS, is to treat late-stage disease when people have already developed symptoms and signs. You know, it wasn't really possible to identify people earlier, but it is now, and Our Future Health will provide the evidence base to show that prevention really is better than cure, and to show that these approaches both lead to better clinical outcomes, but also are cost effective and a good use of resources. Of course, the new government is very much committed to this as well, you know moving from acute care to prevention, from hospitals to community, and from analogue to digital.     Finally, because our cohort has now become so large and does cover every part of the UK, and this wasn't something I necessarily thought about when we started Our Future Health, we are able to have unique insights into the health of the population across every age group, across every ethnic group, across every geographical area, and by deprivation, and to understand not just observationally in terms of risk factors, but also the impact of interventions on those different populations.   We can look at that, as I said at an individual level on millions of people to gain intelligence about what is going on in terms of public health, but also to see what will hopefully improve their health in the future. So, there are really, you know I have described transformational opportunities to improve health through both biomedical research and populational health insights now through the resource, and I look forward to working with colleagues across the UK and globally to deliver them.   Natalie: We will wrap up there. Thank you so much to our guests, Dr Raghib Ali, Professor Naomi Allen, and Dr Andrea Ramírez for joining me today as we discussed how collaboration, scale, ongoing engagement, can really unlock the potential of large-scale health datasets to drive brilliant new research and ultimately improve the lives of patients and the population.   If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.

The Genetic Rare Syndromes Observational Cohort (GenROC) study aims to improve our understanding of how rare genetic conditions affect the way children grow, their physical health and their development. Through actively involving parents as experts in their child's condition, the study seeks to gather valuable insights and ensure that family experiences shape future research and care strategies. You can find out more about the study and eligibility criteria via the Bristol University website. In this episode, Jillian Hastings Ward, patient advocate and former Chair of the Participant Panel at Genomics England, is joined by Dr Karen Low, a clinical geneticist leading the study at the University of Bristol, who shares insights into its objectives, the importance of a co-production approach with families, and the vital data being collected in the study to improve support for these children and their families. We'll also hear from Lindsay Randall, a parent who discusses the journey of receiving a rare diagnosis for her child, highlighting the critical need for more comprehensive information and community support. "If you join GenROC, that data will be used to develop a growth chart for your child essentially and their genetic condition, so I'm really excited about it because I feel like that's a very concrete definite given now for all the families in GenROC, which is just brilliant." You can download the transcript or read it below. Jillian: Welcome to Behind the Genes Lindsay: Historically, there's been a significant absence of patient voice in rare disease research and development, and knowing that's changing, I think that's really empowering for families and to know that professionals and industry are actually listening to our stories and unmet needs and really trying to understand, and that offers much greater impact on the care and treatments of patients in the future. Jillian: My name is Jillian Hastings-Ward. On today's episode I'm joined by Dr Karen Low, Consultant Clinical Geneticist and Chief Investigator for the General Cohort Study, and Lindsay Randall, Paediatric Practice Development Nurse and founder of Arthur's Quest, which is a UK registered, non-profit, raising awareness for the ultra-rare condition: SLC6A1, developmental and epileptic encephalopathy. Welcome to you both. Today we'll be discussing the GenROC study, which is aiming to understand more about the health, development and valuing the experiences of children with neurodevelopmental conditions. If you enjoy today's episode we'd love your support. Please like, share, and rate us on wherever you listen to your podcasts. Thank you both very much for joining us today, Karen and Lindsay. There's a lot we want to cover, but first of all it would be great just to put a little bit of context around the Gen-Roc study. Karen, can you tell us a bit about what the study is aiming to do, who is eligible and why do you want them? Karen:  Thank you. And thank you so much for having me today, Jillian. So, the GenROC study, first to just explain to people what ‘GenROC' stands for. GenROC stands for the Genetic Rare Syndromes Observational Cohort Study. Just to give you some context about the study, I'm a clinical geneticist and most of my clinical work focuses on paediatrics, so I see children in my clinics and the sort of children I see generally are children with rare genetic syndromes. The last five to ten years we've got much better at diagnosing children with these rare conditions and that's because testing has got so much better. We can now do whole genome sequencing and we can do that on the NHS, which is amazing, children can get their tests as part of their clinical care, so it means that a lot more children are being diagnosed with rare conditions, about 2,000 per year in the UK. And the thing about that is, that I see these children in my clinics and I give their families that diagnosis. But the problem is for so many of these ultra-rare conditions, like Lindsay's family has, we sit there and we say to the family, “Well, your child has got ‘X' condition,” and we give them some information from maybe one or two publications and linked to a leaflet and a Facebook group. And then we say, “But really we don't know that much about this condition.” And they say, “But what is it going to mean for them when they are growing up or when they are adults? Will they be able to finish school? Will they be able to work? What is it going to mean?” And I have to shrug my shoulders and go, “I'm not really sure.” And as a geneticist and as a doctor and as a mother really, I just felt that wasn't good enough, and I found it really frustrating and I know that the families that I work with, that I look after, also find it frustrating and I wanted to do better. And I also found it frustrating that for many genes, researchers would publish two or maybe three publications about these conditions, and then they would move on to the next novel gene, and actually, the journals are a bit like that as well, they like novel things, they like new conditions, they like the next gene. And so, it means that actually data doesn't always carry on being gathered in these rare conditions, and there are a lot of them. That was another thing, I sort of felt that these conditions were being done a disservice and that we needed to do better, so that's where the whole idea of the GenROC study came from was my drive and desire to improve things for families and actually to work with families to improve that, and that's where so this is a very highly co-produced study and right from the outset I've involved parents in telling me what they wanted to know and I've got a very, very active PPI group, full of parents of children who have got rare genetic conditions, and also I'm really lucky to have a young adult who has a genetic neurodevelopmental disorder herself and they all tell me about essentially what I should do and what I shouldn't do. They tell me when I'm not doing enough or when I need to do something differently, so it's very highly co-produced, they're highly involved all along the way. So, children with a confirmed genetic diagnosis in a list of eligible genes which people can see on our website if they Google GenROC University of Bristol, we've got a very easy checker for eligible genes, but they are essentially the most frequently diagnosed genes in rare neurodevelopmental disorders. And if their child is under 16, has a confirmed diagnosis and doesn't have any other genetic diagnoses then they can go into the GenROC study, that's essentially the eligibility criteria. Jillian: That's really interesting. It's very helpful to hear the background and I think as a parent of a child with a very rare disorder hearing that the clinicians also recognise this gap and the sort of pause that happens once you have your initial diagnosis, is really helpful and really encouraging. Lindsay, can we turn to you next and can you unpack a little bit about what it meant for you to get a rare diagnosis for your child and what point on your family journey was that compared to where you are now? Lindsay: I think to get a rare diagnosis for us was difficult and challenging and I think the first kind of challenge that any family has is actually being well-informed by a paediatrician who is also well-informed, and that's not always the case. That can affect the way we acknowledge or accept a diagnosis and how we also access support and how we understand what more we can do to make more connections. We did have genetic counselling offered, but I think there are families out there who don't get genetic counselling offered to help them understand the child's diagnosis, and then there's a heavy reliance on the internet, and as you said, there's a lack of information out of there. A lot of conditions are newly diagnosed or they're very complicated genes to work with, or as Karen said, they've had a couple of papers and people have moved on. And I think that does cause an immense feeling of isolation. We were diagnosed in 2018, our son, our first child, and exactly as Karen said, it was a fairly quick appointment of, “We don't really know much about this condition at the moment, there's a couple of papers. We know of 34 children in the world at the moment with your condition. Here's a Facebook group,” which we did join. And it is overwhelming to be given a diagnosis that's delivered with such little hope I guess, finding sources of information that's valid and robust is challenging, not everyone knows how to do that or has a skillset to conduct searches of academic research and I think that clinicians could definitely do better in also signposting the kind of umbrella charities like Unique and Contact and Swan and patient organisations, because I know that would have been definitely helpful for us as a family to be able to have opportunities to connect with others. Jillian: Thank you. Our diagnostic journey has been a bit a similar in that we were diagnosed through the NHS, and that at the time my son was the first person diagnosed with his disorder in the whole of the UK so it was really a big question mark, it was a question of our geneticist saying, “Here's the three PDF articles that we know exist in the world about this condition. Can you read them and tell us whether you think that sounds like him in order for us to be confirming our diagnosis?” I very much hear what you're saying there about feeling lost in the wilderness. And we too joined a Facebook group quite shortly after we got our diagnosis, and at the time my son was among the older ones or certainly as time has gone by he has been among the older children, so it can be really hard to know what might happen next. I think that now as Karen was saying we're getting much better at diagnosing people thanks to all the extra testing that's happening, that happens much earlier in life than it has done in the past, but I think then it still leaves a gap in parents' understanding because you don't necessarily know what the next ten years might look like for example. And so, I think making connections with people who are in that age bracket can be really important, but it's very hard to do. So Lindsay, I'm conscious that your professional training as a nurse must have stood you in quite good stead when you were faced with a barrage of medical literature shortly after your diagnosis, but I think one thing that every parent shares is the desire to do the best for their child and especially in this world of rare disorders. There's a huge amount of energy that comes through the community I think, faced with the need to try and self-start and build these networks and connections for themselves. Is that something that you've seen in your community as your experience? Lindsay: Yes, definitely. I think we're a growing community and over the years of course more and more children and young adults have been diagnosed with a few older adults coming through. It is very much a global networking effort and parent/patient organisations have been set up in many countries now by parents of children with children with SLC6A1. I definitely think that drive to become an expert in your child's condition is a long journey and one of continual learning and actually a lot of families simply don't have a capacity to take that on, I think often the medical and scientific jargon is difficult to understand and that makes it challenging to access. And as you said, as a paediatric nurse, I at least have some existing skills to understand healthcare to read the research and speak with medical and scientific professionals with some confidence, but in some ways, that has increased the burden I've placed on myself to become an expert for my children and other children and families who are not in the same position as me. It does require a lot of dedication and time, and that does have implications on families because it's time away from our children and from home, and from the remnants of our lives that we desperately try to cling onto, to not lose all sense of ourselves. It's not often spoken about but I do see the strain it places on the families, as well where there's a lot of separation and divorce sadly in the rare disease communities, and often that's as a result of one parent's drive to be the expert, which seems to cause one parent to fulfil more burden of care and that fosters some level of resentment or sense of loneliness towards the other one. Jillian: There are some scary statistics out there around familial breakdown in this context, and it is something which there are so many factors at play, but it definitely seems to be quite widely recognised and definitely a problem. In terms of the time that people have to spend on liaisons with the research community and the clinical community, that could bring us quite nicely back into a question for you, Karen, about what kind of information the GenROC study is looking to collect from families, can you tell us a bit more about that, please? Karen: Yes, absolutely. As I said before, I've been very conscious of the sort of lives that our families are living, and listening to Lindsay, her story is very reminiscent of so many others and yours, Jillian. So I know families have about a gazillion hospital appointments, their children are often also very, very ill intermittently or a lot of the time, then they've got school stuff to deal with or they've got EHC plans to try and fight for. It's more than a fulltime job in itself just being a parent of a child with a rare disease and it's hard work, so me asking them to do anything else is asking a lot. Luckily, I find, with the families I work with, who are universally wonderful I should add, that they are actually just really enthusiastic anyway about research for their child's condition, and that's because there isn't enough information out there, so it's relevant and important to them. But because they have no time at all, and any time they do give is their own personal time when they could be finally putting their feet up and watching something on TV, I have to make it as low effort as possible. The questionnaire is all online, using a user-friendly and interface as we've been able to develop. It's very user-friendly, it takes 10-15 minutes to complete; they can come and go from the questionnaire as well. We only ask for one time point at the beginning, which is all the sort of stuff that most parents will be able to tell you off the top of their head as well, so they don't have to go looking for loads of information, apart from a height and a weight. Then later down the line we're going to ask for a second questionnaire, it's in the process of being finalised and again that will be the same amount of time, very easy to do, online, at their convenience. It was co-produced with the PPI group, they've tested it for me, I've had really good feedback and I've asked parents who are in the study as well for feedback. Everyone tells me it's not too difficult or burdensome for them to do. The secondary questionnaire has been very much informed by conversations with the parents that I had as part of a nest of qualitative interview study in GenROC, and that has driven that secondary questionnaire quite differently to what I thought it might be when we first set up the GenROC study. At the beginning I thought it might just be: have things changed for your child? Can you give us a bit more clinical data? But actually I realised that probably I will still gather that information, but they probably won't have changed that much within the timespan in the study because it will only be a year or two after they completed the first questionnaire, and actually I realised that it would be much more useful to look at the impact of the genetic diagnosis, look at how they're accessing services within the NHS, what sorts of services they are accessing, Impact on the family and also looking at priorities for families. So families have talked to me about what their priorities are in rare disease, both in service provision but also in research, and I really am a very strong believer that we need to be given the limited funding, we need to be doing the research that matters the most to the families, not to the researchers. What do families actually want us to look into? Actually, do they want us to be looking into behaviour and what strategies work best for example, rather than something else very medical – what matters the most? And so that's going to be a specific question in that secondary questionnaire, really trying to identify what matters to families the most and then how that can be translated into clinical research in the future. So I'm really interested to see what's going to come out of that. Lindsay: I think that sounds brilliant, Karen because I think historically there's been a significant kind of absence of patient voice in rare disease research and development, and knowing that that's changing, I think that's really empowering for families and to know that professionals and industry are actually listening to our stories and unmet needs, and really trying to understand, and that offers a much greater impact on the care and treatments for patients in the future and certainly it makes endpoints more relevant to families as well. Jillian: What kind of outputs are you going to be looking at? Karen: The height and weight, the reason I'm asking for that is really because we are trying to work on growth charts for children and that's because growth charts for children with rare conditions don't exist by enlarge, there are a very, very tiny number of rare syndromes or conditions that have their own growth chart. The problem is that most children with these sort of rare conditions that we're talking about are either quite small or quite big, and the problem is that the paediatricians look at their growth and they go, “Oh well, you're much bigger or much smaller than other children your own age, what shall we do about that?” and particularly the little tiny ones it causes lots and lots of concern, so quite often these sort of growth parameters mean that the paediatricians do lots and lots of tests or put feeding tubes down, or add lots of calories, so it can be quite invasive and interventional actually that sort of growth parameter. But actually, sometimes that's because of the genetic condition and no matter how much feeding you do it's not going to change anything. The difficulty is we don't know that for certain, and actually we need good growth charts where paediatricians can make that call, and conversely sometimes a child actually does need investigating and the paediatrician puts it all down to their genetic condition, and that's why we need these growth charts. So GenROC is aiming to gather growth data from all these children and then we're going to work closely with Decipher, which is a website that was developed through the DDD study, which already holds lots of data from that study, so we're building on the power of that study and we're going to be generating growth charts for all of these genes. We've developed a new method for producing growth charts for rare conditions where you've got small numbers of patients – that was never possible before, so we've already proven now for four conditions we can, so the next stage is using all the GenROC data, putting it into Decipher and coding it in. So, if you join GenROC, that data will be used to develop a growth chart for your child essentially and their genetic condition, so I'm really excited about it because I feel like that's a very concrete definite given now for all the families in GenROC, which is just brilliant. Jillian: And is that something which will be shared with the families individually? Karen: Really great question. I hadn't planned on sharing the growth charts individually with the families, but that's something I can also go back to my PPI group and discuss with them about whether that's something people would want, and also I have a newsletter which goes out every three months to the families, so I can certainly ask that question actually directly. It's going to be widely available, the growth charts, we're going to make sure that they're accessible to paediatricians and clinicians etc. but in terms of output to the study, definitely the growth charts, we're also hoping to have other clinically useful outcomes depending on the different genes that come into the study. We essentially have a cohort of children with rare conditions, everyone puts everything down to a specific genetic condition but we know that there must be other factors at play that influence how children do. And this is a really unique thing we're trying to do with GenROC actually, looking at aside from that genetic variant, that alteration, what other factors are influencing how children are doing? Because some of those might be modifiable, you know, or some of them there could be things that could be put in place to help improve outcomes. So I'm quite excited about that as well, because that's quite new and novel and not really been thought about in this context before, so that will be an output. And the other output is something that I'm working on with Unique, which is the rare disease charity who has worked with us on GenROC from the start, and they are involved in our PPI as well and that is going to be looking at a template, calling it a report at the moment, it's in very early days, but something that parents will be able to hold, it's going to have lots of drop-down boxes that can be tailored and modified for individual patients and children, which will be a bit of a guide that they can give to clinicians, professionals, education, telling them about their condition but also telling them on an individualised basis about what needs to be looked for in the future. Because parents tell me they are fed up of having to tell everybody about their child's condition constantly, all the time, over and over again. So what the point of this output would be is to try and ease that burden a little bit. This is very early stages but we're going to involved parents all along the way. Jillian: And is that something which builds on the hospital passport idea that we've seen emerging around the world over the last few years where parents can start off telling their child's story on their own behalf? Karen: So, it's come from my own lived personal experience of being a mother of a child with autism and I haven't really spoken about that publicly before, so it's something I'm saying for the first time. I have a child who has autism and I have had to navigate things like a DLA application form. Jillian: That's Disability Living Allowance. Karen: Yes, exactly, which is a horrendous form, it's the most horrible form to complete, probably apart from an EHCP plan form but it's a horrible form to complete, it's quite upsetting as a parent and it's also got millions of boxes that you have to fill in. But one of the things that really, really helped me when I was completing that was a charity who had come up with lots of drop-downs that you could select from that might be applicable to your child to help you complete this form. And so it made me really think, “Well, could we do something similar for our children with genetic conditions but come up with lots of dropdown options that might apply to their child in all sorts of different areas?” And that was the inspiration, it was that, and doing the qualitative study that I've already done with parents of children in GenROC who were telling me about how fed up they were of having to constantly tell everybody about their child's condition over and over again. Jillian: Yes, that's probably very helpful to empower families to use standard terminology across the different families because my own son has epilepsy as part of his condition but actually trying to describe what his seizures look like I'm not sure I'm using the right words to fit the right boxes to fit them into the right categories with the neurologist. So that level of standardisation is something that we definitely need embedded into the system in order for more people to be able to use this data more effectively, so that sounds very helpful. Lindsay, coming back to you, what are you hoping to get out of this study, or what are you hoping this study will do on your behalf for the world? What motivated you to take part? Lindsay: I think I would like to see all of the aims of the study realised and for the study data to be used to inform the development of standards of care for a wide range of conditions, those included in the study. I think it would be great if that information, as Karen said, is available not only to the participants but also to children diagnosed with those conditions in the future and also it's an opportunity to consider themes that are identified across the disease groups as that can also help inform future research and look at investigations into the mechanisms of disease and where actually therapeutics could treat maybe more than one disease at a time and increase potential for basket trials and early access programmes – thank you to Dr Karen Low and her team for conducting the project because it included a comprehensive list of rare diseases, it really does give parents and patients an opportunity to have a voice and to contribute, which is empowering, and it gives them a little bit of autonomy as well over their direction that science and research goes to. Jillian: Fantastic, thank you. Karen, can you tell us a little bit about the timeframe for the study? I realise that we haven't really touched on that so far. Karen: Yes absolutely, I'm aiming to recruit 500 children as a total. We're open at 22 sites across the UK. Coinciding with this podcast actually we've opened a second door for recruitment, so the way we've recruited so far has been through clinical genetic sites, which is the way we've done these sorts of studies in the past, like the DDD study. The problem is that that relies on clinicians identifying eligible patients and clinicians are very, very busy in the NHS. I have worked closely with Unique who have been doing a lot of publicity and the genetic alliance have done publicity as well for the study, so that's been one way of identifying eligible participants. And also just parent power through social media has been amazing. The second way we're going to recruit, and this is going to happen very soon, is through Genomics England. So, we are going to trial a completely novel way of recruiting to research through Genomics England and that is for Genomics England to identify eligible participants for GenROC and this would have been through the 100,000 genome study and then they're going to send them invite letters, inviting them to take part. So that's the next phase of recruitment, I think if we have more than 500 then that will be great too, we'll be able to include those comers too, so that's not a problem. But we don't know whether this will work or not in terms of a way of recruiting to research, this is completely new for Genomics England and I'm a bit of a guinea pig if you like through the GenROC study, but I was quite willing to be that guinea pig because I thought it might increase access. So there will be some parents who have not been told about GenROC who have not heard about it, and who would love to take part, so I feel like this is the way of really widening that net as wide as possible. Jillian: I think that is a challenge isn't it, especially in rare disease – there's no point doing a public broadcast about an initiative because you're going to hit so few of the people that you're interested in, so actually how you access the community is the first challenge and I'm really pleased that Genomics England will be able to help you there because I think that is a very useful route through. I think it will probably be quite reassuring to quite a lot of families who were on the 100,000 Genomes Project who have got a diagnosis of one of the conditions that you're interested in, and are now perhaps subsequently in the fallow period after you have a diagnosis, wondering what happens next, so I can imagine it might be quite good news for some of them at least that they are now being invited to do something further. And the reason that you're building forward and you don't want people who are currently in the deciphering developmental disorders study is because you're already using their data through another source, is that correct? Karen: Exactly. So absolutely, I don't want anyone to feel that I don't want them, that's really not the case. I do want them but we have their data already from Decipher, so we're building on the DDD data already, so they're already contributing which is just the beauty of it, because that's what we should be doing in rare disease, we should be building on previous research because you know, you don't want to be trying to reinvent the wheel. Jillian: Agreed. So if someone is listening to this and has a child with a rare developmental disorder and they are interested in finding out more, what are the steps they need to take? Karen: If they Google Bristol University, GenROC, they'll come straight to the webpage and everything is on there. There's a link that they can sign up, the patient information leaflet's there, the eligible gene list is there, all the information they need, including our email address. Jillian: And is there an upper age limit for recruitment? Karen: Yes, children have to be under 16 and that's because once they get to 16 many of these conditions have associated learning difficulties, and it's just very much more complex to try and recruit young adults, young people, with learning difficulties and given it was a cohort study we felt it was going to be too difficult at the moment. Saying that, I have a huge interest actually in how these conditions present in adulthood, and I'm actually conducting a much smaller study at the moment in KBG syndrome, looking at adults, and so I hope that my future research career will allow me both to follow-up the children in GenROC, so that would be my vision but also to be able to take this forward for other adults with rare conditions, that's my aim and goal in the medium to long-term, so watch this space for that. Jillian: That sounds very exciting, thank you. Lindsay: I think I would like to say to Karen that I really like the sound of the idea of following patients up into young adulthood and adulthood, as you said, that is definitely a kind of an unknown area in lots of the rare diseases, especially in our condition, SLC6A1, it was mutation and the disease was only really discovered in 2015, so it is fairly new and we have very, very few young people and adults coming through and being diagnosed and connecting with the rest of the community. So, being able to understand the trajectory of conditions better and especially conditions where actually the presentation it's quite a spectrum, and so the long-term outcomes for people with SLC6A1 can look quite different, so it's good to collate more information about that I think. Karen: I think it's really important, so that's definitely where I'm looking to for the future with GenROC and more widely, I think it's just something I'm really interested in and has huge relevance for parents and families. Jillian: Well, I think we need to wrap up there but thank you both very much Dr Karen Low and Lindsay Randall for joining me today as we've been discussing the GenROC study, and how the study aims to improve understanding of how rare genetic syndromes affect the way children grow, their physical health, their development, but also how the patient and parent communities can work more closely with researchers to end up delivering something which is of a huge benefit to everybody. If you would like to hear more about this, please subscribe to ‘Behind the Genes' on your favourite podcast app. Thank you for listening. I've been your host, Jillian Hastings Ward. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.

As 2024 comes to a close, we take a moment to reflect on what has been a busy year at Genomics England and in the wider genomics community. Throughout the year, guests have joined us to discuss groundbreaking research discoveries, important ethical considerations, and share their personal stories. It was also a year of transformation: we rebranded our podcast as Behind the Genes, welcomed Dr Rich Scott as our new Chief Executive Officer, and launched the Generation Study, in partnership with NHS England. The Participant Panel also saw changes, with Kirsty Irvine stepping into the role of Chair and Adam Clatworthy and Helen White becoming Vice Chairs. In this special end of year episode, Adam Clatworthy, Vice-Chair of the Participant Panel, sits down with Dr. Rich Scott, CEO of Genomics England, to look back on the highlights of 2024. Together, they revisit key podcast moments, reflect on research discoveries, and share insights into the evolving world of genomics. Below are the links to the podcasts mentioned in this episode, in order of appearance: Celebrating genomic breakthroughs - Insights from the Festival of Genomics Shining a light on rare conditions How has a groundbreaking genomic discovery impacted thousands worldwide? How can we work in partnership towards a new era of genomic medicine and research? How has design research shaped the Generation Study? How can we bridge the gap between diverse communities? Can Artificial Intelligence accelerate the impact of genomics? "It's really important that we just continue to bring that patient and participant community on that journey, just to ensure that they really understand the full benefits. And we've talked about that on the episode today. I know that the panel has always encouraged the Genomics England team to look at its boots while shooting for the moon. I really like that phrase just to make sure, look, we can't forget where we've come from to make sure we're taking people on that journey" You can download the transcript or read it below. Adam: Welcome to Behind the Genes.  Rich: Our vision at Genomics England is a world where everyone can benefit from genomic healthcare, thinking about how we ensure the lessons we've learnt through our diverse data programme is embedded across all of our work.  So that word “everyone” applies to people in lots of different ways, different communities people come from, different socioeconomic backgrounds, making sure that equity is baked into all of our work.  And there's real opportunity for genomics to play a broader role than in rare conditions and in cancer, we're proud of the impact we're already having there, and we should really look to the future.  Adam: My name is Adam Clatworthy, and I'm the Vice-Chair for rare conditions on the Participant Panel at Genomics England.  On today's episode, I'm going to be joined by Rich Scott, CEO of Genomics England.  We're going to be taking a look back at the key milestones from 2024 for Genomics England, and really discussing our hopes and aspirations for the year ahead.  During this episode we'll also hear from some of our guests we've had on the show this year, who have helped shape our discussions and shared some of their most impactful moments and insights.  And if you'd like to listen to more like this, then please subscribe to Behind the Genes on your favourite podcast app.  So, with that, thanks for joining me, Rich, how are you doing?  Rich: I'm great, thanks for hosting today, I'm really excited about it.    Adam: So, Rich, it's been a pretty exciting year for you, you've taken on the CEO role at Genomics England full-time, so why don't you just start by telling us about how those first few months have been for you?  Rich: It's been a really exciting year, I think for us overall at Genomics England, and obviously personally taking on the CEO role, which is an enormous privilege.  I've been at Genomics England nine years, and I think both a privilege and a real responsibility to take on the role.  To think both about how we continue to honour the commitments we've given our participants and those we work with, and to think about the future, where we might go together, what evidence we need to generate, what our systems need to support.  So it's been great taking on the role, and thinking about that, both the present and the future, and there's been lots, as we'll talk about, there's been lots going on.  Adam: No, that's great.  And I must say for myself as well, I started the Vice-Chair role at a very similar time to you early in the year.  When I started, we were in the process of looking for our next Chair.  Obviously, we had Jillian and Rebecca, both standing down, after many years in the role.  They've been there from the start, really guiding the Panel through this amazingly successful period.  But for me, I've really enjoyed working in partnership with Helen, who is our Vice-Chair for cancer.  It's been a real partnership, in terms of filling in for that interim leadership role.  And we wanted to make sure that we weren't just caretakers, we were really continuing to be actively involved in a lot of the discussions that are happening with your colleagues across Genomics England.  Very much leading the Panel, and starting to have those important discussions around, where does the Panel go next?  And what's our strategy for the next two to three years?  What are the key areas that we can drive real value and impact, in line with your own milestones at Genomics England?    And, of course, I've just loved getting stuck into chairing the Panel meetings as well, for me, that's the best part, is really bringing together these amazingly diverse and passionate people.  With so many different personalities, lived experiences, and a combined passion for just taking this forward together, and making sure that the benefits of genomics really impact, and that's felt by the wider community itself.  So there's been lots of highlights to recognise this year, a real stand-out for me has to be the Genomics England Research Summit, from what I understand it was the most attended event to date.  And it was just so good to see that a lot of the Panel were front and centre across that event, sharing their stories, having a really active role, whether introducing speakers, or telling their own journeys as part of the Q&A sessions.   I myself was really privileged to be on stage with Baroness Nicola Blackwood, literally nine days after I officially started the role.  So it was great to just dive in at the deep end, get in front of an incredible audience, and just see that the broader Panel was front and centre of the event itself.  And it was just great to see how popular the event was, many more people coming to have a chat to us on the stand than would have found us before, so, all in all, a really big highlight for myself.  So, for you, Rich, are there any other highlights that you want to call out for this year?  Rich: And first to say, absolutely agree with the Research Summit being, you know, a highlight.  The diversity of the discussions that we had, it's one of the things we enjoy most about thinking about creating the summit, as you say, involving the participants very much at the centre.  Like, physically at the centre of the room, for people to come and talk to participants and hearing stories.  And then really seeing how over the years we can see the impact growing, and having talks, whether it's about individual findings, or big research studies.  So the final talk of the day was from Charlie Swanton.  He was talking about some really exciting work that his team have done in our National Genomics Research Library, making a really important discovery about extra chromosomal DNA in cancer, and that's now been published in Nature.  And then right next to him, we were having a policy talk from Sam, who's the CEO of NICE.  And you can see the range of things, the sorts of evidence, sorts of conversation, we need to have, so that was really fantastic.  I'd call out one discovery this year that maybe we'll come back to, and one other big highlight.  So I think the big discovery this year was the discovery of this piece of non-coding sequence in the genome called RNU4-2, which turns out to be pretty much the most common cause of developmental disorders that's been discovered.  And it's just so exciting to see that having been discovered in the National Genomics Research Library.  And then the news, the knowledge spread, across the world, and family support groups coming together to understand and learn more about what that means for them.  So that was, I think, the discovery over the years at Genomics England that's touched me most, seeing that story.  And I'd say for us, organisationally, another big highlight has been the launch of our newborns programme, the Generation Study.  So as lots of people listening will know, we've been actually thinking about what the questions underlying this study are for a good number of years, doing a lot of preparatory work.  Actually, before we even started, setting up public dialogue jointly with the National Screening Committee about what the public were keen to understand and the appetite for research in this area.  And then we've been spending several years designing the study, working with the NHS how to design, safely launch it, National Screening Committee involved all along, and working with patients and the public to design it.  And this year now launching the study at a public launch, just a couple of months ago, by the time people are listening to this, and at the time of recording, more than 2,000 families have joined the programme.    So really exciting, us exploring a really big question for genomics, about the use of whole genome sequencing in newborn babies.  Whether that should be offered to every baby at birth, primarily driven by that desire to do better for those children born with treatable conditions, where genetics, genomics, can be a way in to finding them, but doing that at the right pace, and very much in a research setting.  That's been a real, a moment, I think there's been so much work on the path to it, but it's right to sort of celebrate these staging posts on the way.  We're early in the programme, there's lots to do, lots to work through, lots of evidence that we'll accrue, but it's really exciting to be at that staging post.  Adam: No, absolutely, and from my side, I think seeing all of the media pick up for the Generation Study launch, you could really see the excitement in the wider kind of community.  Seeing it shared on social media, obviously those part of the 100,000 Genomes Project, seeing things like this.  It's like they can see the tangible outcomes of all the work that they've done as part of that initial project, and seeing how those learnings are then taken onto this new study.  So we'll now hear a clip from earlier in the year from Louise Fish, who is the former CEO of Genetic Alliance UK, who shares her thoughts on the potential of the Generation Study.  Louise: The Generation Study is looking at 200 conditions and whether it's possible to screen for them.  And for all of those 200 conditions, it's a really exciting opportunity to see if we can learn more.  Both about the potential to understand and develop treatments early, but also just about the chance to understand the natural history of that condition so much earlier than we do at the moment.  And I think that's it, it's that understanding the natural history of the condition really early, and understanding how a family can be helped, through all aspects of the condition, which is giving people most excitement I think, alongside the potential to develop treatments.  Adam: So now, let's look back at the priorities for Genomics England for 2025.  Now, Rich, would you like to just take us through some of the things you'll be focusing on next year?  Rich: Yes, one of the things that we've been doing this year, but also actually in the year before, is really looking to the future.  And saying, where might we be in terms of genomics really living up to the impact it could have, if we collectively, in the UK and working with international partners, sort of get things right?  And that's very much about balancing the realism of where we are, and the impact we're already having, and being proud of that, and then getting that same sort of ambition and realism casting to the future.  And I'd say, I think there are two really broad themes.  I think the first thing is, we're enormously proud of the impact we've had already for families with rare conditions, and people with cancer, and that impact will continue to grow in the coming years, in those areas.  And in the next few years, that's where the biggest impact of genomics will continue, and the rare disease programme we have thinking increasingly about how we support the generation of evidence and pathways that lead to rare therapies.    So building, getting better all the time at finding diagnoses, which is still a long journey we're on, and continuing that work.  Increasingly thinking about how we can support therapies, and in cancer, again, playing a better role in cancer, both by driving efficiency in diagnostics, and efficiency in identifying where therapies enabled by genomics can be targeted.  And we see lots of different examples of that, clinical trials is a big area where we hope to have more impact in the future, but also thinking about some of the novel therapies that are there, both for rare conditions, but also, for example, the cancer vaccines.  And I think we're uniquely placed in the UK, because of our partnership at Genomics England with the NHS, and the broader science ecosystem, to have that impact.  So that's the sort of like continuing very much where we are, but really pushing those boundaries.  And then also, if we look to the future, to say, what role could genomics play?  And we, as you know, our vision at Genomics England is a world that everyone can benefit from genomic healthcare, and I think that plays out in a couple of ways.  Firstly, thinking about how we ensure the lessons we've learnt through our diverse data programme is embedded across all of our work, so that word “everyone” applies to people in lots of different ways, different communities people come from, different socioeconomic backgrounds, making sure that equity is based into all of our work.  And then also, to say there's real opportunity for genomics to play a broader role than in rare conditions and in cancer, we're proud of the impact we're already having there, and we should really look to the future.  And as we set out where we think what evidence is needed and where we need to learn what the digital infrastructure that we build and others build, need to build that to support that, we look across a few different areas.  But really you can see genomics playing a role across the lifetime, in different places in different roles.   To pick one really powerful example is something people often refer to as pharmacogenomics.  Which is a medical term for what boils down to look at a person's DNA sequence, that's the genomics bit, and making decisions based on what drug to give them, what drugs to avoid, or perhaps what dose to drug to give them.  Based on, for example, the desire to avoid adverse drug reactions that people might be at high risk of, and you can identify that risk looking at the DNA.  That is one example of genomics playing a role in being increasingly sort of preventive, getting away from disease, getting upstream of disease arising, or harm arising.  And there are other opportunities in common disease as well, sort of casting forward to what that impact might be, and we feel that genomics could play a role, really broadly, across healthcare, in probably as many as half of all healthcare encounters.    But what we need to do over the coming years for that to potentially be the case is we need to build out the evidence, and we also need to understand what digital infrastructure we need, to make that a possibility.  So that the information is there in simple format, for patients and the public, for their GPs, for their pharmacist, for people in any speciality in hospital, not just sort of rare disease clinics or in cancer, as we are at the moment.  And so very much we're thinking about the programmes that we and others could run to ask some of those questions, to think about what we need to build out.  We feel that the UK's uniquely placed to develop that evidence, so that we can make the choices about how genomics is used, and so we can be ready to embed it.    And it really aligns with that shift that we see and we hear, for example, in government being talked about, when we're looking about sort of the shifts that the NHS sees as essential.  You know, increasingly preventive, increasingly digital, increasingly in the community, and that point of sort of getting upstream.  And genomics is going to be an important part of that.  And we at Genomics England are really excited about the role that we can play, whether it's through the digital infrastructure we build, whether it's the programmes that we run to develop the evidence.  Or whether it's through the ethics and the engagement work, the work with the Panel, and the work with the wider public, to understand how we might develop this evidence, what people are comfortable with, what the expectations are.  And I think that, pulling that together is complex, it's really exciting to think about how we do it.  I think we in the UK are uniquely placed to take advantage of that.  Adam: That's great, and I think the pharmacogenomics piece is fascinating.  I mean, you hear many stories of people having adverse reactions to certain medications, and you wouldn't even think it's something that may be linked to their genetic makeup.  It's so important that we take people along that journey, around what the benefits are, the ethics, to make sure that people really understand the journey that we're making and what the potential impact could be.  Whilst there's lots of amazing new areas to develop into, a key focus for us on the Panel is really continuing to demonstrate how the 100,000 Genomes Project participants continue to have an impact, and they're helping shape a lot of these developments.  So they generously donated their data, it not only helps Genomics England develop the systems and services that now benefit many families, but it also continues to drive that scientific and technological enhancement.  So it wasn't just about reaching that 100,000 genomes, that project was really the starting point, as it were, it's not the finish line, it laid the groundwork for a lot of these developments.  So it's about how do we focus on maximising the benefit for those participants over their lifetime, not just at that one point in time.    We know genomics is evolving so rapidly, what you can glean from a genome today is far more than what was possible in 2013.  And we know the Diagnostic Discovery team is continuing to analyse the data for participants in the project based on these new advances, the team led by Suzi (Walker), who's doing some amazing work there.  Using all the latest tools and enhancements, just to make sure that those participants are really benefiting from that learning.  So, we just need to make sure we stay close to that wider community, and just ensure they're not forgotten, that's really a key north star for us as the Panel.  And something that we've been pushing is better ways that we can help to communicate the ways that you're celebrating these successes, providing regular updates on research progress, offering personalised reports based on the latest findings.  And it's all about providing them with that hope.  Some people may never get a diagnosis, but it's about giving the hope that one day they might get that phone call out of the blue, so it's about giving the hope that those possibilities are out there for others.    So we're now going to shift gear onto hearing from Shaun Pye, who is the father of Joey.  She was diagnosed with DYRK1A syndrome, which is a rare chromosomal disorder, which causes a degree of developmental delay or learning difficulty, at the age of just thirteen.  In this podcast episode, Shaun and his wife Sarah told us of their journey to Joey's diagnosis, and how their role in writing the BBC television comedy drama series, There She Goes, has helped to shine a light on the rare condition community.  Shaun: Then the opportunity came along with 100,000 Genomes, and we signed up immediately.  And then that, they did that, and it was a few years before that went through the system, and then we had, out of the blue really, we were asked to go and see a geneticist, and we had no idea that this is what it was.  I honestly thought it was just a routine sort of, we've got a few more theories or something, and she just said, “We've found out what it is.”  And it's like, that moment is, well, we tried to describe it in the TV programme, but it is quite hard to describe what goes through your mind, when after thirteen and a half years somebody suddenly says, “Oh, by the way, that thing that happened with your daughter, we've worked out what it is.”  Adam: So here, Rich, did you want to provide some updates around future progress, particularly in diagnostic discovery and expanding the research?  Rich: When we're looking to the future, we're looking sort of in two areas.  How we can build the impact we're having today for families with rare conditions and cancer, and that very much includes the participants in our programmes, 100,000 Genomes, those through the NHS Genomic Medicine Service, who joined the National Genomic Research Library.  And we've seen, I think the number that I'm most proud of at Genomics England is that number of diagnostic discoveries returned to the NHS, which has just hit the 4,000 mark.  And for those less familiar with the terminology, essentially what that means is where either researchers or the internal team at Genomics England have identified changes in the genome data, that with new knowledge, often with a fine tooth comb, it's considered likely that that is the answer to the cause of the rare condition in that person in the programme.  So that's 4,000 of those returned to the NHS.    And that tells you a lot about where we are for families with rare conditions, and I think there's two points here.  The first one is, we've got a long way still to go to do what we want to for families with rare conditions.  I'm a doctor and still see families in my clinic once a month at Great Ormond Street, even with the incredible advances we've had over the last particularly 10or 15 years, with the changes in sequencing and analysis, we still find an answer for the minority of families.  So that number is growing, and we're really proud of how much better we've done, and there's a long way left to go.  And the really critical thing is designing a system which we're so lucky with in the UK here, where we can continue to learn.  And that's not just for learning for the knowledge of people who might encounter the health system in the future.  It's to learn for those people who've joined the National Genomics Research Library, who've already trusted us to be the custodians of their data, and to do better in the future.  And that's what our diagnostic discovery work really aims to do.  And sometimes that's about new gene discoveries.  So all the time new things are being discovered each year.  And if you look at the DNA code, if you like, boil it down very simply.  99% of it is what we call non-coding DNA, I'll come back to that, about 1% is the genes, which if you like are sort of the books in the library of the DNA, overall DNA code, that we understand relatively well how they're read by the body.  The bits in between, it's a bit of a funny, well-spaced out library this one, that's the 99%, actually we've had very little understanding of most of that code in between.  But we're beginning, and particularly this year, to gain an understanding of how we might interrogate some of those pieces.  And not all of the answers lie in that non-coding DNA, there's lots of answers still left in genes that we don't understand well.    But one of the examples I mentioned earlier, and in fact the thing, the single discovery I guess which I'm most proud of having happened in the National Genomic Research Library is this discovery of this non-coding region called RNU4-2.  Which is a funny, like technical series of letters and numbers, but basically it's a very small patch of the whole DNA code.  Where this year, scientists discovered actually about 60 patients in the families in the National Genomic Research Library where that was the cause of their child's developmental disorder.  Actually, that knowledge has really rapidly spread across the world.  So I actually saw on social media at the weekend, from one of the scientists involved in the discovery, that the family support group that's been set up for what they're calling ReNu syndrome, which I think is a lovely name in itself, speaks to that word hope that you mentioned, Adam.  There are now 248 members of that group, and that's how fast that knowledge spreads across the world.  And what we're doing is thinking how we can support those discoveries more broadly, and non-coding DNA is one of those areas where that growth is, but it's not the only one where we're looking to support things.  But it's so exciting, and I think it gives you a sense of the scale of progress that is left to make.  And I think a really important point is that remains a really important area of our focus, it's not about moving on and looking just to the future, but we need to keep working for the families who are already part of our programmes.    Adam: That's incredible, that 248 members in such a short space of time.  And I love the ReNu name for that, I agree, I think that's a fantastic way of positioning it.  Earlier this year, we heard from Lindsay Pearse, whose son Lars received a diagnosis through that groundbreaking discovery of the genetic change in the RNU4-2, or ReNu gene, which was made possible by whole genome sequencing.  She told us what the diagnosis meant for their family.  Lindsay: This feeling that, like, we've been on this deserted island for eight years, and now all of a sudden, you're sort of like looking around through the branches of the trees, and it's like, wait a minute, there are other people on this island.  And in this case, actually there's a lot more people on this island.  Yes, it's very exciting, it's validating, it gives us a lot of hope and, you know, it has been quite emotional too (laughter).  And also, a bit of an identity shift, because I spoke earlier about how being undiagnosed had become quite a big part of our identity, and so now that's kind of shifting a little bit, that we have this new diagnosis, and are part of a new community.  Adam: You talked about it there, Rich, I mean, it's been really seen as a success story for the whole genomics ecosystem, especially the speed at which it all came together.  From the conversations I had with some of the individuals that were involved in the study, from the date of seeing the first findings in the lab meeting to a polished pre-print going live, was exactly 47 days, which in science terms is less than a second.  So that's how they positioned it to me, incredible.  And you've just said there, they set up this support group earlier this year, and already got 248 members, which is incredible.  The impact on families is significant, the mother touched upon it there.  I mean, for many parents there is that relief that it wasn't something they did during pregnancy, but instead, it is a chance occurrence.  For some, this knowledge means that they can make important decisions, choosing to grow their family, for example.  And it really ends that diagnostic odyssey that many families face, providing answers and potentially ending unnecessary testing that their child is going through.  But I think, and I can talk from personal experience here, that the largest impact is really being able to connect with other families and building that community, you cannot really understate that.  If I look at our own experience of getting a CRELD1 diagnosis for our children, the first time we didn't feel alone was when we could find that community.  We can support each other, we can learn from each other's experiences, and really also drive forward further research into that condition through advocacy.  So, I remember seeing that post on the Facebook page, about that RNU4-2 discovery, and this was before I'd even started in the role at Genomics England on the Panel, but you could really feel that excitement and the relief that they had.  And they mentioned that the official paper only had 36 other people worldwide, they found this little Facebook group that they created with five families in, and in the space of, what, 6, 7 months, they're already at 248.  That's all people that understand what they're going through.  And it's really hard to describe, it's like finding your family that you've never met, people that understand, and they really get what you're going through.  And being able to share tips, advice, learnings, and things that everyone's going through at different stages in their child's life.  So, I really don't think you can talk highly enough of that, that community aspect, and that's just been amazing to see.  And, look, this new era of research into the role of non-coding RNA genes, it really may open more opportunities for diagnoses for patients, participants potentially leading to hopefully more breakthroughs in the year ahead.  So now we're going to move on to why it's so important to engage patients and participants in the genomics world.  So, we'll now hear a clip from Helen White, who is the Vice-Chair for cancer on the Participant Panel.  Now Helen and I have been working really closely together as Vice-Chairs in this interim leadership role, to really ensure that we continue advancing the Panel's strategic initiatives while we recruit that new Chair.  So it's been amazing learning and working with Helen.  In this clip, she discussed an important topic that's been very much top of mind of the Panel, which is the importance of involving the patients and public in genomics research.  Helen: I think, you know, as patients, members of the public, we're eager to get on and for change to happen and things to be better, but it's, yes, a big, big process.  But also, good to hear that you talk about it being a collaborative approach, it's not just Genomics England, it's the NHS, it's members of the public and patient voices, it's other organisations working in partnership.  Adam: Now I think we all recognise the importance of engaging patients and public to ensure diverse communities understand the benefits of genomics, and actively involving patients and participants in the research, to make sure that they're including the perspective of what matters most to them.   Rich: I mean, it goes back to the thing that we really see as central to the value that we at Genomics England can provide.  So we increasingly think of ourselves as a data and evidence engine for national scale genomics, and I think a really important to call out there is that evidence is broad.  And part of that evidence is about public expectations, public preferences, and patient preferences.  And if you think about the big things that we do and where we bring that value, and bring that data and evidence engine role, is, you know, firstly in the digital infrastructure that we build and the data that we hold and present to our various users.  Secondly, it's in the evidence that we distil from that, and very much thinking about part of that being evidence in and around, including that piece on what people expect, this isn't just about hard science and health economics, this is an equally if not more important part of that.  And then thirdly, it is the third area of our focus is on that engagement piece, because that's so fundamental.  And I think you and Helen called that out absolutely right, about that being, that's integral to the whole process, and it's the beginning of any programme you need to start with understanding what the big drivers are, what the expectations are, and doing this very much together.  That's one of the reasons we're so fortunate to have the Participant Panel we do, in our Newborns Programme the Panel have been an important part of that design from the outset.  It's also about broader engagement with different communities, people who currently don't engage with genomics, because they've had no need to, sort of understanding that piece.  And I think we've definitely seen over time in health data research, but also research more broadly, where it's quite easy for these things to be disconnected.  And that results in two things.  It results in research happening about interesting esoteric stuff, but not on the stuff that makes a difference for families.  And I think that's really important, because researchers need to be directed in the resource limited world towards the things that really make a difference.  So that's the first thing.  And the second thing is, it's very easy, with the best will in the world, for people to make wrong judgements about what people are or aren't content with, and you need therefore to be absolutely transparent about what the research is.  Be really clear about what those questions are, and let people challenge you, right from the outset, so that we can design research studies, but also, the system as a whole, together in a way that everyone has a say.  Not everyone has the same view, but how we can develop a system that takes into account those things and gets that balance right.  This is about making a difference to people's health outcomes, thinking about how we achieve that, while also balancing off all of the different views there are, is really important.  And that's at the heart of it.  And it can be scary, because it's right that there is that challenge out there.  And it's one of the things that I think we've learnt at Genomics England, how important it is to be really open to that challenge, and to do that piece really early in all of our work, and have it there baked into our governance as well, for example, the Participant Panel.  Adam: Absolutely, and I think you've summarised all the key areas there really well, in terms of the importance of that engagement.  And one other area I'd just like to pick up on is the impact it can have on the patients or the participants, simply by having that connection with the researcher, that's doing all of the amazing stuff that for some of us, it's really hard to comprehend.  But having that interaction and collaboration with them, it's so important in terms of, again, I go back to giving you that hope.  And a real highlight for me at the Genomics England Research Summit was when Hannah, one of the members of our Panel, she came running over to us and she was just beaming.  And she said, “Guys, you'll never guess what, I've just met the scientist who discovered my daughter's diagnosis in the NGRL.”  And you could see that she was so excited, you cannot understate the impacts that can have on them as a family.  Like having that interaction and that personal connection with the person that really in some ways kind of changed their lives, in terms of understanding more about what that could mean for their daughter growing up, and how they're managing the condition.  So, it's amazing when you can see those highlights and hopefully we'll see more of those.  And it's also really important that we get that diversity I think, as well, in that collaborative approach, just to make sure that it is equitable for all.  And that really brings us on nicely to the next topic, which is about how do we bridge the gap between those diverse communities, and make sure that we're reaching everyone as best as possible?  So we're now going to hear a clip from Sandra Igwe.  Sandra is a CEO and founder of the Motherhood Group, speaking about the Generation Study.  Now, Sandra spoke about the importance of building trust, and how it is vital to engage with a diverse group of communities in the design of research studies.  Sandra: Every community's different, and every patient is different as well.  And so that may require different focuses or different formats or different messengers for different groups.  And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well.  But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake.  So it's really important to have representation, because the lack of it in research can overlook communities' specific concerns and needs.  Adam: So, Rich, did you want to talk about why it's so important to have that diversity?  Rich: Yes, I mean, it's critical.  One, I mentioned earlier, our vision as an organisation is a world where everyone benefits from genomic healthcare, and that word “everyone” really resonates.  I think Sandra has been really an important part of the work that we've done over the last couple of years, particularly through our Diverse Data programme.  But I think one of the real challenges for us is how we make sure that that is something which is embedded across all of our work.  And that's something that we're really focused on at the moment, how we embed the learnings that we've had through that standalone Diverse Data programme into everything we do.  Because we're absolutely committed to that, and I think that is engagement with the diversity of different groups relevant to each programme.  I think one of the real important things is that transparency piece about actually that it's hard to achieve equity in healthcare, full stop, because of historical underinvestment in some of these areas.  And I think being clear with people about that is a really important step, and then talking really practically about why it really makes sense to take different approaches.  And so one thing about our programmes and how we think about the future overall, if genomics is going to make a difference to more than half of healthcare encounters, it needs to be something that across all communities, and across the large majority of people in each of those, that this is something that they want to be part of.  Because it's going to make a difference for them or their families or something they really buy into.  And that's why this isn't just about thinking only about specific programmes where this is a question, it's about making sure that we're designing a system, developing the evidence that is really broadly applicable, and continues to learn.  Because we know that what we learn today is hopefully an improvement on where we are, but we continue to learn and learn and learn.  And it's about creating a system that does that, and does that equitably, or as equitably as we can.  Adam: So we're now going to hear from Moestak Hussein, who works to build and embed cohesion, inclusion, and social justice, in her role at Bristol City Council, in public health and communities.  Moestak talks about the value of co-production, and how this can help to build trust with communities who have historically been underserved or mistreated.  Moestak: If we talk about co-production, true co-production is really creating a power balance where there's no hierarchy, it's an empowering model.  It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve.  Adam: So, if I look at that from our perspective on the Panel, I think co-production in genomics research, so using participant data in the NGRL, is certainly what we'd like to see much more of.  To ensure that research is not only relevant to its intended audience, but also aligns with broader democratic principles of citizenship, accountability, and that transparency as well.  But look, we have to be realistic.  Some genomics research projects are not going to lend themselves to meaningful patient and public involvement in the early stages, but it's really important later on in the research pathway, if the findings identify a patient population who might benefit from that research.  At the moment, involvement of patients and participants, carers in research, is really not great, in terms of the researchers using the NGRL.  So, in conversations what we're hearing is they're saying, “Well, we don't know how to do it, we don't know what steps we should take.”  Or “We don't think it's relevant because we do this particular research.”    But really, our view is that some PPIE, or patient and public involvement engagement is better than none.  Some may not be relevant for all stages of the research pathway, we're not really seeing enough of that happening at the moment, and some papers are even being published without any context of the participants' lived experience at all.  Which can actually be quite frustrating, if you're that patient or parent, and you see a paper published, and you think, well, actually, why didn't they reach out to us?  Just to understand a bit about the symptoms that we're experiencing, what are the challenges that we're facing, just to really add that important context.  So, I think there's certainly an opportunity for us on the Panel, certainly for Genomics England, to be that kind of guiding light for those researchers.  Whether it's providing them with researchers, research papers, or a hub of patient advocacy organisations that are already connecting those patients with researchers.  It's all about signposting them the relevant information, so I think there's certainly things we can do there.  And it really fits in with the bigger engagement piece.  So, whether there's a landing page or a dedicated website that shows them, where do they go, what are the steps that they can take, what's the best practice, what's worked well for another researcher, and how did that lead to really great outcomes for the families involved?  That's where I think we can all play a part in guiding them on that journey, rather than it just being a case of, they're not doing that patient and participant engagement very well, and kind of criticising it.  Let's reach out to them and say, “Look, we can help you and guide you on that journey.”  Rich: I really agree with the need to make those connections happen.  One of the things I think that is often missing is just a confidence just to crack on and do some of this stuff.  And I think, actually, looking at the ReNu syndrome experience, that was work that was swiftly done.  Scientific at the beginning, the initial publication put out there so that people could understand, and was quite medical by necessity, in terms of the speed of getting information out there.  And then very quickly, and quite organically, patient support groups have formed, and also, the scientists are working with that group.  I had a really interesting conversation with Sarah Wynn, who's the CEO of the Unique last week, about how some of that has played out, how the role they've played in facilitating some of that.  And some of it just comes down to sort of really simple things, and working through how you can set up Zoom or whatever meeting, for people to learn about the condition.  And how you preserve anonymity, where that's appropriate, but also allow people to have discussions about their loved ones where they want to, etc.  So it's partly just about giving people the space and the confidence to get on with some of these things.  And as you say our, one of the things we at Genomics England are quite thoughtful about, and I think it's a really good topic to continue talking to the Panel about, is how we get that balance right.  Where, actually, us being a connector and, as you say, signposting useful resources or ways of doing these things, just to break down some of those barriers.  Because almost always the research groups, when they discover something new, this is really new territory for them, and they're often nervous about doing the wrong thing.  And so it's about breaking down some of that anxiety actually I think.  Adam: Yes, absolutely.  In our case, with our condition that we're advocating for our son, we've been working with a researcher.  And it's almost on us as well just to kind of share our story with them, and making them feel more comfortable to ask us questions and be very open and transparent about the more we can share, the more that can hopefully benefit their research moving forward.  It's very much a two-way thing as well, but I like what you said there about having the confidence just to kind of reach out and start those conversations, and have that starting point.  Next topic, we're going to look at some of the innovations that are on the horizon, that we're seeing in the world of genomics.  So, Rich, do you want to take us through what are the most exciting things that you're exploring at the moment?  I know we hear a lot about AI and the technological aspect, so why don't you take us through some of those?  Rich: Yes, so I guess this comes back to that question where we've been looking forward, you know, where might genomics be impactful and making a real difference to people's lives, to helping us have a more efficient healthcare system in the future?  And I think part of that is about this general shift.  You know, genomics technology, we just take for granted now how much it's shifted, how it's within the means of the healthcare system to generate genomic data.  And we're really fortunate in this country because of the digital infrastructure that we've been able to build together with the NHS, that opens up a lot of these questions.  And it's just extraordinary the time we're at in genomics, so almost take those two things for granted, which we should never do.  The change in genomic testing technology, which continues to advance, and secondly, thinking about the digital infrastructure, like the nuts and bolts of what we've got, and the ability to safely store and reuse and analyse some of that data at scale.  And point at two big things.  Firstly, genomics enabled therapies are changing a lot.  So, our understanding, our ability to make a diagnosis, or understand what's different about a cancer, for example, mean that in various ways it's becoming feasible to do more tailored therapies.  Where knowing that, the genomics nitty-gritty of that condition, helps you tailor that, or create sometimes even a bespoke personalised, truly for that one individual, therapy.  And in rare conditions we see that with the so-called N=1 therapies, but also with gene therapies and so forth.  And in cancer we see that with the cancer vaccines, for example.  So that's an enormous area of change, and one of our responsibilities is to support that sort of research, to help identify people who might be eligible for trials or treatments.  But it's also to work with the ecosystem to think about how we can help support the generation of evidence that means that those therapies can be affordable and so forth, on a scalable basis.  So that's one really big area of excitement.  And we see our Rare Therapies Launch Pad being part of that, the National Cancer Vaccine Launch Pad, being part of that.  So that's thing one.  Thing two is AI and machine learning, and I think sat on alongside the sort of broader picture of saying, there's a lot left to learn, there's enormous potential in genomics in terms of playing a role in many different situations, not just in rare conditions, in cancer.  And we know doing that well, but also scaling it, making it really efficient, so that we can do that in a context of a really busy health service, one of the answers is making sure that we're leveraging everything we can about the potential of AI.  And there's lots of different ways in which that can be supportive, I won't list lots of them.  But one of the things that we're doing at Genomics England and working with the NHS is thinking about the most promising areas.  And some of those are quite, like, down and dirty, if you like, so sort of saying, which jobs are there that we can use AI, if you like, as a co-pilot, alongside experienced scientists, to speed up their work?  And we're really excited about the role we can play in a few ways actually.  So the first one, back to that sort of data and evidence engine point, is helping organisations who have a tool, help validate it for use in the NHS, and say, “Does it perform to this standard?  What do we want to say about how it performs from an equity point of view?  And from a clinical safety point of view?” etc.  And making that leap from stuff that makes a Nature paper to stuff that lands in clinic is surprisingly challenging, and that's one of our roles.  And we really enjoyed working with various companies and academics over the last few years on that.  We did some work recently with Google DeepMind, on their AlphaMissense tool, thinking about how we can think about that role that might play, for example, in speeding up the interpretation of rare variants that might cause rare conditions.  And there's enormous potential in all sorts of different parts of the sort of end to end of genomics playing a role in healthcare.  And then I'd also say one of the really important things is because genomics in many ways just needs to be part of healthcare and not be treated differently, we also need to recognise where there are questions we need to work through really thoroughly that are a bit more bespoke.  And one of the things that we're really committed to doing, as we look to the future, is making sure that we can support on some of those questions that we really need to be clear on.  I'll go back to that point on, what do we mean about making sure we understand how a tool is working, and whether it's producing results in an equitable way for all different communities?  How do we understand that?  How do we explain what we understand about the performance of a tool?  How do we make sure that patient identifiable data remains non-identifiable if a tool's been built, trained on data?  Working through some of those questions.  But they're really important for us to do, and we're enormously excited about the potential, and we're really committed to working through in detail how we can make that path to adoption safely and in the way that everyone would expect and desire as rapid as possible.  We're just one step in that process.  But we really see a sort of important role for helping people who are producing various tools or various use cases, helping them prove them, helping them validate them, and making the system more efficient overall, but in ways that we really understand.  Adam: That's fantastic.  Look, not that I'm biased at all, but I can tell you that the AlphaMissense innovations that are being developed are shared a lot internally at Google, it has been seen as an amazing success case.  So hopefully we'll see more on that moving forward.  But in the next clip, we're going to hear from Francisco.  So Francisco is the Director of Bioinformatics at Genomics England, who tells us more about the application of AI and its benefits in genomics in healthcare.  Francisco: So AI is already driving the development of personalised medicine for both research and healthcare purposes.  Now at Genomics England we are investigating the use of AI to support a number of tasks, for the potential impact in both research and healthcare.  In the context of healthcare, we are talking about AI tools that can support the prioritisation, the ranking of genomic variants to allow clinicians to make more accurate and faster diagnosis.  Adam: While all of these innovations sound really exciting, it's really important that we just continue to bring that patient and participant community on that journey, just to ensure that they really understand the full benefits, and we talked about that on the episode today.  I know that the panel has always encouraged Genomics England team to look at its boots while shooting for the moon.  I really like that phrase, just to make sure, look, we can't forget where we've come from to make sure we're taking people on that journey.  So, we're going to wrap up there.  Thank you to Rich Scott for joining me today, as we reflected on key milestones for 2024, and looked at the year ahead for both Genomics England and the wider genomic ecosystem.  If you enjoyed today's episode, we'd love your support.  Please like, share and rate us on wherever you listen to your podcasts.  I've been your host, Adam Clatworthy, this podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.  Thank you everyone for listening. 

On this week's episode of CMDA Matters, Dr. Mike Chupp and Dr. Bill Griffin sit down with Dr. Mark Topazian and Dr. Gábor Győri to talk about the new opportunities to participate in the Saline Process Witness Training.  RESOURCES FOR THIS EPISODE:  Give to CMDA Email CMDA Matters CMDA Bookstore Faith Prescriptions 2025 CMDA National Convention Saline Process Witness Training – IHS Global Email Dr. Bill Griffin Whispers in the Wind by Dr. Al Weir

In this episode, we explore the importance of patient involvement in shaping rare condition research initiatives. Our guests discuss why it's crucial to involve individuals with lived experiences, including patients and caregivers, in setting research agendas. In doing so, this approach ensures research can be more inclusive, efficient, and impactful, addressing the issues that matter most to those affected. Mel Dixon, Founder Cure DHDDS and member of Genomics England Participant Panel is joined by Jo Balfour, Founder of CamRARE and Dr Rona Smith, Senior Research Associate at the University of Cambridge and Honorary Consultant in Nephrology and Vasculitis. Find out more about the Cambridge Rare Disease Research Network, discussed in the episode, which aims to support the rare condition community in building an online network of partnerships and resources to facilitate new patient-centred research opportunities. "We're really turning research on its head, moving away from it being a researcher-led activity where they decide on the idea and the research concept and bring patients in at different points along that research journey and instead starting with the patient's idea in the first place.  It can only be a better system for all because it improves efficiency, it improves potentially the long term outputs and, most importantly, outcomes for patients." You can download the transcript or read it below. Mel: Welcome to Behind the Genes. Rona: I think it really means that we measure what matters to patients and individuals that are affected.  Often, it's really difficult to capture kind of the real impact of disease and there's a tendency for researchers to measure things that are easy to measure and are reproducible, which of course is important but what's most important is actually being able to truly capture the impact of an intervention on an individual's condition.  So, I think that's another key aspect of having people with lived experience involved right from the start. Mel: My name is Mel Dixon and I'm a member of the Participant Panel at Genomics England and founder of Cure DHDDS, a charity set up to raise awareness, support families and help drive research into the ultra-rare DHDDS gene variant.  On today's episode I'm joined by Jo Balfour, Managing Director of CamRARE, which is the Cambridge Rare Disease Network.  This network unites patients, advocates, experts and leaders to address the challenges faced by people affected by rare conditions.  I'm also joined by Rona Smith, Associate Professor at the University of Cambridge and honorary consultant in nephrology and vasculitis.  Today we'll be discussing the role of patients in setting research agendas and how their involvement can lead to more impactful and patient-centred research.  If you enjoy today's episode we'd love your support.  Please like, share and rate us on wherever you listen to your podcasts. Before we begin the interview I'd like to share a little bit of my story.  In November 2022, following whole genome sequencing, we received the news that two of our three children carried a neurodevelopmental and neurodegenerative DHDDS genetic variant.  At the time of our children's diagnosis there was very little information on our gene, minimal research happening into it and no treatment pathway.  Through our charity, Cure DHDDS, we have worked tirelessly to instigate research and create a collaborative scientific research community.  I am a huge advocate for patient-led research and have witnessed first-hand the positive impact it can have on patient lives.  Thanks to the work of the many scientists that we have had the honour of collaborating with, within two years of our children's diagnosis we have a disease-modifying therapy in our sight and an ASO (Antisense oligonucleotides) therapy in development.  We are incredibly grateful for the opportunities genetic testing has given us but I also appreciate how overwhelming a genetic diagnosis can be and how challenging it can be for families to initiate research projects with little to no resources, and that's why initiatives such as CamRARE that we'll be discussing today are so important.   On that note, let's get back to our podcast guests.  I wonder before we dive into today's topic if you could both give a brief introduction, and, Rona, if you could also give the less scientifically-minded of us an explanation about what nephrology is. Rona: Thank you for inviting me today.  So I'm Rona Smith, I work in Cambridge and I'm a nephrologist and that means somebody that looks after individuals who have diseases that affect their kidneys.  My specialist interest is in something called vasculitis which is a rare autoimmune disease that affects all organs in the body but kidneys as well.  Mel: Thank you.  And Jo?  Jo: Hi Mel.  I'm Jo Balfour, the Managing Director and one of the founding members of Cambridge Rare Disease Network, or CamRARE for short.  I think we're often described as the ‘Chief Everything Officers'.  I manage the charity and all of our operations and our wonderful team.    Mel: Lovely.  Thank you very much.  Rona, I wonder also if you could explain to our listeners what is a research agenda?  Rona: So in brief a research agenda is really a strategy that outlines key questions or topics that a research community, and that might be investigators, clinicians, scientists, patients, industry,  and they are the priorities that they want to explore and address over a period of time.  So it's really a direction of travel and identification of areas of importance and where there are gaps in knowledge so that it then leads to the opportunity to form specific research questions that you can then go on and address.  Mel: Why do you both think it's important to involve patients in setting these research agendas?  Jo: Well I think critically one of the things that I've learnt over my time working, not just in the rare disease sector but also earlier in social care and education, is that we should as professionals never assume anything; you know, we have not lived in their shoes and we don't know what the daily life of people living with rare conditions is like.  So gathering that day to day lived experience is really crucial.  And I have a unique opportunity to see into that daily life with our local community of rare disease families who have a range of different rare conditions.  I'm party to their conversations, to their daily trials and tribulations, the things that are difficult, the things that they find joy in but I still will always go back to them and ask their opinion.  I see myself as a spokesperson for them as we're an umbrella organisation but I certainly never really know what it's like to live with their conditions.  I think they bring with them diverse experiences which we really need and value in setting research priorities, they have unique knowledge of their own conditions.  They ethically have a right to be involved from the start and to set that priority and agenda but, equally, it's valuable for us as researchers because if we can involve people early we have definitely more chance of good engagement and later success, better outcomes for everyone.  Mel: Couldn't agree more.  And, Rona, is there anything you'd like to add to that? Rona: I think it really means that we measure what matters to patients and individuals that are affected.  Often it's really difficult to capture kind of the real impact of disease and there's a tendency for researchers to measure things that are easy to measure and are reproducible, which of course is important but what's most important is actually being able to truly capture the impact of an intervention on an individual's condition.  So I think that's another key aspect of having people with lived experience involved right from the start.  Jo: Another thing that's actually quite interesting that I'm going to mention here is that I think when you live day in, day out with a condition your perception of things like pain is different from your average person's so you become almost accepting of your daily norm, and I think that's really critical to understand as well.  And it's only by getting to really know patients and understand. When we say, “What's your pain like on a scale of 1 to 10?” you know, something that I feel as pain because I get it rarely I probably am going to put it at a higher score than somebody who has that every day.  So I think there's subtleties and nuances like that as well which are really critical to get across by conversation with patients.  Mel: That makes absolute sense.  And I see that from the patient perspective myself.  I was out with my friends the other day and they said, “Oh my goodness, you're constantly taking your children to sports activities.”  Because of their physical needs we're constantly,  they go to Pilates, they go to swimming, they go to gym class – we try to keep them fit and healthy – and we, even though they're older, have to take them there and back and that's become our norm but when you're speaking to families whose children don't have those difficulties they have no idea how much time that actually takes up.  And I had no idea how much like time it takes up compared to what other people are doing because that is our norm, that's what we've accepted as the norm.  Patients and patient groups are incredibly driven and invested in their rare disease as well so they make really good rare disease research partners.     And, moving on, what do you see as the challenges and barriers to patient involvement and how do we overcome these? Rona: I think probably the biggest barrier is time.  So, the most important thing is investing time to build relationships, to really understand in-depth perspectives both from the patient's side but also the researcher's side. And, inevitably, we always want to do things faster and actually this is one really, really critical aspect is investing time.  Funding is also a challenge.  Often you have to do a lot of upstream work before you have got funding for a project and that takes time from individuals and that's another challenge.  And I think the third thing for me is individuals that are patient partners in research, they're not just patients, they're people - they have lives, they have work, they have families, they have everything else that goes on in life - and so actually fitting this all in is really challenging.  Mel: Jo, is there anything you'd like to add there?  Jo: Yeah, I think just a word about diversity really and, you know, how do we uncover those hidden families and patients who currently don't really have a voice.  I think we'd all acknowledge that there are key voices within the rare disease community who will share the views of their community and they've become well-oiled machines almost at being great advocates but, as I mentioned earlier, even though I'm perhaps one of those people, you know, I speak for a community, I would never assume anything.  So, I still need to uncover the thoughts and the feelings and the emotions and the needs and the what matters from those people, and, as Rona mentioned, that takes time and it takes building relationships and trust with people.  So, we have a wonderful community in the Eastern region of England which is made up of families affected by all different rare diseases, and undiagnosed.  And some are babies and have been lucky enough to get a very early diagnosis and others are young adults but what we're finding through that is that experience is diverse and experience changes over time as families go through transition periods or they meet a roadblock and they're having to navigate things differently.  So, it's about building those relationships.  That takes times, it takes resources, it takes sometimes a reset in the way that we think things need to be done.  So instead of asking questions all the time and putting surveys out and trying to get response that way it takes a bit of thinking about how do we listen better and how do we give those people who don't have a voice, who are non-verbal or perhaps have a learning disability, how do we ensure that we're capturing their views as well.    And we did a really lovely project actually last year, it was something funded by the NHS called My Story, My Way, where we actually spent three months with our young adults working out what it was they wanted from our community next, how did they want us to follow them into adulthood.  And we knew that there were a number of young people in that group who were non-verbal and had some learning differences and we knew that we couldn't just do it in the normal format, we couldn't just do a focus group and ask their opinion, so we actually did it through photography.  So each of the familiess well, the young person themself was given a simple camera.  They basically had thirty-six shots.  You got thirty-six clicks to capture the things, the people, the places that you love and then to share them with us as a community.  And then we all discuss, you know, how these things might be something we can build into our future plans for them.  And it was such a wonderful activity.  We gave them plenty of time, plenty of opportunities to ask questions.  If the young person themself couldn't physically click the camera their sibling got to help them.  And their sibling or their parent was given another camera in black and white so we had distinctive pictures, pictures that the kid themself had taken, pictures that the family had taken, but all together, you know, it gave this lovely kind of medley, this beautiful visual representations of what mattered to them.  And I think it's about taking the time to be creative with people like that and really get to the bottom of “How do we find out what matters to you?” Mel: Although it takes time to think about those ideas.  That could be translatable across the board really, couldn't it, throughout various conditions.  I think that's fantastic.  Rona, I wonder if you can tell us how has the work that's already been done through the patient-led research hub facilitated addressing research priorities.  Rona: So just a tiny bit about the patient-led research hub.  So, this has been now running for nearly ten years through Cambridge.  It's a partnership between the Cambridge Biomedical Research Campus and we're based within the university and the Trust.  And in essence it kind of was set up because of really a mismatch between what many patients wanted from research and what investigators' views were.  And so really the premise is that we welcome patients to come to us with an idea, a problem, an unmet need in their disease area – and we do focus on rare disease – and we work with them to see “Well actually what do we already know about that?” and then if there is a gap in knowledge we then move to kind of trying to work and develop a question that we can then address.  And that might be a question that's addressed through generating more information through surveys or it may actually be a question of an intervention that we can test.  So, we've had lots of projects come through and we, just an example of a project was from a group of patients with a rare kidney condition called autosomal dominant polycystic kidney disease, and that is a condition where over time you accumulate cysts in your kidneys and the kidneys become large, they become very painful and eventually they can fail.  And a question that the patient group had was about whether drinking more water could impact the rate of growth of these cysts, and there's a strong hypothesis behind that that drinking lots of water reduces down the level of a particular hormone.  And we actually worked with the charity behind this group, the Polycystic Kidney Disease Charity, and designed a study to test a very high water intake to a normal water intake to see whether it was possible over a period of eight weeks for patients to actually stick to this.  It's quite difficult to do.  And they recorded how much water they'd drunk, they tested their own urine and actually it showed that this was feasible to do this kind of work.  So, I think the patient-led research hub is kind of taking the research priorities that are important to patients but working in a patient-led way to come right through to a project.  Mel: That sounds great.  And if the patients are engaged from the start of the project and it's led by them they're obviously going to be much more driven to take part in the actual research and see the research through themselves.    So, Jo, I'm very excited to hear about the launch of the Rare Disease Research Network.  Can you please tell me what the research network is and what you hope to achieve with it?  Jo: So the Rare Disease Research Network is first of all a bit of a mouthful so we're going to try and encourage people to call it the RDRN.  It's a co-created project which really the patient-led research hub in Cambridge approached us about in 2022, I think, we started talking about this, approached CamRARE as a partner to apply for an NIHR partnership grant, and we were successful with that to really take the model that the patient-led research hub had already developed and found was successful, and perhaps too successful for its own good – they were receiving more applications and more ideas than they could manage – and to develop that into an online platform.  So taking the same model, making it more accessible to a wider group of people, potentially worldwide, and providing the hand-holding that the patient-led research hub has always done, helping patients really consider their question, formulate that into a research idea, then do the literature search to find out “Is this question already answered, and if it is, great, can we provide that information to our community?  If it's not, how do we then build a team?  Who needs to be in my research team?  How do we then get funding together to take this idea forward?”  So, it's really taking the model, taking the good practice that already existed and creating an online platform to really attempt to replicate that as best we can. So the platform will launch on 23rd November (2024) at CamRARE's Rarefest which is a lovely in-person activity that's going on in Cambridge, and that platform will be open to anyone who has an interest in rare disease research.  But I think, critically, what's different about this is that, you know, we've talked about setting research agendas and we've talked about patients contributing to that, contributing to setting the priorities, what's different here is that the patients decide on the questions; it's what matters to the patients coming from them and their community.  And it's an opportunity for them to showcase those questions and those idea on a platform and almost to have a call to action, “Is there anyone else on this platform who has similar research interests to me?”  The platform will matchmake them together through a series of choosing tags, choosing tags about particular disease areas -  It's linked to the Orphanet database - choosing tags about the type of research that you're interested in.  That matchmaking process will happen, which at the moment is a very serendipitous process but we hope to take it a little bit further on from that.  It's still going to be a little bit of potluck who's on the platform at the time who's got similar interests as you but hopefully it will improve that serendipitous system.  And it will allow them to access resources on the platform, which is the kind of hand-holding bit, and also, critically, some mentoring.  So, there's a real sort of opportunity here for professionals – researchers, industry partners, healthcare professionals – who have particular skills in research to be able to say, “Well I can help.  I might not be able to be part of your team at this point but if you need half an hour on a Zoom call with me to think about your research question I can offer to mentor you on that.”  But, likewise, I think there's going to be lovely opportunities here for patient groups to support each other too because what we've always realised is that patient groups are at different points of their research journey.  You know, we see some organisations that are really well-funded now who are in partnership with industry, you know, they have a group of pharma companies that are supporting the development of treatments and they've kind of reached that point where they're very highly skilled and very well experienced.  And then there's others who are mum and dad who've just had a recent diagnosis for their child, they've gone searching on the internet, they can't find information, they don't have a patient organisation to rely on so they're going to make one themselves.  This happens all the time in the rare disease field.  There are 11,000 different rare conditions and there's not a group for all of them so mum and dad will often start something themselves and then in lots of cases want to do some research, they want to answer some of these questions.  So, you know, they're really starting from a very different beginning stage here where they've going to need some help, and sometimes the best help comes from their peers, it comes from other patient groups.  So that's in a nutshell what it's about; it's about providing opportunity for patient groups to showcase their great ideas, build partnerships and take research forward.   Rona: The only thing just to add there is I think, although rare diseases are individually rare, collectively, as Jo said, they're quite common, there's 11,000 rare diseases, and often, although they all have distinct features, there are common threads through rare diseases in terms of maybe symptoms that patients experience or challenges that their rare disease brings.  So, for example, you may have symptoms of pain or seizures that are common across many conditions, there may be educational needs that are threads going through.   And groups could work together maybe to answer a question that's relevant to a number of conditions and so bringing people together for that.  Or there may be another group that's already tried to answer that question in their condition and you can learn what worked, what didn't work.  I think that's the other thing, is there will be common threads that come through, and I think that would be a real strength of the network to draw those people together. Jo: I think as well, Mel, if we take this back to what we said right at the outset about optimising success for patients by bringing them into the conversation early, I think this platform provides the perfect opportunity to do that.  So we're moving away from, we're really turning research on its head, moving away from it being a researcher-led activity where they decide on the idea and the research concept and bring patients in at different points along that research journey and instead starting with the patient's idea in the first place.  It can only be a better system for all because it improves efficiency, it improves potentially the long-term outputs and, most importantly, outcomes for patients.  Mel: We were that family, that mum and dad setting up the charity a year and a half ago for the ultra-rare disease that our children had.  I think, you know, the match-making opportunities that are here are fantastic because finding yourself in that position is incredibly isolating.  And not only the matchmaking opportunities with the researchers but, as you were saying, Rona, as well with similar diseases; there's so much to learn from other diseases that may have, I don't know, a similar phenotype in the cells or similar symptoms.  That's what we found from connecting with these other rare conditions.  So, for us it's lysosomal storage diseases, we've now got the opportunity potentially to piggyback on drugs better used for their diseases for our own ultra rare condition, you know, where for us to run a full-on clinical trial by ourselves with a new drug, I mean, we just wouldn't have,  there's no funding, there's not enough interest.  So, I think the opportunities that lie in this network are really, really exciting.  Jo, can you tell me a bit more about who can join the research network?  Jo: So anyone with a rare disease research interest. That's everybody from individuals affected themselves, their family members, their caregivers, the patient organisations, that support them, and then, you know, all sorts of rare disease professional researchers.  So, we're looking for PhD students who are looking for their first exciting project to undertake, have they taken a look at the Rare Disease Research Network to see if there's any ideas that might pique their interest.  We're looking for established researchers, medical professionals who are undertaking clinical research but also I think, importantly, companies.   You know, we hear more and more about concepts like drug repurposing for rare diseases where we're looking at the opportunities for taking drugs that already exist and have been proven safe to be redeployed to other rare diseases. It's quicker, it's more efficient, it's cheaper, so does it open up opportunities for companies that are using that technique to get involved.  And also pharma companies.  This platform is not all going to be about finding cures and treatments but it certainly will be a priority for some groups.  So we really are welcoming everyone with an interest in rare disease research to get involved, be part of the network, collaborate, help where you can. Rona: And also, as we've said before, once you've got that level of engagement and the patients leading these initiatives we've found, certainly with our group, the patients are much more willing to, say, find the MRI scans for the scientists, to have a blood sample done, to have skin fibroblasts taken.  If they know and they understand and they're driven and, as you said, the research idea has come from them as a patient group it certainly increases the chance of them being fully involved in the project from the start to the finish.  And all these things are imperative to understanding rare conditions because without researchers having the opportunity to look at these various samples you're not going to stand much of a chance of finding a treatment.  Jo: And we want the opportunity to upskill patients as well.  I think there are many people out there with great ideas who haven't yet found the confidence to promote those ideas because they're not quite sure of what the research journey looks like or what it might entail or whether they've got the right skills.  But I think by joining the platform and almost kind of watching how other people are managing these things and utilising the resources and the mentoring I do really hope that will build that confidence and those skills sets in people so that they can engage.  Rona: Yeah, just to add to that, I don't think it's just upskilling patients and patient groups, I think it's upskilling everybody involved in rare disease research.  This is quite a different way of approaching research, it's something that maybe academics may feel a little bit uncomfortable with, it's not how it's normally done, so I think there's a whole learning process.  And the aim is that this RDR network will evolve and will develop and the direction it goes will be driven by the community that are engaging with it.  So I think it's a really exciting time just as we're coming up to launch to see where this goes.  Jo: Mel, you've been involved in this project, it would be really interesting actually to hear from you. I was just thinking, as part of the co-creation community we had 25 individuals from the rare disease community who built this platform from scratch with us; Rona and I might have set out all the vision for how we wanted the platform to be or what we thought might be a good idea but ultimately it was the community who decided and they literally have fact-checked and cross-referenced every word that's gone on the platform. What has that experience been like for you as a patient representative?  Mel: I think it's been really welcome to see a network that is truly putting patients at the centre of everything.  So, from the very beginning foundations you have the rare disease community involved which is exactly what you're trying to create through your network.  So, I think it's been very welcome to be involved in the project and I also think that hopefully it will sort of be self-perpetuating that this will start to press a reset button on how we think about rare conditions and how it needs to be a more equitable field with patients.  Because I think, as you've both alluded to, while some clinicians and researchers are very onboard with this, for others it's a new concept that they still need to potentially adjust to or get their head round because it is a different way of thinking.  But in rare disease, well, in any condition really but particularly rare disease because there's so few experiences to draw on, I think that patients are vital to moving forward and to making that change so that diseases and conditions that have previously had no treatment, like, hopefully this way of thinking can expedite those treatments because, well, as a rare disease representative myself for our community that's one of our biggest drivers.  We're dealing with a condition that's progressive that affects most of our community's children; that is what we want, we want treatment, we want something that can stabilise the conditions.  You know, you can have researchers doing random projects that would make no difference to the final outcome of patients but if researchers know it's a priority of this particular group, hopefully that can channel in their focus and get the outcomes that the patients want in a more timely collaborative way.  So, I am a huge advocate for what you're doing, I think it's an incredible initiative.  Is there anything either of you would like to add to that? Rona: Rare disease disproportionately affects children and young people.  So, 7 out of 10 rare diseases develop in childhood and at the moment the Rare Disease Research Network hasn't really got a forum for including children and young people, and really that's partly because, and Jo can speak much more eloquently to this with her experience.  Actually, we didn't do that at the start because we feel that this is actually a discreet piece of work that really needs to be done in collaboration with children and young people to make sure that it's done well so that they can engage in the platform. So, Jo, I don't know if you want to talk about how we're hoping to take this forward.  Jo: Yeah, so we're busy developing a project plan at the moment which we're hoping to get funding for to work over eighteen months with a team of young adults with rare conditions, probably from our Unique Feet community and keep it local because we already have a good relationship with them and they have our trust.  But the idea would be to work with lots of other young people's forums.  So there's already ones established in and around our area, such as Pedal, which works with really small children, and there's also groups that are set up for young people with cancer.  So we've already had lots of great conversations with them about how we can work with them, how they can help us sense-check our project, and then in return we can help them better understand research and their ability to be involved in that.  But ultimately by the end we want to run focus groups, we want to develop some peer mentors within our community, so young adults who've, you know, perhaps come out the other end of a period of transition into adulthood who can support other young people with rare diseases to also become researchers, to come up with their own ideas and their own questions, and to sense-check projects that come through the platform.  So it's a really exciting opportunity to truly involve the people who are affected most by rare conditions but we know through our My Story, My Way project that this has to be done gently, carefully, given time and done really thoughtfully.  So that's our next step and we hope to be able to share those learnings with people so that it can be done elsewhere.  Mel: And do you see the network also working with children with learning differences? Jo: Absolutely.  We'll invest a lot of time and energy in ensuring that materials are accessible, inclusive and suitable for the community that we're working with.  Mel: So looking to the future, how do you think, Rona, can patient-led research help to shape the future landscape?  Rona: So I think, Jo used the term earlier, kind of this is really turning research on its head, so it's really putting patients right at the centre of research, so it just makes sure that it's absolutely driven by what matters to them to get the outcomes that matter.  And, again, it's just got all that benefit of efficiency and really answering those questions that matter.  Mel: And, Jo, do you think this could lead to more collaborative partnership, for example, between industry and academia, potentially leading to quicker clinical advancement? Jo: I would absolutely like to think so.  You know, as CamRARE we run a companies forum which is a roundtable meeting for pharma and biotech companies and other organisations like Genomics England who are involved in the rare disease therapeutic space and diagnostics, and I think one thing that I find really heart-warming about those meetings is that, you know, different companies are able to sit around a table as competitors but with a very open mind to addressing the barriers and the bottlenecks that prevent them from getting drugs to patients.  Because of course it's not just the research journey that's a challenge, it's the regulatory side of things at the end of that journey; just because you've created a great drug it doesn't matter in the end if it doesn't get to the patient.  So, you know, access is critical and involving patients at the earliest possible moment to ensure that that treatment gets through to the regulators and gets access to patients is the only way forward.  We had a recent companies forum meeting where we were exploring health-related patient reported outcome measures, or PROMs, and we had a speaker from NICE who's the regulatory body, we had a speaker from Sheffield University who was talking as an academic about developing PROMs for industry and for patient groups and we had Emily Reuben, the CEO of Duchenne UK, and we had an amazing discussion about the importance of involving the patient community from the outset.  And the academic explained that developing a PROM for Duchenne UK had taken them two years and it had taken them that length of time because they'd followed this careful thoughtful pathway of making sure that they didn't assume anything about what matters to patients.  But that of course, as we said earlier, involves time, it involves financial commitment, it involves resources and the right attitude, but I do think that a platform like the Rare Disease Research Network can really try to harness all of those things by bringing the right people together – industry, academia and patients – to work together equitably. Mel: And with the network do you think you'll be getting the regulators in at that initial stage as well so that, like you said, the patients can gain access while we're dealing with their priorities, the regulators are informed at the very earliest stages so that we know the process that's being followed will ultimately lead to patients gaining access to the relevant therapies?  Jo: Yes, I think this is really important, and there's actually, we've got a section on the new platform which really talks to each of the different stakeholders.  ‘What's in this for me?'  ‘Why is it important for you to be here and to join?'  And one part of that is funders and that includes the regulatory bodies.  And at the next companies forum meeting we're actually going to be bringing the Rare Disease Research Network Platform and its potential to the companies forum meeting and we'll have regulators involved in that.  So, you know, we are constantly talking to people about why it's important for them all to be involved and all to see what matters. I think I'd like to advocate for an extra letter at the end of PPIEP - if we could squeeze a D in there at the end too.  So over time that terminology has expanded to be Public Patient Involvement Engagement and Participation, which was added I think this year, but it would be lovely to have the D on the end and to include ‘Driven' because I think what's really important about this platform is that it's not just engagement and involvement, it's not just participation, it's initiated by and driven by patients. Mel: So I think we'll wrap here.  Thank you to our guests, Jo Balfour and Dr Rona Smith, for joining me today as we discuss the role of patients in setting research agendas.  If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I've been your host, Mel Dixon, and this podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand. 

In this episode, we explore findings from a groundbreaking study recently published in Nature which revealed potential targets for bowel cancer prevention and treatment. The study provides the most detailed understanding yet of bowel cancer's genetic makeup. The research, which used data from the 100,000 Genomes Project identified over 250 genes that play a crucial role in the condition, driver genes and potential drug targets. Our guests discuss the potential impact of these findings on patient outcomes, screening for bowel cancer, and future prevention strategies. Helen White, Participant Panel Vice-Chair for Cancer at Genomics England is joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University. "The people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldn't benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what we're seeking to realise now. But, you know, it's not a given when we treat people in the clinic so we're very, very grateful to those individuals." You can read more about the study in our colorectal cancer blog and our study findings news story. You can download the transcript or read it below. Helen: Welcome to Behind the Genes. Ian: One of the great hopes is that some of these new genes that we've found could be useful in preventing cancer and it doesn't necessarily matter that they're rare, even if they're only 1% of cancers, by using those and changing those in the normal individual before they have had cancer then we may be able to reduce that risk. So, there are lots of potential new targets for prevention that are coming through.  My name is Helen White and I'm the Participant Panel Vice-Chair for Cancer at Genomics England. Today I'm delighted to be joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University.   Today we will be discussing a pioneering colorectal cancer study which using data from the 100,000 Genomes Project has uncovered new insights that could transform diagnosis and treatment for patients with bowel cancer. If you enjoyed today's episode we would love your support, please like, share and rate us on wherever you listen to your podcast.  Thank you for joining me today. We're going to be discussing the findings from a landmark study that has been published in nature. This study used data generously donated by people with bowel cancer who took part in the 100,000 Genomes Project giving us the most detailed look yet at the genetic makeup of colorectal cancer better known as bowel cancer. But before we get into that let's start by hearing from my guests. Could each of you please introduce yourselves.  Ian: I'm Ian Tomlinson, I work at the University of Oxford and most of my work is research into bowel cancer, it's genetic causes, the genes that are involved in actually causing the cancer to grow which may be different from genetic causes and also the use of that data to help patients whether guiding future treatments or potentially helping to prevent bowel cancer which would obviously be our optimum strategy to have the biggest impact on the disease and its incidents.   Claire: So, I'm Claire Coughlan, I'm the clinical lead for Bowel Cancer UK and my remit at the charity is to ensure that everything we do is clinically relevant and that we're providing services that meet the needs of those affected by bowel cancer and the educational needs of those health professionals that work with people affected by bowel cancer. I'm also a nurse consultant in colorectal cancer at Lewisham and Greenwich NHS Trust and I lead an urgent referral service there and also work with patients with late effects of bowel cancer.  David: I'm David Church, I'm a medical oncologist and Cancer Research UK advanced clinician scientist at the University of Oxford. I treat bowel cancer clinically and do research on bowel cancer and womb cancer including a lot of research using samples and data from Genomics England data service we're discussing today of course.  Helen: Great, thank you. Now let's turn to Claire to learn more about bowel cancer. Claire, can you share with us how common it is, how treatable it is and if there are any trends in terms of which groups of people are affected?  Claire: Of course, bowel cancer is a relatively common cancer, there are about 46,000 people each year in the UK diagnosed with bowel cancer so that is quite a large number. The thing that really drives us forward in bowel cancer is that the earlier stage you're diagnosed at the greater chance of survival. So, the figures for that are quite stark, we stage bowel cancer through stage one to 4 with one being the earliest stage and 4 being the most advanced.   If you are diagnosed with bowel cancer at stage one you have a 9 in 10 chance of being alive and well 5 years after your diagnosis of bowel cancer. And if you're diagnosed at the other end of the spectrum at stage 4 that drops to a 1 in 10 and should people survive after a diagnosis of stage 4, which more people than before do they will have had a lot of treatment for their bowel cancer so the burden of the treatment will also be with them after that. So, it's really important that we diagnose at the earliest possible stage which is why studies such as the one we're going to talk about today are so important.   We have noticed that there has been a slight increase in being diagnosed at a younger age. That said the latest statistic is 2,600 people were diagnosed under the age 50 in the UK last year so it's still a disease of older people, you still have a greater chance of getting bowel cancer as you get older but it's really, really important that we're aware that you can still get bowel cancer as a younger person.   Probably one of the most exciting things that has happened for bowel cancer of recent years is our bowel cancer screening programme and the age for that now has been brought down to 50, we're not quite there all over the country, but in the UK that is the aim that everyone will be screened for bowel cancer at the age of 50. So, yes it's a common disease and staging an early detection is vital. Helen: That's lovely Claire, thank you very much for that. David, turning to you could you please explain to us how bowel cancer typically develops? David: Yes, so we know compared with many cancer types quite a lot about how bowel cancer develops because the bowel is accessible to collect samples by a technique called endoscopy which is putting a camera into the bowel from which you can sample tumours or lumps. And so from genetic research done in the last 10 years we know that, or we've known for many years actually, for much longer, that cancer is a genetic disease, it's a disease caused by alterations in genes and particularly genes that control whether the cells in our bowel grow normally and die normally as they should do. And collectively when there are alterations in genes that regulate those processes you can have a cell or collection of cells which are able to grow without restraint and don't die when they should do which are some of the hallmarks of a cancer and they also require the ability to spread elsewhere in the body which is what kills people with cancer including bowel cancer. We know from research done in the last 10 to 15 years that some of the alterations in genes that can cause bowel cancer in combination occur very early in our life, even in the first and second decade of life, but don't cause cancer. The earliest detectable abnormality is typically a polyp which is a tumour, a lump within the bowel which is detectable and if removed is almost certainly cured by removal alone but if it's not detected then as that grows and acquires more alterations in genes then it can become a cancer and cancers develop the ability to invade the bowel wall, to spread to what we call lymph nodes or glands nearby and also to spread further afield, most commonly to the liver or to the lungs.   And for most people whom bowel cancer has spread to the liver or to the lungs or elsewhere unfortunately we're not able to cure their disease which as Claire has said is why there is such an importance in detecting cancers and pre-cancers as we call them so that the tumours are not actually cancerous but come before bowel cancer as early as possible.  Helen: Thank you David. Moving on to the study, Ian perhaps you can take this, in the study that you carried out my understanding is that the whole genome sequencing was used to investigate the genetic changes that lead to the development and growth of bowel cancer. And for this participants with bowel cancer in the 100,000 Genomes Project donated both a blood sample and a tumour sample while those with rare conditions only provided a blood sample, can you explain why that is?  Ian: As you said the study really looked at 2 quite separate arms albeit with a little bit of overlap as we'll see. So, one very important aim was to look at individuals, both children and adults, who had medical problems or other conditions that were unexplained but which had some features that suggested that they weren't necessarily inherited but there may be some variation in their genes that had caused them, and roughly half of the programme was dedicated to that.   Within that there was a small number of people who had a strong family history of bowel cancer or who had large numbers of polyps in the bowel and they were analysed in a separate part of the project from what we're mostly discussing. Within the cancer arm there was a collection really throughout England of patients who had most of the common types of cancer and a few with less common cancers.   And because when we're looking at genetic and related changes in cancers we need to make sure that those changes have actually occurred in the cancer as it started growing from its earliest stages with a small number of cells in the body that were slightly abnormal and then progressing. We need to look at what genetic variation the patient has in all the cells of their body. We don't want to look at patients and say that looks an interesting change, we may be able to use that if it's present in all of the normal cells in that patient's system.   We want to make sure the change is specific to the cancer itself and therefore we have to sequence both a sample probably taken from blood and a sample taken from the actual cancer. And in a way we subtract out the changes in the blood to identify the changes that have actually occurred in the cancer itself.  Helen: That's a very helpful explanation. Does this research show that there is a role for whole genome sequencing in clinical care?  Ian: I think my own view is it is all a question of cost. I think the advantages it provides it can assess multiple types of genetic change at once. It is relatively consistent across each cancer's genome between cancers, even between centres mean that it is the method of choice. There are undoubtedly developments that will happen in the future, maybe being able to sequence longer stretches of DNA in one go that will help the analysis.   And some of the computational methods are likely to develop to identify some of the slightly difficult to identify genetic changes but it ought to be the standard of choice. There are issues and potential difficulties in collecting the high-quality samples that have been needed from pathology laboratory and that will be difficult going forward with current budges and there are lots of challenges but ultimately it in some form has to be the method of choice. What wasn't done is to look at other molecule tests or essays, looking at RNA wasn't really done on a big scale as well as DNA and other changes to DNA apart from the genetic changes were not looked at.   So, there are certainly ways it could be improved if you had limitless money but I think the project, 100,000 Genomes has shown the whole genomes are. They have a lot of advantages and ultimately probably will be adopted by the NHS and similar organisations.  Helen: David, could you now tell us about the findings of this pioneering study and what impact these findings might have on people with bowel cancer in the future?  David: So, this is the largest study to date to analyse the entire genome of bowel cancer by some margin and the fact that we've done whole genome sequencing and in so many people it has really given us an unprecedented ability to identify the genetic alterations that drive bowel cancer. And within bowel cancer we've known for some time it is not a homogeneous entity that bowel cancer is not all created equal, that there are sub-groups of bowel cancer and we have been able to refine those over previous efforts. And I guess if you were to ask what the biggest take home for me from the study is it's just the complexity of the disease.   So, as we've mentioned we know that cancer is a genetic disease, that it's driven by genetic alterations, alterations in genes which regulate the growth of cells or the death of cells or the spread of cells. And we've known for many years that there is a modest number of genes which are commonly malfunctioning in bowel cancer and they would be in the tens to dozens really. But with this work we've hugely extended our understanding of the genes that drive bowel cancer and in fact we've discovered nearly 250 genes which are altered in bowel cancer and appear to drive the growth of the cancer.   Now we know that not all of those will be validated and by that I mean that there are associations that we find at the moment, not all of which will be biologically relevant but interpreted in the data we know a large number that are previously undiscovered are or we can be fairly confident of that. And one of the take homes from that is that many of these are only altered in a small fraction of bowel cancers.   So, rather than being perhaps half of bowel cancers or a third of bowel cancers there are a good number of genes, a very substantial number of genes, which are altered in say 3 to even 1% of bowel cancers. And if we think about how we go about targeting those and perhaps we'll come onto treatment later that poses really challenges for how we work and we would think about treating patients with bowel cancer who have those particular alterations in their cancers.  Helen: Thank you David, yes we'll come onto treatment shortly, but I think Claire has a question for you.   Claire: Yes, thank you. For me as somebody who works in this every day this is such an exciting and interesting study, particularly in light of what we said earlier about early detection and how critically important that is for improving outcomes in people with bowel cancer. So, in your view do you think this research could help shape future screening programmes or prevention strategies?  David: That's a great question, I suppose in terms of screening at the moment the majority of screening is done in the UK at least by testing for blood in the stool which is relatively non-specific so I'm not sure that that would be directly impacted by this research. But one area of early cancer detection that is perhaps more relevant is quite a lot of work including from Oxford actually in recent years looking at blood tests. So, testing blood samples for early detection of cancer whereby you can test for genetic alterations, fragments of DNA that have alterations from the bowel cancer or any cancer that circulates in the blood and that tends to rely on a small number of common alterations.   And with this data I could see that we might be able to refine those tests and in so doing improve our early detection of cancer but that would need quite some work before we could actually say look that had real potential I think. And in terms of prevention there are, I think Ian may want to come in on this, one or 2 sub-groups which you might think that you could try to prevent but of course that needs a lot of extra work really.   But I think we have some clues of the biology of bowel cancer and particularly some of the sub-groups where you might think well this drug would work better in terms of preventing that sub-group or that sub-group but that will need to be the subject of future study.  Helen: Ian, did you want to come in on that at all?  Ian: So, at the moment prevention is a fairly new way of helping to reduce the number of people with bowel cancer at the level of the whole population which is what we have in the UK above a certain age group as we heard from Claire earlier. The methods used, again as we heard, are screening for occult blood in the stool and then colonoscopy to identify either hopefully early cancers or polyps and remove those. But when we think about the methods that we use for preventing other diseases then normally where they're successful using a more easily delivered and I have to say less expensive method.   So, high blood pressure is treated to reduce the risk of cardiovascular disease and there are other diseases where those what you might call molecularly-based prevented strategies are coming in. We really lack that for bowel cancer in particular, it does happen for some other cancers, but one of the great hopes is that some of these new genes that we've found could be useful in preventing cancer. And it doesn't necessarily matter that they're rare, even if there are only 1% of cancers, by using those and changing those in a normal individual before they have had cancer then we may be able to reduce that risk.   So, there are lots of potential new targets for prevention that are coming through and as David said it is going to take a lot of work to work out which of those are deliverable and who will benefit. But we have quite a lot of opportunities in that space and although that may not be us that takes that forward, it may be, but it may not be. We think it is a lot of material for those interested in chemo prevention using drugs of cancer that they can work on and with luck deliver some new ways of preventing cancer that may be simply popping a pill every morning to take your risk right down to as close as zero as we can.  Helen: Thank you Ian. David, I think you had something to add here.  David: Thanks Helen. One area of prevention that we're really interested in Oxford and many others are is using the genetic alterations that we find in bowel cancers and other cancers as targets for vaccination. Now we know that gene alterations will cause abnormal proteins which while they might drive the cancer, make it grow or not die, can also be recognised by the immune system so the abnormal proteins can be recognised by the immune system as being foreign and as foreign they can be targeted by the immune system so the immune system will try and kill the cells carrying those alterations. And we know for some sub-sets of bowel cancers those alterations can be relatively predictable actually, they occur in quite a sizeable fraction of some sub-groups of bowel cancers.   And one area that we're particularly interested in at the moment and actively pursuing is using those targets where you need some additional work to demonstrate when they are particularly recognisable by the immune system. But to use these genetic alterations is potential targets for vaccination with the intention ultimately of preventing bowel cancer in at risk individuals or ideally in the full-term time the whole population. And we've received some funding from Cancer Research UK to pursue this line of research and we have a group working on this in Oxford and as I say many others do elsewhere.  Helen: Thank you David, yes I have a vested interest in this because my understanding is this work is aimed primarily at people with a genetic condition called lynch syndrome which predisposes the people who have inherited this gene change alteration to bowel cancer, womb cancer and other cancer. And I had womb cancer, as I think David you know, a few years back and discovered it was due to lynch syndrome and so it's really exciting that you're now looking at vaccinating preventing because yes I take aspirin every day, I have my colonoscopy every 2 years which have some effect on preventing these cancers but it's not 100% guaranteed. And I don't suppose it ever will be but having the vaccination in that armoury would be fantastic I think for future generations, it's very exciting and we look forward to hearing more about it.   Thank you Ian and David. I mean we've heard a lot there about preventing bowel cancer but I think moving back now to potential treatments, you know, we've heard from David how this study has shown a number of actionable findings but what are the next steps towards treatment? How can these findings be turned into real actions that will benefit those people diagnosed with bowel cancer in the future? Ian, perhaps you would like to pick up on this to start.  Ian: That step is one, you know, in which I'm not personally an expert but a lot of the newer treatments are based on the finding of so called driving mutations which are simply genetic changes that occur as the cancer grows and contribute to that growth and ultimately if it's not treated to the spread and dissemination of a cancer. And the fact that we have reported 250 which need validation but of which a large proportion are likely to be true drivers means that anyone of those can be a potential new target.   The criteria to be used for which of those mutations to pursue, which of those driver genes to chase up are quite complicated normally, depend on many things such as the interest of research groups and small and larger drug companies. And the similarity of those genes to other genes that have evolved and the processes that they make to go slightly wrong in the cancer.   So, there is also the issue that because these are uncommon, everybody talks a lot about personalised medicine or precision medicine, this would be truly precision or personalised medicine because a genetic change that was driving the cancer in only 1% of patients is obviously not a huge number of patients although bowel cancer is a common cancer so it's not a tiny number either. But it would mean investment at that level to benefit let's say 1 to 2% potentially of all patients with bowel cancer but I think that's a nettle we have to grasp. And I think our results are showing that most of the really common drug changes either have not yet been successfully targeted in treatment or are too difficult to target.   So, we're going to have to start looking at these less common genetic drivers and design strategies, inhibitors, you know, again that can be delivered to patients relatively straightforwardly in order to see whether they benefit the patients concerned. But there is this problem of getting enough patients enrolled in clinical trials where a change is only present in a relatively small proportion of all the patients with that cancer type.   Helen: Thank you Ian. Presumably if there is a relatively small number of patients the people who are looking at running these trials might be looking at perhaps international trials, would that be one way to go?  Ian: So, I think David can speak with more personal knowledge but there are international trial networks and there are collaborations along these lines already under way. I would hope that those could be made use of even more than they are already. There is, you know, a financial consideration for those developing new anticancer treatments which are, you know, high risk work and also the costs of setting up trials and enrolling people is not a trivial thing. So, I think those are hurdles that can be overcome but it would need a concerted effort to do that. Patients will play a major role in that and patient organisations as well as 100,00 Genomes and other similar projects.  Helen: Yes, thank you, David I don't know if you want to come in on that.  David: Yes, the challenge of testing therapies in small groups is a very real one and there is lots of interest at the moment in exploring alternatives to conventional clinical trials. And as we use more electronic patient records and we have pharmacy records so there is the potential to get those data from routine clinical practice and there is lots of investments and attention on that at the moment so called real world data which is always an interesting term as if patients in clinical trials aren't in the real world which of course they are.   But it's perhaps a little more cost effective sometimes in clinical trials, of course it does pose its own challenges in how you disentangle true treatment effect from other factors because there are many factors impacting on how long people with cancer live. But there is a lot of investment and effort going into that at the moment and it will be interesting to see how that develops over the coming years.  Helen: Turning to you Claire based on your experience how well do you think people with bowel cancer understand how genomes can help with their care and what support is currently available to them in this area?  Claire: I think the answer, as it is so often is, it's dependent on individuals and not just one individual. So, I think some patients are very motivated to know as much about this as possible and to understand and to know what the next steps may be in their own treatment that may be helped by this. Others don't want to have the same knowledge and want to be guided very much by their medical teams but I think oncologists obviously are at the forefront of this and we see at the charity … we have services at the charity that supports patients and we see lots of queries into our ask the nurse service where people have been given variable information about I suppose personalised medicine as Ian alluded to and how their very specific bowel cancer may be treated, so I think it varies from patient to patient.   There is support available so we have the ask the nurse service I alluded to. We have a brilliant patient forum actually and everybody in clinical practice will have seen this, patients often become more expert than anybody and they share advice and they're moderated forums that are a very safe place for people to ask questions where there is a moderator to ensure that it is made really clear that circumstances are individual.   And the same with the ask the nurse service because you don't have all the clinical information so it is about empowering people, so there is support available. I think the other thing that is really important is equipping specialist nurses with the knowledge that they need to support their patients. This is a really exciting area of evolution for bowel cancer particularly I think in all cancers at the moment but for bowel cancer I think things have changed fairly rapidly in recent years and specialist nurses really need support in knowing that they have up-to-date information to give their patients.   So, that's another challenge for us and any specialist nurses that might be listening to this podcast we have online education on genomics for specialist nurses. Just while we're talking about that and you mentioned lynch syndrome earlier, so there has been a lynch syndrome project as I'm sure you're aware where we're trying to get testing for lynch syndrome brought into local hospitals.   So, there was some funding via NHS England so that the testing be done at time of diagnosis, so a pre-test and then a final test if that's appropriate, for everybody diagnosed with bowel cancer to see if they have lynch syndrome. And in some trusts that has been done and in others it hasn't yet and the funding hasn't quite followed in the way that we need it to enable that to happen. It's vitally important, we think there are about 175,000 people in the UK with lynch syndrome and we only know about 5% of them. And this is a gene change that is an inherited gene change so we can do what we call cascade testing where we test family members and we can then employ preventative strategies to prevent people from developing bowel cancer.   So, it's a really important project, so I think as well as supporting patients with the information around the changes that are happening in this area we also need to ensure that we support the workforce and have investment there to enable the support of all the changes and the genomic landscape.  Helen: Absolutely Claire and so much resonates there with what you've said. Having myself had cancer discovered that was due to lynch syndrome, cascade testing offered to my family members so valuable. It turns out I inherited my change from my mum who is 83, has never had cancer, so I think that's a very good example of, you know, it doesn't necessarily mean that you will get cancer but actually on that point that you made about empowering patients I always have a right smile because there is my mum going off to all her other medical appointments because at 83 she sees quite a few people and she is always the one telling them about lynch syndrome and educating them because most of them haven't heard of it, so yes it's really, really important.   And that patient forum, you're probably aware of Lynch Syndrome UK, I don't have any involvement in that other than being a member but that is so valuable for people with a particular condition to go somewhere where they can talk to or listen to other people with a similar condition, really, really valuable.   Right, well I think circling back really to the 100,000 Genomes Project I think you touched on this earlier David but reflecting on what you and Ian have told us about your study what is it about the 100,000 Genomes Project bowel cancer dataset that made this work possible?  David: There are a few things, one of which and not least of which is the sheer size of the effort. So, to have whole genome sequencing for more than 2,000 individuals is previously unprecedented and we'll be seeing more of this now as we scale up our research efforts but at the inception of the project it was very, very ambitious and to be able to deliver that is a huge achievement. And the quality and breadth of the analysis is very strong as well.   And ultimately, you know, the former gives thanks to the people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldn't benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what we're seeking to realise now. But, you know, it's not a given when we treat people in the clinic so we're very, very grateful to those individuals.   And I think also to the scientists who worked incredibly hard over the last 5 years to deliver this work actually. So, having been part of the team and being lucky enough to be part of the team along with Ian we've had hugely motivated individuals that really have dedicated a large fraction of their working lives to delivering this project which I think is a fantastic achievement as well.  Helen: Thank you, thank you to all those participants who at a time when their lives probably were turned completely upside down by a cancer diagnosis were offered the chance to join the 100,000 Genomes Project and said yes. As you say most of them will have known that it won't have helped them but by donating their data, you know, it has allowed this work to happen and potentially it could change lots of people's lives in the future, so thank you to them.  Ian: Could I also just emphasise and agree with what David has said, I won't go through all the individuals by name, but if anybody wants to read the published report of the work there are several people on there, Alex Cornish is the first author, but many colleagues from an institute of Cancer Research, The University of Manchester, Birmingham, Leeds, other universities in London that all contributed, but also colleagues in the NHS and/or universities who recruited patients, collected samples, processed them etc and of course the people who did the preparation of the samples in genetics laboratories and actually did the sequencing and basic analysis too.   So, it is a truly huge effort across particularly all the cancer types which is particularly a complex collection given the fact the tumour is needed and a blood sample. It's quite difficult in a way to find a formal way of thanking them for all of this but without them it wouldn't have happened.  Helen: On that note I think we'll wrap up there. A huge thank you to our guests, Professor Ian Tomlinson, Clare Coughlan and Dr David Church for an enlightening discussion on the groundbreaking study published in nature. This research is set to reshape our understanding of colorectal cancer and pave the way for new possibilities in treatment and patient care.   If you would like to hear more like this please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand. 

On this week's episode of CMDA Matters, Dr. Mike Chupp sits down with Dr. Bill Griffin to have a conversation with well-known financial advisor and author David Bahnsen to talk about his new book, Full-Time: Working and the Meaning of Life.  RESOURCES FOR THIS EPISODE:  Give to CMDA Email CMDA Matters CMDA Bookstore Center for Well-Being 2025 CMDA National Convention Full-Time: Work and the Meaning of Life by David Bahnsen Margin: Restoring Emotiona, Physical, Financial, and Time Reserves to Overloaded Lives by Dr. Richard Swenson CMDA Stewardship and Development Faith Prescriptions

The Generation Study is a research initiative aiming to explore the use of whole genome sequencing in newborns, to screen for more than 200 rare genetic conditions. This study will recruit 100,000 babies across England, and you can learn more about the Generation Study via the study's official website. Design research has played a vital role in shaping the Generation Study. Parents, NHS staff, and the public have been involved from the start, providing input through public dialogues and usability testing to guide the development of the study. In this episode, our guests discuss the use of design research in the Generation Study, and the importance of designing a robust and inclusive consent process, focusing on building trust and engaging diverse communities. They also discuss how the design of study materials such as posters, videos, and written content was shaped by community feedback. Our host, Öznur Özkurt, Director of design and research at Genomics England is joined by Mathilde Leblond, Senior Design Researcher at Genomics England, Rebecca Middleton, a rare condition patient, and Chair of the recruitment working group of the Generation Study and Sandra Igwe, CEO/founder of The Motherhood Group.   "It's not enough to just ask people afterwards. It's also not enough to engage just at the beginning and then stop listening once we're live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn't considered before we launched, and just continue to learn."   You can hear more information about Generation Study in our previous podcast episodes too: Genomics 101 with David Bick - What is the Generation Study? Which conditions will we look for initially in the Generation Study? With Vivienne Parry and David Bick You can read the transcript below, or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/How-has-design-research-shaped-the-Generation-Study.docx  Öznur: Welcome to Behind the Genes.  Sandra: Every community's different and every patient is different as well, and so that may require different focuses or different formats, or different messages for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so it's really important to have representation because the lack of it in research can overlook communities' specific concerns and needs.  Öznur: My name's Öznur Özkurt and I'm the director of design and research at Genomics England. On today's episode, I'm joined by Mathilde Leblonde, senior design researcher at Genomics England, Rebecca Middleton, and Sandra Igwe, CEO and founder of the Motherhood Group. Today we'll be discussing how design research was used in the Generation Study by involving participant and users' voices to address ethical considerations, implementation and consent. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts.  So, before we dive into our questions, would our guests like to briefly introduce yourselves to our listeners? Sandra, let's start with you.  Sandra: Hi everyone, I'm Sandra Igwe and I'm the founder and chief exec at the Motherhood Group. The Motherhood Group is a social enterprise that supports black mothers, birthing people in their pregnancy and beyond.  Öznur: Great to have you on the podcast, Sandra. Rebecca?  Rebecca: Hi everyone, I'm Rebecca, I'm a rare condition patient, and I also have the pleasure of chairing the recruitment working group of the Generation Study.  Öznur: Fantastic, thank you, Rebecca. And over to you, Mathilde.  Mathilde: Hi, I'm Mathilde. I'm leading design research on the Generation Study, and I have had the pleasure of working with Sandra and Rebecca and many others, trying to shape the processes and materials of recruitment and consent in the Generation Study.  Öznur: Fantastic, thank you. Mathilde, let's start with our first question. What is the Generation Study?  Mathilde: Sure. So, whole genome sequencing is a technology that's improving. We're finding new ways of using that, and there's interest globally to explore the use of this technology to screen for rare genetic conditions in babies, so that we can treat them earlier on, so they're not having two different departments trying to figure out what's wrong with them. And because we can look for hundreds of conditions with whole genome sequencing, it's really much more efficient, and we're able to look at these rare conditions, so it's really exciting. There's still a lot of questions about implementing this operationally within the NHS, and so the Generation Study is aiming to explore this. We're going to be aiming to recruit 100,000 babies across England to take part in this, and they will be staying on the Generation Study for 16 years, or until they withdraw, so that we can see how their health develops, and really understand how genes affect their health.  Öznur: Thanks Mathilde. And if you'd like to learn more about the Generation Study, you can listen to our previous Genomics 101 podcast called What is the Generation Study, and Which Conditions Will We Look for Initially in the Generation Study.  Mathilde, can you briefly outline for us what we mean by design research?  Mathilde: So, design research is a design and research methodology, which involves users from scoping through iteration. So, even back when we didn't know this would be called the Generation Study and we weren't even sure of the boundaries of that, we were involving parents, NHS staff and other users of the service to try and understand what it might be. And later down the line it went all the way through to iterations once we started having materials and a better idea of what it could be like (inaudible 0:04:18) with users outside of the company to understand what their needs are, what would work well for them, and how we can shape the whole service to do things better.  Öznur: And how have we implemented design research in the Generation Study?  Mathilde: Yep, so we've also done a lot of engagement, which was bringing public views in the form of public dialogues, so understanding which conditions should be looked for, what principles should be guiding that work, but also we've been involving users in regular rounds of codesign and usability testing to understand what works and what doesn't work. It's been around 105 people now that have taken part, and it's only going to be growing. Involving users has been shown to improve the implementation of interventions in the healthcare context, so we really hope that this will help the Generation Study when it launches. And regular rounds of codesign have had to be balanced with ethics, operations, feasibility, but I'm proud to say that user perspectives have been central to the decisions of the programme throughout.   Öznur: That's fantastic to hear. I'm going to come to Rebecca and ask, why is it important for us to be guided by the patients and the participants?  Rebecca: It's absolutely central, and the public dialogue that really underpinned this, which started in 2020, the messages from that have really come through to the whole codesign process of the project. The public consultation really told us that people were genuinely keen about the project, but wanted to ensure that they were part of the process, and that coproduction really began from day one. This is a new world leading project. This has not been done before, so we needed a whole new approach to how we produced and how we designed this with patients and with parents, and that's exactly what we've done. And why we have done it is because we know ultimately it leads to trust within the project, within the research study, which is essential, as I say, ‘cos this is a world first. But it also leads to better consent, a better pathway through the study, a better results pathway as well, and all the way through, ensuring that expectations are managed, that there is transparency, and people are fully informed and can make the right decision for themselves and for their baby. Öznur: Thank you. And would you like to add something, Sandra?  Sandra: Yeah, so I know from my community that we represent black mothers and black ethnic minority patients and participants, and we have very unique lived experiences that many research may not be privy to or just do not understand. And so engaging with patients from the community ensures that research is grounded in real authentic community needs and priorities. And also involving women like myself and those from my community, it can really help to identify and overcome barriers to inclusion or getting mums involved. I know I always hear, you know, “Sandra, black mothers are so hard to reach, they don't really get involved in research.” Well, if you include those from the community to lead in the research or support in engagement, you will have a lot more uptake, and it leads to more accessible inclusive research, which of course everyone really, really desires to have more of.   And then also participants from the community can flag issues and suggest solutions that researchers may miss, because it's not knowledge, it's experience. It's, you know, having someone go through the experiences without necessarily studying it, but again lived experience to me, it's more crucial than any other experience that you could possibly have.  Öznur: 100 percent, lived experience is really, really crucial for us to make the services that we're making really speak to the actual context of our users. Thank you for that. And Rebecca, how has this process been different to the 100,000 Genomes Project? What was your experience? Rebecca: I was consented onto the 100,000 Genomes Project back in 2015, and I can remember that experience very vividly, on a cold, wet December afternoon, going off to meet my genetic counsellor, and receiving the consent form for the 100,000 Genomes Project, which was very much like War & Peace. Scratching my head at the time, going, “Gosh, I'm going to have to (inaudible 0:08:54) to go through this.” And then going home that evening and sitting on the sofa, and, you know, considering myself an educated woman, just realising I had so many questions. I really didn't understand it, and I needed somebody to help me unpack this, and translate it. And I'm pleased to say that our consent process and our recruitment process is very different to this, which is a fantastic thing. And what's really key about the lessons that we have learnt from the 100,000 Genomes Project is that, to really build trust in a research programme and a new research programme, you need to manage expectations, and that's wrapped up in building trust around the programme as well. And with the 100,000 Genomes Programme, there have been challenges and issues around that expectation management, and some expectations weren't managed. And even now nearly ten years on, we are still feeling the effects of that, and patients and families are still feeling hurt because of that. So, we have learnt from that and therefore we have designed a process with patients and with parents. We know that no two experiences are the same, that we have to ensure that we remain flexible, and we have to ensure that we are addressing any misconceptions, any misunderstandings. Perception and reality have to be treated the same. We have to understand how people are understanding genomics, because outside of pockets, genomics is not a standard NHS piece of healthcare. So, people come to this study with different assumptions, and we have to learn to go beyond them. We have to understand what their health literacy needs are, and how we can help manage that, how we can help translate, so that nobody is stuck at home on a cold, wet December evening, scratching their head, going, “Well, I don't know what this actually means.” We are ensuring that the NHS professionals and everybody involved in the pathway is fully aware of how to explain the project, explain the risks, explain the benefits, and be fully transparent. And we know what the risks and the benefits are that need to be addressed because we've asked parents and patients as well. So, we know the challenges and we're trying to address them head on, and that's essential. It's essential in building trust, and that's one of the key learnings from the 100,000 Genomes Project. And it has been brilliant to be involved in this project and really kind of learn from that past experience, but move forward in such a unique and fresh way that really will have benefit to those new parents. Öznur: Thank you, Rebecca. And we have been talking about the consent process in the context of newborns, and we know that, while consent given for newborn screening is really high in the UK, parents often leave this conversation relatively uninformed. Sandra, can you tell us a little bit about what you think the risks of not designing this consent moment appropriately might be? Sandra: I guess not designing appropriately can break down trust. So, I think engaging in a variety of parents in this research and design is crucial for trust. And that's a topic that's come up many times in our community is that they believe that there is a lack of trust between research practitioners and this wider system as a whole, and the community of marginalised patients, parents, mothers. So, I think it's really important that communities have this. But also researchers must make the effort to meet parents where they are at, not just physically but also conceptually, as well as emotionally. So, hosting conversations in familiar, comfortable community spaces is essential. We had our session in our hub, our community hub, and mothers were really familiar with the space and with each other as well. And so partnering with local grassroots organisations and leaders to create inroads is so beneficial, and I can hand on say that when you connect with the community, you've already done the first step in building trust. And consent conversations should be guided by what matters most to each parent within each community, ‘cos every community's different and every patient is different as well, and so that may require different focuses or different formats, or different messengers for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so it's really important to have representation because the lack of it in research can overlook communities' specific concerns and needs. Öznur: Absolutely, and that inclusion is really important for the study. Is there anything you'd like to add, Mathilde? Mathilde: Yes. When we talk about consent, oftentimes we think about that one moment, the moment of conversation with a clinician, and signing on the dotted line, and I think what we have done here in the Generation Study is to consider recruitment from the very first time that they hear about the Generation Study all the way down to that moment. And it's been really important because, yes, the moment of consent - you know, during pregnancy, you've got a lot of information coming in, a lot of different priorities, so you may be a little bit all over the place and not understand specific things, or not have the time to really spend thinking and understanding jargon, etc. And that presents a big risk because, when you may receive results, there may be confusion. There may be a loss of trust if there's media coverage that talks about the Generation Study in a way different from what you had understood it. So, these are some of the risks that we're trying to avoid.  But the big risk is also, as Sandra has said, the risk of not engaging a wide variety of parents, not just in the moment of consent but the whole process. So, if we're thinking about where we're using the word genomic and how are we using that, this is a word that's actually really scary for a lot of people. And we might be very proud of the cutting edge technology that we're using, but actually it can sound very science-y and almost sci-fi to people. So to us, the moment of consent is really from the first time that you hear about the Generation Study, you start creating a mental model about what that means, all the way down to the consent moment, when the samples are taken, the results and beyond. It's really been looking at this whole journey holistically. Öznur: And that language point is a really interesting one. I know that the study is obviously being communicated to the public through posters, leaflets, websites, which speak to how the study works, you know, the conditions we test for, and the benefits and risks of joining. There's a lot of language. There's written words in there, there's audiovisual content, videos, images. How did we inform what type of content is needed to communicate the depth of the study? Mathilde: I think the example of the introduction video is a really good one, and I want to discuss this a bit with Sandra, because actually it was quite a crucial turning point. We tested the video several times in user research before and after the Motherhood Group workshop, but the thoughts that her community gave us really helped change the tone of this video from something very professional to a conversation between parents raising questions. I wonder, Sandra, if you remember what your community's feedback had been, and if you can talk a little bit about that. Sandra: Yes. So, the mothers from our community at the Motherhood Group definitely gave lots and lots of feedback that the initial posters didn't really resonate with mothers from our community. They said that the visuals and the language felt a little bit generic and also too clinical, and it didn't speak directly to our community. They also expressed that seeing more black parents and more black families represented signals for us too as well – so, seeing people like look like us in the posters and the media would have allowed a lot more uptake. So, narratives and videos featuring real people that looked like members of our community, they expressed that would go a lot further. And also it made them feel a lot more relevant, and again it goes back to the notion of having more trust and feeling less abstract, but more like an authentic way of engaging or directly communicating with our community. They also appreciated the effort to be more upfront, but the risk and also the downside, not just selling only the positives. You know, members from our community were saying they wanted to know the real deal. And also our community have been misled in the past. You have to understand that. The history kind of shows that there has been a breakdown in trust, and so transparency, they shared, was really, really key to rebuilding that trust, as well as materials that are culturally tailored and designed for different formats for our community. Mathilde: It's really exciting how much this feedback has pushed all of us in the team and the designers – pushed us to think about how to talk about the Generation Study, what narratives to use, what tone of voice, but also you'll see on the posters there's space there to have photos of several different family types and people of different backgrounds. It's not just one photo. And there's also some very small tweaks, it seems like, but it actually has a very big impact, about what it is that you're trying to say and what people understand in a split second when they're seeing that. Öznur: Absolutely, and that open dialogue is definitely key to keeping on bringing those perspectives in, and keeping updating and moving the language of the study as well. Obviously, the study will keep being shaped. I'm curious about how will design research continue to shape the Generation Study going forward. Mathilde: Yep, so we will have an iterative process, where we're still listening to the sides as they're launching to hear what are the questions that are being raised, what are some of the challenges that they're facing. At the same time, we have a survey that parents will be able to fill in, and we have an evaluation partner, UCL, who is doing an independent review of how well all of this is landing, and evaluating the work that we've been doing to see is it really hitting all of these points, and what we may need to be iterating or changing as we learn. Rebecca: I should also point out that the recruitment working group is very much in the background, but we are still very much alive, and we will come back to look at those first pieces of feedback and to look at what the experiences have been, and how we can learn and how we can help kind of shape what comes next. Because it's critically important that we have this always learning philosophy. It's critically important that now, you know, the rocket has launched, how will it land, and we don't know until we've actually had that feedback. So, we can plan and absolutely plan to the nth degree, but actually how it exists out there in the real world, we won't know until the project goes live and that feedback comes through. And that's what we're also really excited about is to actually learn those first lessons and see how we can support going forward, and see what needs a tweak here, a change there. And again, it's that dialogue that started with the public dialogue back in 2020, and here we are in 2024 and that dialogue will still continue, and we are still listening and we are still learning. Öznur: Thanks Rebecca. I'd like us to reflect on the importance of continuous learning. What's the importance of continuous learning in this project? I'll start with Sandra. Sandra: Continuous learning to me and my community really means listening to the voices that are often seldom heard. It means trusting and placing trust in the community to be a part of or lead or be involved in research, changes that affect our community. It also means actively and proactively working to rebuild that trust, because there's been a lack of trust from the community, and that means transparency. It also means honesty, and it also means continuous involvement as well. There's no point in involving us at the end of a study for our feedback, but at the very start to show that you are trying to be authentic.  Rebecca: Ultimately, genomics is the science of people. Genomics is people, so we have to keep talking to the very people that we are looking to try and support, help, care for, and ultimately impact them and their families as well. So, I completely agree with Sandra, continuous learning, it's a continuous dialogue, and understanding how our opinions differ, how our opinions may shape and grow as the general conversation about genomics continues as well in the public discourse. So, we have to understand and we have to stay sort of on our feet, that this is a dynamic conversation, therefore we need to change and we need to remain flexible as well. And if we keep our ears open and if we keep our minds open, then we will continue to build that trust, and we will continue to ensure that we have a robust study that will ultimately fulfil its research aims. Öznur: Thank you. And Mathilde?  Mathilde: I think there's only so much that we could really cover in theory before we launched, and now, you know, it's going to go out into the world, and there's many things that we couldn't have predicted that will happen. We have that humility to understand that. And what's super important going forward is that we have a team there to keep kind of staying on our toes, listening to what's happening, to make sure that we respond to that, so that, as Sandra said, it's not enough to just ask people afterwards. It's also not enough to engage just at the beginning and then stop listening once we're live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn't considered before we launched, and just continue to learn. Oznur: We will wrap up there. Thank you to our guests, Rebecca Middleton, Sandra Igwe and Mathilde Leblonde for joining me today as we discussed the use of design research in the Generation Study. If you'd like to hear more episodes like this, please subscribe to Behind the Genes on your favourite podcast app. I've been your host, Öznur Özkurt. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.

Digital consent models, language barriers, and cultural differences are just a few factors that can exclude people from participating in genomic research. In this episode, our guests discuss these issues, and explore alternative methods such as in-person discussions and the use of trusted community figures to engage with their communities to increase awareness of genomic research. They also highlight the importance of communicating consent in ways that respect cultural dynamics, such as family involvement in decision-making. Our host, Naimah Callachand is joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager at Southall Community Alliance and Trupti Patel, Policy Manager at Genomics England.   "I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community"   You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/How-can-we-ensure-equitable-access-to-genomic-medicine.docx   Niharika: People are usually comfortable giving their data when they feel that there is transparency from the data collector, they're being completely transparent, they come with you with clear benefits, how it's going to benefit the community.  And you are equally sort of agent of your own data and you feel involved in the research and you feel that you have power to give out your data and have control over the journey of that research. Naimah: My name is Naimah Callachand, and I'm the Head of Product Engagement and Growth at Genomics England. On today's episode, I'm joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager for Southall Community Alliance, and Trupti Patel, Policy Manager at Genomics England.  Today, we're going to be discussing some of the ethical, legal and social implications of genomics research for diverse communities, and how we might overcome them to address the challenge of diverse communities health needs.  If you enjoy today's episode, we'd love your support, please like, share and rate us on wherever you listen to your podcasts.  First of all, I'm going to ask each of our guests to briefly introduce themselves. Maili: I'm Maili Raven-Adams, I lead on work at the Nuffield Council on Bioethics to do with genomics.  This has predominantly been looking at how to develop a best practice approach for genomics, and looking at the ethical implications of AI and genomics when they're used together in healthcare.  Before here, I worked at the Global Alliance for Genomics and Health, where I developed policies related to diversity in datasets and genomic discrimination, so I have a particular interest in this area. Naimah: Niharika, can we come to you? Niharika: Hello, everyone, I'm Niharika Batra, I'm the Community Projects Manager at Southall Community Alliance.  We are a charity based in Southall.  Prior to joining the charity, I was working as a Youth Community Engagement Assistant in United Nations Development Programme in India, and I have a background in gender and development.  I also bring with me lived experience of being a South Asian immigrant woman, and I'm really passionate about working with the immigrant communities in the UK. Naimah: It's lovely to have you.  And Trupti, can we come to you? Trupti: Hi, I'm Trupti Patel, I'm a Policy Manager at Genomics England.  I work primarily within the diverse data initiative and I lead the equity in health research workstream.  My background is in responsible research and innovation, as well as co-production, and more ethical ways in which members of the public can shape the direction of scientific advancements. Naimah: So, first of all, Trupti, can we talk about the challenges around equity in data, and what this means for diverse groups in the context of genomics? Trupti: Yes, as I mentioned, I lead the equity in health research workstream.  Now we talk very specifically about equity in health data.  As Genomics England, we are a biobank, and we hold health data on individuals who have consented to be a part of genomic research. When we talk about equity, primarily we're talking about those of non-European ancestry, and there are very specific reasons as to why that is.  So firstly, there's a wider issue about representativeness within health datasets more widely.  We know that across all health data sets that are located within Global North countries, the data held within them tends to not be representative of their populations. And what I mean by that is that they tend to overrepresent those of European ancestry, and underrepresent anyone who is not of European ancestry.  The consequences of this is that healthcare innovation might stand to leave these population groups behind. One of the other reasons that we talk about equity specifically, as opposed to things like equality, is that we're also aware that if we look at research on a global level, the majority of research funding is given out through grant bodies located in Global North countries.  So we already know that research portfolios can actually be quite skewed towards population groups who live in those countries themselves.  We know that there's a lack of financial investment as well within developing economies.  So it's natural to assume that health innovation projects which address the needs of these communities are more likely to be conducted by researchers who are based in developing economies.  However, their access to funding is very limited, and on top of that they tend to have much smaller life sciences sectors, so their access for private funding, as well as opportunities to collaborate with industry can actually be quite limited in itself as well. Another reason that we care about equity is that we actually know that there are some sub-populations that are very diverse within themselves.  So a good example is the genetic diversity of Africa as a whole is much larger than those who live outside of Africa itself.  And for that reason there tends to be a focus on actually oversampling from people who are of these ancestries.  And another example being South East Asians as well.  The final challenge when it comes to equity is that we also know that there has to be a need for medical innovation for these population groups, and a desire for people to actually buy this type of innovation.  So there's a need for demand for these therapies and medications.  Now if we already know that developing economies might be less likely to be able to afford these medications, then the demand will always be lower for these population groups.  And therefore the demand for innovation might also be lower population groups.  But as a country, because we would want to make sure that we're able to provide medication to everyone equally, we need to take an equitable approach. So one thing about the lack of diversity within datasets actually means that we can't always accurately predict whether or not someone does or doesn't have a condition.  So we're still at the stage where accuracy is not as good for these population groups as it is for others, and it leads to things that we call false positives and false negatives.  So where we think that someone does or doesn't have a condition, and in fact, they might or they might now.  The incidence rates of that happening for anyone of non-European ancestry are higher.  That's one of the tensions that we're playing with at the moment, especially when it comes to providing genomic healthcare via a healthcare service.  Understanding people's cultural background and nuances I think is really important.  For example, a lot of those cultural practices can actually play into whether or not someone decides to receive or not receive a form of healthcare.  And it's also important to understand things like timing, so the decision around whether or not someone decides whether or not they're going to take a preventative medication might be based upon cultural timings around things like giving birth or something. Naimah: How can we ensure equitable access to genomic medicine for all of these communities? Maili: So I think we need to understand that there are several understandable reasons that people might not have been involved in genomic research to date.  Efforts have been made to engage with different communities, but this has sort of been piecemeal and we need to see how that engagement can feed into research practices. So that people feel as if their information that they've given has been taken on board, and that those research practices have been co-developed, and they feel more willing to engage so that that representation can increase.  There's also been examples where research has been actively untrustworthy in the past.  You know, there's well known stories of Henrietta Lacks, whose cancer cells were taken without her consent, and then used to develop research.  And there's different examples across the globe that kind of mirror that sort of exploitation.  So we kind of need to take note of these, and understand why people aren't there, and then allow that to inform engagement practices.  So that research practice can change over time and be more inclusive and encourage people to get involved and give good reason for them to get involved in that. Niharika: Also, to add on to what Trupti and Maili mentioned.  First of all, why this data gap exists, why is there inequity in genomic data?  It's because historically South Asian communities or the marginalised communities have been used to extract a lot of data, be it social research or medicine research.  So when a researcher approached them or a data collector approaches them, they feel that they're just going to collect the data and there will be no feedback process, or it might not benefit the community.  The communities do not understand what the clear benefits of these researches are.  And in terms of genomics, when we talk about medicine research, historically these communities have been exploited.  There has been information asymmetry, and we have observed a case in 1960s where in Coventry Punjabi women, or South Asian women, were given radioactive rotis, and they weren't even aware what they were consuming.  And it was in the name of research.  So there's always this hesitancy when it comes to medicine research. One way to tackle the problem of the data gap in genomic research is by co-production . So when you're approaching the communities, it sort of helps who is collecting the data, there is no skewed power dynamic involved.  People are usually comfortable giving their data when they feel that there is transparency from the data collector, they are being completely transparent, they come with you with clear benefits, how it's going to benefit the community.  And you are equally sort of agent of your own data, and you feel involved in the research, and you feel that you have power to give out your data and have control over the journey of that research. So it is also important how you frame the message when you're collecting the data.  In our communities, the idea of sevā or Kismet is very embedded in the communities, which mean either giving out your services or your time for the benefit of the communities.  So it's not just donation, but it's just spending more time or just working with the communities for a common or a collective benefit.  So when the message is framed in such a manner that you are doing a sevā or you are helping your communities bridge the health inequalities and there might be a collective benefit for the communities, people are more motivated to give their data.  But when the word donating data is used, then it puts a sort of emotional burden on the participant.  So it all depends on the messaging, how you frame your messages when you're collecting the data, and it's important to be cognisant of the cultural sort of ideas.  And this is something that can be used with South Asian communities, sevā and giving back to the communities. Maili: I was just going to say, I completely agree with that, like 100%, it's really important as well that the global majority don't feel pressurised into giving that data because of the language that's being used.  You know, the global majority are not represented in these datasets, so it could be that the language used might put pressure on people to donate that data to fill that gap, but that's not the right language.  I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community, so it just wanted to say that.  And also, it's important when we're using language like genetic ancestry that those aren't conflated with things like race or ethnicity, which are social uses of that language.  So I think this is just another area where it is really important to think about language and work with communities, to figure out what the right language to use it, and understand the benefits of using certain types of language. Naimah: And it just kind of highlights how many different nuances there is, and areas that need to be considered. Maili: Yes, I was just going to say, within that, we need to think about barriers to participation as well that might affect certain communities.  You know, there might be some language barriers, to making sure that we've got translators, or there's investment in making sure that the resources are there to make the engagement and also the research accessible to people.  There's things like people have lives, they have childcare, they have jobs, so making sure that they can donate data if they want to, at times that work for them and environments that work for them.  And things like transport costs and that sort of thing might be covered by a research organisation, so that people are empowered to get involved, and there's not too many barriers to become involved if they want to be.  I think that's really important to address as well. Naimah: Trupti, did you have something to add? Trupti: Yes, I was just going to say, I think it was really interesting that Niharika actually framed the benefit around community benefit.  Because within the policy sphere, and actually even within wider conversations on data and health, people use frame benefit in terms of patient benefit specifically.  And what we find is that when we engage with diverse communities, most of their concerns around harms are actually not harms necessarily to themselves specifically, but harms around their whole community.  And I do wonder whether there needs to be a slight reframing in how we talk about benefit when it comes to genomics in particular.  Because most people when they donate their data they know that it has consequences for those who are related to them. Naimah: So I wanted to talk about research governance as well.  And in the context of history of medical racism, with medical innovation now heading towards personalised healthcare, what are they key considerations we should have when it comes to rules around access to data? Trupti: So, I mean, one of the rules that we have within our biobank, when it comes to access to data, is that we don't want it to lead to any discrimination, and we won't allow access for things, for research projects, that do lead to discrimination.  However, we already know that there are lots of unintended consequences when it comes to research in general.  And when it comes to medical research in particular, and thinking about genomics in particular, lots of communities are aware that because in the past there has been a lot of research outputs have been used in ways that actually don't benefit these communities, and actually have negative consequences for these community groups, it means that the barrier to encourage people to take part is actually quite high.  When it comes to genomics in particular, obviously there's been a history of eugenics, and at the moment, that's quite a big area that lots of universities, especially in the UK, are going through eugenics inquiries.  It has effects upon people's perceptions of genomics as an area, and whether or not people can be confident that those types of research won't be repeated, and the types of research that will happen will actually benefit them. I mean, there's a good example that one of the community members gave, not directly to do with genomics, but actually they knew that if you're first name is Mohammed, your car insurance is actually much higher, your premiums are much higher.  And so they were concerned that if you were grouping people within genomic ancestries, or genetic ancestries, what consequences that has for them can be quite nuanced in the first instance.  But in the long-term it would actually mean that people might be grouped within these ancestries and policies and things that are created as a consequence were quite concerning for them. Naimah: And Maili, I wonder if you could tell me how people might feel more comfortable in the ways in which their data is being used? Maili: I guess if there's transparent governance mechanisms in place and they can understand how their data is being protected, you know, that goes right through data access committees.  There's one at Genomics England that as Trupti said reviews data.  So if they can understand what sorts of considerations that committee are thinking about in respect to genetic discrimination, and they can understand that certain considerations have been taken into account when their data is being used, that's one thing.  Another could be through consent processes.  So there's different sorts of consent models that could be explored with communities to figure out which one they'd be more comfortable with.  So broad consent I think is the one that's used at Genomics England at the moment.  So that means that people give their consent once, and then that data can kind of be used for a broad range of purposes.  But it's not always clear to people what those purposes are, or where that might be used over time. So there's different sorts of mechanisms that could be explored, like dynamic consent, where people are updated over time about what their data is being used for, and they can either opt out or opt in to those research practices.  Or forms like things like granular consent, where when people give their consent there's different options of people that they'd be happy for their data to be shared with.  So we know that people are less trusting of private companies, for example, so people might be able to say, “Yes, my data can be shared with nonprofit organisations or research organisations affiliated with universities or the government, but I don't want my data to be shared with private companies.”  And that might make people feel more comfortable in donating their data, because they might feel like they have some more control over where that is ending up.  And I think transparency there is really important, so people can understand when they give their data or they donate their data, they can understand what benefit might be coming from that.  And that might encourage people to get involved as well. Trupti: I was just going to add to that comment about dynamic consent.  So actually an interesting thing that Niharika mentioned earlier was this feeling that the people that we engage with actually really wanted a sense of control over their own data still.  Obviously when you give broad consent, your giving your consent, as Maili said, to a wide range of research that will happen or can happen in the future.  But interestingly, dynamic consent, I think culturally it is really valuable for some population groups, partly because it fits in very nicely with the idea that your biological data is actually a part of who you are. And that cultural philosophy can still exist within a lot of these communities that we're engaging with and a lot of these communities that we're trying to encourage to actually provide us with data.  Do you ever think that there could be like a medium position, where it was actually dynamic withdrawal? Maili: Yes, I guess that is something that could be explored, and I think that's one of the models that sometimes is talked about in academia or in these sorts of forums.  I think if people were dynamically kind of withdrawing, it might be interesting to understand why they're withdrawing and their reasons for that, so that research practice can change and take account of why people maybe no longer want to get involved in a certain type of research.  And I know that's something that you've spoken about in your community engagement groups. Naimah: Niharika, do you have something you want to add? Niharika: Yes, so when we were engaging with our communities, we primarily engaged with Hindi speaking people from Indian origin, Punjabi speaking people from Indian origin, and Urdu speaking people from Indian origin, and we spoke to them about genomic research.  We also spoke to them about the branches of genomic research and how their data could be used.  So while their data could be used for innovation in pharmacogenomics, which seemed to be more palatable for the people as this is an extension for treatments they've already been using.  For example, treatment for a chronic condition like hypertension or diabetes.  Whereas they were quite reluctant when it came to their data being used for gene editing.  So in Hindu religion, humans are considered the creation of Brahma, who is one of our main Gods.  And similarly in Islam, humans are called (Islamic term), which means God's greatest creation.  So when it comes to gene editing, some people believe that it means you are playing God, it means that you're tampering with the DNA, you're tampering with God's creation.  So they were really reluctant in providing their data for an innovation that entails gene editing or genetic screening or gene therapy. And when it comes to consent, I know Genomics England takes a broad consent, and there's scope of dynamic consent.  Where people are constantly engaged on where their data is being used, how their data is being used, which innovation their data is being used for, which research their data is being used for.  And they have an opportunity to withdraw their data if they're uncomfortable with any aspect of research. Maili: I was just going to say something else about consent models.  When we're thinking about different forms of consent, like dynamic consent, it's also important to consider the accessibility of those, lots of those models would rely on the internet and people having access to laptops or phones.  And so when we're exploring those models, we need to make sure that people have access, and if they don't have access that there's other ways that that sort of consent model might be able to be replicated, or there is an alternative way, so that people aren't excluded through that. Naimah: Is there a question around language barriers as well with the consent models? Maili: Yes, when verbal consent is taking place, the same problems of language barriers are there within the online version.  You know, how do you make sure that things that are translated, and translated well as well?  Because genomics is a complicated area with lots of jargon and complex language.  So how can we make sure that we translate that language in a way that's done, where the meaning is kind of translated as well. Trupti: The language thing was something that came up within some of our community workshops.  And I think one of the things that really came out was that genomics research itself has so much technical language that often you simply cannot translate the word into other languages.  And different ways in which you can convey information, so that you're still making sure that you're getting informed consent from participants I think is really important for these groups, beyond simply translating written material.  Whether that's through analogies or visuals that convey information, I think that's quite an underexplored area actually, within research more generally, but as a starting point genomics. Naimah: And did any of those community groups identify any preferences for what way they wanted to be communicated with, for consent and things like that? Trupti: I mean, certainly having online consent was a huge barrier.  So the idea that you log into a platform online in order to provide your consent to something wasn't something that people were that comfortable with.  Especially since these participants are often very reluctant to take part in the first place, so you're almost creating a barrier to them as well, it's an extra thing that they have to do.  They did feel that consent should really be in person.  They also preferred the idea of being able to discuss genomics widely within less formal settings, so outside of healthcare settings, or outside of research settings.  Because it meant that they felt that they were primed for the questions that they might have. One of the things that I was going to add is actually for genomics in particular, I mean, I mentioned before about when people decide whether or not they would like to consent to take part in genomic research..  They feel like they're not just consenting for themselves, they're also consenting for people within their network.  And so these are people that they would consult probably as to whether or not they should or shouldn't take part.  And so when you are making that decision and you're having those consenting conversations, whether that be within a research setting or a healthcare setting, it's important I think for people to understand that those decisions have been taken not just by an individual, they are actually reaching out to a much wider range of people within their own communities. Naimah: And is there something around that these decisions are often made with family members as well? Trupti: Yes.  So in situations where there are people from some cultures who are much more likely to take part in cousin marriages, these particular populations have scientifically been shown to have much higher likelihood to develop genetic conditions.  Now if that is the case, that can lead to a lot of stigmatisation, and it can proliferate a lot of discrimination that these population groups might be facing already.  So I think that's something to be considerate of.  And it might influence their decision making as to whether or not they or their family members should or shouldn't take part. Niharika: Yes, just to add onto what Trupti and Maili actually said, while language plays a very important role in terms of consent, how consent is being taken, it also depends on the setting.  In our areas where we engage with communities, usually the consent, or consent regarding medical research or genomic research is taken via the GPs.  And the GP services here in our areas are so overwhelmed at the moment, there are long waiting lists, like three months.  And when people actually get through the waiting list and go to their GP, they're so done with the process of waiting that when their GPs ask them for consent, they just either feel that they need to succumb to the pressure of, okay, giving the consent.  Because there's this skewed power dynamic over them as their white man or white doctor asking for the consent.  But also, they don't know what exactly to do in that moment, they're very frustrating from the long waiting line.  And they feel they're okay, they might need a little time to sort of cool down, go back home, look at the consent form, what is it about?      And in South Asian settings usually the decision making is done in family setting, where you consult your families.  And when we spoke to older South Asian women and asked them how would they give their data and why would they give data, they mentioned that they would give data because their children or husbands have advised them to do so.  So yes, it's important to see the setting of where the consent is being taken, who is taking the consent, and if they have enough time to think about it and go back and give their consent.  Also, it came up during the workshops that it helps if the consent is being taken by someone the communities already trust.  So having accredited community champions seek the consent.  So once they're trained, once they have enough knowledge about genomic research and how it can benefit their communities, they're able to better bridge the gap between the researchers or the research organisations and the communities.    Maili: Yes, I completely agree.  And I was just going to add that it's important that healthcare professionals are properly informed and open and aware of those different cultural or contextual dynamics within those consenting conversations.  So that they can properly listen and understand where people are coming from and give that time.  And I get that that's difficult in pressurised situations, where healthcare professionals are under a lot of time pressure.  But that needs to really be built into that healthcare professional training over time so that carries on and people can talk about genomics in a really accessible way.  And that carries through as well to genetic counsellors who give results to families, they need to be able to do that in the right sort of way.  And they need to ask the right questions and understand the patient that they're talking with so that that information can be translated or got across in the best possible way.      And that's even more important I think where there is a lack of diverse data that's informing research and informing healthcare outcomes.  I think healthcare professionals should be transparent with patients about some of the accuracy of certain things or how different results might mean different things for different people.  And it's really important that those conversations are had very openly and for that to happen, healthcare professionals also need to get the training to be able to do that.    Naimah: Okay.  So we're going to move on to talk a bit about developing countries.  Niharika, I wanted to come to you for this question.  Why would diverse communities benefit from research being more collaborative with developing countries?    Niharika: So in recent times, we have witnessed growing diaspora in the UK.  And when it comes to collaboration with developing countries, there's increased collaboration with these developing countries.  It can be a win-win situation for both the countries, for example, there can be increased innovation for these developing countries in exchange of information.  And at the same time, people in the developing countries, if they provide their data, they have the sense that they are helping their own communities who are living abroad.    Naimah: You've touched on a few points already, but, Trupti, I wonder if you could talk about the considerations we should have when considering international partnerships?    Trupti: Yes.  So one of the things that Genomics England has tried to do in the past and is still trying to do is increase the number of international academics that can have access to our biobank.  Now we already know that internationally, especially in developing economies, there's often a lack of data purely because the resource to do things like whole genome sequencing is so expensive.  The resource to even have or host a biobank itself is so costly that the barrier to even developing the infrastructure is so high.  So one way that we're looking to encourage innovation within those settings is actually to allow access through particular partnership agreements to academics who are based abroad.  Now obviously that means that there's a benefit for them in terms of being able to do the research in the first place.  But one of the things is that as a biobank we're also known for being a very highly secure biobank, compared to others.  So that's something that as a data store people actually highly respect, and in particular, a lot of the data regulation within the UK is highly respected by other countries.      One of the things that we have seen happening recently is that essentially some of our data security laws and data protection regulations are being reproduced in other countries as a way to ease working with research datasets across geographic political boundaries.  When it came to engaging members of local primary communities they have three primary asks when it came to the international partnerships that we might be developing in the future.  One of them was that at the very least there would be tiered pricing.  If we ever came to a situation where we were charging for access to our data, that pricing should be tiered to address the fact that if you are someone based in a developing economy, your access to financial resource to do research is much lower.      The second ask was that there'd be some way for us to foster collaborations.  Now, whether that be led by an academic who is based abroad or an academic based in the UK was up for debate.  It was more that those collaborations have to continue and have to be enabled in some capacity.  And then the third thing that was a big ask was actually around IP sharing.  So what happens to the financial benefits of doing this type of research?  And also, more equitable basically knowledge sharing across these regions was what was asked.  So what we're looking at in the near future is whether or not these principles could be used in order to guide some of our international partnerships' work.    Naimah: And I think just on that point you raised about fostering collaborations, Maili, I wonder if you could comment on how we could foster collaborations between the researchers and the communities that they serve?    Maili: Yes.  I think here is when engagement is really important, and we need to get researchers and communities speaking to each other, to have some sort of meaningful dialogue that doesn't just happen once but is embedded into whole research practices.  So there's many different opportunities to feed in and that practice is shaped based on the feedback the researchers receive.  I think engagement is a really amazing thing, but it does need to be done well, and there needs to be clear outcomes from that engagement.  So people need to feel that the information that they're giving and the time that they're giving is respected, and that those practices do change as a result of that.  So I think we really need to make sure that engagement and practices are done well.  And I was just going to say something on collaboration between different researchers.  When researches are happening across borders, it's really important that that's done in a really equitable way, and that those conversations are had between different researchers to figure out what's going to work well.      We need to avoid instances of things like helicopter science, and sometimes it's called other things.  Where researchers for example from the UK would go into a developing country and undertake research and then leave, taking all the benefits with them and not sharing them.  And that's something that we really need to avoid, especially in the UK, we don't want to exacerbate colonial pasts.  And I think it's really important in this context that those benefits are shared with communities.  And again, we can do that through engagement and understanding that relationship and making sure that collaboration really is collaboration, and that we can provide things that maybe others need or want in the right sort of way.    Niharika: Just to reiterate our communities are still haunted by the colonial pasts.  There's always this constant fear that our data might be misused, there might be data breaches and we won't be protected.  And your DNA data contains a lot of personal information, so there's constant anxiety around your DNA or genetic data.  So it's important that the researchers maintain utmost transparency.  There's a constant focus on flattening the hierarchies, where you sort of bridge the power gap between the researchers and the communities.  And it can be done through, again, as I mentioned before, having community champions on board who understand the communities better, who are constantly in touch with the communities.  And they provide that sort of semi-formal settings, where they know that where they're in constant touch with the authorities or the GPs or NHS, but also at the same time have very good relationship with the communities.  So this is something that should be taken into consideration.  And then just be cognisant of the cultural values, and not have very imperial ideas when you sort of approach communities.    Maili: I think this becomes even more important as genomics continues to evolve and new genomic techniques are developing.  For example, with things like polygenic scores, where we can look at people's genomic data and predict how susceptible someone might be to developing a certain disease or trait or outcome, in relation to the rest of the population.  Those are developing, and people are interested in them, but the data that they're based off again is that European genetic ancestry data, and therefore is not accurate or applicable to lots of communities.  And it's not just genes that we need to be aware of, it's people's environments, and that data is really important to integrate with things like polygenic scores.  I think we need to really address these issues now and make sure that as genomics develops that these things aren't perpetuated and existing health inequalities aren't continued to be exacerbated.    Naimah: Okay, we'll wrap up there.  Thank you to our guests, Maili Raven-Adams, Niharika Batra and Trupti Patel, for joining me today as we discussed the ethical, legal and social implications of genomics research for diverse communities.  If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I've been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

For Sickle Cell Awareness Month, our sickle cell Patient Voice Group discuss their lived experiences with sickle cell, shedding light on how organisations need to be considerate when engaging with patients. They emphasise the need for genuine engagement and transparency from researchers, while highlighting the importance of building trust within communities that have historically been overlooked. The discussion looks to the future, advocating for more personalised support, better treatment options and a stronger focus on the diverse experiences of those affected by sickle cell. Marie Nugent, Community Manager for the Genomics England Diverse Data Initiative co-hosts this episode with Natasha Gordon-Douglas, sickle cell patient advocate for the Genomics England Diverse Data Initiative and Lead Mentor at the Sickle Cell Society. They are joined by Oleander Agbetu, who cares for her son with sickle cell, and is also a member of the Solace sickle cell and thalassaemia support group board, and Jayson Kupoluyi, sickle cell advocate and volunteer for the Sickle Cell Society. The episode also features insights from some of the other members of the Patient Voice Group; Hazel Attua, Samuel Chuku and Zainab Garba-Sani. The Patient Voice Group are a group of people affected by sickle cell who share with Genomics England their expertise, based on their lived experience, to inform our sickle cell programme within the Diverse Data Initiative.   "If we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone's care, that's what I want to do. That's why I'm here."   You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/How-can-organisations-support-those-living-with-sickle-cell-1.docx  Marie: Welcome to Behind the Genes.  Natasha: I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient's voice in order to make things better, and not just be in a room where you've got all board members that think, “Okay, this is what is good for the patient.” No, actually, they've got the patients there to help support that voice, and saying, “Well actually, this is the reality,” rather than what you think might be the reality.  Marie: My name is Marie Nugent and I'm the community manager for diverse data at Genomics England. I'll be co-hosting today's special patient takeover episode of Behind the Genes with Natasha Gordon-Douglas, who is a member of our sickle cell patient voice group. On this episode, we're going to be speaking to two people who are also part of our patient voice group, Oleander Agbetu and Jayson Kupoluyi. Today we'll be discussing what it's like to live with sickle cell, and how organisations who wish to engage with patients need to be considerate of what is going on in people's lives, and what good advocacy and support for patients who want to be involved in research looks like. If you enjoy today's episode, we would love your support. Please like and share, and rate us on wherever you listen to your podcasts.  Welcome everyone, thank you very much for your time today to talk about the patient involvement and engagement work we've been doing as part of our sickle cell and genomics programme at Genomics England. My name's Marie, I'm the community manager for the diverse data initiative, and I am really involved in doing the sickle cell engagement work. I'm going to pass straight to Natasha now, who's going to be my lovely co-host for this podcast. So, over to you, Natasha.  Natasha: Thank you, Marie. I'm Natasha. I would say my background is nothing to do with the medical side. My background is in marketing and the corporate world. That's how actually I got introduced by John James, because I actually got him into our workplace to do a podcast about sickle cell. So, you know, just – I'm working in an environment, which obviously – it's about people understanding about my illness, so I actually got him in speaking, and then he mentioned about a project, “Oh, you might be interested in this.” So, that was kind of the introduction I got from John James. But as I said, doing patient work and engagement stuff was completely new to me, so this is my – I'm a rookie, I should say. But I feel like now after the two years, I know now, I understand [laughter]. But yeah, that's kind of a quick background. And how I got introduced to Marie is from John James at the Sickle Cell Society.  Marie: Great, thank you, Natasha. So, coming straight to you now, Oleander, I think it's a bit different for you. So, you joined this particular group not too long ago, but from what I know, you've been doing this kind of advocacy work and engagement work for quite a while. So, tell us a bit about yourself.  Oleander: Well, I'm a parent/carer of a teenager, young man with sickle cell, and I think I've been part of the Solace sickle cell and thalassaemia support group board for more than ten years now. And what we do is we support patients through our WhatsApp group, as well as through inviting different people to come and talk. We've had doctors, nurses, etc. And I have supported people who have called me personally to ask me questions, from advice, for help. Also written a letter to the hospital, which we are now working on with the hospital itself, to try and get things moving and make improvements for the patients who are actually patients there at Homerton Hospital and Royal London Hospital.  Marie: And then over to you, Jayson. So, similar to Oleander, you joined this group fairly recently actually, but just tell us a little bit about the kind of work that you've done before.  Jayson: My name's Jayson Kupoluyi. My background is totally different from the sickle cell background. Because of the plight that I have with my health, I now decided that I wanted to make a change, so I – unbeknown to me – I didn't know what advocacy was. I just – when I meet people, I ask them questions, and, you know, thankfully enough, they really try and help and support in terms of advising me and those kind of things. So, I took that advice on board, and through the years I've met fantastic people, i.e. Oleander and her son. I met her son during a trip – we took the kids to a trip for a week for self-discovery, self-awareness, teaching them how to cope, and probably to see where – you know, try to make them open up.  So, I now decided to volunteer for the Sickle Cell Society and give them seven years of my time, in which I've met fantastic kids and fantastic people. And through that, I've learnt to be able to teach people and the kids under 16 – well, I'm teaching from 26 year olds down to 13 year olds on how to advocate for themselves in hospital now. I teach the adults how to fill in application forms for PIP. I also write complaint letters and help them deal with complaints. And I also – sometimes I have the chance, from Royal London and Queen's Hospital, to enter and view the situation, and ask information from the patients, from the nurses, carers and things like that, to be able to compile my own findings. And all in all, it's been rewarding, because I just wanted to give back.  Marie: That's incredible, you know, because something that we've been talking about more recently as part of our sickle cell patient voice group is this idea of advocacy, and I'm just reminded that I'm with a great group of people to actually explore this because of the experience that you've got, so this is wonderful. Now, you've all just said you've got varying like degrees of previous experience of being part of advocacy work. Natasha, I'll come straight to you, what were your initial expectations as to what it would mean or look like to be part of like a patient voice group?   Natasha: To be honest, very sceptical [laughter]. I was like, “What are they really going to – are they really going to take our voice on board, and is it just another tick box that they could say, “Okay, we've funded a group for you to – with sickle cell,”” and I was very, yeah, sceptical. But actually I would now advocate for everybody to be part of a patient voice group. I think it's so important. And the collaboration that happens with all these different organisations as well that you open up your mind to – ‘cos I didn't know – you know, especially for this particular project that we're working on, you've got the James Lind Alliance, never knew this organisation existed. I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient's voice in order to make things better, and not just be in a room where you've got all board members that think, “Okay, this is what is good for the patient.” No, actually they've got the patients there to help support that voice and saying, “Well actually, this is the reality, rather than what you think might be the reality.”  So yeah, I would definitely champion anybody regardless, even – yeah, you've got sickle cell, of course, but any kind of illness, if there's any kind of projects, trying to get involved, to really be able to try and shape what can happen. Because, you know, I guess what we're working on at the moment, the opportunities for development within sickle cell are endless. And yeah, it's just being part of that steering group, part of that voice to actually make change, especially with sickle cell. You know, it's one of the ones that has never had anything – hasn't had change for I don't know how many years - I'm going to give away my age, for at least 40-odd years, I'll say [laughter]. But yeah, so from what I can see, it's slowly now changing and we're in that wave, and I'm so excited to be part of that.  I know Oleander, so you with your son, you've obviously seen the kind of – if there has been change for you. I guess for me as a patient, I might see it slightly differently, whereas you as a carer, a parent, you might see it completely differently. So I guess for you, what would you say for a person who might be considering joining a patient group or a parent/carer group?  Oleander: I too was sceptical at first, but at the same time I can say that I'm really happy that I have been involved, because it means that all the information that I find out about that might be relevant to other parent/carers, I can pass that on, and vice versa. Any questions that they might have or issues that they might be going through, I can also get those considered. And I just think that it can be quite sad when a patient goes into hospital and they are on their own, they don't have anyone with them. And so for me, for example, when my son was in paediatrics, and I'm sure the two of you would also know that, the treatment is just very different to when you become an adult. I could see from my son's face, he just was not impressed with the adult care at all. And he more or less says, “Mummy, I'm not coming back to hospital unless it's really like a dire situation. I just don't want to go back.” And that's quite sad because really we're supposed to be able to support our loved ones in hospital. When they need the care, they absolutely need the care.  I actually spoke to a parent today of a young man in hospital right now. His PCA was failing, which is, you know, the pump that gives the medication, right? And they actually asked her, “Is he still in pain?” If he's been put on a PCA, how can you ask that question? So, you know, it's so good that she was there to advocate on his behalf. He couldn't even talk. And, you know, I know for my son also, when he's in really, really deep pain, he stops talking, just doesn't talk. And if he's there by himself, it's a real issue. And so, you know, I think from that point of view, all of these kinds of stories are really important to bring to forums like this, so that people can understand that of course, yes, it first affects the actual patient themselves, but it has a knock-on effect for the families, and the carers and the people that are involved with that person's care. So, if we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone's care, that's what I want to do. That's why I'm here.  Marie: Thank you so much, Oleander. I think that's a really powerful story as well, and it just shows so – I couldn't help but think, as you were talking there, about this idea of – we use the word community quite a lot in this kind of engagement space, but I must admit, you know, I've been working in public engagement with health and research for well over ten years, and I must say that I really felt the sense of community in this sickle cell space, particularly with patients and the wider sort of community, and that feels like it's a really important part actually. And it kind of speaks to what Jayson mentioned about, you know, he's now reached this point in his own life where he wants to be actively kind of contributing back to the community. So, I'll come to you now, Jayson. Again, what was your expectations about joining a group like this, and what were you thinking when you joined? And how has that maybe transformed now? Or potentially not? How has your experience been so far?  Jayson: It's been great actually, pleasant people, likeminded people working towards a common goal. When I first heard about this group, I said to myself, “Do I have space for another WhatsApp group?” It's not because I don't have space on the phone. It's because getting calls in the middle of the night at the same time – and you can't turn it down sometimes, especially if it's in the family, ‘cos I have these people – I have - you know, it's in our family and it's very, very rampant. And when you say community, you can have a mother of your nephew, your niece call you, knowing fully well that you've gone through that, this sort of thing, what's going on, blah-blah-blah, “Okay, this is what you need to do. This is what you need to do.” Then getting to the hospital is another ballgame, do you understand? And you just have to say, “Okay, you know what, if I take a moment of my time and say, “I'll see you in the morning…”” I've had two incidents that I didn't make it, and it's a guilt trip to me, because I was thinking, “Hold on, if I had gone…” And then I was okay – if I wasn't feeling okay then, yeah, but I was okay. I was just tired.   And when I started, I was a one-man band, and I realised the last 20 years that it's definitely not going to work, hence the community comes in. And the time I tapped into this community, I met people – “Okay, so, you could help me out, you could help me out, you could help me out.” And the more I meet people, the more my voice goes bigger, louder and reaches more people that I want to reach. So, when I first met Hazel, she was in pain, so I called her and I was like, “Madam, you don't know me, but I know that you're in pain, are you okay?” And she goes, “No, I just wanted to sit down.” I just sat down beside her, didn't speak to her, just sat down, and she didn't utter a word, but she came to a conference and I'm thinking, if you're in pain, you know, okay, I'm the same – I just started explaining myself to her, “I have this, I've gone through this,” blah-blah-blah, and she was looking at me and she was like, “You don't look like (inaudible 0:15:54).”   So, meeting and coming to this group, my expectation was a bit elevated actually because, when I was speaking to Hazel, she said, “No, Jay, seriously, you need to be in this group because we need the other…” And I was like, “Not another one,” and blah-blah-blah. Hazel said to me, “Can you join the Solace group?” I was like, “Who's in it?” She goes, “Oleander.” I was like, “Oleander's good.” And everybody keeps on calling me, and I do appreciate that people want my advice sometimes, but this health is very precious to us. I am looking forward to greater things with this group. I am looking forward for us to reach some targets, some funding, some people out there, to be able to change so many things. And any time I see a sickle cell person in good health, no pain, no nothing, I give myself thumbs up. You don't want to see anybody in that kind of pain, and people don't recognise or have that empathy to share or say, “Just another sickler.”  Sickler, that's a word, hmm, I don't like it. So, whenever I go to hospital, Queen's or Royal London, they know, “Jayson, are you here to cause problem?” “As long as you answer the question, I will be fine. As long as we're okay, I'll be fine.” And, you know, we're now friends. In the midst of adversity, we're now friends.    Marie: There is just so much I think in what you've just said, and I think that again something that I'm really struck by – so obviously, you know, I don't come from any lived experience. I didn't have people in my life that I knew that had sickle cell before starting to work on this as part of my job. And something that I'm really struck by is, first and foremost, from the No One's Listening Report, the quite staggering evidence that, as a community of people, people living with and affected in some way by sickle cell are very neglected, and there's all sorts of complex layers of like challenges and difficulties that people have to deal with, and it seems to come from all sorts of places and all sorts of kind of parts of life.  I was just really struck by this really daunting situation actually to be put in. As someone who's part of, you know, let's be honest, quite a sort of – maybe quite far down the road in terms of direct benefits, like piece of work – so we're here, I'm part of an organisation that is interested in supporting research and providing good quality research data, and research is a really important part of this whole system, but again it's something that maybe will take five, ten-plus years before you're seeing any direct benefit from in terms of the data that we're creating.   But something that I'm really struck by is this idea of, if we know that there's going to be maybe a bit of a delay in the kind of benefits that we can bring to patients through the data that we're generating, how can I try and build in as much benefit right now for the people that we're engaging with and we can bring into this work right now? And that's something that we've talked about and we're about to initiate a bit of a project around exploring a bit further, but I just wonder if I can now come to you all and get your thoughts on what can organisations like Genomics England or other research based organisations – what in your view does being a good supporter or a good advocate for people living with sickle cell – what could that look like from a research organisation in your view? I'll come to you first, Oleander.  Oleander: I think a really massive thing is to support the removal of barriers. There's so many people who would love to get involved with this, that and the other, but actually the barriers are there and the barriers are real. Even like from a personal point of view, the thing I was interested in attending, I can't. It's just not within my means. So, things like that are really important, because most people who are living with sickle cell, we are from marginalised groups. We're from groups that are not known to be flushed, and we need the support from – you know, if you really want our help in terms of research and so on, we absolutely need your support and your help to provide you with that research and that help. So, it's real. Giving someone a £20 voucher is nice and dandy, but actually if they've had to pay for whatever, accommodation or travel costs and all these things, they're out of pocket before they even start.  Marie: Yeah, this is something that we've been talking about recently, isn't it? I know that organisations like ours do want to do better, but sometimes there's just that not quite as good an understanding as to what these barriers really look like for people. Over to you, Natasha, what do you think about that?  Natasha: There's a couple of things I wanted to pick up on. One is definitely, yeah, the barriers. It's funny, I was at a hospital this morning and I was talking to one of the consultants. He asked me the question, which I thought was quite weird, but he asked me, “Why do you think that sickle cell patients have to pay for prescriptions?” Like that alone, prescriptions, we're on medication forever, you know, from the moment you're diagnosed, which for me was at six months, so in my entire life, and you're paying for prescription, that's going to keep happening over and over, and you're just – you know, there's people, because of their sickle cell, they can't work. There's, you know, barriers of not being able to work. And then you've got potential – you apply and say your disability, and sometimes that's not even taken on board either. So, you've just got these barriers in place that just make living day to day so exhausting, so tiring, and basically you're fighting those barriers at every – you think you've passed one, you've come onto another.  And I guess also the research side, which – it's funny because I would say, when it comes to research, it's fantastic, yes, that organisations like yourself are looking into it, but actually sometimes it's not even – you can't make the change where it's going to matter immediately. It's literally the frontline, you go into hospital and A&E, that's your first barrier is trying to just get some pain relief or get any treatment. You're sitting there for four hours. Four hours in pain for a person with sickle cell, that can really, you know, make things worse. And that's the kind of – you kind of want the immediacy – like the frontline, those kind of things to change. And of course, yes, we do want more research and we do want people to take part, but it's those things where you might not necessarily have the power to make those changes immediately that people will be willing to take part in research like this, because you can't even just get the treatment that you need from the moment you step into a hospital.  That's kind of what I was thinking of as you are speaking about this. I'm like, you know, yes, this is great, but we just need sometimes just going into hospital to make it easier. Like what Oleander said, it's unfortunate that the persons being asked about their PCA, if they're in pain – well, what do you think? Like that's just the basic [laughter], you know. It's kind of like, how can you ask that question and you're a healthcare professional being on the frontline? And that's the worst. It's the frontline staff sometimes which actually need the education. So, some of this research, it needs to go to education in these staff actually, you know. That's maybe an area that needs to be sorted.   Marie: For me, I completely have a whole new deeper appreciation for almost seeing people as the whole, how you work with the person. And it's never been clearer to me - as I say, you know, in ten-plus years' experience of doing this kind of work, it has never been clearer to me how important that is than now I work on sickle cell and how important that is. And I think that actually you've touched on a really important point there, which is that, you know, I know for sure that there's incredible work going on through NHS England, through the inequalities workstream and in response to the No One's Listening Report. There seems to be, you know, a huge increase in sort of focused action being taken to address a lot of these challenges that are being brought up in our conversation now.   But actually, what you said, Natasha, did kind of really hit the nail on the head a little bit for me, which is that actually we kind of still look at this as kind of separate organisations, like, “Well, this is my bit and that's your bit, so you stay over there.” And I think that something that we're trying to start working towards through the Sickle Cell Society is actually how do we bring together a better sort of alliance of work and of people who are across research and healthcare, because these things feed into each other, right? So, how can we do better to sort of show that we are all aligned, that there isn't just this one person or one group over here looking just at this little bit and then there's a completely separate group, that we are all actually united in our, you know, intentions here to really improve the lives of people that are living with this condition. But of course, there's just so much work to do, isn't there? I think that's another overwhelming thing, that everything needs to be better when it comes to sickle cell.  Oleander: The thing I wanted to just add to this whole talk about what researchers can do in terms of supporting advocates, etc. Two things, understand that there is an issue for trust from our communities, because we've been burnt. And the second one is, we need transparency. So, be real when you talk to people about the information you're gathering, what you're going to do with it, how it's going to impact the research, timetable of whatever's happening, all of those things which will help people to gain more trust.  Natasha: Yeah, Oleander, that's so – yeah, I think definitely, that's been echoed throughout this whole project, hasn't it? It's always about gaining that trust, because it is a case of, is this another where we're going to have support and we're going to be let down, or, you know, lied to, whatever you're going to find out. And trust is a huge part of that, definitely, yeah. I think, yeah, definitely. Thanks Oleander for saying that, it is.   Marie: Yeah, thank you all. So again just to say that I'm always blown away by just how generous you all are actually with what you say and with what you share, and with the messages that you're ultimately trying to get across. And it's very humbling, you know, to be able to work with you all, ‘cos you all are so incredibly passionate and driven, despite so many challenges, and it is nothing but inspiring. So, I can see absolutely why, you know, people living with sickle cell, for example, are called warriors, because you need to have that sort of fighting spirit to just keep going, and I have nothing but, you know, boundless like respect and admiration for people who are able to do that and contribute to the community in the ways that you all do.   And I just think that again, you know, so talking now back to this idea of how research is set up, you know, I myself am part of an initiative that's been, you know, initiated and only kind of guaranteed funding for this kind of iteration, for three years. It's very difficult to sort of initiate and establish really good long-term relationships, and have like a longer term strategic sort of way in which you're bringing in people and taking that long sort of like approach to building relationships, but it's something that I've tried to be really mindful of actually, and to address a lot of the things that you just mentioned.  You've heard us refer to other members of our patient voice group. Let's now take a moment to hear from them.  Samuel: Hello, my name is Samuel and I'm from Leicester. I have had the great privilege of working with some amazing people in Genomics England over the last few months, to hopefully one day be a part of something that takes down this condition that I struggle with known as sickle cell. Since John James of the Sickle Cell Society introduced me to Marie from Genomics England, there has been a door opened where the voice of a person dealing with the condition matters and holds weight, to help know what is required to further improve matters for people dealing with said condition. Hopefully, after reading the blog and hearing this podcast, you will know more about the work we've been doing, and feel as encouraged as we do. We don't just want to stop here. There's a long way to go, and we need all the help we can get to reach our goal together.  Hazel: Hi everyone, I'm Hazel. I hope you enjoyed the podcast. Now we're not done just yet. Keep your eyes out for our sickle cell and Genomics England patient takeover blog, where Natasha, Sam and I take you through what we've been up to and the future of genomics.   Zainab: Hi, my name's Zainab and I co-chair the Genomics England diverse data advisory board. I also have the pleasure of being part of the patient engagement group for this important piece of work. I've been a sickle cell advocate since before I even knew what advocacy was. As a child with sickle cell, I was exposed to different ways to help the community pretty early on, and have loved working with others to transform care for the better. Today, I hold a number of advocacy related leadership positions, including being a trustee of the Sickle Cell Society, chair for NHS England's patient advisory group for sickle cell health inequalities improvement, and a member of faculty for Medscape's committee on rare diseases. I also contribute to global sickle cell policy, practice and research.  I'm super excited about the work we do with Genomics England because I think they're a blueprint for what good patient centred work really looks like. My background is in health policies specifically related to research and innovation, so to see sickle cell being prioritised in this space is really special to me. We have an incredible opportunity to advance equity through research and innovation, especially related to genomics, and I myself am lucky to experience the transformative power of regenerative medicine. I'm excited for this group to continue to advocate for and enable better access for such incredible science.  Marie: We're very lucky to have such a wonderful group of people who are part of our patient voice group, and I hope you enjoyed meeting them. Just going back now to sort of what can be achieved, and if we, say, come back together in a year's time, knowing the kinds of things that we've just talked about briefly that we maybe want to look at – we've mentioned things like doing more family sessions, looking at how we can engage young men in particular, doing what is needed to kind of give that really strong message about how you support people to be part of these kind of patient advocacy roles. But what would you really like to see that we've achieved together by say this time next year? I'll come to you first, Jayson, this time.  Jayson: Thank you very much. Going straight to the point, I would like us to have more one to one with the patients and family in terms of – mainly I think to move towards the male, because, you know, I'm a living experience of some of the things that's happening, and put the awareness out there, and let them know that – not to scare them, but to give them adequate information to be able to arm and tool themselves for a better life for themselves, a better respite for themselves, and a better understanding of the situation. I know if sickle cell patients have enough time at work, at uni, at school, during their exams, they will achieve great results, and I would want that to be one of the forefronts of this campaign, to make sure that, you know, the male side – I do know a bit of the female side but I'll leave that to Oleander and Natasha, but the male side of what they should expect, and how to – if I could put this in (inaudible 0:33:59), I am making myself a role model for them, because I have leapt over barriers and over so many expectations, and if I could do it, with the science and the support we have now, they can double it, they can triple it, they can do more. My journey hasn't ended yet, but before it does, I want to tap into every organisation to hear more voice, to just give me five minutes to hear my voice.  Marie: Thank you so much, Jayson. I can't think of a better role model for young men who are dealing with this than you, so it's brilliant to see your dedication to that. Over to you, Oleander, what would you like to see – if we're here together in a year's time, looking back on what we've done over the last year and what's been achieved, what would you really like to see?  Oleander: I'd like to see sickle cell actually being taken seriously, that people don't make assumptions that, “Oh, it's just a small, you know, blood thing, it's nothing that deep, nothing that big,” whatever. Because the reality is, for a lot of indigenous people here, the majority ethnicity in this country, sickle cell is spreading because more people are mixing, more people have come over, refugees, economic migrants, etc, and mixing, and so they will find that actually it isn't just a tiny minority of people. We're told it's 17,000 people in the UK, but actually that number's going up. So, you know, it is a bit of a shame that it takes it to affect the ethnic majority in this country that anything would change, however this is the reality we live in. So for me, that's what I would like to see, that sickle cell is taken seriously, that we're not just stuck with one or two authorised drugs for people living with sickle cell, and actually one of them is not even a sickle cell specific drug.  So yeah, we want sickle cell to be taken seriously, and so that people can actually trust the process and trust the people who are genuinely trying to research issues to do with sickle cell, so that we can make the difference that we need to make for people's lives.  Marie: Thank you, Oleander. That just reminds me that, you know, hopefully – so, one of the projects that you are also involved in that we're doing is – and that's been already mentioned, the James Lind Alliance and the Sickle Cell Society partnership that we've got, the priority setting partnership. Hopefully, one of the things that's part of doing that is that we do create that sort of focused priority areas, and that's really strongly centred on the voices of people living with the condition, supporting people with the condition, whether they're parents, carers, healthcare professionals. So yeah, I completely agree, you know, really putting it on the map, taking it seriously, raising the understanding, raising it as a priority, I think that would be great to see in a year's time for sure. So of course, last but not least, over to you, Natasha.  Natasha: Well, Oleander has literally taken the words out of my mouth. That is exactly what I would want to see in the next year, and to me, it can be done. There should be no reason why it can't be, with all the technology, with all the advancements that's happening. There is no reason why sickle cell should not be leaps and bounds with the information, with the project, of getting this information from sickle cell patients. It should come to a point where actually no one has to suffer from sickle cell because, you know, the – what's it called, the medication, that one that's recently come out, that's way overdue. I can't even believe it's taken this long to just come up with that one, you know. The stem cell treatments and what they give as an alternative, it's not good enough basically. And, you know, we had this new one come out – I say new one, but this hydroxycarbamide, it's like that wasn't even for us. It was all by mistake that, “Oh actually, this might help sickle cell, let's see.” And that's what's the afterthought, and we shouldn't be an afterthought. It should be a priority.   And yeah, having that priority setting that we're doing with the James Lind Alliance – it's funny, ‘cos I remember, we had a call in our patient voice – I think he mentioned – I think it was something about maybe the questionnaire that we were going to give people, or – I can't remember the particular thing which I said to you, you're having trouble – you know, we're underrepresented, there's no data on us for a reason, and you had a template, and it's like this template's not going to work, because you have to approach it differently. Like you have to literally rip it up and start from the very beginning, because what you've tried to do in the past hasn't worked, or, you know, the majority of people, especially in the European world, it works for them, great, but you're coming to an underrepresented community and you're thinking, “Oh actually, we can just use that thumbprint and put it on this.” No, you've got to start again.  And I think it brings the importance of actually taking part in things like this, is that without actually knowing this, you would have thought, “Oh actually, people just aren't interested, you know. Patients don't want to know. They don't want to give any information over to us.” But it's like, well no, it's not that at all, it's just that you need to approach us differently. You need to, you know, understand what actually we're going through before you can then try and fix anything or provide information, or get, you know, medication advancements. Like these things need to be done and the groundwork first, and not thinking, “Oh okay, we can just put a little plaster and that'll heal that.”  So for me, definitely, more options when it comes to treatment. And, you know, that we're not the minority when it comes to data. Because especially with sickle cell, it affects different people in so many different ways, and they're just trying to understand, “Oh, why does it affect this person this way but it hasn't done it in this person?” And it's just like, great, you're asking these questions, but now let's move it forwards. Like let's not keep talking and let's start the action. And that's probably one of the other things is, I want to see the action. It's the action now. You know, of course, if you want us to talk, we'll talk, you know. We won't stop, and we can keep going. But ultimately let's actually have some movement. Let's have an action that you're – I say you as in you as an organisation, but wider, everybody that's part of the process comes and says, “Look, this is what we've been able to achieve.” And, you know, then you know you have been listened to. A bit like Jayson said, you know, still not listening. Actually, now you can say, “Yes, we've heard and now this is what's come from it.” So yeah, that's probably I think for me the biggest utopia is that actually sickle cell just won't exist. It's done. They've been able to sort it out [laughter], it's no longer an issue at all. But yeah, we won't get to that next year, but, you know, hopefully eventually down the line there is that cure or change that they can do.  Marie: I think for me, it kind of just brings me back to this point that there needs to be a united front in terms of like dealing and addressing with this. And also importantly, it needs to come from the community itself in terms of setting the priorities of what is done now, what is immediately needed to be done now, what can be looked at maybe a little bit later down the line, as there's maybe a bit more information, a bit more understanding, a bit more knowledge to kind of maybe base some things on. But yeah, every time I hear, you know, people speak about all the various challenges that, you know, of course, come from their own lived experience and having to see how this affects their community, and yes, there are steps being made in the right direction, but I think we all probably agree that we could all probably be doing more to just improve the way we're uniting this work, and we're doing it in a way that is really coming from the community themselves and saying, “We want this to happen now and in this way, and this is what we want you to look at addressing.”  We'll wrap up there. Thank you to my co-host Natasha Gordon-Douglas, and guests Oleander Agbetu and Jayson Kupoluyi for joining me today as we discussed engaging people with lived experience of sickle cell in research and advocacy. If you'd like to hear more about this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host, Marie Nugent. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand. 

In this episode of Behind the Genes, we explore the challenges diverse communities face in accessing genomic medicine. The discussion focuses on issues including language barriers, cultural differences, and socioeconomic disparities that hinder marginalised communities from accessing and benefitting from genomic medicine. Our guests delve into successful strategies for engaging these communities in healthcare research and decision-making, highlighting the importance of building trust with groups that have historically been underserved or mistreated. The episode also emphasises the need for culturally sensitive communication from healthcare professionals and how meaningful community engagement can foster collaboration and trust within genomic research. Our host, Naimah Callachand is joined by Aman Ali, a Community Ambassador at Genomics England and Community Engagement Manager at Our Future Health, Anna Smith, Child and Adolescent Integrative Psychotherapist at Rareminds, and Moestak Hussein who works for Bristol City Council in Public Health & Communities, working directly to build and imbed cohesion, inclusion and social justice approaches in her role.   "If we talk about co-production, true co-production is really creating a power balance where there's no hierarchy. It's an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve."   You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/Bridging-the-gap-between-diverse-communities.docx  Naimah: Welcome to Behind the Genes.  Aman: It's really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with.  Naimah: My name is Naimah Callachand and I'm Head of Product Engagement and Growth at Genomics England. On today's episode, I'm going to be joined by Anna Smith, child and adolescent integrative psychotherapist for Rare Minds, Aman Ali, a community ambassador for Genomics England, and Moestak Hussein, community coordinator at Bristol City Council. Today, we'll be discussing the disparities in access to genomic medicine amongst diverse communities. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts.  Aman: Hi, my name's Aman Ali, I am an ambassador at Genomics England, a person very passionate about health research and ensuring that diverse communities are involved in health research, and I work as a community engagement manager at Our Future Health.  Anna: My name's Anna Smith, I'm a psychotherapist. I work in private practice and also with Rare Minds, who are a company who provide therapy to people with rare and genetic conditions.  Moestak: Hi, my name is Moestak Hussein and I have a background in community development, and I'm passionate about tackling health inequalities, and building social justice and inclusive approaches to address health inequalities. I work at Bristol City Council in the public health team, and I've participated in the Bristol workshops around equity in research in genomics.  Naimah: So, let's jump in and first of all I want to talk about barriers to access for diverse communities. I want to talk about how there are language barriers, cultural differences and socioeconomic factors that impact access to genomic medicine for marginalised communities. Anna, I wonder if you maybe could talk to me a bit about this.  Anna: Yeah. So, I'm talking about the traveller community, and we refer to this community as a GRT community, which is Gypsy, Romany and Traveller, so it encompasses people in the UK, people living in Ireland as well. And some of the barriers to accessing healthcare are a lack of understanding of culture. There's been studies done where it says that people from GRT communities show up lower on all markers for poor healthcare and poor mental healthcare, and part of the reason for that is things like illiteracy. You know, you're dealing with people who can't read or write. They can't read appointment times. They don't have access to public transport. A lot of women don't drive in this community, and also women are not very well supported within the community by the people who can drive and who can get them places, because it's not seen as something that they need access to. Because the community is so closed, everything sort of takes place within the community.   In terms of genomic healthcare, access right from the start of life, if people are not accessing healthcare right from birth, they're not getting the genetic testing that's needed, so then a lot of these things don't even show up until the illness presents itself, and then accessing healthcare from there is really difficult. You know, it's something that – it doesn't happen a lot. Only 67 percent of people from the GRT community were able to get a doctor's appointment when they needed it, compared to nearly 90 percent from other communities, and that's through things like not having a fixed address. Lots of GPs don't offer temporary registration, which means that if you are travelling, you do not have access to a GP, which is your first port of call if you need any access to healthcare. So, many people from the GRT communities are using A&E services in order to get healthcare, which – you know, they are not set up for dealing with long-term life changing conditions. They're there to deal with what's right in front of them and then they move on. There's no sort of continuity of care.  Naimah: Thanks Anna, that's really highlighted a lot of barriers for the GRT community. And I wonder, Aman, if you want to come in now and maybe discuss some of the barriers that maybe the Muslim community might experience.  Aman: Yeah, I think anyone involved in medicine or anyone who's a doctor is really well respected in the Muslim community. That profession is something that every parent aspires for their children to get involved in. They at least want one of their children to be a doctor. Having said that, there's this willingness to engage with the space, but there's a lack of knowledge, which is a huge issue here. People don't know what the word genomics means or genes, or understand DNA. Some of this language is a huge barrier to understanding and then eventually accessing some of the services that could be available to people from Muslim communities. Because when we speak about Muslim communities, we're talking about a huge, diverse group of people from South Asia, from North Africa, from the Middle East, and they all have their nuances and different cultural experiences as well.  Just to kind of point out maybe one or two, most people in the UK have grown up in the UK, where access to healthcare is free, whereas this is quite a strange phenomenon for people who may have not been born in the UK and then access healthcare services in the UK. And the context being here is usually they pay for healthcare in other countries, and whenever any public or free healthcare is provided, it's usually seen as kind of not very good or suboptimum, or yeah, it's not going to be very helpful for us. So, when they see free healthcare in the UK, there's that kind of apprehension, “Actually, is this going to be worthwhile? I'm not paying for this, so it's not going to be very much good for me.” So, those are some of the cultural nuances that certain communities where healthcare is not for free in certain countries that poses a barrier.  Language in terms of speaking and reading is an issue. So, a lot of people, they may speak a language, but they don't know how to read a language. So, even when services are translated – I, for example, can speak Bangla, but I can't read or write Bangla, and not a word of Bangla at all. So for my parents, who can speak Bangla very well, their reading level is actually quite good, but I know that many within the community, they didn't get education back home, and therefore reading and writing is a challenge as well. And then you have the issue of dialects. There's so many dialects within so many different communities, so when a language is spoken or written in a particular way, if that dialect isn't your mother tongue or a dialect that you're familiar with, then that causes challenges to access as well.  Naimah: Moestak, how do cultural beliefs and values influence attitudes towards genomic medicine within each of these different cultural communities?  Moestak: I think Aman and Anna touched on it a lot, and it's about communities being able to coproduce that historically hasn't been there. The supremacy of certain communities to have a voice and be able to express how they would like to shape their healthcare, but also access to healthcare barriers have been part of having a barrier in access. And I think Aman touched on like even the term genomics, I don't think it exists in particularly my community. I come from the Somali community, and I've tried to look at historical kind of words and terms. I mean, our language only got developed in 1973, the written language, so you can imagine that there's a lot of gaps or there's other terminologies.  So, the cultural beliefs and values is also communities' recognition to be driving their own health needs and priorities is not valued within those sectors such as healthcare. I mean, we're still talking about holistic medicine. People go to their faith leaders in the first instance to have support around prayer. That's not necessarily recognised by mainstream health provision. And I think it's about how do we build on those strengths and how do we recognise that that is a really great part of communities. And it's also tradition and customs within childbirth, from birth, understanding what children and young people and families will need. I know there's customs and traditions for women to stay at home, for example, for 40 days, and those are the kind of traditions that could be built on. And I think it's about making sure that the child doesn't pick up bacteria or things like that.   So, there is an understanding and knowledge within communities of genomics. It's the awareness and the training around patient centred approaches are still missing, in my opinion. And I think that influences how people view genomic medicine. It goes back to the lack of trust and historic past abuses and cases, that communities has resulted in lower participation and a reluctancy to be part of genomic testing, but also that lack of understanding.  Naimah: Anna, did you have something you wanted to add in there?  Anna: What you were just saying about keeping it within the community, that's something that we see with the GRT community massively is everything is handled within the family, and I think that's not necessarily valued outside of that community. If you arrange an appointment with someone and the whole family turns up, it's like, “Woah, what's going on here? You know, how is this managed?” And it becomes a safeguarding issue, when actually that is how it's managed, and very often you need to get the whole family on board before you can start working with an individual. Because within the GRT communities, individuals do not exist outside of their families. Even what we're saying about language, a lot of the GRT community who live in England now speak English, but the words that they use for mental health are very different.   You talk about mental ill health, that translates as psychosis in the GRT community, whereas if you're talking about depression and anxiety, somebody might say that they've got bad nerves. So, if you come up and say, “We're dealing with mental health now,” people would say, “Well, I don't have psychosis, I don't have that, this is not an issue for me.” And it's like you're speaking different languages even though you're using the same words.  Naimah: From what all of you have said as well, it does sound like there are a lot of similarities in the barriers in each of the different cultural communities.  I wanted to move on to ask about what strategies have been effective at engaging these diverse communities in healthcare research and decision making processes.  Aman: There are a number of ways I've seen best practice take place in regards to kind of community engagement. The approaches have been one of two approaches. One, either inviting the community to come to your spaces, i.e. organising events or having opportunities where people can engage with your service. Or the alternative approach, which I think is actually more effective, is actually going to the spaces where communities are most familiar with. So, whether that's holding a focus group at a community centre, at a church or at a mosque, or engaging in coproduction with a community organisation, to come together, to come up with an idea of how to best engage communities. And I also feel like there's a difference between PPI, patient and public involvement, versus community engagement.   And those are the two major approaches that I've seen when it comes to community engagement, and I'm a big advocate of community engagement, because you're going into spaces which are authentic to the very communities that we are hoping to engage, but you're going into an unfamiliar environment as opposed to bringing that community into an unfamiliar environment, where they might be a bit guarded with what they want to share and how comfortable they feel. So, those are some reflections on good practices in community engagement.  And I think one of the key things that we need to do is understand who are the key community leaders within that community, ‘cos it's one thing being within that community, and being able to speak about that community are two different things altogether. So just to articulate what I mean by that, I live in Luton, but I've just moved to Luton two months ago, so if you ask me about what life is like in Luton, I'll be able to speak about my experience, but if I was to live here for 20, 30 years then I'd be in a better position to speak about how people in Luton live and what their experiences are like, and that's two different perspectives you're going to get. So, it's really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with.    Naimah: Thanks Aman. I think you made a couple of really good points there, and I think you kind of have this overarching feeling of building trust, which is what Moestak mentioned in the previous question as well. I thought maybe now would be a good time to discuss your first responders project, Aman, if you could tell us a bit about that. It'd be good to hear the kind of developments from that community work.  Aman: Yeah, so one of the ideas that came about from engagement actually that we had with some community leaders within the Muslim community, primarily some imams, they heard about the work of Genomics England, they heard about the work of research in particular, and they were really keen to get involved even further, but they were honest in saying that, “I know very little about this space. And it's one thing for me not to know much, but then if I don't know anything then I'm not able to then advocate for this within the community. So, two things you need to help me with. One, help me understand this space, but also allow me to then be able to advocate for services or information that my community can benefit from.”  So, that's where the inception of this first responders idea came about. The idea being that community engagement happened with some imams from all across the country, where we trained them to understand a bit more about genomics, and genomic healthcare and medicine, but also to be able to navigate a number of scenarios that they may face in the community. For example, there's a mother who has been recommended by their GP to go see a genetic counsellor, but they're really worried about broaching that conversation with their husband or their family, because of the challenges that they may face. So, how would you support someone in the community when that scenario comes up? Or for example, someone like Genomics England or Our Future Health or another organisation has approached you about a research study, and they want to engage your community, how would you have that conversation with that particular organisation, advocate for those health programmes within your community?  So, we just presented a number of scenarios. But I think the main thing that we ended with was giving the imams in this particular incident the ability to signpost to services, be it helplines that are available for communities to access more information, or websites that people can access in order to understand more information about different issues to do with health conditions, or whether it be better understanding issues like cousin marriages or kind of accessing genetic testing.  Naimah: That sounds like you're empowering the leaders to advocate for healthcare and share this with their communities through this work. I wonder, Anna, is that something that you could do in the GRT community as well, like empower the leaders of the family to disseminate these healthcare messages, and how would we do that?  Anna: Yeah, I think so. I think a lot of it would need to be outreach, and there are people out there who can help bridge that gap. For example, there's a great team called Family Friends & Travellers, and if you get in contact with them and let them know which community you'd like to go into, they can help arrange, or they will come with you to go into that community. Because the GRT community, you know, is very mistrustful of anyone coming in, and rightly so. It was only in 2011 that they were included on the national census as an option to say you're from that community, so I think there's massive mistrust there of anyone coming into the community.  So, if you want to engage the leaders of the families or of the communities, you're going into a settled traveller site, there will usually be somebody who is in charge of that site, not officially, but maybe their family might be the biggest family or they might be the most important family. And there are people out there who will allow you to start to engage with that person, who can then disseminate the information. But it needs to be outreach care, and the information that you disseminate, it needs to be tailored to people who have left school at primary age, who don't have the skills to read or write, or to manage appointments or read prescriptions, or have access to that type of healthcare. That's where it really needs to be tailored.  And I think confidentiality as well needs to be tailored a lot, because gossip and reputation and shame is huge in the GRT community, and if you are seen to be engaging with someone outside of the community, that is something that can bring a lot of shame to you and your family, so it needs to be handled really, really carefully.  Naimah: Just to kind of go along with this theme of trust that you've all now mentioned, Moestak, I wonder if you could maybe comment on what strategies can healthcare organisations and researchers employ to build trust with these communities who have historically been underserved or mistreated?  Moestak: Yeah, I think I mentioned earlier about the hierarchy of power around superiority and also mistrust of medical professional generally, and I touched there on how safeguarding concerns are triggered on not understanding cultural norms and practices within communities, and misconstruing that with safeguarding. There is generally that mistrust is there. And I think what Aman touched on there is really the importance of asset based approaches, and really building on transparent and really embedding transparent and inclusive practices from the onset. I mean, if we talk about coproduction, true coproduction is really creating a power balance where there's no hierarchy. It's an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve.  And I think it's important to embed those kind of approaches, and it's Covid-19 – I mean, we took part in Bristol in King's Fund research around the community champions model. It's exactly that, about engagement, about community driving their own solutions, and being able to collectively collaborate, drive their health piece forward, but also increase the capacity of communities. We worked with clinicians who come from those communities, and it's no surprise that the uptake of covid-19 vaccine increased as a result of working with those trusted voices.   Quite often, those really effective programmes and engagement often are not funded adequately. They're not sustained. And what happens is that we constantly are having to rebuild and restart, and that really does affect trust as well with communities. And when something works, why not build on it? And even now with that Covid-19 learning from the community champion model, the resource is not there anymore. It's not valued anymore, sadly. That in itself is a risk, I think, in building the trust, but also the strength to continue that work and adapt in other ways around genomic medicine, and even increasing and diversifying the genomics data pool, helping communities understand and drive that. And that first responders project, communities being trained to capacity build and then being able to drive that within their communities, that's the only way that we're going to have effective strategies.  Aman: I think adding onto what's been mentioned, with regards to building trust, it's really important to understand the motivations of communities, and to understand what messaging is going to resonate with different communities, and it's going to be a different message for each community. You can't have the same approach for all communities. A recurrent theme that I've come across when engaging different communities is this difference between messaging which is individualistic and then messaging which is about the community and more the collective message, and how that resonates a lot more with certain communities that I've engaged with, particularly within Muslim communities. And that's something that I think is a bit untapped in regards to kind of any materials that are created, be it posters or videos or any content looking to reach out to communities.  When we did some focus groups with some communities in Watford, who are primarily from the Pakistani community but also other parts of Asia in that region, the biggest response or biggest positive response that we got was when we posed the question, “If you were to know that people who look like you, from wherever your parents are, family may be from, would you be motivated to take part in that research?” And the biggest yes came on the back of that question. And that speaks to the fact that, “If I know that my family or my community, not just in the UK but abroad can benefit, then that would really motivate me and build trust that actually you're not just here to benefit me as an individual, but you're here to benefit my community as a whole, and therefore, yes, I'm going to be more trusting of this programme and be more motivated to take part.”  Naimah: I just wanted to go briefly back, Moestak, you mentioned cultural norms, and I wanted to talk about the cultural norm in societies where maybe people may marry someone from the same ancestor, and what the societal fallout from these practices might be.  Moestak: The stigma and the stereotypes often for communities comes from those beliefs and messages that are often sometimes not even backed up with scientific evidence. It can be seen as Islamophobic sometimes of Muslim communities that practice that. But also I think what's important to understand is that concept around hereditary conditions and how that can determine one's health, and it's not really fully appreciated or desired. And so as a result, for example, a lot of people refuse to even have those early onset maternal testing for the foetus. My personal experience, I have three children, teenagers now, and I refused those tests as well, because my belief and my religious beliefs would kind of not align with being able to terminate a foetus if there were some genetic conditions. And so I think that is often not understood and made very clear to communities, and build on their beliefs and attitudes and values. And so those are the kind of cultural norms that are not fully understood.  But also the opposite side of that actually around being able to prevent a good life for somebody or a bad life for somebody, and being able to prevent genetic conditions is also part of the religion on the flipside, but again it's not creating that link. That cultural beliefs is not understood. I think also the community implications around the stigma. I mean, autism's a big issue in the Samali community, and I remember years ago when I was working in education, we had a big issue around even acknowledgement of diagnosis and referrals, and it's because of the stigma. Those perceptions do exist within communities that if someone has a genetic condition or ill health or a disease, it's almost like being a black sheep in the community. And so it's being able to build on those desires of the community wanting to be healthy and well, I think is not often understood.  Naimah: And do you think it's partly as well education of healthcare professionals to communicate in a really culturally sensitive way?  Moestak: Yes, exactly, that's exactly what it is. It's missed opportunities really that we can build on. In that particular example of autism within the community, I was able to do a really positive piece of work with the community, and building on their interest and their skills, but using my own lived experience and understanding and knowledge, and being able to inform that within education sector but also the health sector, and providing that training and upskilling. And there is unfortunately a lack of diversity within the workforce if you look at the NHS. The lower level kind of cleaning and porter staff are ethnic minorities. And so it is about using those clinicians, as I mentioned earlier, that are coming from those communities are the forefront.  We've recently had a really positive piece of work in Bristol around let's talk about MMR, and we had a cohort of unvaccinated community, a Somali community, young people between the age of 16 to 25, and we worked with a Somali clinician, who led on that piece of work, and it was absolutely amazing. The young people as a result trusted her information and took up – but again also another thing that's important is that a lot of data in the medical system is missing. I for one migrated here from the Netherlands, where I came there as a refugee at the age of three years old. My medical history is completely missing in both the UK records but also in the Netherlands, so I didn't know if I had MMR vaccine. So, it's a lot of gaps in information that people have, newly arrived communities that still need to constantly be updated and informed and education awareness raised with those communities.  Naimah: Anna, I wonder if you wanted to add anything onto that point.  Anna: It's really difficult with that mistrust and sort of how closed the GRT community is to getting that information in, and I think to getting that information understood as well and to make it seem like it's important. Because family is the most important thing, people are accepted the way that they are. You know, if we're talking about autism, people are accepted the way that they are, and it is a bit like, you know, “There's nothing wrong with my child, how dare you suggest that there is?” That testing isn't done because the access to healthcare is so difficult, because people can't register with GPs, because they can't access maternity care, they can't access postnatal care. Because they can't register with the GP, they're not on the system, and then the records don't exist. Still now there's birth records and death records that do not exist for these people within the communities, never mind medical history throughout their lives.  Naimah: I think it really highlights a lot of gaps, doesn't it? Aman, do you want to add anything to that question?  Anna: Your opening remarks is that it's a cultural norm in all societies, and we see even within the royal family in the UK, that it seems to be that any disparaging comments are targeted towards certain communities, and even then unfairly. I mean, often it's associated with Muslim communities, but I would say the majority of Muslim communities don't practice marrying someone from within the same ancestor. It's certain cultural communities who do practice this. Having said that, even that practice shouldn't be seen in a disparaging way, because it's how those communities live their lives, and so we should be respectful of that and not speak in any way disparaging towards that community. And I think we have responsibility – ‘cos obviously nationally the conversation then moves onto increased risks of genetic disorders, and so we should be very matter of fact about what the percentage increase is when it comes to the likelihood of genetic disorders within families who marry with the same ancestor.   Because what happens is, if we're not very clear with what the actual facts are with regards to the increased risk of genetic order then even within the community which practices marrying someone from the same ancestor, that figure can be inflated, and so this perpetuates fear and perpetuates the stigma even more. Whereas if we are just matter of fact, “This is the increased risk of genetic disorders,” and leave it there, then the communities can decide and they'll have a more informed position. I think the figures are an increase from two to six percent increase, but if you were to ask people within the community, “What's the increase of genetic disorders if you're marrying someone from the same ancestor?” they might think it's 40 percent or 50 percent or a really high figure. So, that's something that we need to work towards better understanding, which will lead to removal of that stigma as well.  Anna: Again, that's something that we see in the GRT community as well, there's been research done by a woman called Sally Anne Lynch into cousin marriage within the Irish travelling community, and when they tested people, they found more than 90 genetic conditions that are present within people's DNA within that community that just aren't tested at birth. And I think, you know, you're right, it's something that is not talked about, because outside of these communities it's seen as wrong and it's not seen as something that's normal. It's seen as abnormal. But within this community, it is very normal and it's very accepted. But then the testing isn't done because of the access to healthcare.  Naimah: I think it just seems like it does kind of boil down to education and educating healthcare professionals that it is kind of normal practices. Aman, did you want to add something else?  Aman: Yeah, Anna made a really good point about testing. I think there's something that is a gap in the service that we probably don't provide more widely is that, when it comes to people who practice marriage within the same ancestor in other countries, testing is very normal. So, I know there's many countries around the world where it's very standard practice and even a requirement in certain countries that you must be tested before you get married, and so maybe that's something that we can learn from in the UK.  Moestak: I think it's important to understand that some communities, decision making of consent is sometimes done by the head of the family, and I think that that is not fully understood as well, and often can be a barrier to participation. And I think that there's an element of empowerness that is needed, particularly around women that need that empowerment model around consent of decision making around their testing and genetic testing, and just medical consent.  Naimah: That's an excellent point as well, thanks Moestak.  So, I know we've touched on aspects of this already, but I wanted to finish on this question, how can meaningful community engagement foster trust and collaboration in genomic research and healthcare initiatives?  Aman: I think one of the things that I would really improve is just awareness around genomic healthcare and genomics in general. It's a learning curve that's going to happen within communities at different rates, and we need to be mindful of this because that rate will determine also health inequities that are experienced by those communities as well. So, we need to make sure that we are adequately approaching all communities to the best of our abilities. Having said that, target maybe more resourcing and educational opportunities for communities which have been underrepresented in health research and in genomic health research as well primarily, so we need to sort of prioritise certain communities in regards to our community outreach, because then we'll dispel any myths that people might have and work towards chipping away at the mistrust that certain communities may feel towards just healthcare in general, but more particularly about genomic healthcare, ‘cos genomic healthcare brings up some unique challenges and some unique perspectives within communities.  So, there's a number of fears about the future, but also misgivings about healthcare in the past as well that we need to acknowledge. So, by having community engagement initiatives, which are prioritised from the beginning and not just an afterthought, we can go a long way towards getting over some of the challenges of the past, but also not making new challenges for us in the future.   Anna: I think as a whole, the UK has got a long way to go with building trust with the GRT community. I think it's going to take some time. They still are one of the most marginalised communities. For example, in the area that I live, there was a GRT funeral going on a few weeks ago, and all the pub shut because they didn't want GRT communities in their establishments, and there is no other community or minority that that would happen with now. So, I think there is still quite a long way to go to gain the trust of the GRT community. And in terms of healthcare, I think we need to go right back to the start and learn about these communities, and understand their cultures and their practices, and how they work without that judgement. Living a nomadic lifestyle is still criminalised. There needs to be a decriminalisation around these communities before we can even start to begin to work out how to go there and allow them to access healthcare and knowledge and information around genetic conditions, and around health and mental health.   It's going to be a very long road from here, but I think what we can start doing is to start that destigmatisation. If you are a doctor and somebody turns up in your surgery identifying as someone from the GRT community, understanding the background they come from, and not having all those prejudices, you know, which is very difficult to do, to get rid of those thoughts that you already have about someone. I think we need to make a real effort to start, and I think there needs to be changes within the NHS in order for people to access healthcare better. I think the resources that are given and the information that goes out needs to be more specifically tailored to these communities if that's who you're trying to engage with, because there's so much that goes on in the community that's not known outside of the community, and it's not spoken about, and within different GRT communities as well. You know, there are different GRT communities all around the UK, and what goes on in them is not known to other GRT communities either.   So, it's about being specific with the information that you're getting out, with who you're actually targeting. And I think a bit like we were saying earlier, it's the women, you know. The women have childcare responsibilities almost all of the time, and they are the ones who bring up the children, but they're not necessarily the ones that make the decisions about the children or the child healthcare. You know, women are expected to do jobs in the morning. Women are not available before 11 o'clock in the morning. So, think about when you're making appointments for. Think about when you're going. I think it is going to be a long, long road before we get there, you know, with building trust and getting the information out there, but I think we can make a start.  Naimah: Yeah, it does seem like there is lots of ways we can start tackling it slowly. Moestak, I wonder if you had anything you wanted to add.  Moestak: As a public health specialist, you know, we've not been taught genomic medicine or genomic health at all in terms of how that can benefit and radically change the NHS and improve determinants of health, so that's a massive gap of knowledge within the healthcare sector and professionals. But I think in terms of addressing the historic mistrust, I think there needs to be an acknowledgement and a real openness around the historic, you know, abuse and unethical practices that have existed within health. There are other countries that are much more advanced in that and really embedding that within communities through pledges. That long-term kind of piece of work for me is missing. You know, it's that wider education piece that's missing that needs to be really embedded in the culture.  But I think also investing in the infrastructure in the community. Like far too often, if the long-term vision is not there, communities are reluctant to get involved and have trust within that, so I think that's an important part as well. And I think it's also about demonstrating the benefits of genomic medicine. I think that needs to be done in a community level way, through storytelling. I know that there's now a lot of development around cancer treatments around genomics, but I think it's about having those people who have those lived experiences from different communities to be able to share the benefits and demonstrate that through their way, and being appropriately reimbursed as well. I think that's really important.  I think generally, I think there's a long way we've got to go. I'll never forget when I went to Vancouver on a conference around health, and there was a lot of reconciliation there, where there was really acknowledgement, and the indigenous communities there that have a lot of health disparities were able to kind of overcome some of that and start building as a community and addressing tackling health inequalities because that trust was built and that acknowledgement from high up, from government level, all the way trickled down to local. I think also patient centred approaches around – like we mentioned, we talked about linking the cultural norms and the values and the beliefs that people have, and the skills and the assets that they have to be able to lead on these solutions themselves, that really needs to be embedded to build trust.   Aman touched on the perception around what could be done with genomic data. I don't know if Aman wants to elaborate a bit on that, but that's really important. It's a big barrier. It's how do we create transparent ways of storing data, but also use various ways of communication. It doesn't have to be traditional reports. It could be through podcasts. It could be like community messaging.   Naimah: Yeah, I think that's a really important point. Aman, did you want to come in on that?  Aman: Yeah, I think sharing the stories of the past in an appropriate setting, in an appropriate manner as well – ‘cos it's a bit of a double edged sword, ‘cos you don't want to scare people who are unfamiliar with these stories, but at the same time there's a moral responsibility for all of us involved in this space to speak about these issues, one from the perspective of acknowledging what's happened in the past, so then people feel like, “Okay, you're not trying to hide anything here,” but from the perspective of also that we need to make sure that we don't repeat some of the mistakes in the future, and that as people involved in genomic healthcare and involved in this space, that we're cognisant of these misgivings in the past, and we're cognisant of our responsibility to safeguard communities in the future.  Naimah: Okay, so we're going to wrap up there. Thank you so much to our guests, Anna Smith, Aman Ali and Moestak Hussein for joining me today as we discussed the barriers to access to genomic medicine for diverse communities, and the impact it has on these communities. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

Pharmacogenomics plays a critical role in personalised medicine, as some adverse drug reactions are genetically determined. Adverse drugs reactions (ADRs) account for 6.5% of hospital admissions in the UK, and the application of pharmacogenomics to look at an individuals response to drugs can significantly enhance patient outcomes and safety. In this episode, our guests discuss how genomic testing can identify patients who will respond to medications and those who may have adverse reactions. We hear more about Genomics England's collaboration with the Medicines and Healthcare products Regulatory Agency in the Yellow Card Biobank and our guests discuss the challenges of implementing pharmacogenomics into the healthcare system. Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Anita Hanson, Research Matron and the Lead Research Nurse for clinical pharmacology at Liverpool University Hospitals NHS Foundation Trust, and Professor Bill Newman, Professor of translational genomic medicine at the Manchester Center for Genomic Medicine, and Professor Matt Brown, Chief Scientific Officer at Genomics England.   "I think we're moving to a place where, rather than just doing that one test that might be relevant to one drug, we'd be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it's required, so that they're not waiting for the results of a genetic test, it's immediately within their healthcare record."   To learn more about Jane's lived experience with Stevens-Johnson syndrome, visit The Academy of Medical Sciences' (AMS) YouTube channel. The story, co-produced by Areeba Hanif from AMS, provides an in-depth look at Jane's journey. You can watch the video via this link: https://www.youtube.com/watch?v=v4KJtDZJyaA  Want to learn more about personalised medicine? Listen to our Genomics 101 episode where Professor Matt Brown explains what it is in less than 5 minutes: https://www.genomicsengland.co.uk/podcasts/genomics-101-what-is-personalised-medicine  You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/Can-genomic-testing-prevent-adverse-drug-reactions.docx   Vivienne: Hello and welcome to Behind the Genes.  Bill: What we've seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They've been easier to identify and there's a clear relationship between some drugs and some genetic changes where that information is useful. So, a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you're given that treatment, then you can end up on intensive care and die, so it's a really significant side effect. But as you say, the most common side effects aren't necessarily fatal, but they can have a huge impact upon people and on their wellbeing.  Vivienne: My name's Vivienne Parry and I'm head of public engagement at Genomics England, and today we'll be discussing the critical role of pharmacogenomics in personalised medicine, highlighting its impact on how well medicines work, their safety, and on patient care. I'm joined today by Professor Bill Newman, professor of translational genomic medicine at the Manchester Centre for Genomic Medicine, Anita Hanson, research matron, a fabulous title, and lead research nurse for clinical pharmacology at the Liverpool University Hospital's NHS Foundation Trust, and Professor Matt Brown, chief scientific officer for Genomics England. And just remember, if you enjoy today's episode, we'd love your support, so please like, share and rate us on wherever you listen to your podcasts.  So, first question to you, Bill, what is pharmacogenomics?  Bill: Thanks Viv. I think there are lots of different definitions, but how I think of pharmacogenetics is by using genetic information to inform how we prescribe drugs, so that they can be safer and more effective. And we're talking about genetic changes that are passed down through families, so these are changes that are found in lots of individuals. We all carry changes in our genes that are important in how we transform and metabolise medicines, and how our bodies respond to them.  Vivienne: Now, you said pharmacogenetics. Is it one of those medicine things like tomato, tomato, or is there a real difference between pharmacogenetics and pharmacogenomics?  Bill: So, people, as you can imagine, do get quite irate about this sort of thing, and there are lots of people that would contest that there is a really big important difference. I suppose that pharmacogenetics is more when you're looking at single changes in a relatively small number of genes, whereas pharmacogenomics is a broader definition, which can involve looking at the whole genome, lots of genes, and also whether those genes are switched on or switched off, so the expression levels of those genes as well would encompass pharmacogenomics. But ultimately it's using genetic information to make drug prescription safer and more effective.  Vivienne: So, we're going to call it pharmacogenomics and we're talking about everything, that's it, we'll go for it. So Matt, just explain if you would the link between pharmacogenomics and personalised medicine. And I know that you've done a big Genomics 101 episode about personalised medicine, but just very briefly, what's the link between the two?  Matt: So, personalised medicine's about using the right dose of the right drug for the right individual. And so pharmacogenomics helps you with not only ensuring that you give a medication which doesn't cause problems for the person who receives it, so an adverse drug reaction, but also that they're actually getting the right dose. Of course, people's ability to metabolise, activate and respond to drugs genetically is often genetically determined, and so sometimes you need to adjust the dose up or down according to a person's genetic background.  Vivienne: Now, one of the things that we've become very aware of is adverse drug reactions, and I think they account for something like six and a half percent of all hospital admissions in the UK, so it's absolutely huge. Is that genetically determined adverse drug reactions?  Matt: So, the answer to that is we believe so. There's quite a bit of data to show that you can reduce the risk of people needing a hospital admission by screening genetic markers, and a lot of the very severe reactions that lead to people being admitted to hospital are very strongly genetically determined. So for example, there are HLA types that affect the risk of adverse drug reactions to commonly used medications for gout, for epilepsy, some HIV medications and so on, where in many health services around the world, including in England, there are already tests available to help prevent those leading to severe reactions. It's likely though that actually the tests we have available only represent a small fraction of the total preventable adverse drug reactions were we to have a formal pre-emptive pharmacogenomics screening programme.  Vivienne: Now, I should say that not all adverse drug reactions are genetic in origin. I mean, I remember a rather nasty incident on the night when I got my exam results for my finals, and I'd actually had a big bee sting and I'd been prescribed antihistamines, and I went out and I drank rather a lot to celebrate, and oh my goodness me, I was rather ill [laughter]. So, you know, not all adverse drug reactions are genetic in origin. There are other things that interact as well, just to make that clear to people.  Matt: Yes, I think that's more an interaction than an adverse drug reaction. In fact frankly, the most common adverse drug reaction in hospitals is probably through excess amounts of water, and that's not medically determined, that's the prescription.  Vivienne: Let me now come to Anita. So, you talk to patients all the time about pharmacogenomics in your role. You've been very much involved in patient and public involvement groups at the Wolfson Centre for Personalised Medicine in Liverpool. What do patients think about pharmacogenomics? Is it something they welcome?  Anita: I think they do welcome pharmacogenomics, especially so with some of the patients who've experienced some of the more serious, life threatening reactions. And so one of our patients has been doing some work with the Academy of Medical Sciences, and she presented to the Sir Colin Dollery lecture in 2022, and she shared her story of having an adverse drug reaction and the importance of pharmacogenomics, and the impact that pharmacogenomics can have on patient care.  Vivienne: Now, I think that was Stevens-Johnson syndrome. We're going to hear in a moment from somebody who did experience Stevens-Johnson's, but just tell us briefly what that is.  Anita: Stevens-Johnson syndrome is a potentially life threatening reaction that can be caused by a viral infection, but is more commonly caused by a medicine. There are certain groups of medicines that can cause this reaction, such as antibiotics or anticonvulsants, nonsteroidal anti-inflammatories, and also a drug called allopurinol, which is used to treat gout. Patients have really serious side effects to this condition, and they're often left with long-term health complications. The morbidity and mortality is considerable as well, and patients often spend a lot of time in hospital and take a long time to recover.   Vivienne: And let's now hear from Jane Burns for someone with lived experience of that Stevens-Johnson syndrome. When Jane Burns was 19, the medicine she took for her epilepsy was changed.  Jane: I remember waking up and feeling really hot, and I was hallucinating, so I was taken to the Royal Liverpool Hospital emergency department by my parents. When I reached A&E, I had a temperature of 40 degrees Celsius. I was given Piriton and paracetamol, and the dermatologist was contacted. My mum had taken my medication to hospital and explained the changeover process with my epilepsy medication. A decision was made to discontinue the Tegretol and I was kept in for observation. Quite rapidly, the rash was changing. Blisters were forming all over my body, my mouth was sore and my jaw ached. My temperature remained very high. It was at this point that Stevens-Johnson syndrome, or SJS, was diagnosed.  Over the next few days, my condition deteriorated rapidly. The rash became deeper in colour. Some of the blisters had burst, but some got larger. I developed ulcers on my mouth and it was extremely painful. I started to lose my hair and my fingernails. As I had now lost 65 percent of my skin, a diagnosis of toxic epidermal necrolysis, or TEN, was made. Survivors of SJS TEN often suffer with long-term visible physical complications, but it is important to also be aware of the psychological effects, with some patients experiencing post-traumatic stress disorder. It's only as I get older that I realise how extremely lucky I am to have survived. Due to medical and nursing expertise, and the research being conducted at the time, my SJS was diagnosed quickly and the medication stopped. This undoubtedly saved my life.  Vivienne: Now, you've been looking at the development of a passport in collaborating with the AMS and the MHRA. Tell me a bit more about that.  Anita: Yes, we set up a patient group at the Wolfson Centre for Personalised Medicine approximately 12 years ago, and Professor Sir Munir Pirmohamed and I, we wanted to explore a little bit more about what was important to patients, really to complement all the scientific and clinical research activity within pharmacogenomics. And patients recognised that, alongside the pharmacogenomic testing, they recognised healthcare professionals didn't really have an awareness of such serious reactions like Stevens-Johnson syndrome, and so they said they would benefit from having a My SJS Passport, which is a booklet that can summarise all of the important information about their care post-discharge, and this can then be used to coordinate and manage their long-term healthcare problems post-discharge and beyond. And so this was designed by survivors for survivors, and it was then evaluated as part of my PhD, and the findings from the work suggest that the passport is like the patient's voice, and it really does kind of validate their diagnosis and raises awareness of SJS amongst healthcare professionals. So, really excellent findings from the research, and the patients think it's a wonderful benefit to them.  Vivienne: So, it's a bit like a kind of paper version of the bracelet that you sometimes see people wearing that are on steroids, for instance.  Anita: It is like that, and it's wonderful because it's a handheld source of valuable information that they can share with healthcare professionals. And this is particularly important if they're admitted in an emergency and they can't speak for themselves. And so the passport has all that valuable information, so that patients aren't prescribed that drug again, so it prevents them experiencing a serious adverse drug reaction again.   Vivienne: So, Stevens-Johnson, Bill, is a really scary side effect, but what about the day to day benefits of pharmacogenomics for patients?  Bill: So, what we've seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They've been easier to identify and there's a clear relationship between some drugs and some genetic changes where that information is useful. So a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you're given that treatment, then you can end up on intensive care and die, so it's a really significant side effect. But as you say, the most common side effects aren't necessarily fatal, but they can have a huge impact upon people and on their wellbeing.   And it's not just in terms of side effects. It's in terms of the effectiveness of the medicine. Because if a person is prescribed a medicine that doesn't or isn't going to work for them then it can take them longer to recover, to get onto the right medicine. That can have all sorts of detrimental effects. And so when we're thinking about introducing pharmacogenetics more broadly rather than just on a single drug or a single gene basis, we're thinking about that for common drugs like antidepressants, painkillers, statins, the drugs that GPs are often prescribing on a regular basis to a whole range of patients.  Vivienne: So, to go back to you, Anita, we're really talking about dose here, aren't we, whether you need twice the dose or half the dose depending on how quickly your body metabolises that particular medicine. How do patients view that?  Anita: Well, the patient in question who presented for the Academy of Medical Sciences, I mean, her take on this was, she thinks pharmacogenetics is wonderful because it will allow doctors and nurses to then prescribe the right drug, but also to adapt the dose accordingly to make sure that they get the best outcome, which provides the maximum benefit while also minimising any potential harm. And so from her perspective, that was one of the real benefits of pharmacogenomics. But she also highlighted about the benefits for future generations, the fear of her son taking the same medicine and experiencing the same reaction. And so I think her concerns were, if we have pharmacogenetic testing for a panel of medicines, as Bill mentioned then, then perhaps this would be fantastic for our children as they grow up, and we can identify and predict and prevent these type of reactions happening to future generations.  Vivienne: And some of these drugs, Bill, are really very common indeed, something like codeine. Just tell us about codeine, ‘cos it's something – whenever I tell this to friends [laughter], they're always completely entranced by the idea that some people don't need nearly as much codeine as others.  Bill: Yeah, so codeine is a drug that's very commonly used as a painkiller. To have its real effect, it needs to be converted in the body to a different drug called morphine, and that is done by an enzyme which is made by a gene called CYP2D6. And we all carry changes in CYP2D6, and the frequency of those variants, whether they make the gene work too much or whether they make it work too little, they vary enormously across the world, so that if you go to parts of Africa, about 30 percent of the population will make more of the CYP2D6, and so they will convert the codeine much more quickly, whereas if you go to the UK, maybe up to ten percent of the white population in the UK just won't be converting codeine to morphine at all, so they won't get any benefit from the drug. So at both ends, you have some people that don't respond and some people that respond a little bit too much so that they need either an alternative drug or they need a different dose.  Vivienne: So, all those people who say, you know, “My headache hasn't been touched by this painkiller,” and we say, “What a wimp you're being,” actually, it's to do with genetics.  Bill: Yeah, absolutely. There's a biological reason why people don't – not for everybody, but for a significant number of people, that's absolutely right, and we can be far more tailored in how we prescribe medication, and get people onto painkillers that work for them much more quickly.  Vivienne: And that's so interesting that it varies by where you come from in the world, because that means we need to give particular attention – and I'm thinking, Anita, to working with patients from different community groups, to make sure that they understand the need for pharmacogenomics.  Anita: I think that's really important, Vivienne, and I think we are now having discussions with the likes of Canada SJS awareness group, and also people have been in touch with me from South Africa because people have requested the passport now to be used in different countries, because they think it's a wonderful tool, and it's about raising awareness of pharmacogenomics and the potential benefits of that, and being able to share the tools that we've got to help patients once they've experienced a serious reaction.  Vivienne: So, pharmacogenomics clearly is important in the prevention of adverse drug reactions, better and more accurate prescribing, reduced medicines wastage. Does this mean that it's also going to save money, Bill, for the NHS?  Bill: Potentially. It should do if it's applied properly, but there's lots of work to make sure that not only are we using the right evidence and using the right types of tests in the laboratory, but we're getting the information to prescribers, so to GPs, to pharmacists, to hospital doctors, in a way that is understandable and meaningful, such that they can then act upon that information. So, the money will only be saved and then can be reused for healthcare if the whole process and the whole pathway works, and that information is used effectively.  Vivienne: So, a lot of research to make sure that all of that is in place, and to demonstrate the potential cost savings.  Bill: Yes. I mean, there are very nice studies that have been done already in parts of the world that have shown that the savings that could be accrued for applying pharmacogenetics across common conditions like depression, like in patients to prevent secondary types of strokes, are enormous. They run into hundreds of millions of pounds or dollars. But there is an initial investment that is required to make sure that we have the testing in place, that we have the digital pathways to move the information in place, and that there's the education and training, so that health professionals know how to use the information. But the potential is absolutely enormous.  Vivienne: Matt, can I turn now to the yellow card. So, people will be very familiar with the yellow card system. So, if you have an adverse reaction, you can send a yellow card in – I mean, literally, it is a yellow card [laughter]. It does exactly what it says on the tin. You send a yellow card to the MHRA, and they note if there's been an adverse effect of a particular medicine. But Genomics England is teaming up with the MHRA to do something more with yellow cards, and we're also doing this with the Yellow Card Biobank. Tell us a bit more.  Matt: So, yellow card's a great scheme that was set up decades ago, initially starting off, as you said, with literally yellow cards, but now actually most submissions actually come online. And it's important to note that submissions can come not just from healthcare providers, but majority of submissions actually come from patients themselves, and that people should feel free, if they feel they've had an adverse drug reaction, to report that themselves rather than necessarily depending on a medical practitioner or the healthcare provider to create that report. So, Genomics England is partnering with the MHRA in building what's called the Yellow Card Biobank, the goal of which is to identify genetic markers for adverse drug reactions earlier than has occurred in the past, so that we can then introduce genetic tests to prevent these adverse drug reactions much sooner than has occurred previously.   So, what we're doing is basically at the moment we're doing a pilot, but the ultimate plan is that in future, patients who report a serious adverse drug reaction through the Yellow Card Biobank will be asked to provide a sample, a blood sample, that we then screen. We do a whole genome sequence on it, and then combine these with patients who've had like adverse drug reactions and identify genetic markers for that adverse drug reaction medication earlier, that can then be introduced into clinical practice earlier. And this should reduce by decades the amount of time between when adverse drug reactions first start occurring with medications and us then being able to translate that into a preventative mechanism.  Vivienne: And will that scheme discover, do you think, new interactions that you didn't know about before? Or do you expect it to turn up what you already know about?  Matt: No, I really think there's a lot of discovery that is yet to happen here. In particular, even for drugs that we know cause adverse drug reactions, mostly they've only been studied in people of European ancestry and often in East Asian ancestry, but in many other ancestries that are really important in the global population and in the UK population, like African ancestry and South Asian ancestries, we have very little data. And even within Africa, which is an area which is genetically diverse as the rest of the world put together, we really don't know what different ethnicities within Africa, actually what their genetic background is with regard to adverse drug reactions.  The other thing I'd say is that there are a lot of new medications which have simply not been studied well enough. And lastly, that at the moment people are focused on adverse drug reactions being due to single genetic variants, when we know from the model of most human diseases that most human diseases are actually caused by combinations of genetic variants interacting with one another, so-called common disease type genetics, and that probably is similarly important with regard to pharmacogenomics as it is to overall human diseases. That is, it's far more common that these are actually due to common variants interacting with one another rather than the rare variants that we've been studying to date.  Vivienne: So, it's a kind of cocktail effect, if you like. You know, you need lots of genes working together and that will produce a reaction that you may not have expected if you'd looked at a single gene alone.  Matt: That's absolutely correct, and there's an increasing amount of evidence to show that that is the case with medications, but it's really very early days for research in that field. And the Yellow Card Biobank will be one of many approaches that will discover these genetic variants in years to come.  Vivienne: Now, Matt's a research scientist. Bill, you're on the frontline in the NHS. How quickly can this sort of finding be translated into care for people in the NHS?  Bill: So, really quickly is the simple answer to that, Viv. If we look at examples from a number of years ago, there's a drug called azathioprine that Matt has used lots in some of his patients. In rheumatology, it's used for patients with inflammatory bowel disease. And the first studies that showed that there was a gene that was relevant to having bad reactions to that drug came out in the 1980s, but it wasn't until well into this century, so probably 30-plus years later that we were routinely using that test in clinical medicine. So, there was an enormous lot of hesitancy about adopting that type of testing, and a bit of uncertainty. If you move forward to work that our colleague Munir Pirmohamed in Liverpool has done with colleagues in Australia like Simon Mallal around HIV medicine, there was this discovery that a drug called abacavir, that if you carried a particular genetic change, that you had a much higher risk of having a really severe reaction to that. The adoption from the initial discovery to routine, worldwide testing happened within four years.   So, already we've seen a significant change in the appetite to move quickly to adopt this type of testing, and I see certainly within the NHS and within other health systems around the world, a real desire to adopt pharmacogenetics into routine clinical practice quickly and at scale, but also as part of a broader package of care, which doesn't just solely focus on genetics, but thinks about all the other parts that are important in how we respond to medication. So, making sure we're not on unusual combinations of drugs, or that we're taking our medicine at the right time and with food or not with food, and all of those other things that are really important. And if you link that to the pharmacogenetics, we're going to have a much safer, more effective medicines world.  Vivienne: I think one of the joys of working at Genomics England is that you see some of this work really going into clinical practice very fast indeed. And I should say actually that the Wolfson Centre for Personalised Medicine, the PPI group that Anita looks after so well, they've been very important in recruiting people to Yellow Card Biobank. And if anyone's listening to this, Matt, and wants to be part of this, how do they get involved? Or is it simply through the yellow card?  Matt: So at the moment, the Yellow Card Biobank is focusing on alopurinol.   Vivienne: So, that's a medicine you take for gout.  Matt: Which I use a lot in my rheumatology clinical practice. And direct acting oral anticoagulants, DOACs, which are used for vascular disease therapies and haemorrhage as a result of that. So, the contact details are available through the MHRA website, but I think more importantly, it's just that people be aware of the yellow card system itself, and that if they do experience adverse drug reactions, that they do actually complete a report form, ‘cos I think still actually a lot of adverse drug reactions go unreported.  Vivienne: I'm forgetting of course that we see Matt all the time in the Genomics England office and we don't think that he has any other home [laughter] than Genomics England, but of course he still sees some patients in rheumatology clinic. So, I want to now look to the future. I mean, I'm, as you both know, a huge enthusiast for pharmacogenomics, ‘cos it's the thing that actually, when you talk to patients or just the general public, they just get it straight away. They can't think why, if you knew about pharmacogenomics, why you wouldn't want to do it. But it's not necessarily an easy thing to do. How can we move in the future, Bill, to a more proactive approach for pharmacogenomics testing? Where would we start?  Bill: Yes, so I think we've built up really good confidence that pharmacogenetics is a good thing to be doing. Currently, we're doing that predominantly at the point when a patient needs a particular medicine. That's the time that you would think about doing a genetic test. And previously, that genetic test would only be relevant for that specific drug. I think we're moving to a place where, rather than just doing that one test that might be relevant to one drug, we'd be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it's required, so that they're not waiting for the results of a genetic test, it's immediately within their healthcare record. That's what we'd call pre-emptive pharmacogenetic testing, and I think that's the golden land that we want to reach.  Vivienne: So for instance, I might have it on my NHS app, and when I go to a doctor and they prescribe something, I show my app to the GP, or something pops up on the GP's screen, or maybe it's something that pops up on the pharmacist's screen.  Bill: I think that's right. I think that's what we're looking to get to that point. We know that colleagues in the Netherlands have made some great progress at developing pathways around that. There's a lot of public support for that. And pharmacists are very engaged in that. In the UK, the pharmacists, over the last few years, have really taken a very active role to really push forward this area of medicine, and this should be seen as something that is relevant to all people, and all health professionals should be engaged with it.  Vivienne: And on a scale of one to ten, how difficult is it going to be to implement in the NHS?  Bill: So, that's a difficult question. I think the first thing is identifying what the challenges are. So I have not given you a number, I've turned into a politician, not answered the question. So, I think what has happened over the last few years, and some of our work within the NHS Network of Excellence in pharmacogenetics and some of the other programmes of work that have been going on, is a really good, honest look at what it is we need to do to try to achieve pharmacogenetics implementation and routine use. I don't think the challenge is going to be predominantly in the laboratory. I think we've got phenomenal laboratories. I think we've got great people doing great genetic testing. I think the biggest challenges are going to be about how you present the data, and that data is accessible. And then ensuring that health professionals really feel that this is information that isn't getting in the way of their clinical practice, but really making a difference and enhancing it, and of benefit both to the healthcare system but more importantly to the patients.  Vivienne: Now, when I hear you both talk, my mind turns to drug discovery and research, and Matt, I'm quite sure that that's right at the top of your mind. Tell us how pharmacogenomics can help in drug discovery and research.  Matt: So, pharmacogenomics, I think actually just genetic profiling of diseases in itself just to start off with is actually a really good way of identifying new potential therapeutic targets, and also from derisking drug development programmes by highlighting likely adverse drug reactions of medications that are being considered for therapeutic trials, or targets that are being considered for therapeutic development. Pharmacogenomics beyond that is actually largely about – well, it enables drug development programmes by enabling you to target people who are more likely to respond, and avoid people who are more likely to have adverse drug reactions. And so that therapeutic index of the balance between likely efficacy versus likely toxicity, genetics can really play into that and enable medications to be used where otherwise they might have failed.  This is most apparent I think in the cancer world. A classic example there, for example, is the development of a class of medications called EGFR inhibitors, which were developed for lung cancer, and in the initial cancer trials, actually were demonstrated to be ineffective, until people trialled them in East Asia and found that they were effective, and that that turns out to be because the type of cancers that respond to them are those that have mutations in the EGFR gene, and that that's common in East Asians. We now know that, wherever you are in the world, whether you're East Asian or European or whatever, if you have a lung adenocarcinoma with an EGFR mutation, you're very likely to respond to these medications. And so that pharmacogenomic discovery basically rescued a class of medication which is now probably the most widely used medication for lung adenocarcinomas, so a huge beneficial effect. And that example is repeated across multiple different cancer types, cancer medication types, and I'm sure in other fields we'll see that with expansive new medications coming in for molecularly targeted therapies in particular.  Vivienne: So, smaller and more effective trials rather than larger trials that perhaps seem not to work but actually haven't been tailored enough to the patients that are most likely to benefit.  Matt: Yeah, well, particularly now that drug development programmes tend to be very targeted at specific genetic targets, pharmacogenetics is much more likely to play a role in identifying patients who are going to respond to those medications. So, I think many people in the drug development world would like to see that, for any significant drug development programme, there's a proper associated pharmacogenomic programme to come up with molecular markers predicting a response.  Vivienne: We're going to wrap up there. Thank you so much to our guests, Bill Newman, Anita Hanson, Matt Brown, and our patient Jane Burns. Thank you so much for joining us today to discuss pharmacogenomics in personalised medicine, and the benefits, the challenges and the future prospects for integrating pharmacogenomics into healthcare systems. And if you'd like to hear more podcasts like this, please subscribe to Behind the Genes. It's on your favourite podcast app. Thank you so much for listening. I've been your host, Vivienne Parry. This podcast was edited by Bill Griffin at Ventoux Digital and produced by the wonderful Naimah. Bye for now. 

On this week's episode of CMDA Matters, Dr. Bill Griffin is joined by Dr. Van B. Haywood, who was the recipient of CMDA's 2024 Educator of the Year Award. Listen to hear more about how Dr. Haywood is using dentistry to bring the hope and healing of Christ to the world.  RESOURCES FOR THIS EPISODE:  Give to CMDA Email CMDA Matters CMDA Bookstore CMDA Dental Ministries CMDA Annual Awards Great Commission Dental Conference Global Health Outreach 2025 CMDA National Convention

In this episode, we delve into the impact of the new groundbreaking research uncovering the RNU4-2 genetic variant linked to neurodevelopmental conditions. The discovery, made possible through whole genome sequencing, highlights a genetic change in the RNU4-2 gene that affects about 1 in 200 undiagnosed children with neurodevelopmental conditions, making it more prevalent than previously thought. This discovery represents one of the most common single-gene genetic causes of such conditions. Our host, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Lindsay Pearse who shares her journey through the diagnosis of her son Lars. They are also joined by Sarah Wynn, CEO of Unique, and Emma Baple, Clinical Genetics Doctor and Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. We also hear from the 2 research groups who independently discovered the findings: Dr Andrew Mumford, Professor of Haematology at the University of Bristol Link to the research paper: https://www.nature.com/articles/s41591-024-03085-5  Assistant Professor Nicky Whiffin, Big Data Institute and Centre for Human Genetics at the University of Oxford Link to the research paper: https://www.nature.com/articles/s41586-024-07773-7 To access resources mentioned in this podcast:  Unique provides support, information and networking to families affected by rare chromosome and gene disorders - for more information and support please visit the website. Connect with other parents of children carrying a variation in RNU4-2 on the Facebook group.   "I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future."   You can read the transcript below or download it here: https://www.genomicsengland.co.uk/assets/documents/Podcast-transcripts/How-has-a-groundbreaking-genomic-discovery-impacted-thousands-worldwide.docx  Naimah: Welcome to Behind the Genes. Lindsay: So, this feeling that like we've been on this deserted island for eight years and now all of a sudden, you're sort of looking around through the branches of the trees. It's like, wait a minute, there are other people on this island and in this case actually there's a lot more people on this island. Yeah, it's very exciting, it's validating. It gives us a lot of hope and, you know, it has been quite emotional too and also a bit of an identity shift. Being undiagnosed had become quite a big part of our identity, and so now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. Naimah: My name is Naimah Callachand and I'm Head of Product Engagement and Growth at Genomics England. On today's episode, I'm joined by Lindsay Pearse whose son Lars recently received a genetic diagnosis, made possible by research using data from the National Genomic Research Library, Sarah Wynn CEO of Unique, and Emma Baple, a clinical genetics doctor. Today we'll be discussing the impact of recent research findings which have found a genetic change in the non-coding RNU4-2 gene, to be linked to neurodevelopmental conditions. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Naimah: And first of all, I would like everyone to introduce themselves. So, Lindsay, maybe if we could come to you first. Lindsay: Great, thank you. So, thank you for having me. I'm Lindsay Pearse, I live outside of Washington DC and I'm a mum to 3 boys. My oldest son Lars who is 8, he was recently diagnosed with the de novo variant in the RNU4-2 gene. Naimah: Thank you. And Emma? Emma: My name is Emma Baple. I'm a Clinical Genetics Doctor which means I look after children and adults with genetic conditions. I'm also a Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub. Naimah: And Sarah? Sarah: Hi, thank you for having me. I'm Sarah Wynn, I'm the CEO of a patient organisation called Unique, and we provide support and information to all those affected by rare genetic conditions. Naimah: Great, thank you. It's so great to have you all here today. So, first of all Lindsay, I wonder if we could come to you. So, you mentioned in your introduction your son Lars has recently been diagnosed with the de novo variant. I wondered if you could tell us a bit about your story, and what it's been like up until the diagnosis. Lindsay: Sure, yeah. So, Lars is, he's a wonderful 8 year-old boy. With his condition, his main symptoms he experiences global developmental delays, he's non-verbal. He's had hypertonia pretty much since birth and wears AFO's to support his walking. He has a feeding disorder and is fed by a G-Tube. Cortical vision impairments, a history of seizures and slow growth, amongst other things. So, that's just a bit of a picture of what he deals with day to day. But he's my oldest child, so first baby. When I was pregnant, we were given an IUGR diagnosis. He was breech, he had a hernia soon after birth, wouldn't breastfeed. But all of these things aren't terribly uncommon, you know. But once he was about 3 or 4 months old, we noticed that he wasn't really able to push up like he should, and we were put in touch with early intervention services for an assessment. So, we went ahead and did that when he was about 4 or 5 months old. And as parents, we could just kind of tell that something was off from the assessors. And, you know, they were very gentle with us, but we could just get that sense that okay, something is off, and they're worried here. So, that kind of kickstarted me into making appointments left, right and centre with specialists. The first specialist that we saw was a neurologist. And yeah, again, that's another appointment that I'll never forget. She referred us to genetics and to get an MRI and some lab work but at the end of the appointment, she said to us, ‘Just remember to love your child.' And, you know, that was quite shocking to us at the time because it wasn't something that had ever crossed our mind that we wouldn't do or felt like we needed to be told to do this. But on the other hand, it certainly set off a lot of worry and anxiety of okay, well, what exactly are we dealing with here? So, fast forward, we saw genetics and that was about when Lars was about 8 months old. We went through a variety of genetic testing, a chromosomal micro-array, a single gene testing, then the whole exome testing. Everything came back negative, but it was explained to us that what was going on was likely an overarching genetic diagnosis that would explain his like, multi-system symptoms. And so meanwhile as he was getting older his global delays were becoming more pronounced and we were also in and out of the hospital a lot at this time. At first, he was in day care and, you know, any sort of cold virus would always turn into like a pneumonia for him. So, we were just in and out of hospital seeing a myriad of specialists, trying to put together this puzzle of what's going on and it was really hard to accept that nobody could figure it out. That was just, you know, sort of mind-blowing to us I guess. So, we applied for and were accepted into the Undiagnosed Diseases Programme at the National Institute of Health over here. The NIH as it's commonly referred to. So, we first went there when Lars was 2. He was one of their youngest patients at the time. But that was a really great experience for us because we felt like they were looking at him holistically and across a bunch of all of his systems, and not just seeing a specialist for sort of each system. So, we really appreciated that. We also did the whole genome sequencing through this research study. Although that also came back negative and so at that point, we were told to kind of keep following up symptomatically. Keep seeing the specialists and eventually maybe one day we'll find an overarching diagnosis, but that science just hadn't quite caught up to Lars. It was hard for me again to believe that and to sort of wrap my head around that. But certainly, it was an education from all of the doctors and geneticists and everyone we saw at NIH, to realise like how far there still was to go in terms of genetic research. How it wasn't also that uncommon to be undiagnosed in the rare disease community. I would say that being undiagnosed sort of became part of our identity. And it's, you know, it was something that, you know, you had to explain to like insurance companies and to his school, and it became part of our advocacy around him. Because without being able to say oh, it's this specific thing and if it was someone who hadn't met Lars before, trying to explain to them that, you know, yeah, within the range of this community you can be undiagnosed, and they just haven't found it yet, but I promise you there is something going on here. And I'd say the other thing too without a diagnosis you have no prognosis, right? And so, trying to figure out what the future would look like. Also, family planning. We waited 5 and a half years before we had another child and, you know, it was certainly an anxiety ridden decision. Ultimately after seeing as many specialists as we possibly could, we still were left with the same answer of well, we just don't really know if it will happen again. So, that was a big decision to make. But again, it just kind of became part of our identity and something that you did eventually accept. But I would say in my experience I feel like the acceptance part also of Lars' disabilities perhaps took me a little bit longer. Because again, I didn't have a prognosis, so I didn't exactly know what we were dealing with. Only as he has become older and, you know, you're sort of getting a better sense of what his abilities might be than being able to understand, okay, this is what I'm dealing with. I need to accept that and do what I can to care for him and our family in the best way that we can. Naimah: Thanks so much for sharing that, Lindsay. I feel like you've touched on a lot of really, you know, a lot of complications and difficulties for your family. Especially, you know, with regards to keeping hopeful and things about the prognosis as well, I'm sure it was really difficult. You've mentioned that Lars was able to be diagnosed recently due to recent research efforts. So, Sarah, I wonder if you can tell us a bit more about these and what the findings have meant for patients with neurodevelopmental conditions. Sarah: Yes. So, I think we know that there are lots of families that are in Lindsay and Lars' position where they know that there is almost certainly an underlying genetic condition, and it just hasn't been found yet. And so, I think we know that lots of researchers are working really hard to try and find those causes. I think over time we know that as time goes on and research goes on, we'll find more of these new genetic causes for neurodevelopmental conditions. I think particularly as we start to look at regions of the genome that we haven't looked at so much so far. But I think one of the things that's really extraordinary about this one is that actually it turns out to be much more common than we might have expected, for one of these new conditions that we haven't found before. But I think it's about one in 200 of those undiagnosed children with neurodevelopmental conditions, have this diagnosis so that's not a small number. That's not a rare finding at all actually, that's much more common than we could ever have anticipated. But I think one of the things that we do know is that as we look further and deeper into that genomic sequence, so, we've started off looking at the bits of the sequence that are genes that code for proteins. This changes in a gene that actually doesn't code for protein, so it's less obvious that it would be important but clearly it is important in development because we know when it has a spelling mistake in it, it causes this neurodevelopmental condition. But there will be as researchers look more and more at these kinds of genes, and also the other part of the genome that is not genes at all, we'll find out more and more the underlying genetic causes of these neurodevelopmental conditions. I think it's also really important to stress why this is so important to find these genetic changes and it's because families really need a diagnosis. Lindsay talked quite eloquently and a lot about that knowing something was off and really wanting to know the reason why. Getting these diagnoses might change care management or treatment, but actually really importantly it just gives an answer to families who have often been looking for an answer for a really long time. Naimah: I just wanted to go back to the point that Sarah made that actually this genetic change is relatively common. Emma, I wondered if you could tell us a bit more about maybe why it took us so long to discover it? Emma: That's an interesting question actually. I suppose the sort of slightly simplified answer to that question is we haven't been able to sequence the whole of a person's genetic information for that long. And so, children like Lars would have had, as Lindsay described lots and lots of genetic tests up until they had a whole genome sequencing which is what Sarah was talking about. The types of tests that we had up until the whole genome sequencing wouldn't have allowed us to look at that bit of the genetic code where this RNU4-2 gene can be found. So, we can only really find that using whole genome sequencing. So, before that existed, we wouldn't have been able to find this cause of developmental condition. Naimah: Okay, thanks Emma. Naimah: Now we're going to hear from one of the two research groups who are responsible for these research findings. First of all, let's hear from Nicky Whiffin. (Clip - Nicky Whiffin) Naimah: How were the findings possible using the Genomics England dataset? Nicky: So, most previous studies have only looked at genetic variants that, in genes that make proteins, but only a subset of our genes actually do makes proteins. The Genomics England dataset we have sequencing information on the entire genome, not just on these protein coding genes and that means we can also look at variants in other genes. So, those that make molecules other than proteins. And RNU4-2 for example, makes an RNA molecule. Naimah: These findings translated to direct patient benefit for patients like Lars who were able to receive support from Unique. How does this demonstrate the value of the dataset? Nicky: Yes. So, it was incredible that we could find so many patients with RNU4-2 variants so quickly. This was enabled by access to Genomics England data but also to other large sequencing datasets around the world. So, we worked with people in the US, in Australia and also in mainland Europe. These large datasets enabled us to spot consistent patterns in the data and by looking across multiple datasets we can also make sure that our findings are robust. When we realised how significant this was and how many families would be impacted, we very quickly contacted Sarah at Unique to see if we could direct patients to them for support. (End of clip) Emma: There's one thing I wanted to raise. It's important to recognise the way that was discovered was through the National Genomic Research Library that Genomics England hosts. To highlight the value of that, and the value of having this centralised resource where families have been kind enough really to allow their data to be shared with some limited clinical information that allowed these researchers to be able to pull this out. And I think it highlights the power of the National Health Service in that we were able to create such a resource. It's really quite astounding that we've found such a common cause of a rare genetic condition, and it wouldn't have happened in the same timescale or in this way without that resource. And then to just say that as Sarah talked about the fact that we've been able to get that information out there, also the researchers were able to get out there and contact the NIH and all of these other programmes worldwide. In Australia, America, everywhere in the world and quickly identify new patients who had this condition and get those diagnoses out really rapidly to people. But all that came from that power of sharing data and being able to have that all in one place and making it accessible to very clever people who could do this work and find these answers. It's so important for families like Lindsay's, and all the families in England and around the world that have got these answers. So, I guess it's a big plug for the value of data sharing and having a secure place where people feel that it's trusted and safe, that enables these diagnoses to be made. Lindsay: If I could just echo that, we're so grateful that that exists in the UK. Just acknowledging like the privilege here that we have had to be able to, I mean for our family in the US, that we've been able to, you know, get ourselves into the NIH study and into the study at Children's National. That takes a lot of work. I feel like not everybody has that opportunity to be able to spend the time to do these applications and to go to all the appointments and get the testing done and have the insurance to cover it. So, very grateful that the system exists in a way in the UK that made this sort of research possible. I just hope that that can be replicated in other places, and also to what Emma was saying earlier, come up with a lower cost test as well for this to further the growth of the community and of course then the corresponding research. Sarah: I think firstly we have to sort of thank all of those families that took part and do share their data, because I think it's not always clear why you might want to do that as a family. I think this is really a powerful example of the benefit of that. I also think the data sharing goes one stage further. So, it's partly about getting the diagnosis, but the data sharing going forward about how this condition impacts families, both clinically and sort of day to day lived experience, is how we'll be able to learn more about these conditions. And so, when families get this diagnosis next week or next year, not only will they get a diagnosis, but they'll get a really good idea about what the condition is and how it might impact their child. Naimah: And Lindsay, coming back to you. So, we've talked about, you know, what it meant for your family before the diagnosis, but what has it meant to have a diagnosis and how did you feel? And what happened whenever you received the diagnosis? Lindsay: Sure. Lars was again part of the NIH Undiagnosed Diseases Research study. So, once you attend this programme and if you are not diagnosed like at the end of your stay, they keep your details on file and you're part of this database at the NIH Undiagnosed Diseases Programme. So, if you're undiagnosed after your sort of week-long work up, your samples stay within the research programme. We were also part of a research programme at Children's National Medical Centre, the Rare Disease Institute. So, our samples were sort of on file there in their database as well. And so, at the end of March I was really quite shocked to receive a call from our long time and trusted geneticist at Children's National that they had found a diagnosis. It was quite emotional. I really kind of didn't believe it. I just kept asking, you know, ‘Are you sure? Is this it?' you know, ‘How confident are we?' Because I think in my head, I sort of always thought that we would eventually find a diagnosis, but I thought that Lars would be, you know, a 30- or 40-year-old adult. I thought it would be decades from now. Like I felt like for whatever reason we had to wait decades for the science to sort of catch up to him. So, we were very, very grateful. It felt very validating, I guess. I had always kind of had this intuition feeling that we were sort of missing something and it's more that the science just hadn't quite caught up yet. But, you know, it was validating to know that okay, Lars is not the only person in the entire world with this, it is something that is relatively common in fact within the rare disease community. That is also very exciting to me personally because I'm hopeful that that will lead more researchers to be interesting in this, given how, quote on quote, common it is. I've sort of been describing it as like a mass diagnosis event but also more so this feeling that like we've been on this deserted island for eight years and now all of a sudden, you're sort of like looking around through the branches of the trees. It's like, wait a minute, there are other people on this island ad in this case, there's actually a lot more people on this island. Yeah, it's very exciting, it's validating. It gives us a lot of hope. And, you know, it has been quite emotional too and also a bit of an identity shift. Because I spoke earlier about how like being undiagnosed had become quite a big part of our identity. So, now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. But yeah, we're just very grateful that the research had continued. And, you know, I think sometimes you sort of have this feeling of okay, our files are up on a shelf somewhere, you know, collecting dust and are people really looking at them? And actually, it turns out that the research was ongoing and yeah, we're just very grateful for that. Naimah: Thanks so much for sharing, Lindsay. It sounds like it's been a real rollercoaster of emotions for your family and I'm glad to hear that, you know, you've got some hope now that you've got a diagnosis as well. So, moving onto the next question. Emma, I wanted to ask you then, how will these findings improve clinical diagnostic services for those for neurodevelopmental conditions? Emma: So, you asked me earlier about why it had taken so long to find this particular cause of neurodevelopmental condition, and I gave you a relatively simple answer. The reality is one of the other reasons is that almost eight out of ten children and adults who have RNU4-2 related neurodevelopmental condition have exactly the same single letter spelling change in that gene. So, actually that in itself means that when researchers are looking at that information, they might think that it's actually a mistake. Because we know that when we sequence genetic information, we can see mistakes in that sequencing information that are just because the machine has, and the way that we process that data, it's not perfect. So, sometimes we find these little mistakes and they're not actually the cause of a person's problems, they're just what we call an artefact or an issue with the way that that happens. So, that is part of the reason for why it was tricky for us to know whether this was, or rather the researchers to know whether this was or was not the cause of this particular condition. But that in itself is quite helpful when we think about how we might identify more people who have this going forwards. Because unlike in Lars' case where we didn't know what the cause was and so we were still searching, and we didn't know where to look in the billions of letters that make up the genetic code to find that answer, we now know that this is really very common. It's unbelievably common. I think we didn't think we would be finding a cause of a rare genetic condition that was this commonly occurring at this stage. But the fact that it's just a single, it's commonly this one single change in the gene means that we can set up pretty cheap diagnostic testing. Which means that if you were somewhere where you wouldn't necessarily have access to whole genome sequencing, or a more comprehensive testing in that way, we could still be able to pick up this condition. And it's common enough that even if you didn't necessarily recognise that a person had it, you could still have this as part of your diagnostic tool kit for patients who have a neurodevelopmental condition. It's common enough that just doing a very simple test that could be done in any diagnostic lab anywhere in the world, you would be able to identify the majority of people who have this. Naimah: Now let's hear from the other research group who are responsible for these findings. Here is Dr Andrew Mumford. (Clip - Dr Andrew Mumford) Naimah: Why are these research findings significant? Andrew: It offers genetic diagnosis not just for a handful of families but potentially for many hundreds of families, who we all know have been searching often for many, many years for a genetic diagnosis. But actually, there are other gains from understanding how this gene causes neurodevelopmental disorder. We know that there's GRNU4-2 in codes, not a protein actually, but a small nuclear RNA which is unusual for rare, inherited disorders. It's a component of a very complicated molecule called the spliceosome which in turn regulates how thousands of other genes are regulated, how they're made into proteins. So, fundamentally this discovery tells us a lot about the biology of how the spliceosome works. We already know that some other components of the spliceosome can go wrong, and result in diseases like neurodevelopmental disorders. This gives us an extra insight and actually opens the door to, I hope, a whole load of more discoveries of genetic diagnosis possible from other components of this complicated molecule. Naimah: Your research group used a mathematical modelling approach. Can you tell me a bit about this, and what this means for other rare conditions, Andrew? Andrew: So, identifying relationships between changes in individual genes and different kinds of rare, inherited disease is notoriously difficult because of the volume of data that's involved and the need to be absolutely certain that observed genetic changes are actually the cause of different rare, inherited disease. So, applying statistics to that kind of problem isn't new. But what my collaboration group have achieved here, is to develop, actually developed some years ago a completely new approach to applying statistics to genetic data. We call that BeviMed and we've been working for many years on the genes in code that make individual proteins. Most rare disorders are caused by genetic changes in genes that make proteins. What this discovery comes from is actually we've applied the BeviMed statistical technique to genes that don't make proteins, they're non-coding genes. For example, genes that make small nuclear RNA, it's just like RNU4-2. What's unusual about the BeviMed approach is that it's very sensitive to detecting links between genetic changes and rare diseases, and it can detect statistical associations really driven by very, very small numbers of families. So, we apply it to datasets like the 100,00 Genomes dataset and identify associations using statistics that have got a very high probability of association. Other members of the team then seek to corroborate that finding by looking at if we can see the association in other datasets, and we certainly achieve that with RNU4-2. But also, assessing biological plausibility by investigating what we understand already about in this case, a small nuclear RNA, and how it can possibly result in a disease. And we normally try and employ other independent evidence such as experimental investigation. Or going back to our families and asking for additional data to help really test this sort of theory that changes in this particular gene have resulted in a problem with neurodevelopment. (End of clip) Naimah: Emma, are there any other ways that we can identify these conditions based on their clinical presentation? Emma: So, Lindsay and I were talking with you just yesterday, wasn't it? And I asked Lindsay about what sorts of things Lars had in common with other children and adults who have been diagnosed with this condition? I actually think Lindsay probably gives a better summary than I would, so I might ask you to maybe repeat what you said to me yesterday. But the bit of it that really stood out to me was when you said to us that a lot of parents have said, ‘I'm not sure how we weren't all put together in the first place because you notice so many things that were in common.' So, maybe if you can give that summary and then I can translate that back into medical terms, if that's okay Lindsay. Lindsay: Sure, of course. Yeah, it been again, kind of mind blowing, some of the similarities. Especially as we've exchanged pictures and such, and baby pictures especially where some of the children like look like siblings. So, definitely some similarities in facial features, you know, everyone seems to experience some of the slow growth, so a short stature or quite skinny. There's feeding issues also that seem to be quite common. Also, you know, things like the global developmental delays, that's certainly across the board and histories of seizures, that's also quite common. Some people have experienced also some, like, bone density issues, that's not something that we've experienced so far, but that also seems to be quite common. But then also, behaviourally, there's a lot of similarities which has been, I think, quite exciting to a lot of us because you've always thought okay, so this is just my child. And of course, some of that is true but it's also interesting to find out some of these other things that are, you know, are quite similar. So, a lot of people have mentioned their child having, like, an interesting sense of humour. Kind of like a very slapstick sense of humour which is quite interesting. Or everyone seems to love water, everybody loves swimming pools and bathtime, and all of that. Lars loves a windy day. Something about the wind, he just loves it and plane noises and things like that have also come up with other people. So, yeah, it's been really interesting and cool to see. Emma: So, I guess Lindsay's sort of very beautifully summed up what is written in the research publication. So, there's only two research publications so far on this condition, it's all really new. And I am definitely not claim to be a clinical expert on this condition, and I don't think there are any yet. It will take people time to see lots of children and adults who have this particular condition. But ultimately what Lindsay summarised was the common clinical features that have been described by parents. In my job as a clinical genetics doctor, part of what we look at is a person's appearance. So, Lindsay described the photographs of children particularly when they were little, looked very similar. In the photographs that I've seen, I would agree with that. And so obviously those children look like their mum and dad, but they have other features that are in common. They have a characteristic appearance and that helps doctors like me to have an idea as to whether a child or an adult might have a particular condition. Then put together with the sorts of information that Lindsay gave us around the low tone, so being a little bit floppier particularly when they're little. The slow growth and growth problems, problems with eating, also with seizures. Those are all common things that were pulled out of both of the two research publications on this condition and putting that all together into one picture helps doctors to have an idea whether somebody may have a particular condition. That would help us in this case to potentially request that simple test I was talking about, if maybe we were practicing in a part of the world where we wouldn't have the resources that we thankfully do have in the United Kingdom, and in the USA. Naimah: So, Sarah, just coming to you next. How does this research spread awareness and help other patients with these conditions? Sarah: So, I think one of the things that's been really great about research now is that we are able to, you know, social media and things like that mean that we can spread this information really quickly across the world basically. I think what that does is that as well as helping bring people together that they've got this diagnosis, what it does is I think it provides hope for all of those people that Lindsay was talking about at the beginning who don't have a diagnosis. So, that piece around people are still looking, the researchers are working hard and that even if you don't have a diagnosis today you might get one in the future. Lindsay talked about your sample being dusty and not being looked at. I think it gives lots of families, not just those that get this diagnosis but all of those that haven't got a diagnosis, hope, that hopefully in the future they will get a diagnosis. I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future. That prognosis information that Linsday said is really missing when you don't have a diagnosis. And I think the other thing that hopefully is the next stage in this journey with this discovery is that those two science publications that Emma talked about, what we will want to do here at Unique working with the researchers and those families that have got a diagnosis, is to produce a patient family friendly information leaflet about this condition. One of the things we know is really important about those patient leaflets is including the photos. Because as both Emma and Lindsay have said that idea that they have facial features in common. And so, if you look at a leaflet and you can recognise your child in it, and you can see others that look like it, that can be a really sort of quite heartwarming experience in what often is a lonely experience with a rare condition. Naimah: And I think kind of on that point about it being a lonely experience, I wondered Lindsay if you could talk a bit more if this research has allowed you to connect with other parents and families who have received a diagnosis, and what impact that's had on your family? Lindsay: Yeah. I mean, and I think everything that Sarah has said was spot on. It's wonderful to have resources like Unique to connect families and have those diagnoses on the platform, so other clinicians can look for it and sort of grow this group. I think that has definitely been the highlight of getting this diagnosis at this stage, right. Because there's not much more you can do with it, with someone so brand new so being able to connect with the other families has been wonderful. One amazing mum who with this diagnosis set up a Facebook group, RNU4-2 Family Connect. And, you know, it's just been amazing to see people from all over the world joining this as they receive this diagnosis, you know, sharing their stories. We've spent countless hours on the weekends over the past couple of months on Zoom calls with total strangers, but just you find that you can just talk for hours and hours because you have so much in common. It's great to see what has worked well for other families and, you know, what has not worked. Sharing resources, just kind of all learning together. Also seeing the spectrum of this diagnosis, I think most genetic disorders have a spectrum and this seems to be the same here. So, that's been very interesting. And of course, our son is 8, Lars is 8. There's now a 33-year-old and a 29-year-old in the Facebook group. Speaking for me personally it's just amazing to see them and like it's very cool to see where they're at. That sort of helps you answer some of those questions about that before were quite unknown when you were thinking about the future. Obviously, everybody's development whether you have a genetic disorder or not, it is going to be what it's going to be, and everybody is going to do their own thing. But being able to see what a path might look like is just so helpful. And, you know, we all want community and connection, and so this has been really, really great to have that now. Sarah: I don't think there's much more that I can add because Lindsay articulated so well. But it's really heartwarming for us to hear the benefits of those connections because that's really why Unique and other support groups exist. Is to provide, partly to provide information, but I think predominantly to put families in touch with other families so that they can find a new home and connect and share experiences. And, you know, stop feeling as alone as they might have done before. Naimah: Okay, we'll wrap up there. Thank you to our guests, Lindsay Pearce, Sarah Wynn and Emma Baple for joining me today as we discussed the research findings which found a genetic change in the RNU4-2 gene which has been linked to neurodevelopmental conditions. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.

Genomics has changed considerably over the past 10 years, and we are now exploring how to integrate it into routine healthcare. In this episode, our guests reflect on this evolution and discuss how the key learnings from the past 10 years can shape the genomics ecosystem of the future. They highlight the importance of partnership across teams, organisations and participants, emphasising the importance of keeping participant and patient benefit at the heart of research, whilst also addressing the ethical and safe storage of patient data. In this episode, our host, Helen White, who is the Participant Panel Vice-Chair for cancer at Genomics England, speaks with Dr Rich Scott, CEO of Genomics England.   "Our goal is to ensure that everyone can benefit from the advancements in genomics, but this requires collaboration across disciplines and a commitment to ethical practices in managing and sharing genomic data."   You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/How_can_we_work_in_partnership_towards_a_new_era_of_genomic_medicine_and_research.docx Helen: Welcome to Behind the Genes.  Rich: There's a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care.  Helen: My name is Helen White and I am the Participant Panel Vice Chair for Cancer, at Genomics England. On today's episode I'm joined by Dr Richard Scott, Chief Executive Officer for Genomics England. And today we'll be discussing Richard's recent appointment as CEO, lessons learnt from the last ten years in the evolution of genomics in healthcare, and how these learnings will be taken forward in the next ten years. And we'll also visit the importance of keeping participant and patient benefit at the heart of research, as well as the ethical and safe storage of patient data. If you enjoy today's episode we would love your support: please like, share and rate us on wherever you listen to your podcast.   Before we dive into the interview with Rich, I wanted to take a moment to share my story and tell you a little bit about myself. I have been a member of the Participant Panel at Genomics England since 2018. It was the year before that when I was diagnosed with endometrial, or womb cancer, and was offered the chance to join the 100,000 Genomes Project, which felt like something positive at what was otherwise quite a scary time. It turns out that I have something called Lynch syndrome, that's a genetic condition that increases my chance of developing certain cancers, particularly womb and bowel cancer, which is actually a really useful thing to know as there are things I can do to reduce my chance of getting cancer; things like having regular colonoscopies and taking daily aspirin. I have now been on the participant panel for six years and one year ago I was appointed as Vice Chair for cancer. This is a new and developing role and I am excited to have so far helped recruit more people with lived experience of cancer to the panel and to be assisting Genomics England with connecting to organisations that advocate for people whose lives have been touched by cancer.   So that's enough about me. I am delighted to be joined today by Richard Scott, and I am very much looking forward to our conversation. Welcome, Rich.   Thank you. So Rich, you've recently been appointed CEO of Genomics England. Can you tell me a bit about your background and what brought you to this role?   Rich: It's a really good question and it's one that doesn't have a really very simple answer. I guess what it boils down to is I guess I've always had an interest, even as a child, for whatever reason, in genetics and genomics. I have also then always been drawn to things where I can have an impact and particularly the impact in healthcare and that's what took me to being a medical student. And I guess it's that combination of that particular interest in genetics and being able to see, even when I was at medical school I qualified in 2000 that this was an area of medicine that was going to be really important in the future. And then as I trained, as I did a PhD and as I saw the technology develop and change and then when I saw the UK government and the NHS investing in genomics in a really foresighted way, I found myself eight or nine years sitting at Great Ormond Street as a consultant in clinical genetics where I still practice, I still do one clinic a month there as a clinical genetics consultant seeing families with rare conditions.   But I could see when Genomics England was established that this was something, as I said, really foresightful where we could really collectively across the country make more of a difference together in terms of patient and healthcare outcomes. So I joined GEL eight or nine years ago initially in a subject matter expert role, and really found myself the more time it passed, understanding how working in my role at GEL and helping GEL be a really productive part of what is a busy genomics healthcare ecosystem in the UK, we can make a big difference, and that's the thing that just wakes me up in the morning, is realising how much there is left to do, being proud of the stuff we've done, the difference we've made to participants in our programmes already, but realising that many of those still need our support to do better and the big distance left to go before we really deliver on I think the long-term promise of genomics, and I feel my mixture of skills and experience make me really excited to be in the middle of that.   Helen: Thank you. Yes, it sounds like you've brought many skills and experience, and interesting to hear that as a child you already had that interest in genetics and where that's taken you. Can you tell me what being CEO Genomics England means for you? What are your aspirations for your first year in this position?   Rich: Well, I guess, as you can tell, I'm really excited to take on this role. As I said, as a doctor I'm always focused on the impact for patients and our participants and ultimately it's the broader health of the nation. And the role I see Genomics England playing and being able to play in the future, sort of building on that, the leadership position the UK's always had in genomics – you know if you look back to the discovery of the structure of DNA, the invention of sequencing technologies and also the clinical implementation coming from that government investment and the NHS investment, what excites me most about GEL is that we can be there, playing a critical role alongside others in that ecosystem, whether that's in the NHS, whether it's our participants and the patients who we're aiming to support academia and industry, to create a whole that's greater than the sum of the parts, and I genuinely feel that the UK remains uniquely placed to live out that potential that genomics has, engaging in the questions, not just you know, the scientific questions of: what could genomics test for? Or, how could this be implemented and is it cost-effective?  But also being able to have the nuanced conversation of what we all and our participants in the public and general, expect in terms of the care we receive or how our data is looked after, and getting that really balanced view on how we chart a path forwards where we can really see big differences being made in the future, and I think always being honest to ourselves about where we are today and that things don't come in spotting some position a long time in the future that we want to navigate to, but also being really focused on the here and now and what is possible and what is evidenced, and what the next set of evidence or discussions or conversations in the public we need to have to help navigate ourselves there and that's where at the moment our focus at Genomics England is both being very clear sighted on where Genomics could go, and also thinking very clearly about where we are today, and so very much at the moment for us it's about focusing on the life service we offer to the NHS and we're really proud to be part of a world-leading whole genome sequencing service, the first national health service in the world to be providing that in the context of cancer and rare disease, and so offering and providing our service that contributes to that.   Supporting researchers so that we can keep the flow of discoveries coming and also for example, making sure that our participants in existing programmes continue to get new answers as the science evolves. So, the last year more than 2,000 families had new findings fed back because of new knowledge that's accumulating, keeping that flow going. And then we've got three big research initiatives going on at the moment where we're really focusing on delivering around them. We've got a diverse data initiative where we're really focused on making sure the research library, the National Genomic Research Library, our participants are representative of the UK population, so the discoveries that we're supporting are relevant to everyone; our cancer initiative which is exploring the use of new sequencing technology in the context of cancer, and also looking at the use of image data and other modalities of data, alongside generic data to drive new discoveries.   And then the third initiative is our newborn genomes programme, where we're asking a big question through a research study to generate evidence to ultimately answer the question: should every baby when they're born be offered whole genome sequencing? Most pressingly to improve and broader the range of conditions that we can look for that are severe and treatable. So, this year we're very much focused on delivering on those promises that we've made to our participants and our partners and through those programmes and very much with an eye to the future thinking about what we need to change in terms of the use of underpinning technology, so that we know that we've got the potential to scale, to think about the broader use of genomics in years to come as evidence evolves.   Helen: So Rich, there have been many advances in genomics in the last ten years. What do you think are the big lessons from those last ten years, and what do you think the next ten years will look like for the genomics ecosystem, what impact will this all have on healthcare as we know it?   Rich: So, genomics has changed extraordinarily in the last ten years thanks to shifts both in the technology, particularly the sequencing technology but also some of the computing technology that's there to deal with the scale of data. Ten years ago we were talking about the 100,000 genomes project and beginning the project itself, but it was still very early in the use of whole genome sequencing, that's gone from something where the big question around the 100,000 genomes project was: can this technology be used in routine care in cancer and for rare conditions, and if so, how do we do that?   And we've learnt both I think about that specific question and as I mentioned, we're enormously proud to be part of enabling the NHS whole genome sequencing clinical service, so that has entered routine care. I think along the way the biggest lesson for me is actually one about this being about partnership and about working as a team across many different organisations and with our participants, and recognising that this isn't just about one set of questions, or it's not just about clinical or scientific questions, it's about joining everything up together back to that point around, so a discussion about what people expect – this is about doing stuff together and learning often quite complex lessons about practicalities is one things, for example, one of the really big lessons we learnt around the use of whole genome sequencing in cancer are just practical lessons about handling of tissue samples and the need to make sure the right fridges are available on the right corridor of a hospital, with plugs available to plug them into, through to questions around, as I say, people's expectations around how their data is stored, which it's used for, which again there's really strong precedent for, and as we explored, different uses of genomic technology, we shouldn't just take those previous answers for granted, we need to make sure we validate and check with people what their expectations are.   So I think that's the big one for me is sort of the number of different angles with which one explores questions and the fact that this is very much about doing it together. I think just one other piece which is so easy for us here to take for granted is that doing things at national scale with national scale investment from government, from other funders and from the NHS is absolutely critical and when you look across the world, we are in an extraordinarily privileged position here in this country because of that investment and because that investment recognises the need critically to join clinical care and research in a whole, where you recognise that you're doing multiple things at once, but joining them up rather than them being two worlds, is really, really critical, and we're really lucky to be able to do that at national scale.   So then thinking about what the next ten years might look like for the genomics ecosystem, I think lots of those things continue, so I think national scale and the need for ongoing investment to keep up our position at the forefront in terms of answering these big questions about the use of genomics in healthcare, and to where the evidence supports their implementation to roll them out and keep that link there between healthcare and research, and so making sure the systems talk to each other and I mean that in a digital sense as well as a human sense is absolutely critical.   And then, so in ten years' time what are the areas of healthcare that will have been impacted, or could have been impacted by genomics, I'm really pleased that we're doing a better job for families with rare conditions and people with cancer than we were ten years ago, I think there's a long distance left to run even in those settings for us to do better and to continue to learn, so we expect our major focus to continue to be in those areas where we know they can have an impact and there's more to do. We also then have the different areas where if the evidence pans out to support the use of genomics or if we can implement systems that can support it there can be a big sort of area of growth. For example, our newborn genomes programme is asking questions and developing evidence so that in the future policymakers can decide should that become part of routine care, and I think that's something that could have become part of routine care in the next ten years if the evidence supports it and if that's something that the public support.    If I were to pick one other area where there's a real potential for growth in the coming handful of years it's in something we refer to as pharmacogenomics. What that means is looking at your DNA code (genomics) to help make decisions about prescription of medicines and sometimes that's about avoiding these medicines in people who are at a higher risk of having an adverse reaction, or it's about tailoring the dose because of something about for example the way the person metabolises, chews up, the medicine and so can influence how much dose they need. That actually has an enormous potential; we all have variations in our DNA code that influence how we respond to or metabolise medicines. If you look across primary care, GPs and so forth, primary care physicians and in secondary care, hospital care, I think there's good evidence that actually probably half of all appointments, interactions in those settings, if you were to have DNA data available that could influence how prescription choices are made; sometimes that's about knowing that you're doing the right thing, giving the normal prescription, but sometimes it's about modifying it, that's an area where I think there's a real potential for growth and that's an area that the NHS also really recognise and we're exploring ways in which we might look into that and think about how that might be implemented, because actually a lot of the questions there are about how you make sure the right data, the right information is available to clinical teams and patients at the time that prescriptions are being made.   There's also real potential more broadly in thinking about more common disease settings, there's lots of work going on from various research studies looking at the value of what people sometimes refer to as polygenic risk scores or integrated risk scores, where we use genomics as an element of estimating risk for common diseases like heart disease or cancer, that's something where the evidence is being worked on and is developing, I think we'll see a lot of evidence come out in the coming years and I think that will then influence how we implement genomics to help as part of that risk estimation process, which is routine now in GP practices where you go for an NHS health-check they do it with lots of complicated stuff, at the moment not genomics, and we'll see how that plays out in the years to come.   So I think there's enormous room for growth where genomics where at the moment it's making an important difference to people with certain conditions that we can do better on. In the future I see it becoming very much more part of the routine day to day of healthcare. As we make that transition there's lots to work through about the evidence, the order in which that's done and the way in which we, for example, store data, and make people part of the choice about how their data is used and what I'm really excited about in Genomics England is the role we play in the middle of that, bringing our particular expertise around what we call bioinformatics, which is sort of managing genomic data at big scale, particularly national scale to support healthcare and research, generating evidence that can help inform policy, and also critically drawing things together into the conversation amongst different players in the ecosystem and participants in the public so that we can not just think about evidence in a sort of terribly scientific way but we think about it in the round.   Helen: That's really interesting to hear you speak a lot about getting that evidence because that's critical, but that takes a long time doesn't it, so for example with the generation study, the newborn study it's really important to measure the benefits of that if you're testing young babies, newborn babies for diseases that if you pick up a condition that condition can be treated and something can be done about it early rather than poor parents going through this diagnostic odyssey, but also it's that balance isn't it with not leading to any harm, so if a number of parents come out of that thinking their baby might get a condition and it never happens there's potential there isn't there. But I think in terms of the public understanding of how long it takes to get evidence and everything else that needs to go on in the background I don't think it's always particularly clear that that's a massive process that has to be gone through and there's a lot of work going on behind the scenes – you can't just do these things.   I think as patients/members of the public we're eager to get on and for change to happen and things to be better but it's a big, big process, but also good to hear that you talk about it being a collaborative approach, it's not just Genomics England, it's the NHS, it's members of the public and patient voices, it's other organisations working in partnership, it's a big undertaking.   Rich: No, it is and I think that one of the words you used there was impatience, and I think that's healthy and important to recognise, it can be easy, particularly for example as a doctor, sat in a clinic room to accept the status quo, and at the same time, one needs to recognise the complexity of the questions, the balance, the need to generate high-quality evidence to inform those opinions and I think combining both that sort of impatience and dissatisfaction with the status quo, and that mind-set about thinking really thoroughly and collaboratively about the right evidence that is needed to change policy.   Helen: Yes, really important that those patient voices are there from the beginning, from the planning of obtaining this evidence and that you're measuring the things that matter most.   Rich: One of the areas where I think we've seen that play out, another area where I really see the potential for growth in the future is much more genomics-enabled treatments. We and you and the participant panel have helped us think about there's a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer and thinking as we do that about how we structure the system to generate evidence and to respond to it and have a conversation about what the right balance of evidence for patients to make a choice about their own care, but also policymakers to make choices about funding, decisions and safety decisions, is really important and we've been supporting to a wider work in cancer in the UK called the Cancer Vaccine Launchpad, and likewise we're part of something we call the Rare Therapies Launchpad, where in those two areas we're exploring that, and that's another area I think of real potential in the coming years, and also real nuance as we construct a way of navigating that together and making the most of the potential, but not just sort of rushing in and pretending we know all of the answers at the outset.   Helen: And those launchpads are of particular interest to participants in the wider patient population, there are a lot of people and children with rare, ultra-rare conditions who are desperate for treatments that just aren't available right now, equally for cancer patients there's a big need isn't there for more effective treatments, fewer side effects, that target that person's particular cancer, so it's good news I think for the wider public.   It does seem that innovation and partnerships are crucial to Genomics England's activities so how does Genomics England ensure that participant and wider patient benefit are at the heart of these activities?   Rich: I think one of the really important things is actually governance is sometimes a boring word, sounds like it, but I think thinking about how we've structured the organisation and placed you, as the participant panel, as part of our governance to make sure that when we're thinking about for example access to data in the National Genomic Research Library, participants are sort of driving those decisions, it's an independent committee that makes those decisions with representation from our panel. One of the things is thinking about the governance and making sure that you as our participant panel hold us to account for the decisions that we're making, which I think is really critical.  I think then also as we've learnt a lot over the years, not always getting it right, about how we make sure that participants, or potential participants in the public are involved from the outset in the design of programmes because it always helps. I think certainly before I joined Genomics England I think I would have been unsure about the best ways of going about that and that brings with it sometimes a nervousness. I think the main advice I would say to people listening is to have confidence that just getting stuck in and have conversations is the way to do it. There are then also all sorts of expertise that we've really benefited from being to bear in terms of ways of doing that engagement work and that will come; the first thing is to have the confidence and the desire to put that at the centre of how you decide where your focus should be and how you design programmes.   Helen: I think Genomics England has been very successful with that by integrating that patient voice from the very early days and here we are what eight years on I think now, and yes, hopefully we'll be there for some time to come yet, as long as Genomics England exists. So Rich, with more and more health data being stored, how do we ensure that this sensitive personal data is stored and used safely and ethically across the genomics ecosystem. And actually while we're on this question, can you just explain what genomics ecosystem means, because we use that term I think quite a lot, but I think it's not necessarily understandable to the wider public? Rich: What I mean when I talk about it is I mean the mixture of different people, whether that's sometimes organisations, us, Genomics England, the NHS, the NIHR, National Institute for Health Research; industry partners whether they're people who are from pharma companies or from biotech, academic researchers, participants in programmes – everyone who comes together to work on genomics in the UK and a bit like the word as it's used in biology, it's a sort of busy ecosystem with all sorts of people playing their own role and then working together, and so I think it's a really important thing to recognise that we're part of that and in fact it's one of the things I love most about my role at Genomics England is thinking about all of the different partners that we need to work with and to those outside it I think it can also be a bit intimidating, because it's hard to keep up with who on earth everyone is. So then thinking about the question of how we make sure that data's stored and looked after and used in the ways that people expect and safely and so forth, I think that's absolutely at the heart of my role and our role. And I think one thing is actually always sort of starting at the: why are we doing this? What benefits are we seeking to bring to people? Is that what they expect? What have they signed up for if you like? But that's in a research study or when they've decided to say yes to having a particular test, which is the same in any part of medicine. And if we use that to drive our decisions, that's what's so critical. And so that's where thinking about programmes we run, and also the things that we think might be worth something that we should prioritise in the future is always first driven by the benefit that you might be bringing, weighing up the costs and the potential downsides and harm that might be caused by the use of genomic data in that way and that's what should always drive things, and there isn't a one-size-fits-all, you know, genomic data should be used and stored in this way and that's one of the things that I think making sure that participants and the public are at the centre of the conversation is absolutely critical, it turns out that genomic data is very much like health data at large in many senses and it's very precious for those reasons. It is also special in a few ways. One of the ways that's sort of peculiar if you like is that pretty much the DNA sequence, the genome, that you're born with, is the same one that you hold throughout your life, that's different from say if you do a blood count or something that varies for various reasons over your life and most things in medicine do change quite meaningfully over a much shorter time period. One of the things about the DNA code: A) it makes it more precious because it's very much about you, your whole life; also it makes it more useful and reuseable in many ways, so one of the things that we think about a lot more in genomics is about the storage and reuse of data on an ongoing basis through the lifetime. And I do think that that model in certain settings and potentially more broadly as evidence accumulates, may well be the path that we take forward where you consider your genomic data part of your health record where it can be used and reused. And what we need to do is explore why you would in the first case generate someone's DNA sequence, and what sort of sequence, is it a whole genome or less than a whole genome? What would you use it for in the first place when you first generate it? And what other uses could there be to support the healthcare and have you involved them or the public more generally in decisions about how it's used? Because we do, as I said, see the potential for genomics being just becoming part of the fabric if you like of healthcare, good healthcare, the best healthcare.   Linked to that is the point on research as well, like where people are happy for it, holding their genomic data and understanding how that impacts on longer term health outcomes, something we'll continue to learn about for years and years. So I think the first point is about focusing on the why and whose data it is, one's own genome belongs to you, it doesn't belong to anyone else, what people are happy with and consent to and expect and then always holding that in mind as one makes the choices is critical. I've talked about how we think the governance and the involvement of the participant panel is really critical for that as well. And then it also comes down to doing in various ways, the job that people would expect in terms of, for example, that safety piece, using the very latest tooling to make sure that it's held in a secure way, that it's backed up so that it won't be lost etc. and bringing sort of the right, very good minds around some of those more technical questions, but always with the expectations of the people whose genomes they are in mind and to say are we living up to their expectations, are we doing what they would expect?   So, Helen, I wondered if I could ask you a couple of questions. The first one I wanted to ask is what you're hopeful for in the coming years as a participant panel member?   Helen: Thank you. I've actually already posed these questions to some of the other panel members, so I'll try and make sure I include their responses here as well as mine, but I think it's important to hear from everybody, not just me, Rebecca Middleton and Emma Walters have recorded their responses as well. I think the four main things that panel members are hopeful for is the coming years, the first is equitable access to whole genome sequencing, basically everybody who needs whole genome sequencing should get access to it regardless of where they live, their income, ethnicity or disability, so that's something that we're hopeful will get better over the years.   We know this is essential to improving healthcare, to improving outcomes for patients and generally for sort of greater inclusivity and in genomic research, we want as well as Genomics England, the data is the National Genomics Research Library to be representative of the population as a whole, not just the people who 1) are offered, and 2) agree to have their data in the library. And also, obviously the more data that is held in that library, the more opportunity there is for research across those rare and ultra rare conditions and rare and less common cancers, where it's all about numbers, you need numbers of sets of data in order to draw things together and make conclusions to look for patterns.  And the other thing which I guess comes more under the umbrella of the NHS is that the panel is quite keen, they want everybody who's undergoing genomic testing to receive good support and after care, I think regardless of whether that testing is via the NHS or as part of a research study, sometimes it will be both, but that's for the patients at the coal face that is obviously critically important.  The second, I think broad theme, coming from the panel members' responses is that I think you've mentioned this already, is increased understanding of genomics amongst the general public is really important – there's a need to demystify genomics and to generally improve public awareness of its benefits and to get those conversations going around its regulation and its ethical use, but to do that you need to get meaningful engagement from a wide range of people, you know, that's not always straightforward, there are lots of challenges there, it's all about prioritising inclusivity, accessibility, to make sure you get diverse views and perspectives on genomics and on genomics research.   The other thing that came out very strongly from the responses which we have talked quite a bit about already is about this individualised healthcare. I think we as a panel are very hopeful that there will be this shift towards treatment strategies that are tailored more to the individual and their specific health condition, rather than a one-size-fits-all approach, we want effective treatments that will minimise side effects but also through the use of pharmacogenomics, to make sure if there's a risk of a severe, sometimes life-threatening side effect that that can be identified and that individual doesn't have that treatment either at all or has a lower dose, so it's not so toxic.   And let's hear from Emma who talks about this.  Emma: My hope is that we move to a truly individualised healthcare system and I'm really excited to see how in particular pharmacogenomics changes the healthcare landscape. For a long time we've gone with a one-size-fits-all approach, and that's easy to deliver on a large scale basis that the NHS works on, but we know fundamentally that's not how patients work, so to be able to consider individualising medication and knowing which won't work, interests and excites me.   Helen: So the panel is also very hopeful about the development of those innovative therapies, and you talked about the rare therapies launchpad and the cancer vaccine launchpad, because those offer real hope for treating previously untreatable conditions and generally improving accessibility to treatments. And we're also hopeful that there will be a much better understanding of diagnosis of cancer, through things like the multi-model programme, because although there's lots and lots of research going on with cancer there's still a long way to go to have more effective treatments and to improve diagnosis of cancer.   And then just finally just in response to your question, patient and public involvement, this is what the participant panel is all about, we are a group of individuals whose lives have all been touched by either a rare condition or by cancer currently, either we've had that condition ourselves or it's affected our loved one, and we do bring these diverse views and perspectives to Genomics England and I think we have a crucial role in influencing its decisions about what it does with participant data and who has access to that data. It's critically important that Genomics England listens to what matters to the people whose data it holds and who do that, as Rebecca here explains.  Rebecca: Genomics is a fast-moving science and it has the impact to change lives and healthcare for future generations, but genomics is a science of people and therefore the only way you can truly understand the limitations and opportunities of it is to talk eye to eye to the very people it will impact, and not everyone will agree on everything. But how we understand genomics and its power to transform healthcare, our own and that of our children and the ones we love, can only progress at the pace of the people that it will benefit. It's a simple equation but it's not maths and indeed not science: we are all different and unique, our emotions, experience and history will be wrapped up in our viewpoints and thoughts, and that's where the panel comes in, representing and advocating for the very many different voices of genomic healthcare, ensures Genomics England is stronger, healthcare design is more meaningful and research is more impactful.  I have no doubt that the panel of the future will continue to be heard and understood at Genomics England, and I hope it continues to grow to reflect more diverse voices and experiences and continues to be the people inside the science.   Helen: Finally, the panel is also hopeful for increased public and patient involvement in genomics research, this is integral for shaping research both academic and commercial, it helps with identifying research priorities, developing new treatments, basically getting that voice of the patient in there to tell researchers what's the most important and what matters to them.  Rich: So another question Helen, how do the panel feel about the changing genomics landscape? Helen: A good question and I think overall it's a balance between excitement and hope on the one hand, and a bit of apprehension and caution on the other. So the panel is really excited about the advances going on in healthcare, we're entering an age now where we're promised a much more proactive, as opposed to reactive approach to healthcare. You were talking earlier Rich, about having your genome sequence, and this is something that you have for life, it's like your passport, your fingerprint, so from infancy to old age you've got this data which is held somewhere which holds so much promise of predicting if you might develop a disease, whether you might react badly to a drug, so ultimately it offers great potential to improve outcomes for patients, their families and the NHS. Again, we spoke earlier about this holds so much promise for producing the diagnostic odyssey that so many parents go through when the children are born with a condition that doesn't have a diagnosis, potential to diagnose things like cancer a lot earlier where it's more treatable and to prevent disease as well, I know that's something Genomics England isn't specifically looking at, but through screening programmes, using things for example like circulating DNA which may be able to pick up that there are things going on and picking things up earlier means that those things can be dealt with earlier.  I mean thinking of my own personal example, I know I have Lynch Syndrome, I know that I am at risk of developing bowel cancer now, but that means I can do something about it. So I have my colonoscopies every two years, I take aspirin every day because that reduces my chance of getting bowel cancers and I'm much more symptom-aware, so having that knowledge up front is very helpful in being able to move forward and reduce my chance of getting an advanced cancer.  The panel is also very excited about the ongoing collaborations and the novel therapies that are being developed through the rare therapies launchpad, these offer a lot of hope for treating previously untreatable conditions, and improving accessibility to treatments, and obviously more targeted treatments for cancer, you know, we'd need more effective treatments for cancer but with reduced side effects, so that in a nutshell, those are the other positive sort of things that the panel feel excited about. Where they're slightly more apprehensive or concerned, I mean they do acknowledge that there are challenges ahead and there are big concerns about the NHS's ability to cope with increase in demand for genomic testing and particularly worries about education and training of healthcare professionals in genomics, how do they effectively communicate research findings or results to patients if they don't have a broad understanding of genomics?  And then finally, let's hear from Emma.  Emma: I think I'm excited but cautious. I think it's really important to acknowledge that the research being undertaken is groundbreaking and the vast majority of clinicians have very little to know genomics education, and translating these findings into tangible benefits for participants is so very important, and something I think we've really got to make sure we don't lose sight of.   Helen: We talked earlier about awareness among the public about genomics and we do feel that there's a need to drive education forwards, you know but this is challenging, given the rapid pace of developments that we've spoken about, I think even for the panel members who I would say are relative experts in genomics now it's hard to keep up to date, so how do we do that moving forwards? We've talked about security of data, we understand there are moves to link more genomic data sets both nationally and internationally and that clearly has significant benefits because that brings bigger numbers of patients data together, but opens up potential risks in terms of security, so how do we make sure that the security of that data is as good as it is currently when it's held in one pot in Genomics England Research Library.   And just a couple of final concerns that were flagged by panel members, there is some apprehension regarding potential misuse with genomic data by insurance companies; we're given a lot of reassurance about that but there are concerns that could potentially lead to the most vulnerable in society being unable to get affordable cover if they're found to have genomic changes that mean they are at risk of conditions or have certain conditions and there are also concerns about the ethical implications of AI in diagnosis and clinical decision making, you know, AI is obviously a fantastic thing for looking at patterns amongst a big lot of data, but how accurate is it and where does the human come in, in terms of decision making?   So those are, I think, the broad concerns from the panel. I don't know if you have any thoughts on those, Rich? Rich: I think the big thing to say is I think having the participant panel there, you said in the middle of that, become collectively quite expert and you recognise that. Having the ability to have these complex nuance conversations and have people share that and speak directly to us about it I think is the biggest thing – lots of those points there made by the panel, I think both things that we have very much in our mind about things that one needs to balance and focus on, and there are also things that we already talk about which is reassuring I think as well, we talk about with the panel. I think one of the things for us as well is sort of being clear on some of the things where there are really clearly well-established red lines, for example, that point on insurance, but that is very clear and part of our role is making sure that that is there and people can feel comfortable in that context to understand that.  I think the main thing that I would say is thank you to you Helen, and to all of the panel and all of our participants because I said earlier, this is a team thing and you are all very much part of the team and we would not be able to do our jobs in any way, I wouldn't even say effectively, I would say with the relevance, which is the thing that we drive for, the relevance to have impact for people's lives whose data we hold and will hold in the future. And so thank you for being part of the team. Helen: Thank you. And I think thank you to Genomics England for having the foresight to create the participant panel in the first instance, it was there from the get-go and I think a really great opportunity for all of us to be involved in this, to have our voices heard and listened to, so thank you.  We'll wrap up there. Thank you for joining me today and thank you for discussing your appointment as CEO for Genomic England, and your view on what the genomics ecosystem might look like over the next ten years. If you would like to hear more like this, please subscribe to the Behind the Genes, on your favourite podcast app. Thank you for listening. I've been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand. 

Dr. Walt Larimore is hosted by Dr. Bill Griffin and Dr. Mike Chupp in this podcast, which was previously released as a CMDA Matters episode.  Dr. Larimore has been a pioneer for spiritual interventions in healthcare since 1995, when he co-led (along with Pastor Bill Peel) the Saline Solution resource.  Hear how this first resource came about and how Christians in healthcare can best address their patients' spiritual needs.

Ethical considerations are essential in genomic medicine and clinical practice. In this episode, our guests dive into the details of ethical principles, highlighting how they can be brought into practice in the clinic, whilst considering the experiences and feelings of patients and participants. Our host, Dr Natalie Banner, Director of Ethics at Genomics England, speaks to Professor Sir Jonathan Montgomery and Dr Latha Chandramouli. Jonathan is the Chair of the Genomics England Ethics Advisory Committee, and a Professor of Health Care Law at University College London. Latha is a member of the Ethics Advisory Committee and the Participant Panel at Genomics England, and is a Consultant Community Paediatrician working with children with complex needs.   "You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don't want to have separate discussions of things."   You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Why-are-ethical-considerations-crucial-in-genomics-research-and-clinical-practice.docx Natalie: Welcome to Behind the Genes.   Jonathan: The first difference is that the model we've traditionally had around clinical ethics, which sort of assumes all focus is around the patient individually, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions. Families differ enormously, some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approaches to  genomic issues must respect everybody in that.  Natalie: My name is Natalie Banner and I'm the Director of Ethics here at Genomics England. On today's episode, I'm joined by Chair of our Ethics Advisory Committee, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli, member of the Ethics Advisory Committee and the Participant Panel, who's also a community paediatrician working with children with complex needs.  Today we'll be discussing why ethical considerations are crucial in genomics research and clinical practice and what consent means in the context of genomics. If you enjoy today's episode, we'd love your support. Please like, share and rate us wherever you listen to your podcasts.  At Genomics England, we have an Ethics Advisory Committee, which exists to promote a strong ethical foundation for all of our programmes, our processes, and our partnerships. This can mean things like acting as a critical friend, an external group of experts to consult. It can mean ensuring Genomics England is being reflective and responsive to emerging ethical questions, especially those that arise as we work with this really complex technology of genomics that sits right at the intersection of clinical care and advancing research. And it can also ensure that we are bringing participant voices to the fore in all of the work that we're doing.   I'm really delighted today to welcome two of our esteemed members of the ethics advisory committee to the podcast. Professor Sir Jonathan Montgomery, our Chair, and Dr Latha Chandramouli, member of our Participant Panel. So, Jonathan, if I could start with you, could you tell us a little bit about your background and what you see as the role of the ethics advisory committee for us at Genomics England?  Jonathan: Thanks very much, Natalie. My background professionally is I'm an academic, I'm a professor at University College London, and I profess healthcare law the subject that I've sort of had technical skills in. But I've also spent many years involved in the governance of the National Health Service, so I currently chair the board of the Oxford University Hospital's NHS Foundation Trust.   I've spent quite a lot of time on bodies trying to take sensible decisions on behalf of the public around difficult ethical issues. The most relevant one to Genomics England is I chaired the Human Genetics Commission for three years which was a really interesting group of people from many backgrounds. The commission itself primarily combined academics in ethics, law and in clinical areas, and there was a separate panel of citizens think grappling with things that are really important. Genomics England has a bit of that pattern, but it's really important that the ethics advisory committee brings people together to do that. You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don't want to have separate discussions of things. My aim as Chair of the advisory committee is essentially to try and reassure myself that we've heard all the things that we need to hear and we've had a chance to discuss with each other as equals what it is that that leads us to think, and then to think about how to advise within Genomics England or other people on what we've learnt from those processes.  Natalie: Fantastic. Thank you, Jonathan. And as you mentioned, the necessity of multiple different perspectives, this brings me to Latha. You have lots of different hats that you bring to the Ethics Advisory Committee, could you tell us a little bit about those?  Latha: Thank you, Natalie, for that introduction. I'm Latha Chandramouli, I'm a Consultant Community Paediatrician and I'm based in Bristol employed by Siron Care & Health. I'm a parent of twins and from my personal journey, which is how I got involved, my twins are now 21 so doing alright, we had a very, very stormy difficult time when they were growing up with our daughter having epilepsy, which just seemed to happen quite out of the blue sometimes. It started to increase in frequency the year of GCSE, to the point that she would just fall anywhere with no warnings and hurt herself. This was difficult for me because as a clinician, I was also treating patients with epilepsy. I also was looking at the journeys of other people and was able to resonate with the anxiety as a parent. Worry about sudden death in epilepsy, for example, at night, these were the kind of difficult conversations I was having with parents, and I was now on the other side of the consultation table.  I was also doing neurology in those jobs in a unit where there was epilepsy surgery happening, so it was, in very simple terms, very close to home. It was quite hard to process, but equally my job I felt was I should not separate myself as a parent but also as a clinician because I had information, I had knowledge, and we had conversations with my daughter's clinician.   We were then recruited into the 100,000 Genomes Project which had just started, so we were just a year after it had started. That was an interesting experience. We were in a tertiary centre with a lovely clinical geneticist team, we had the metabolic team, we had loads of teams involved in our daughter's care. We could understand as a clinician, but there was also my husband, although a clinician, not into paediatrics and was in a different field. It was important that it was the whole family getting recruited into the journey. My daughter also was quite young, so obviously we have parenting responsibility, but we were very keen to make sure they knew exactly what they were getting into in terms of the long-term issues. Despite being informed, at times there were things that we went in with without understanding the full implications because life happens in that odyssey.   I think that was my biggest learning from those exercises when I began to question certain other things because I then had a breast cancer journey, but obviously I was not recruited as part of that process for the 100k. Those were kind of some of the questions coming in my head, how does the dynamic information sharing happen, and that's how I got involved, found out a bit more about the participant panel, and that's how I got involved from 2018 which has been an interesting experience.   Firstly, I think with Genomics England they are probably one of the groups of organisations having a big panel of people, genuinely interested in wanting to make a difference and represent thousands of participants who have got their data saved in the research library, recruited under the two broad arms of cancer and rare disease. We were under the rare disease arm, although I could resonate with the cancer arm because of my own experience.  At various times there were lots of opportunities to think about how data is accessed, are we getting more diverse access to data, all those different issues. At various points we have been involved in asking those questions. We all have different skillsets, you see, in our group. Some have got information governance hats; some have got data hats and PR hats. I've got a clinical hat and a clinical educator hat. I am a paediatrician, so I have recruited people for the same, for the DDD, for CGH etc, and I've always gone through the principles of consenting, confidentiality, the ethics. I also work in a field, Natalie, where there is a huge, as you are aware with the NHS resource issues, there's huge gaps and waiting lists, so it's trying to make sense of what is the best thing to do for that patient or that family at that point in life. Are we obsessed by a diagnostic label? Are we going down a needs-based approach? It's having always those pragmatic decisions to be made. That's one of my clinical hats.  I also am an educator so I'm very keen that young medical students, be it nursing students, everybody understands genomics and they're signing up to it so that we can mainstream genomics. Those are some of my alternative hats which kind of kick in a bit.  Natalie: Fantastic, thank you, Latha. As you say, there are so many different perspectives there. You talk about kind of the role of the whole family as part of the journey. You talked about consent, confidentiality, data access issues, lots of questions of uncertainty. Perhaps, Jonathan, I can come to you first to talk a little bit about what is it about the ethical issues in genomics that may feel a little different. Are they unique or are they the same sorts of ethical issues that come across in other areas of clinical practice and research? Is there something particularly challenging in the area of genomics from an ethical perspective? Jonathan: Thanks, Natalie. I think all interesting ethical issues are challenging, but they're challenging in different ways. I'm always nervous about saying that it's unique to genomics because there are overlaps with other areas. But I do think there are some distinctive features about the challenges in genomics and I suppose I would say they probably fall in three groups of things that we should think about. The first you've touched on which is that information about our genomics is important not just for the individual person where you generate that data but it's important for their families as well. I think the first difference is that the model we've traditionally had around clinical ethics, which sort of assumes it all focuses around the patient individual, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions and families differ enormously. Some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approach is genomic issues must respect everybody in that, so I think that's the first difference.  I think the second difference is that the type of uncertainty involved in genomics extends much further than many other areas. We're talking about the impact on people's whole lives and it's not like a decision about a particular medication for a problem we have now or an operation. We're having to help people think about the impact it has on their sense of identity, on things that are going to happen sometime in the future.   And then thirdly, I think the level of uncertainty is different in genomics from other areas of medicine, and the particular thing I think is different that we have to work out how to address is that we can't really explain now all the things that are going to happen in the future, because we don't know. But we do know that as we research the area, we're going to find out more. So, what are our obligations to go back to people and say, “we worked with you before and you helped us out giving data into the studies. We couldn't tell you anything then that would be useful to you, but actually we can now.”. Now, that's different. That continuity sometimes talked about, you know, what are our obligations to recontact people after a study. You don't usually have those in the ethical areas we're familiar with; you're usually able to deal with things in a much more focused way.   I think those differences, that it's not just the individual, it's the family, that it's not just about a specific intervention but it's about an impact on people's lives and that we will need to think about what we had to do in the future as well as what we do immediately. They make it different in genomics. Some areas of healthcare have those as well, but I'm not aware of anywhere that has all of that in the same position.  Natalie: Latha, I'm wondering if that kind of resonates with your experience, particularly the navigating of uncertainty over time?  Latha: Yes. I would say that's exactly what you've said, Jonathan. I think it's the whole process of consenting with the view that you do not know much more beyond what you know about the situation here and now. Part of that is like any other situation, that's why we have evolved from I would say penicillin to the SMA gene therapy. If we did not do this, we wouldn't reach frontiers of medicine and kind of that's how I explained to families when I'm recruiting and I'm also very clear that it's not all about research but it's combination of the tool and focusing on your, but it's also helpful for research even if you do not get answers. I think it's very important at that stage, Natalie, that we have to be clear we may not get many answers at the very outset and also when do we really look at data, do we have that kind of realistic pragmatic resources to be able to relook every time? Is there a method of dynamically having that information from our NHS spine if somebody of the trio has contracted a condition, would that be fed in.   Those are the kind of questions parents and families ask. I cannot honestly answer that, and I often say that is optimal plan. If things go to plan, that will be the area we'd be heading towards, but currently I can't give you timelines. I think it's important we are honest at the outset and manage expectations. That's how you engage families and, in my case, it's more these children and families, so engaging is crucial. As you mentioned, it's also the question that gets asked is very simply in my mind, you know, sometimes there is that conflict because of my own personal recruitment to the 100k project, I have an interest in genomics and, therefore, I would be very keen to embark on that journey and I feel that is the way forward.   I also understand as a member of my clinical team, for example, where I know there's a huge waiting list, how am I best using the taxpayers' money that's been entrusted to us. If I think the waiting list is so high, can I see two further patients in that time that I'm using to consent which is not going to add much more to that child's journey, for example, with autism or ADHD. It's trying to be careful where is the ethics in doing an investigation, and that's like in any situation as a clinician. I think that's not much different, but it is kind of similar, but it opens up a huge area of uncertainty. As you would with any investigations, if you just went and did scans on everybody, you might pick things up which you don't need to do anything about. It's being sensible and being honest.  Jonathan: And for me, Latha, that raises two areas which I think are really interesting about genomics. The first of those is the language we've tended to use about consent I don't think captures all the ethical issues that we raise, because we've tended to think about consent of something that happens once and then gives people permission to do things. Whereas what you've described, and what we find ourselves often thinking about, is that we have to get a respectful relationship with people, so the consent is not to doing certain things, it's to agree to part of what I think about as a common enterprise. So, patients and families are partners with the clinicians and the researchers, and it's not that they sign a form and then the consent issue goes away, which is how lawyers tend to think about it, it's that we're starting something together and then we need to think about how do we keep the conversation going with mutual respect to make sure that everybody's values are there.   I think the second thing you picked up is a sense of the need for a better explanation of how research and care interact with each other. Because the care we get now is built on the evidence that people have contributed to in the past, so we're benefitting from our predecessors, and we want to contribute to our successors and our family getting better care in the future. I think one of the things about genomics is that the gap between those two things is really non-existent in genomics, whereas if you take a medicine, the research that's been done to make sure that medicine is safe and effective will have been done on a group of people some time in the past that I'll never meet, whereas in genomics I'm part of the production of that. I may get some benefit now, my friends or family may get some benefit, but there isn't this sort of separation between the care and the research bit that we're used to being able to think about. This is a much more mutual exercise and the stakes that we all have in it are therefore intertwined much more closely than they are in some areas of medicine.  Latha: I agree totally. In our case, for example, I went in in thinking we might get a targeted medication. I know there are certain levels of epilepsy medications anyway, so in principle it wouldn't have mattered a lot. However, it was important to know what the outcome was going to be because we had various labels, potential mitochondrial disease, potentially some susceptibility disorder, so we were on a spectrum from something very minimal to the other end on neurodegenerative situation. We were left dangling and we thought it would be good to embark on this journey, at least there'll be some outcome, some prognostic outcome, and more importantly we don't have any answers, but we actually can be a hopeful story for someone else in that same position, and I think that's how we've embarked on it. That's kind of my personal experience. But in just harking back to some of the ethical issues, it's again very clear educating the clinicians, as you said, it's that relationship; it's not just a piece of paper, it's that development of relationship with your families, some of whom have got very complex issues going on in their lives themselves. I work in a very, very deprived part of Bristol, which is the highest deprivation index, so they have got lots of intergenerational things going on, there is poverty, there is learning issues and crime, lots of things going on. You've got to time it right, what is important for this family here and now, and then work on it. There's also the other issue that we may not continue to remain their clinicians after recruiting. I think that's so important to recognise because the results might come back but you kind of discharge them and it may take a few years by the time the results come. How do you then cross that bridge if some unexpected results come, which then means contacting various other extended family members. I think that's the bit we all do because that's part of the journey we've embarked on, but it's also thinking is there someone else who's probably better placed, like a GP or a primary care person who's actually holding the entire family and not just one person, not just the adult who has been the index patient. It's just trying to think the ethics of it because it's all about engagement and being transparent with families.  Jonathan: I think you've put your finger on another element that's really important about the ethics. In the same way as in relation to the position of the individual patient, and we need to see them in families, which doesn't fit very easily with lots of the clinical ethics that we've been used to. It's also the case that a lot of the traditional clinical ethics has focused on the individual responsibilities of clinicians, whereas what you've just described is that we have to work out what the system's responsibilities are, because it may not be the same clinician who is enabling good ethical practice to be pursued. These are both ways in which our paradigm of ethics has to be expanded from other areas of medicine.  Latha: Yes, I agree. And the other bit I think we can probably reassure quite nicely is about the ethics about information governance and we as data custodians storing information, how do we give with great ethics and discussion the access to research and being mindful that it is again thinking along the same principles GMC kind of had about the good for the common good and using resources equitably, but again being sensible with equality issues that a single condition doesn't get forgotten. It's that right balance that whilst we are doing common good, we might have a condition which might have a treatable medication, but we have to focus on that as well as research. I think it's interwoven, all these ethical questions.  Jonathan: I completely agree, Latha. That interwoven bit is something where we need to be able to think through, “what is the role of Genomics England to improving that?”. I think we've got issues around the good stewardship of information which can't be left with an individual clinician, they can only do that effectively if the system supports them and their colleagues in doing that. But we've also got to be proactive, we've got to recognise the limitations of the system, so one of the really important initiatives from Genomics England is the Diverse Data initiative because we know that without aiming to solve the problem, we will get a skewed dataset and clinicians can't properly look after people. That tells us that the ethics in this area has to do more than avoid things going wrong, it also has to work out what it means to do things right, and what systems we have to put in place to do that. I think that's a particular example of a shift we need to do across our ethics around healthcare.   If speak to the sort of things that lawyers have got wrong around this in the past and some of our history, we focused a lot of our effort on stopping things going wrong. That has meant that we haven't spent as much time as we need to on thinking about how to make things go right, because stopping things going wrong is almost always too late. What we have to do if we're being proactive is work out how to set things up in a way that will make sure that the chances of it going wrong are quite small and the chances of doing good are much increased. I think that's one of the key challenges that we have in Genomics England and as an Ethics Advisory Committee. The things we've inherited tell us quite a lot about things that have gone wrong, but actually what we're trying to do is to get our heads around what could go right and how to make sure it does.  Latha: Also, you mentioned about Diverse Data, I think that's another important thing as we noticed in COVID as well. There were lots of disparities in the social model and the inequalities that have resulted in death, but also potentially HLA or epigenetic issues which could have contributed. We do have the COVID-19 genomic datasets, but it's again important to make sure that we don't perceive certain ethnic minority populations. Just not accessing or considering them to be hard to reach, I would say for them Genomics England is hard to reach. It's looking at it slightly differently and thinking, “how can we reach them? how do we maybe use community workers and maybe even clinicians?”, I think they've got the best trusting relationships with their clinicians and using them to recruit. As you say, even before things get more complicated, you recruit them earlier so that you'd go down the prevention route rather than the gone wrong route and then look for answers later.  Jonathan: Latha, I think you put your finger on something really challenging for a group like the Ethics Advisory Committee at Genomics England, which is that however hard we try to get a range of experiences and voices, that's not a substitute for getting out and hearing from people in real world situations. I think one of the things I've learnt over the years from my national health service work is that you cannot expect people to come to you, you need to go to them. In COVID when we were trying to understand why some groups were more reluctant to take up vaccines than others, there was no point in doing that sitting in your own places, you had to listen to people's concerns and understand why they were there. One of the things we're going to have to be able to do as the Ethics Advisory Committee is work out when we need to hear more from people outside of the Genomics England system, and I'm a great believer that if it's right that we need to go where people are, you have to try not to reinvent mechanisms to do that. You have to try and learn where are people already talking about it and go and listen to them there. Latha: Absolutely, yeah. I think they listen because I do work as a paediatrician with a safeguarding hat, and I think the same principles resonate in child death work. For example, simple messages about cot deaths, you would think that if a professional tells the same message to a parent or a carer it's better received if it's another family, a younger person, another layperson giving the same message. It comes back to who's more receptive. It could be a community worker. As you mentioned about vaccination, during the vaccination initiative I decided early on that I'm probably not going to do a lot because I'm not an intensivist, how do I do my bit in the pandemic. I decided to become a vaccinator and I thought with my ethnic minority hat on, if I went out there to the mass centres and actually vaccinated there or in mosques or wherever else, without even saying a word I'm giving the message, aren't I, that, look, I'm fearlessly coming and getting vaccinated and vaccinating others, so please come. I think that has helped to some extent, just trying to reach out. Other than saying these people are not reaching us, it's got to be the other way around.  [Break for advertisements]  Natalie: I'm really enjoying this conversation. In part because I think it highlights just how valuable it is to sort of think about ethics a little bit differently. Historically, and certainly I think within the research community, ethics can just be associated with consent. Consent is the ethics issue and if you solve for consent, then you don't have any other issues to think through. I think what this conversation is really highlighting is just how much broader the ethical considerations are. Beyond that, it's still very important that consent can be that sort of anchor point for communication and engagement, but it's not simply a one-off. And to be able to think through ethics not just in terms of risk or moving forward when things have gone wrong in the past, there is actually a really positive aspect to it which I think is critically important.   It's great to hear your thoughts about that different approach to ethics that I think does embed it much more in community thinking, in questions of equity; it's not just the individual. I want to follow-up by just asking where do you think the future lies in thinking about ethics both for Genomics England and the Ethics Advisory Committee, but in the space of genomic research and medicine more broadly, given that it sits in this kind of very interesting and quite complex space between research and care in the clinic.  Jonathan: I mentioned earlier in the conversation I think about this as a common enterprise that we have shared stakes in. Academic researchers have a stake in trying to build a better more robust evidence base, clinicians have a stake in being able to offer something to the people that they're looking after. Families have stakes not just in their own immediate care, but they worry about their siblings, they worry about their children, their grandchildren. There are also of course industrial players, so people trying to build a business out of making better medicines in the future. There are government players trying to use public resources more effectively. I think what we have to try to create is a mutual process where we recognise that everybody has overlapping but slightly different values that they're pursuing and trying to get out of it, and how can we make sure that we govern our work in a way that reflects all of those stakeholders and recognises the respect that's due to them. I think this is more like a sort of membership of a common project. And the problem with consent is it risks us saying you can be a member of this club but only if you accept the terms and conditions that the committee has decided is there. That's not going to be adequate going forward. I think we need to make sure that everybody feels that they are respected, that they feel they can place their trust in the system that we're designing. As an Ethics Advisory Committee, we have to ask ourselves what justifies us suggesting to people that this is trustworthy. We need to make sure we have good information governance that people are not going to expose themselves to breaches of privacy if they take part in this. But we also need to make sure that we don't waste people's efforts. If people are prepared to be part of the research project, we shouldn't have rules coming down on the data usage that say that we're going to reduce the value of that contribution by saying it can only be used for one project and can't be used for others, because actually that would not respect properly people's contribution to the process.   We need to ask ourselves not just about the protective element of trustworthiness but that element that says we will make sure that you get as much as we can design of the things that you think are important from this project. They won't be identical for each group, and they won't be identical within each group. Different family members of participants will have different balances, but they all have to believe that this is a good club to be part of and that they have been part of agreeing ways of working that they think will produce a better future that they want to be part of and that they want to be proud of saying we have helped create this future.  Latha: I kind of agree with all that you've said. I think it's most important not to forget because I'm also a participant, like my trio sample is there in the pipeline, and I know my data is sitting there. I also have trust that there is good information governance, the data is secure, so it's reinforcing that, but it's also being very honest that it's obviously the data is there, but we can't forget the person or the persons at the centre of it, so it's not just alphabets or sequences of alphabets, but it is that whole person, and that person represents a group of individuals, family members, different generations, and they have embarked on it. Even if they know they may not get hope they might provide hope for others. It's being therefore respectful. I think that is the first thing I think is the principle of it and if you respect. If you think it could be the same principle that we use in clinical practice, the friends and family test, because I've been on both sides of the consultation table, I think I've become a better doctor because I've been an anxious mum, and my anxieties were dismissed as being an anxious mum and I don't care. As far as my child is concerned, my anxiety was valid and so I would do everything to reach an outcome as to what's best for that person. It's made me a better doctor because I can see it from both the perspectives. Most of us are human beings, apart from AI technology looking at the dataset, so we all have conditions ourselves, we've got doctors with health conditions, we've got clinicians, academics, technicians, nurses everybody who's got a friend or a family member or themselves having a health condition. I think its fundamental principle is that friends and family test. How would I like my data stored? How would I like my data analysed? Could it do this, could it give me some information on how I would get cured or treated or be managed? How would it affect my insurance, or will it find out data about who's the father of this child, for example? It's being honest and being honest about the uncertainties as well.   When I'm recruiting, I'm very clear that these are what I know that I can tell you about the risks. But then there may be other risks that I do not know about. If you're honest about it and acknowledge what is the limit of the knowledge of science at this point in time, because you said there are so many stakeholders, there are researchers and academics who've got interest in some areas, it could have developed because of a family member having that problem, but whatever it is that is a great interest because that intelligent mind is thinking ahead and we need to encourage that. It could be for writing up papers, it doesn't matter. Whatever be the reason, if it's for the common good, that's fine. It's also thinking how are we keeping our families in the loop, so you have newborns, you've got young people sometimes with significant disabilities so they are relying on a parent or a carer to consent for them, but some are not so disabled but they have needs, they've got rare conditions, but they can make their consenting issues known when they turn 16, for example. It's the changing policies and they can withdraw at some point in life or there may be a member of the family who doesn't want to be part of that journey anymore. It's allowing that to happen. Jonathan: I think that's a really interesting example you've just touched on, Latha, where I may diverge a bit in terms of what I think is the key issue. The right to withdraw I think is a really interesting challenge for us going forward, because we developed the right to withdraw in the ethics of research studies that had physical interventions. It's really clear that someone who is being put to discomfort and is having things done to her body, if she wants to stop that, we can't justify continuing on the basis of it being a research project. But I'm less clear whether that applies to withdrawing data from data pools. I think there are a few dimensions to that which I hope as an Ethics Advisory Committee we'll have a chance to think through a bit more. One is the mutual obligations that we owe to each other. I'm not in these particular studies but I do try and take part in research studies when I'm eligible and invited to because I think research is important. When I take part in things and when our participants have taken part, they're doing something in which they rely on other people participating because the aggregation of the data is what makes it power. One of the things we have to be honest about is what are our mutual expectations of each other, so I think we absolutely have to hold on to the fact that people should be able to withdraw from further interventions, but I'm not convinced that you should have the right to say the data I've previously contributed that other people have relied on can suddenly be sucked out and taken out of it, because I think it's reasonable for us to say if this is a sort of part of an enterprise. While you're part of it, you've made some commitments as well as, and that's part of the mutuality of the respect. I think I personally would want to argue you can withdraw from new things, but provided that your privacy is not intruded on, so we're talking about data health anonymously, you shouldn't be able to say don't process it anymore. Latha: No, no, no. What I meant was from my perspective I would like to be constantly involved and get information through trickling. I don't know what my daughter feels years down the line, she might say I'm happy for my data to be used for research, but I don't want to know anymore. There are two aspects of that, and I think if we are clear with that and say continue with my data being used for research, but I don't want to get anymore letters. I think those are the kind of questions I face when I tell them families that these are the uncertainties, you can have your blood stored, you may not be approached again for a resampling unless you have some other issues, but are we happy with this? I think that's what I understand, and I try and recruit with that intention. Jonathan: And that makes lots of sense to me. As you say, you probably can't speak for your daughters now, and you certainly can't speak for them when they become parents for themselves and those things, but we do need to create an ethical framework which recognises that people will change their mind on things and people will vary about what they want to do. But because we have mutual obligations, what that means and the control we can give, we have to be open and honest about what choices we can give people without undermining the enterprise and what choices we say, “you don't have to do this, but if you want to be part of it, there are some common mutual obligations that are intrinsic”, and that's true of researchers, it's true of clinicians, it's true of anyone who works in Genomics England or the NHS.   But I don't think we've been very good at explaining to people that there's an element of this which is a package. A bit like when I bank, I allow the bank to track my transactions and to call me if they see something that looks out of the ordinary as a part of the protections from me. I can't opt out of that bit. I can opt out of them sending me letters and just say do it by email or whatever and I have some choices, but there's an infrastructure of the system which is helping it to function well and do the things it's able to do. I don't think we've been very good at explaining that to people, because we've tended to say, “as long as you've signed the consent form at the beginning of the process, it doesn't really matter what happens after that, you've been told.”. That's not enough I think for good ethics.  Latha: And I think that comes back to the other issue about training those who are consenting. I speak from personal experience within my own teams I can see somebody might say, “I don't do whole genomic sequencing consenting; I don't have the time for it.”. I might even have my organisational lead saying when we had a letter come through to say now we're no longer doing this, we're going to be doing this test for everybody, there's a whole gasp because it's at least two hours' worth of time and how are we going to generate that time with the best of intentions. I think that's where I think the vision and the pragmatic, you know, the grounding, those two should somehow link with each other. The vision of Genomics England with working with NHS England and with the future, Health Education England arm that is not amalgamated with NHS England, is trying to see how do we train our future clinicians who will hopefully consider it as part of their embedded working thinking and analysis, but also, how do we change the here and the now? The more senior conservative thinking people, who are worried about how do they have to generate time to manage, we're probably already a bit burnt out or burning out, how do they generate time? If you then discover new conditions whether there is already bottleneck in various pathways, how are we ethically managing the new diagnosis and how will they fit in in the waiting list criteria of those people on the journey who are symptomatic. I find that bottleneck when I have conversations with colleagues is the anxiety, how is that going to be addressed.  Jonathan: Latha, you've sort of taken us around in a circle. We started off thinking what was special about genomics, and we've reflected on ‘we have to solve the problems of the health service'. I think that there's some wisdom in that, because we are learning how to do things that are not unique to genomics, but there's an opportunity in genomics to do it better and an opportunity for us to help other areas of the health service do better, too. I think we've come around in full circle in a sense.  Natalie: Which feels like a lovely way to wrap up our conversation. I feel like we've gone into some of the deep ethical principles but also really shown how they can be brought into the practice, into the clinic and brought to bear the thinking and the feelings, the hopes the anxieties of participants. There's a very, very important range of different voices so a very rich discussion.   I'd just like to thank you both very much for joining us on the podcast. Thank you to our guests, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli for joining me today as we discussed ethics in genomics research and practice. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.

On this week's episode of CMDA Matters, Dr. Mike Chupp and Dr. Bill Griffin talk with Dr. Andre Cipta about an important research project he's been leading that dives deep into the importance of incorporating spiritual care into patient care.  RESOURCES FOR THIS EPISODE: Give to CMDA Email CMDA Matters CMDA Bookstore 2024 CMDA National Convention Faith Prescriptions CAPS Specialty Section Specialty Sections

Joey was diagnosed with DYRK1A syndrome at the age of 13, through the 100,000 Genomes Project. DYRK1A syndrome is a rare chromosomal disorder, caused by changes in the DYRK1A gene which causes a degree of developmental delay or learning difficulty. In today's episode, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, speaks to Joey's parents, Shaun Pye and Sarah Crawford, and Sarah Wynn, CEO of Unique, as they discuss Joey's story and how her diagnosis enabled them to connect with other parents of children with similar conditions through the charity Unique. Shaun and Sarah also discuss their role in writing the BBC television comedy drama series 'There She Goes' and how this has helped to shine a light on the rare condition community. Unique provides support, information and networking to families affected by rare chromosome and gene disorders. For more information and support please visit the website. You can read more about Joey's story on our website.   "Although we're a group supporting families and patients, actually a big part of what we're doing is around translating those complicated genetics terms, and trying to explain them to families, so they can understand the testing they've been offered, the results of testing, and really what the benefits and limitations of testing are...just knowing why it's happened, being able to connect with others, being able to meet others, but actually often it doesn't necessarily change treatment."   You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Shining-a-light-on-rare-conditions.docx   Naimah: Welcome to the G Word. [Music] Sarah Crawford: But I would also say it's okay to grieve the child that you didn't have that you thought you were going to have. I just think that's so important. And I think for me, the most difficult thing in the early couple of years was feeling like I couldn't do that because nobody appreciated that I'd actually lost anything. [Music] Naimah: My name is Naimah Callachand and I'm head of product engagement and growth at Genomics England. On today's episode, I'm joined by Shaun Pye and Sarah Crawford, who are parents of Joey, who was diagnosed with DYRK1A syndrome at the age of 13, and Sarah Wynn, CEO of Unique, a charity which provides support, information and networking to families affected by rare chromosome and gene disorders. Today, Shaun and Sarah are going to share Joey's story, and discuss how their role in writing the BBC comedy drama There She Goes has helped to raise awareness of people with rare conditions in mainstream culture. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. So first of all, Shaun and Sarah, I wonder if you could tell us a bit about Joey and what she's like. Shaun Pye: Yes. So, the medical stuff is that she's got DYRK1A syndrome, which was diagnosed a few years ago, which means that she's extremely learning disabled, nonverbal. Sarah Crawford: Yeah, autistic traits. Shaun Pye: Eating disorder, very challenging behaviour. She can be quite violent. She can be quite unpredictable. Doubly incontinent, let's throw that in. She's 17 but she obviously has a sort of childlike persona, I would say, you know. She sort of likes things that toddlers like, like toys and that sort of thing. But that's the medical thing. What's she like, she's a vast mixture of different things. She can be infuriating, she can be obsessive, but she can be adorable. Occasionally, she can be very loving, especially to her mum. Sarah Crawford: She's very strong willed, you know. Once she knows she wants something, it's impossible to shift her, isn't it? So, she's got a lot of self-determination [laughter]. Shaun Pye: So, her obsession at the minute, or it's fading slightly, which is quite funny, is that she's become obsessed by – there's a toy called a Whoozit that she loves, but she became obsessed by the idea of – she was typing buggy baby Whoozit into her iPad, so that's how she communicates. She's got quite good literacy skills. Sarah Crawford: Yeah. Shaun Pye: And we figured out eventually that what she wanted was she wanted her mum to take her to the park to find a buggy with a baby in it that also had a Whoozit in it that she could steal, and when Sarah explained to her at some length that it was not yours, she would say, “It's not yours,” that drove her insane with excitement, at the idea that she could steal another child's toy. So, it's a good example of her because it's funny, and, you know, it is funny, and she's so cheeky about it and she flaps her hands, she's very hand flappy, and she sort of giggles and she gets really excited, but, you know, the 2,000 time she asked to do that, and we have to walk to Mortlake Green near our house, and to the point where – again, it's funny when it happens, but you get to the green and she doesn't even look for the buggies anymore. So, that's an example. But she's a lot of different things, you know, and I suppose the thing that is dawning on us at the minute is that she's 17, she's going to be 18 very soon, and, you know, the list of presents that she gets on her birthday is always the same, ‘cos she's autistic. So, at Christmas, she always gets the same presents. But the idea that, for her 18th birthday, we're going to have to buy her children's toys and – you know – Sarah Crawford: Toddlers' toys. Shaun Pye: Toddlers' toys and everything, it's sort of hitting home, but that's something – a bridge we're going to cross on July 27th [laughter]. Naimah: Yeah, I can imagine that's quite a difficult bridge to cross, but it sounds like, you know, Joey's got lots of personality and you have lots of, you know, lovely times with her as well. I wanted to go back a bit before the diagnosis. So, you mentioned Joey's been diagnosed with DYRK1A syndrome, but can you tell me what it was like before you both – and a bit about your journey, and when you suspected maybe something might be wrong and what you did first of all. Sarah Crawford: I mean, there were hints that things might be wrong before she was born. The measurements were such that they thought there might be intrauterine growth restriction, because basically my belly wasn't as big as it should be for dates, and that was obviously the working hypothesis. And they actually did a scan, an ultrasound quite late on in the pregnancy, which I picked up when I looked at the report was showing a small head measurement. And I remember querying it with the consultant, who said it was probably measurement artefact and nothing to worry about. But after she was born, she wouldn't latch on, you know. We had to switch to bottle feeding straight away. She was small, and the head measurement actually was small. You know, you could see on the very early one, they must have taken it kind of three times to try and get it bigger, probably angling the tape measure, and it had been crossed out and rewritten. That was the pattern. So, her head simply did not grow in those early days in the way that you would expect. So, I was wildly anxious about this right from the get-go, and very adamant very early on that I thought that, you know, she was learning disabled. And to be fair, you know, the GP took that seriously. You know, at the six-week check-up, things weren't quite how they should be. We got in the system very early on, saw a paediatrician really quite early. So, I was, you know, fairly convinced very early. I mean, I'm a clinical psychologist, I've got training in learning disability, a bit more clued into these sorts of things I guess than the general public on the whole, and I think the bigger challenge for us wasn't so much the attitude of, you know, the healthcare system. It was more trying to debate this with family, who were very much of the, “There's nothing wrong with her,” kind of mantra. Shaun Pye: She wasn't our first child, so we had experience – and all children are different, but because we had that comparison – all children are different. Obviously, there's not a set thing. But we had a benchmark in our own minds and hearts sort of, to know that she was missing things that he'd hit, and something wasn't right. And the parental thing – basically, we're talking about grandparents – it was sort of – there were two approaches that they took, one of which was to tell us nothing was wrong, because they couldn't bear the idea that me and Sarah were in pain or unhappy. It was just out of pure love. It's just a natural human reaction to say, “I'm sure everything's going to be alright.” They were just trying to be supportive because that's, you know, what they thought they should say. And then the other approach from other members of the family was again from just a supportive, loving aspect, but it was a sort of, “They just need a bit of tough love, pull your socks up. Lots of children are different and you just need to learn ways of dealing with it.” And the way I describe it nowadays is that they'd mistaken Joey for someone on the far end of a spectrum of abilities or behaviours, whereas she wasn't really on that spectrum at all. She was on a different spectrum [laughter]. She wasn't a difficult child. She wasn't a naughty child, was she? Sarah Crawford: No, no, she was a child whose brain hadn't developed. Shaun Pye: She was a very, very different child. So, all of that has gone on over the years. And genetics wise, we had early genetics testing. Kingston Hospital took quite a lot of interest early on, and then they sort of didn't take any interest [laughter]. Sarah Crawford: No, it's more that they ran out of technology, so they couldn't pinpoint the diagnosis with the technology they had. I mean, the geneticist was excellent, wasn't he? We really loved him. Shaun Pye: Yeah, Sarah's going to like this, ‘cos I'm about to say I love geneticists ‘cos they're – on the spectrum of doctors, I love them, ‘cos one of the guys we saw just looked at it like a puzzle and he was sort of excited to solve it, and he really wanted to work out – and in a way, you could have walked away from that thinking, “We wanted the bedside manner and we wanted the, “Oh, that's terrible,”” whereas he really was just a sort of – he was terribly excited about the whole thing, and he wanted to solve a Sudoku, basically, yeah. But me and Sarah walked away from that just thrilled, ‘cos we're the same [laughter]. There's not a Sudoku or a crossword that we don't love finishing. So, we walked away thinking, “These are exactly the people we want involved.” And so when I say they gave up, that's not fair. They just ran out of – you know, they can't spend increasing amounts of NHS money. So, they tried – you know, different genes were mentioned. Sarah Crawford: Yeah, they tested for a whole load. I mean, his attitude was right from the get-go, you know, based on the history, everything else that had been ruled out, dysmorphic features, those kinds of things – I don't know if that's the terminology they would use now – but that this was going to be a chromosomal disorder, and that they would do the tests that were available, but that it was possible that those wouldn't pinpoint in, but that the technology was changing all the time, and that if they didn't find it now, they would in the future. And that was how it played out. Shaun Pye: There was one meeting that I did get a little bit – having said that, I got slightly – but you didn't – about one of the geneticists, who sat there and said, “We'll do this test and this test, and if they come back with any interesting things then we can get really excited.” And he used the word excited, and I was sort of a bit, “I'm not that excited by all of this.” But actually I calmed down quite quickly, and in hindsight I really wanted someone to get excited by the idea of working out – but then a long time went past. I wouldn't say that we lost interest in finding out what her genetic condition was, we didn't. It's just it's something that became less and less – it wasn't like a holy grail for us. But then the opportunity came along with 100,000 Genomes, and we signed up immediately, and then they did that and it was a few years before that went through the system. And then out of the blue really, we were asked to go and see a geneticist, and we had no idea that this is what it was. I honestly thought it was just a routine sort of, “We've got a few more theories,” or something, and she just said, “We've found out what it is.” And that moment is – well, we tried to describe it in the TV programme, but it's quite hard to describe what goes through your mind when, after 13 and a half years, somebody suddenly says, “Oh, by the way, that thing that happened with your daughter, we've worked out what it is.” [Music] Naimah: I wonder if you could talk a bit about what the diagnosis meant for you both. Shaun Pye: It was sort of different for both of us, wasn't it? I was a bit more excited, Sarah was a bit more… Sarah Crawford: My attitude early on was that, while the label would be nice to have, it wouldn't make any material difference to anything to do – I mean, it was never going to be precise enough that it would give a map out of what we'd expect for her as an individual, and it wasn't going to change the fact that there was a severe learning disability. It wasn't going to change the challenges that we would have over things like schooling, therapies, you know, what the future holds for her. It is useful to have it, but it doesn't really change the day to day. Shaun Pye: But what it did change, and this is where Unique is so brilliant and important, is that it puts you in touch with people who have children with a similar condition. That's the main takeaway from getting the diagnosis. ‘Cos Unique is great, and obviously in a broad sense it's great, but to actually meet people and be in touch with people whose children have DRYK1A – so, I've met quite a lot of them now and I've met quite a few of the children. There was a meetup last year, and you just walk in and you just go, “Oh my god, oh my god” [laughter]. Literally girls running around, just the same as Joey, just the same, and the different ages as well. So, there were some in their twenties and there were some just starting out on their – who'd only, you know, very young, been diagnosed. But just to see your life just in front of you [laughter] is very useful. So, that's the basic takeaway, I would say, from the diagnosis. Naimah: Yeah. It must have been really nice to be connected with those other parents and to kind of share experiences as well. Shaun Pye: It was, it was. And this applies to most – well, every family from Unique that I've ever encountered actually. Nearly all of the DYRK1A – ‘cos it's spread around the world as well, so, you know, there's slight cultural differences, but just to see that they are all of a very similar mindset is comforting, ‘cos it sort of makes you think, “Actually, we haven't been doing this wrong.” It's a sense of humour thing. It's an attitude to the world. It's the way they see their children. It's the way they see the outside world. I'm not saying we're all uniform, of course we're not, but you can see it. When you talk to them, you can just see that they have the same sensibilities as you about the whole thing, and it's sort of quite reassuring really that, you know, we're not outliers. Naimah: I just wanted to go back to, you know, when you were talking about the bit before the diagnosis, and I wanted to come to you, Sarah, to ask, you know, Shaun and Sarah both described their journey with a lot of uncertainty, but I wondered, could you tell me a bit more about the role Unique plays in this part of the journey for parents? Sarah Wynn: Yes. Well, actually I think Shaun's done such a good job of summing up why Unique exists already, thank you, Shaun. But I think really what we're aiming to do is to try to alleviate that sense of helplessness and being overwhelmed, and isolation that often families feel when they have a child that's got additional needs. I think our experience with our Unique community is very similar to that that Shaun and Sarah have described. So, many parents know that there is something – that their child isn't developing as they would expect. And we hear lots and lots of stories of families going to healthcare professionals and actually not being taken seriously, or like Shaun and Sarah were saying, you know, everybody saying, “No, they're just a bit delayed, it will all be fine.” And so I think that's a common experience of many families, that the parents inherently understand and know their child better than everyone else, and it's very common that families have to wait quite a long time to get to that point where they get to a diagnosis. And often I think the uncertainty continues after you get that diagnosis, because as Shaun and Sarah said, you get a diagnosis of a rare condition and actually there just isn't that much information available. So at Unique, we try to help in various ways. One is by connecting families with other families, and that might be other families who've got the same condition, but it might also be families who are just going through the same experiences as you are, so you've got someone to share your journey with. And the other thing we try to do is to help families understand the kinds of genetic testing they've been offered, and a bit about the results of genetic testing. Because of course genetics is something that lots of people haven't thought about since school, and actually quite often hoped they never had to think about again. Although we're a group supporting families and patients, actually a big part of what we're doing is around translating those complicated genetics terms, and trying to explain them to families, so they can understand the testing they've been offered, the results of testing, and really what the benefits and limitations of testing are. Sarah said, often you get a result and a diagnosis from genetic testing, but that doesn't give you a magic treatment that's going to cure your child. It's really important, for all the reasons Shaun and Sarah have already said, just knowing why it's happened, being able to connect with others, being able to meet others, but actually often it doesn't necessarily change treatment. Shaun Pye: I guess one thing I would say, just ‘cos it was important to us, and it's de novo in our case, but that's comforting to know. We always suspected it was and we were always told it was, but to have that confirmed means – I mean, we're not going to have anymore children, but it's more to do with our son and whether there's something inherent that could be passed on. Sarah Wynn: Yeah, it gives you information that you can use for either your own family planning or other family members. Naimah: You mentioned that Joey received her diagnosis via the 100,000 Genomes Project. How did that come about? Sarah Crawford: I think it was offered, as in the 100,000 Genomes Project was the only way that that was potentially available at the time, that this was effectively a project that was going on to try to answer those unanswerable questions with the technology they had at the time. I mean, it was years between us enrolling in it and getting the answer. Shaun Pye: It's so important to me in hindsight the diagnosis, just for all the reasons that we've been discussing, but without doing down the role of genetics, there was a period of Joey's life when we thought we'd run out of road with the testing, and it wasn't something that really I was obsessed with or occupied my mind massively. It wasn't like me and Sarah were saying, “We must get back to Kingston Hospital. We must get back to the geneticists. We must write to the NHS. We must insist that they do this.” We'd sort of resigned ourselves to the fact that they'd done all that they could and they hadn't found it, and that's what it was going to be. Having said that, when 100,000 came along, we obviously jumped at the chance. We had no misgivings about it whatsoever, ‘cos I think we'd resigned ourselves to the fact that we might never know. Sarah Crawford: I think I thought that at some point we would, because the technology, the methodology that they're using obviously was changing all the time, but it didn't preoccupy me because I didn't think it would make a massive amount of difference. It probably made a bit more difference than I thought it would, for the reasons that Shaun and Sarah have said, about, you know, particularly the sort of connecting with others, you know, just realising how useful it is to be able to hear about the similarities and differences that other families experience. Shaun Pye: I think a key point for us, and I'm sure this is true for the vast majority of Unique families, that we never thought that there was a cure. We never ever, ever, ever, ever, ever thought there was. And nobody in our family did. It's not like anyone was saying, “Oh, with this treatment or that treatment…” Once you know that it's DYRK1A, there's obviously things that you can tailor towards her in terms of therapy, you know, there are things that you can do, but we were never under the illusion that if we found out what it was, she could go on and some sort of drug would suddenly make it better. Sarah Crawford: Yeah, we're not queuing up for experimental stem cell treatment [laughter] in weird and wonderful parts of the world, you know. What's happened has happened. Her brain didn't develop properly in utero and beyond. There is no changing that. Naimah: But I guess with diagnosis, and like you said, if you can get some relief from some of those other symptoms that are caused by it, then, you know, that's some sort of relief for Joey and a bit of help. Shaun Pye: Yeah, there are absolutely concrete things that you can learn that will – Joey will never be better, but talking to the other families – eating disorder, that's one of them. Constipation, that's another thing. But hearing their experiences, hearing the roads they've gone down, finding out that there's, you know, a unit somewhere in the country that specialises in this, that or the other, these are concrete things. It's not just about emotional support. It's absolutely about practical support. But there's no magic wand, but there are things that, you know, we've learnt that can help. Naimah: And then Sarah, to come to you then, do you find that families find it difficult to seek out help from Unique once they've received a diagnosis, or are they likely to come quite quickly to you? What's your experience? Sarah Wynn: It's a really good question, and of course we don't know the ones that never find their way to us. But what we try to do at Unique is to be sort of warm and friendly and welcoming, so that it's not too daunting. ‘Cos I think all of these things are an extra thing for parents who are already busy and dealing with lots of medical appointments and therapies, so we try to make it as easy as possible to join us. Many, many families do join us at that point of diagnosis, because that's when they're looking for more information. Actually, you can get in touch with Unique and if you decided you didn't want to join us, that's also fine. So, we have a helpline that you can call. And for some people, joining a support group just isn't their cup of tea, and that's really fine. Other people find us a little bit later on, you know, perhaps when their child starts school or, you know, there's sorts of crunch points where people are looking for extra information or support that they tend to find their way to us. But one of the things we try really hard to do is to get the word out that organisations like ours exist, so that we can be contacted if people want to. And lots of our families come, like Shaun and Sarah, after the geneticist has told them that we're there. So, that's a really important thing for us is that everybody knows we're there. You can join us and involve yourself as much or as little as you want. So, as we've already talked about, one of the things we do is put families in touch with each other, but not all families want that. So, you know, you can join and remain no contact, and stay quietly under the radar if you'd like to. But those people often want their child to be sort of counted in the system, you know. When you say how x number of people have DYRK1A, they want their child to be in that number even if they don't want to go to the meetups, or they're not quite ready to do that. And of course people change. So, some people join us and think, “We're just going to quietly sit here for a bit,” and then change their mind a bit further down the line. I think, although There She Goes, and what Sarah and Shaun have said about their journey is really similar to many people's journeys, of course everyone is a bit different, and so people want different things at different times. And what we try to do at Unique is to be those things for whenever families need us. Naimah: Yeah, that must be really reassuring for families, knowing that they can come to you whenever they feel ready to more than anything. Shaun Pye: Just to jump in quickly as a sort of user of Unique, from the sort of different perspective from Sarah, that is literally how the service presents. That's not an ideal that they aspire to. That's what it's like. So, I can confirm that – I mean, people think different things, and within our DYRK1A group, for example, you know, there's a broad range of people who think various things, but the one thing about it and Unique is it's very well self-policed, so people know how to behave. You won't be subjected to ill informed sort of medical nonsense. It's very well self-policed, but it's also very, very occasionally – I'm speaking for the DYRK1A group – the example they gave me was around covid and vaccinations, and, you know, people have very strong views about it, and these forums aren't the places to be having that sort of discussion. Sarah Wynn: I think that's exactly it. One of the ways families can connect with each other is via an online forum, and generally we take quite a light touch in moderating it, because the forum is for the families, and we want them to feel ownership and that it's their safe space. But yeah, ever so occasionally, it needs just a tiny little bit of input. But yeah, I think Shaun's right, everybody's there for the same reason, and that's to kind of share experiences, sometimes vent about the world, ask questions, and actually celebrate things that other people might not see as such a celebration. You know, lots of our families, their children might be late to walk, and it's a place where you can celebrate all of those sorts of things as well. [Music] Naimah: So, next I want to move on to talk about 'There She Goes'. So, you mentioned it briefly there, Sarah. So, this is the BBC Two comedy drama, for which Shaun and Sarah were both writers on, and it really draws upon your real-life experiences of caring for Joey. And although the series is posed as a gentle comedy, it also displays really frank and honest emotions experienced by Emily and Simon, who are the parents of Rosie in the programme. Let's listen to the poignant clip from the series by Jessica Hynes, who plays the mother, Emily. Emily: You know, when you're younger and daydream about what family you might have – so, I was the girl who thought Claire always got away with murder. Or when we found out Ben was going to be a boy, if it would be like you and Soph, you know, dorky older brother, biffy outdoor sister who everyone liked, you know. But in none of my dreams was there a girl who… Yeah, who was like Rosie. Yeah… No one ever dreams of a child like Rosie… You know, and I… I love Rosie, but why do I have to be defined by her? You know, for a long time, I felt cheated by her, because she wasn't the girl that I dreamt about, you know. She'd taken her place. And then as she got older and I accepted her more, you know, what if it wasn't that she'd taken her place, what if she just pushed in the queue and then if we started again, then if I had, you know, a normal girl, and then I wouldn't have to… I wouldn't have to resent Rosie anymore because I'd have the family that I'd always wanted, and I'd have – I'd have Rosie as well, yeah. [Sobbing] Just after all these years, haven't I earnt that? [Music] Naimah: Off the back of that, I wondered if you could both tell me a bit more about what it meant for you being able to write for the programme and, you know, what it's meant in the aftermath as well. Shaun Pye: So, it came about - I basically am a TV writer and Sarah's a psychologist, but it came about primarily because I was trying to think of something to write about and we realised that Joey's just an incredible character. Those sort of children aren't featured on mainstream television really at all, I would say. And so we thought it would be an interesting thing to do. But from that sort of slightly selfish motive, I wrote an episode, and Sarah read it and said, “You're not doing that, it's not honest enough” [laughter]. So, Sarah came on board as a writer with me and we cowrote it. The whole thing's cowritten. And it's the most important piece of work I've ever done, I ever will do, and it became far more than just a TV programme. The first series went out and we had a screening, and Unique came to the screening, along with some of the other charities, and we were so terrified of what the response would be. And the fact that the response was what it was, which was overwhelmingly, “It's like looking at our own lives on television,” it was recognition. It was nothing to do with whether the stupid jokes were funny or anything [laughter]. It was purely whether – if anyone had turned round and said, “This has got nothing to do with what it's like bringing up our child,” or our brother or sister or whatever, that would have been quite bad for us, but it wasn't, and that's been the overwhelming response since. It's, “Thank you for putting our life on television, ‘cos it's not normally on television.” So, it became that, and so the second series was even more about that, and then the special that we did was almost totally aimed at, we need to tell these stories because there are so many people in this country who this story isn't being told for them. And it so happened that Joey hit puberty and had some very, very, very problematic behaviours, sort of self-harming behaviours, it happened quite close to her being diagnosed, so we thought this story is just written for us. Joey's written it for us. So, we just sort of wrote down what happened. That was sort of what it was. And then obviously the response to that was very good. So yeah, and we wanted to feature Unique ‘cos that was such an important part of what we'd been through. So yeah, it went from me wanting to further my career to that having nothing to do with it, and me wanting to [laughter] tell the story of children with rare chromosomal disorders and learning disability, and that's what it became. Naimah: I'm sure it must have been almost quite cathartic, I imagine, in a way, to share your story that way, and also, you know, give you a real sense of accomplishment to be able to kind of share your story on that platform. Like you said, like it's never been done before in such a way, and to get that kind of response from other families, it must have really just helped you both in your journey as well, I can imagine. Shaun Pye: For me, because it's what I do for a living, it still retained a certain sense of my job. And, you know, emotionally, obviously, entirely committed to it. All the bits that make you sort of cry, or all the bits that are like, oh my god, Sarah wrote – I wrote all the stupid bits that David Tennant says [laughter]. So, I think it was more cathartic for you. You really had to dig deep into some quite unpleasant memories [laughter]. Sarah Crawford: Yeah, it wasn't always the most comfortable process, you know. We'd sort of agree – I mean, particularly in the earlier process, we'd sort of have a little think about what we wanted to talk about, and then I'd go off and like kind of delve deep into memory, and just type a stream of consciousness, and I'd be sitting there sobbing [laughter], you know, with tears rolling down my face, you know, just reliving these really awful experiences. But yeah, I think the end process ended up being cathartic, and a lot of that was stuff that I would never have imagined sharing with anybody [laughter], let alone, you know, this huge audience of people, which – yeah, strange how things evolve. Shaun Pye: Yeah, I think possibly if we hadn't done this then we might have just tried to not think about these things and not bring them back, and I think we probably wouldn't have spoken to each other – we may have, I don't know. I don't know what would have happened. But I don't think these things would have come out into the open. And very interestingly, another side aspect of it in the catharsis way is the effect the programme had on the wider family. There were certain members of the family who were really shaken by that programme, really shaken, because they had a set view. Even as Joey got older, they had a set view of the history and what had happened, and they were really shaken by the idea that their – out of love again, there's nothing bad here, but they were really shaken by the idea that their actions had a detrimental effect on us when Joey was born. You know, there were people saying, “Well, I didn't say that there was nothing wrong with her,” and, “I didn't say this or that,” but actually when you see it presented in the programme then there was a lot of re-evaluation that went on, in a good way, in a positive way and it's all good. Sarah Crawford: I think there's something about seeing it, you know, and especially given, you know, we were so fortunate with the cast because they're so good at portraying it. And I think there's a power in seeing things played out rather than just hearing about them in the abstract. Naimah: Yeah, definitely. I definitely had moments of crying and laughing, and a range of emotions while I was watching it, so yeah, definitely very powerful. And I guess it's really great for other families going through similar circumstances, for their families to see what's happening and, you know, there's a lot that can be learned from the programme as well. So, you know, it's, yeah, really a powerful piece that you put together. Sarah Wynn: I would really like to echo that. I think Shaun and Sarah have said before that they didn't do it to represent everybody's experience, but actually that is exactly what it has provided. I would say that huge numbers of people are really grateful that that portrayal is there, so that they can be seen and heard and understood so brilliantly. But it has provided other families with the opportunity to show it to their friends and family, so that they understand their life as well. And so I think it's had a hugely positive reaction from our Unique community. And I think it's not always an easy watch, I think lots of families would say it's challenging to see it up close in front of you, but I think it's really cathartic and has been just incredibly powerful at showing these sorts of stories, which, as you said, just don't get shown very often. And I think particularly when we think that rare conditions, although they're individually rare, if you put all of the rare chromosome conditions together, they're not actually that rare, so these are stories that are going on up and down the country and all over the world. Shaun Pye: Just to follow up on something Sarah said earlier on about, you can take as much or little as you like from Unique, it's the same with the show. I've had lots of people get in touch with me or talk to me in person and say, “I'm really sorry, I tried to watch ‘There She Goes' and I can't watch it,” and I have to say, “Don't apologise, you have nothing to apologise for. You take what you need from it. If you can't watch it then don't watch it. If you can watch it then do. There is literally no right or wrong way of doing this. There really isn't.” But having said that, the nicest comment – well, one of the nicest comments I've seen was on the DYRK1A forum. It was someone who casually referred to it as “our show,” as in the DYRK1A community, it belongs to them, and that – yeah, a little tear, a little tear went down my face [laughter]. Naimah: Yeah, that must have been a lovely thing for you to read. That's really nice. Sarah Wynn: Also from the Unique and general people who have rare conditions community, it's been so fantastic for raising awareness about genetic testing and rare conditions in general, and, you know, there just isn't – because these stories don't get talked about or shown about very often, it's been really great from that point of view as well. Naimah: And hopefully this will be the catalyst for similar programmes and, you know, more things in the mainstream media as well. And you did touch on it briefly there, Sarah, about, you know, what the programme's meant for Unique, you know, and the Unique community being very supportive, but have more people reached out to Unique since the programme? Sarah Wynn: I think the main takeaway is that being heard, “Our family's being heard and represented,” which I think is really important. But yes, we've got lots and lots of new families that have come to us through watching There She Goes. And it was really fortuitous that when the special aired last spring/summer, it was the evening before our awareness day, which I think was a complete coincidence but actually turned out to be really great timing. So, we got lots and lots of new families get in touch with us, many of whom then went on to join us. But actually what it also did was get lots of members who'd been members for a long time but perhaps had been a bit quiet, or hadn't been in touch, so it sort of also reinvigorated that engagement from other members who we might not have heard about for ages, and who might have got older children and had been in touch at the point when they were diagnosed, and then hadn't been. So, it has just been such a brilliant, brilliant experience to have Unique as part of it. And I think that's really important. At Unique, we have members from 120 different countries, and the reason is that when you have these rare conditions, you're really unlikely to find someone in the same town as you, possibly not even the same country with some rare conditions, and so the idea that you can connect with people all over the world I think is really important, particularly in rare conditions. Naimah: Yeah, that's great, and hopefully, you know, it just continues to increase support with Unique and, you know, families know they can still come to you as a resource and as that continues. So, I just wanted to kind of wrap up here and come to the final question. So, you know, your story highlights a lot of challenges, a lot of difficulties, a lot of ups and downs, but I just wondered, Shaun and Sarah, if you had any advice for other parents going through similar circumstances. Shaun Pye: Yeah, I think one of the things is what I just said, which is I would tell people there's no right or wrong way of doing this. I would say, from my experience, don't be hard on yourself, and you're going to think that you wish it never happened to you and that's fine. That is absolutely fine. That's normal. We've all thought that. It doesn't make you a bad parent. It makes you a normal human being. I would say to get in touch with Unique. I shied away a little bit from help and charities, ‘cos I think it was a sort of pride. I think I had a preconception that it would be glass half full, put on a happy smile, best foot forward, blitz spirit sort of. We have encountered it a little bit over the years, not very much, but we've encountered a little bit of, you know, “As long as you love them, that's the most important thing,” and, you know, which is fine and that is an okay perspective to have, but there are times when it's just not what you want to hear. I want to be allowed to feel the feelings that I'm having without feeling guilty. So, I would encourage people to seek support from Unique or from wherever. But, you know, generally, the thing I've learnt about people is that the vast, vast majority of people are nice and kind and understanding about this. Not everyone, but most people are good people and, you know, people should remember that, I think. Sarah Crawford: Yeah. I mean, the first thing I was going to say in terms of advice to other people was something Shaun said already, which is the don't be harsh on yourself, because, you know, you're allowed to find it difficult. But I would also say it's okay to grieve the child that you didn't have that you thought you were going to have. I just think that's so important. And I think for me, the most difficult thing in the early couple of years was feeling like I couldn't do that because nobody appreciated that I'd actually lost anything. The world seems to use the word difference a lot at the minute, you know, “These children are different, they're differently abled,” but actually it is disability [laughter], and it is more difficult, you know. There are rewards, there are positives, but, you know, she's 17 and a half now, our daughter. When our son was 17 and a half, you know, the challenges were different, but they were also nowhere near as big [laughter], and I don't think that should get lost. Because I think parents need to feel it's okay to get the help they need and to push for the help they need, and not feel like they've just got to kind of put on a brave face and, you know, as Shaun was saying, the attitude sometimes of, “Well, you've just got to get on with it.” Because while you do, actually, you know, you do need help to do that. It is difficult. Shaun Pye: The only other thing I'd say is, just ‘cos Sarah just mentioned it and it gets forgotten, is the siblings thing. The families with Unique will have all manner of different configurations. I can only speak from our own experience, but Joey has an elder brother, Frank, who is, well, in my opinion, the best human being in the world [laughter], and I'm sure in his mother's opinion as well, but my experience, never forget about the toll it takes on siblings. ‘Cos Frank is a very, very loving brother. Only last night, Joey was typing, “Frank book.” ‘Cos he's gone to university, she likes looking at pictures of him in the photo albums. She likes looking at pictures of old toys mainly. Sarah Crawford: Yeah, yeah, she likes looking at her as a baby and the toys they had. Shaun Pye: Yeah, but it's not really advice, it's just, you know, there's a danger that Joey could have taken over our entire family life, and especially Sarah made sure that didn't happen and that, you know, we were a unit and he was – but, you know, it is possible that it can swallow up your entire life. [Music] Naimah: Okay, so we'll wrap the interview up there. Thank you so much to our guests, Shaun Pye, Sarah Crawford and Sarah Wynn for joining us today as we discussed Shaun and Sarah's journey to Joey's diagnosis, and how charities like Unique can support families of those living with rare conditions. If you'd like to hear more like this, please subscribe to the G Word on your favourite podcast app. Thank you for listening. I've been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

The sudden loss of my brother cast a long shadow, one that followed me into meeting rooms and coffee breaks, reminding me that grief doesn't punch a time clock. Grief isn't an illness or mistake. It is a natural and sacred response to life's inevitable losses, and in this episode, we peel back the layers of discomfort that shroud death and grief in the workplace. I offer up my story as a lesson in vulnerability and as a beacon for those who are adrift in the same stormy waters. There's no suffering Olympics. Your loss could be a parent, partner, pregnancy, pet, or a job. It's still grief. In this episode, we discuss: How to offer support to colleagues experiencing lossWhy we need to reconsider bereavement and expand into compassionate leaveWhat we need from Human Resources and Executive Leadership  Show notes: You can listen to the 7-minute eulogy for my brother Bill Griffin, Jr. Honoring Wisdom: My Grandmother Turns 100  Support the showJill Griffin is committed to making workplaces more successful for everyone through leadership training and development, team dynamics workshops, and employee well-being programs. Her executive coaching, workshop facilitation, and innovative thinking have driven multi-million-dollar revenues for top agencies, startups, and renowned brands. Collaborating with individuals, teams, and organizations, Jill fosters high-performance and inclusive cultures while facilitating organizational growth. Visit JillGriffinCoaching.com for more details on: Book a 1:1 Career Strategy and Executive Coaching HERE Gallup CliftonStrengths Corporate Workshops to build a strengths-based culture Team Dynamics training to increase retention, communication, goal setting, and effective decision-making Keynote Speaking Grab a personal Resume Refresh with Jill Griffin HERE Follow @jillGriffinOffical on Instagram for daily inspiration Connect with and follow Jill on LinkedIn

Dr. Mike Chupp and Pastor Bert Jones chat with Dr. Amy Starr about how her engagement with the CMDA Coaching ministry greatly helped impact her plans for retirement and the next season of ministry in her life.  RESOURCES FOR THIS EPISODE: Give to CMDA Email CMDA Matters CMDA Bookstore Center for Well-Being Contact Dr. Bill Griffin about a THRIVE Event Campus & Community Ministries

Dr. Bill Griffin shares about the exciting opportunities for dentists to use their skills on GHO mission trips. GHO Trip Calendar: https://gho.servicereef.com/events?sort=upcoming

To learn more about us visit faithcenter.tv today!

Dr. Bill Griffin shares about the exciting opportunities for dentists to use their skills on GHO mission trips. GHO Trip Calendar: https://gho.servicereef.com/events?sort=upcoming

Dr. Cathie Scarbrough talks about bringing your faith into healthcare by incorporating spiritual interventions with Dr. Mike Chupp and Dr. Bill Griffin in this month's Dental Sound Bytes podcast, which is a re-release of a prior CMDA Matters episode.

To learn more about us visit faithcenter.tv today!

Dr. Terry Schmidt, who spent more than a decade playing in the NFL before becoming a dentist and CMDA member, chats with CMDA's CEO, Dr. Mike Chupp, and CMDA's Vice President for Dental Ministries, Dr. Bill Griffin, on this release of a recent CMDA Matters podcast.

Dr. Terry Schmidt, who spent more than a decade playing in the NFL before becoming a dentist and CMDA member, chats with Dr. Mike Chupp and Dr. Bill Griffin on this week's CMDA Matters podcast. Continue reading Preventing Touchdowns and Tooth Decay at Christian Medical & Dental Associations® (CMDA).

The Wisdom of God

Find Monica: monicasdeepdives.com twitter.com/MonicaPerezShow rokfin.com/propagandareport Find Different Take Podcast with Bill Griffin: differenttakepodcast.com youtube.com/channel/UCzHi-y_Iy2BZUK6sf_QCWig podcasts.apple.com/us/podcast/bill-griffins-podcast/id1517092565

Dr. Cathie Scarbrough talks about bringing your faith into healthcare by incorporating spiritual interventions with Dr. Mike Chupp and Dr. Bill Griffin on this week's CMDA Matters podcast.

THERAPY FOR HUMANS: BASED ON A DOG'S ADVICE BY BILL GRIFFINCanine experts in human behavior concluded that humans seem very stressed and need a lot of therapy. The only way to communicate stress-relieving therapy was to compare canine and human response to different stress situations. Dog photos and humor were used to express the differences in response. If this book does not make you smile, then you may want to contact a medical specialist treating funny bone disorders. Since canine paws do not work on the keyboard, our knowledge was dictated to the author, Bill Griffin. He learned to bark before he could talk. He has been a Pet Partner Team visiting hospitals, assisted living,  etc. For eight years he was an evaluator  working with potential Pet Partner teams preparing todo visits.https://www.amazon.com/Therapy-Humans-Based-Dogs-Advice/dp/1955944148https://www.dogsnhumans.com/http://www.bluefunkbroadcasting.com/root/twia/litprime.mp3   http://www.bluefunkbroadcasting.com/root/twia/63022litpr.mp3  

We are honored to have Dr. Bill Griffin on this episode of the Mission Minded Podcast. Dr. Griffin serves as the Vice President for Dental Ministries with the Christian Medical and Dental Association, also known as CMDA. He averages four international dental mission trips each year, and he is passionate about opportunities to communicate the love of Christ to others, both domestically and internationally. Dr. Griffin graduated from dental school in 1983 and practiced in Virginia for over 35 years. Along the way God reveled the opportunities to use his skill to serve and invest in others. You will be encouraged as you listen to his story of God leading him to go on that first medical mission trip to working with CMDA on a full time basis today. Mission Minded Podcast: In Matthew 28:18-20, we are commissioned by Christ to make disciples of all the nations. Living in light of this scriptural call can be challenging. Join the Mission Minded podcast and participate in discussions with mission-minded individuals that come from diverse backgrounds, working all over the world, to bring some of the challenges into the light. The ITEC team hosts special guests who tell stories, ask questions, and inspire us to use our God-given gifts to take the Gospel to our neighbors and the nations. Mission Minded Podcast is produced by ITEC. The goal of this podcast is to inspire conversations about Great Commission participation. The views, organizations, and individuals represented, interviewed, and discussed on the podcast do not necessarily represent an official position or formal partnerships with ITEC. Show Notes: https://cmda.org

To learn more about us visit faithcenter.tv today!

Bill Griffin, Vice President of Manufacturing at CaptiveAire Systems, discusses engineering and the ways in which Thales Academy helps prepare students for that career.Mr. Griffin currently oversees CaptiveAire manufacturing, engineering, and R&D and is based in Lancaster, PA.This webinar is also available to view on YouTube: https://www.youtube.com/watch?v=Wxmk13EjAZcThis webinar was streamed on September 23, 2021. Learn more about Thales Press and register for upcoming events and webinars at https://www.thalesacademy.org/resources/thales-pressNext Webinar: Loving and Learning Latin on October 21 at 4 pm with Will Begley of Thales Rolesville!

To learn more about us visit faithcenter.tv today!

Episode 430 - Abe and Adam connect with Bill Griffin and Apex Pro's Andrew Rains in the palatial recording studio. This is Andrew's first Midwest, and he's ready to go racing and do karaoke. --- Send in a voice message: https://anchor.fm/slipangle-show/message Support this podcast: https://anchor.fm/slipangle-show/support

Dr. Grattan Brown speaks on issues related to bioethics and the need to understand the value and dignity of human life, an idea uniquely grounded in a Classical education.Dr. Brown currently serves as the Academic Dean at Thales College and previously taught bioethics and related fields at Belmont Abbey College.Join us on September 23 at 4:00 pm as we hear from Bill Griffin, Vice President of Manufacturing at CaptiveAire Systems, about engineering and the ways in which Thales Academy helps prepare students for that career. Register here: https://bit.ly/2WTu9sa

Dr. Bill Griffin, D.D.S, Vice President for Dental Ministries for the Christian Medical and Dental Association discusses the importance of God and faith in the doctor patient relationship and the power it has to promote healing mind and body. Dr. Bill Griffin, D.D.S, Vice President for Dental Ministries for the Christian Medical and Dental Association discusses the importance of God and faith in the doctor patient relationship and the power it has to promote healing mind and body.  Alongside his private practice career, Dr. Griffin has been caring for the dentally needy. He serves as dental director and board chairman for the Lackey Clinic in Yorktown, Virginia. Also, he has served on about 60 dental mission trips around the world. He is a graduate of the University of Notre Dame. Later, he received his DDS degree at Virginia Commonwealth University School of Dentistry. His career in healthcare has led him to discover the strong ties between physical health and spiritual health. Over the years, he has been greatly inspired by CMDA's medical outreach teaching programs, The Saline Solution and Grace Prescriptions. Dr. Griffin's most recent project is directing the development of CMDA's Faith Prescriptions video series designed to equip healthcare professionals to communicate the love of Christ, in word and in deed, to their patients, students and colleagues. Christian Medical & Dental Associations - Website Like CMDA on Facebook Follow CMDA on Twitter

Episode 418 - Adam and Abe hang with Bill Griffin to talk abou luxury trailers, and his Spec E46 racecar. Great show with a great guest. --- Send in a voice message: https://anchor.fm/slipangle-show/message Support this podcast: https://anchor.fm/slipangle-show/support

Don't miss a single podcast of CMDA Matters. You can subscribe through iTunes or GooglePlay, download our free CMDA app and or listen on our website at www.cmda.org/cmdamatters. This weekly podcast hosted by Dr. Mike Chupp features one interview with brief news and announcements that matter to you. Dr. Bill Griffin joins Dr. Chupp on this week's CMDA Matters podcast to discuss the release of CMDA's new coaching curriculum Faith Prescriptions.

You're listening to the Westerly Sun's podcast, where we talk about the best local events, new job postings, obituaries, and more. First, a bit of Rhode Island trivia. Today's trivia is brought to you by Perennial. Perennial's new plant-based drink “Daily Gut & Brain” is a blend of easily digestible nutrients crafted for gut and brain health. A convenient mini-meal, Daily Gut & Brain” is available now at the CVS Pharmacy in Wakefield. Now for some trivia. Did you know that early professional baseball player Nap Lajoie was born in Woonsocket in 1874? He played for the Philadelphia Phillies, the Philadelphia Athletics, and the Cleveland Naps which were renamed after him because he was so popular. He managed the team from 1905 to 1909. He won the triple crown in 1901 and was the 5 time american league batting champion. Now for our feature story: Bill Griffin waited more than a year for this moment: Newly vaccinated, he embraced his 3-year-old granddaughter for the first time since the pandemic began. “She came running right over. I picked her up and gave her a hug. It was amazing,” the 70-year-old said after the reunion last weekend. Spring has arrived with sunshine and warmer weather, and many older adults who have been vaccinated, like Griffin, are emerging from COVID-19-imposed hibernation. From shopping in person or going to the gym to bigger milestones like visiting family, the people who were once most at risk from COVID-19 are beginning to move forward with getting their lives on track. More than 47% of Americans who are 65 and older are now fully vaccinated. Visiting grandchildren is a top priority for many older adults. Gailen Krug has yet to hold her first grandchild, who was born a month into the pandemic in Minneapolis. Now fully vaccinated, Krug is making plans to travel for her granddaughter's first birthday in April. Kurg said “I can't wait,” whose only interactions with the girl have been over Zoom and FaceTime. “It's very strange to not have her in my life yet.” The excitement she feels, however, is tempered with sadness. Her daughter-in-law's mother, who she had been looking forward to sharing grandma duties with, died of COVID-19 just hours after the baby's birth. Isolated by the pandemic, older adults were hard hit by loneliness caused by restrictions intended to keep people safe. Many of them sat out summer reunions, canceled vacation plans and missed family holiday gatherings in November and December. In states with older populations, like Rhode Island, health officials worried about the emotional and physical toll of loneliness, posing an additional health concern on top of the virus. But that's changing, and more older people are reappearing in public after they were among the first group to get vaccinated. Those who are fully vaccinated are ready to get out of Dodge without worrying they were endangering themselves amid a pandemic that has claimed more than 540,000 lives in the United States. The Griffins were also cautious before they were reunited with their granddaughter. “Everybody wants to live for the moment, but the moment could have been very deadly. We listened to the scientists,” he said. And for more about the latest covid stories in and around Westerly, head over to westerlysun.com. There are a lot of businesses in our community that are hiring right now, so we're excited to tell you about some new job listings. Today's Job posting comes from the Ocean Community YMCA in Westerly. They're looking for a full-time finance associate to help crunch the numbers, keep up with billing and dues, and to help with all facets of the business's finances. Pay starts at $38,000 per year. If you'd like to learn more or apply, you can do so at the link in our episode description: https://www.indeed.com/l-Westerly,-RI-jobs.html?advn=6385150304015669&vjk=29fbf5c0f1dd0e6e Today we're remembering the life of Anne Bentz who was born in Chappaqua NY. She grew up in Chappaqua and graduated from Horace Greeley High School in 1943. Before the 1938 hurricane, she and her family summered at a cottage at Bluff Point in Groton for years. She went to Penn State where she majored in journalism, graduating in 1947. In 1947 she married Alan Bentz, and they moved to Minneapolis MN, where he was pursuing a Master's Degree. She worked at the Univ. of Minn. Press and became Assistant Editor of American Quarterly magazine. They moved to Maryland, New Jersey, and then to Connecticut. Anne did freelance writing involving interviews with interesting people for a local Mystic paper. The final move was to Stonington, where they had vacationed since 1954. They bought a second house and settled down to raise their three sons. Anne became Secretary of the Mystic Art Association and she and her husband were charter members of the Mystic River Historical Society. She served as Secretary of the Stonington Historical Society for 6 years and was a member of the Stonington Garden Club and the Wadawanuck Club. Anne loved the water, and wrote her epitaph: The sun came out and showed me the face of the sea. I was one with it - wedded to eternity. She will be missed by her family, friends and all who knew her. Thank you for taking a moment today to remember and celebrate Anne's life. That's it for today, we'll be back next time with more! Also, remember to check out our sponsor Perennial, Daily Gut & Brain, available at the CVS on Main St. in Wakefield! See omnystudio.com/listener for privacy information.

Bill Griffin, DDS joins Bill Reichart to discuss the role CMDA plays in the lives of Dental School students plus graduate dentists with community, support, prayer and fellowship.

Bill Griffin has worked his way up to through the HPDE ranks to where he is a racing driver as well as an instructor, actually Jennifer's instructor from GingerMan a few weeks back.  We talk with him about his history and progression from having zero experience in performance driving to where he competes regularly with NASA and Grid Life as well as instructing when he can.  Bill grew up liking racing as many people who grew up near Indianapolis did and eventually began driving himself when his work and family life allowed, proving again that it is never too late to start to enjoy performance driving and even racing.  He is a very relaxed and knowledgeable driver and Jennifer loved having him as an instructor.  We cover how the NASA Great Lake GingerMan HPDE classes went without being able to have in car instruction and offer several options that may be ways to improve the teaching methods without right seat instruction as an option due to COVID 19.  The event was awesome, but as with everything else, you can always improve, in everything.  You can follow him on Instagram at Bill Griffin.   On one of our simplest episodes of Dominating with Dawson we review crabbing or cheating into a corner.   We hope you enjoy the episode!   Best regards,   Bill, Vicki, Jennifer, and Alan Hosts of the Garage Heroes In Training podcast and team members in the GHiT Immature Endurance Racing Team   Highlights from the episode include: 1)  We cover Bill's progressions from newbie track driver and not terribly mechanical to a regular racing driver and instructor (who has been to the track 5 weeks straight and counting) (Very jealous) 2)  What is a competition (or race) license, as well as several methods and paths towards getting one. 3)  Bill seeks guidance to how to schedule a season of racing with the rest of our team.  Perhaps an appointment for hearing testing is in order. 4)  Bill also goes into a quick review of some of the exotic sports cars he gets to drive with Extreme Experience and their clients.  This is especially useful if you are taller, like Bill who is 6' 4". 5)  Bill (the other) also goes over the potential limits in size for a driver in a Mazda Miata MX-5.  We have seen one with a cage that fits the owner that was 6' 8" and swallowed Bill up quite easily. 6)  Bill even goes over why he chooses to remain instructing the HPDE 1 group of students. 7)  We cover how the NASA Great Lake GingerMan HPDE classes went without being able to have in car instructional and offer several options that may be ways to improve the teaching methods without right seat instruction as an option due to COVID 19.  The event was awesome, but as with everything else, you can always improve, in everything. 8)  Suggestions included 1) potentially using in car radios to communicate to the students, 2) lead follow groups of only two students, 3) only using partial lead follow (allowing students to assume lead position and instructor to follow), 4) perhaps grouping the instructors and cars to match performance, 5) using better/more universally defined hand signals, 6) more use of different cones for initial track learning, 7)  perhaps adopting an unofficial "HPDE 1.5" level/group within the HPDE 1 population, 8) incorporating the use of in car video, 9) positioning instructors with notebooks around the track to view at significant turns or areas of the track to provide feedback to the classroom or debrief sessions, 10) potential pathways to getting increased options for right seat/in car instruction. 9)  The tricks and differences in being an instructor in a lead follow environment versus being in the right seat and the potential for lead follow groups to become longer groups, which can make some of the instruction into a bad game of telephone. 10)  Riding a bike vs walking the track during a track walk. 11)  Several tips for new to track or high performance drivers. 12)  Bill unprompted supports Bill with the prep required before coming to the track as well as using 2-3 max goals and a few comments for each track session, especially during an HPDE event.  Now if we could only get the Wilson sisters to agree, lol. 13)  How your first few HPDE events can feel like your brain is drinking from a fire hose and how to potentially reduce this effect (like following the ideas from #12 above) 14)  Bill F. tries to sneak in a Good, The Bad, and the Ugly segment on how Jennifer did during here HPDE event.  Bill G. is much too nice to comply, but we will keep trying. 15)  How driving in a lead follow instruction environment make lengthening your vision particularly difficult. 16)  Tips for everyone (and us) on their next HPDE event.  Ours will be at Pitt Race in late July with NASA Great Lakes. 17)  The importance of focusing on consistently hitting your track marks and letting the speed build naturally.  Because it will. 18)  How teaching and instructing has helped Bill's racing and how Racing has helped him as an instructor.  Hopefully, it will help our Bill when he gets there, lol.

Bill Griffin of Los Angeles's Kayne Griffin Corcoran gallery joins Cynthia Sachs and Naomi Baigell of Athena Art Finance to discuss the current state of art market. Griffin discusses the ways that the pandemic has had an impact upon his business and the surprising ways that it has not. Gallerists are traveling less but collectors seem no less keen on continuing conversations and re-thinking the composition of their collections.

Episode 298 - Adam catches up with Bill Griffin while at the #GRIDLIFE KartBattle event during PRI. Bill's been instructing for quite a while, and takes his Spec E46 to events all over the country. Bill tells us about his journey from car curious, to full-blown race maniac. --- Send in a voice message: https://anchor.fm/slipangle-show/message Support this podcast: https://anchor.fm/slipangle-show/support

Bill Griffin, DDS, shares about the Joy we find in Christ and how stupid it looks to unbelievers...until they believe.

Bill Griffin, DDS shares about our responsibilities to witness to our neighbors and all we meet with the good news of Jesus.

Sunday morning service at Indianapolis First Church of the Nazarene, February 15, 1981. This episode begins with a very brief introduction of Jerry by Rev. Bill Griffin. The message is about the discipline of the Gentle Shepherd, and is followed by the closing hymn "Softly and Tenderly."

Being selected by Tom Landry's Dallas Cowboys in the 1971 NFL draft after a stellar college career and three perfect high school seasons including three state championships was just the beginning of God drawing Bill Griffin to Himself. You won't want to miss the incredible stories, featuring legendary sports figures on and off the field, that God used to restore this giant of a man.

Being selected by Tom Landry's Dallas Cowboys in the 1971 NFL draft after a stellar college career and three perfect high school seasons including three state championships was just the beginning of God drawing Bill Griffin to Himself. You won't want to miss the incredible stories, featuring legendary sports figures on and off the field, that God used to restore this giant of a man.

Bill Griffin, DDS, shares from Phillipians about how Jesus should be our source of peace during conflict.

Dr. Bill Griffin, DDS discusses his heart and ministry toward dental students and shares about his new devotional material that can help dental students (and all healthcare students) grow in their faith in Christ. Bill Griffin, DDS lives in Virginia with his wife Linda and their two children. Bill is a graduate of the Medical College of Viriginia and currently has a private practice in Newport News, City Center Dental Care. (www.citycenterdentalcare.com)

Joining us for today’s show is Bill Griffin, an Executive Vice President of Global Sales who knows how to Make the Number. Today’s topic is about winning more deals, winning bigger deals, and winning them faster. Bill uses the How to Make Your Number in 2018 Workbook to access emerging best practices as a guide for our questions.  Leverage the latest Workbook to review the Sales Process phase starting on page 361 of the Sales Strategy section.  Our guest today is Bill Griffin, the Executive Vice President of Global Sales and Services for Aspen Technology. Aspen is the leader in process optimization software, primarily for the process industries, which include oil, gas, and chemical customers. This show is a can’t miss episode for executives who want to yield more deals, bigger deals, and greater success in making your number.   Today’s focus on sales process has an emphasis on pipeline velocity and pipeline cleanliness. To increase deal sizes, improve your win rates, and shorten your sales cycles, you need to adopt a custom, proprietary sales process/methodology. Bill is uniquely qualified to speak on this topic of deploying a custom sales process, as he came up through the ranks of Xerox and Autodesk, and has guided his sales teams to win more deals, win bigger deals, and win them faster.     Why this topic? Standard, one size fits all sales methodologies no longer work. Your competitors can license the same sales methodologies from the same vendors you can, so there is no competitive advantage to be had by adopting the latest sales methodology from the sales trainee industry. Listen to the interview with Bill from May, 2017 that demonstrates how to win more deals, win bigger deals, and win them faster.   We begin the show by providing an overview of how Bill uses sales process to help buyers make purchase decisions.  He describes the sales methodology and the resources the sales team needs to execute the sales process.  Bill describes how to use the sales process to trigger access to higher end sales resources.  We do that by making sure we're giving the customer the right resources they need at the right phase. What is important is that those stages trigger certain activities from your sales organization. I would not send out a pre-sales application engineer or solution engineer - we call it a business consultant at Aspen Technology - unless we've reached a certain stage in the process because it would be inappropriate. Just like throwing a quote out to the customer, doing a deep dive custom demo. You need to make sure you reach a certain stage in the process. By having those stage gates, you can make sure you are applying the right resources because your resources are expensive and limited in a global organization, at the right time in the sales cycle.  In the second segment of the show Bill explains how a custom sales process shortens the sales cycle length, increases win rate, and improves the deal size.  Bill’s straightforward answer provides a sound guide to how this can pay off for you:  You allocate your limited resources on deals that a higher likelihood that are actually going to be closed. And by doing that you're able to grow the deal because you're not wasting your time chasing deals that aren't going to follow through. Bill provides an insight into how to track the right metrics that indicate success of a sales process. What are the leading indicators and ultimately the lagging indicators to show success.  

Una Stubbs discusses her love of painting and her role playing Sherlock's landlady Mrs Hudson Dinosaur expert and primatologist Ben Garrod on how his love of nature started. Bill Griffin founder of the Crowdwish website explains how he helps people fulfil their wishes and tries to set them on the path to happiness Listener and folk singer Ian W. Brown on the perils of sharing your name with someone famous. Plus singer Marti Webb shares her Inheritance Tracks Producer: Steven Williams Editor: Anne Peacock.

Episode 101 or so - We're back at Gingerman Raceway from #Gridlife Special Stage with NASA Buddies Bill Griffin, Nolan Feathers, and Brad Adams.  Bill recently ventured into motor sports headfirst building a Spec E46, Nolan hated #Gridlife but came to an event anyways and surprisingly had a good time, and Brad is....Brad.

Richard Mabion speaks with Bill Griffin of Cromwell Solar.  Your phone calls welcome.   www.cromwellsolar.com The post Little Bit o’ Solar appeared first on KKFI.

Just as we have seen major technological advances in our personal lives, we will now see radical changes in how we clean homes, offices and other types of facilities. What we are seeing today is the beginning steps of an evolutionary process that will revolutionize every aspect of professional cleaning. Bill Griffin is on the cutting edge of these changes. Join IAQ Radio and Bill Griffin as we discuss the present and future of "cleaning for health".

Just as we have seen major technological advances in our personal lives, we will now see radical changes in how we clean homes, offices and other types of facilities. What we are seeing today is the beginning steps of an evolutionary process that will revolutionize every aspect of professional cleaning. Bill Griffin is on the cutting edge of these changes. Join IAQ Radio and Bill Griffin as we discuss the present and future of "cleaning for health".

Woody Overton and Jim Chapman tell the story of Casey White and Vickie White who just last year led authorities on an 11 day manhunt following Casey White's escape from prison in one of the most adrenaline filled escapes in United States history.#CaseyWhite #VickieWhite #PrisonEscape #Podcast #WhenEvilEscapesCheck out past episodes on our website by clicking hereFULL TRANSCRIPTJim: Hey, everyone. Welcome back to another edition of Bloody-Woody: -Angola.Jim: A podcast 142 years in the making.Woody: The Complete Story of America's Bloodiest Prison.Jim: And I'm Jim Chapman.Woody: And I'm Woody Overton.Jim: And we're back with a new episode.Woody: We're back, y'all. And, hey, patrons, thank y'all so much for supporting us. And as any show does, eventually, we took, what, a two-week hiatus? Jim: Yeah, we dropped just for patrons for a couple of weeks.Woody: Right. But we've had meanwhile-- it's funny, we take the little break, and we go to number five again and we're kind of going viral on Bloody Angola and we won't take much time off, y'all, but sometimes it is what it is. That being said, we want to thank everybody and we welcome all you new listeners to this edition of Bloody Angola. What we told y'all, or I've told y'all in every episode of Bloody Angola, is you're always going to get something different. Today's case is really different, because while the story is not directly related to Angola, I can tell you it's directly related to Angola.Jim: [laughs]Woody: The case is about a guy named Casey White, who was a convict, and Vicky White, who was a correctional officer. And we're going to get into it but let me tell you this. I can tell you, I've seen it, I've arrested people inside the prison for doing it. What it boils down to is correctional officers and inmates fucking. Jim: Yeah.Woody: You wouldn't think, Jim, that that would happen, but it probably happens more than inmates doing it. I think the convicts use-- certainly some of the people locked up in prison are geniuses and they are master manipulators for whatever the crimes may have been. They find that weak person, male or female. We've done an episode on Bloody Angola about the lieutenant who was banging a convict. But it happens, male and female. So, it's a very real deal inside the prison. I told you, anytime you go behind those gates or the walls, that that normal rules don't apply. And it is what it is.Y'all, I've actually seen it. I'll tell you one case that really sticks in my head. There was a politician's daughter, and she was an attractive female, who was a correctional officer. Now, naturally, he got her the job and they gave her a cush job. She was in the canteen. She worked where they got all the snacks and shit from. She had an orderly who worked with her when-- we called him, really working her from behind, literally. Jim: [laughs] Woody: And somebody else had snitched on them. So, we set it up and waited for the opportunity and busted in. They were butt naked, and he was balls deep. She didn't get arrested because of who she was, but she got fired, and he got swung to the working cell block. Jim: Oh, very nice.Woody: But this story is super, super interesting. You know what? I told you correctional officers, some of the best people in the world, and then some of them that you work with that are worse than inmates. This story really shows how the human psyche can roll out, because you can be the best correctional officer for years and then sugar turns into shit. Jim: That's right. This is a good example of it. As Woody just told you, it's one hell of a story. The best place to start is, I want to give you guys and gals an idea of the background of these two subjects that we're going to talk about. The first one is Casey White, y'all. Now, to call this guy a stone-cold killer would really be putting it mildly. The first thing you notice when you see Casey White is his size. He's just flat out a giant of a human being. Woody: Like a freak of nature giant.Jim: Freak of nature, 6'9", weighed 330-- [crosstalk] Woody: There's not that many players in the NBA that are 6'9". Jim: There's probably not a bunch of people on Earth that are 6'9" and 330 pounds. And, y'all, this ain't fat. This is solid prison muscle. And prison muscle, as you've heard Woody talk about many times on Real Life Real Crime, is different than free people muscle. [laughs] Woody: Jim and I have been here before, and somebody came in to be a guest on the show, and I was like, "Oh, shit, that's prison muscle." Jim: Oh, yeah. You spot it right off, and that's what he had. The next thing you'll notice about this guy is his tattoos. Now, he has tons of them, but this isn't your typical barbed wire or if you're in the navy, you've got an anchor on your bicep or something. These are mostly white supremacist related tattoos. He was associated with the Alabama-based white supremacist prison gang, Southern Brotherhood. So, not a nice individual. In addition to being a freaking Jolly Green Giant. Woody: We need to cover this one day, and we will on prison gangs, different ones, maybe episode on each one. Let me tell you about the Aryan-based prison gangs. They're like the military. On your yard time, you have to work out. They work out in formation. They stay to themselves, etc. The prison muscle deal, if you don't work out and you're not swole, they'll beat your ass. If you don't do what they order you to do, they'll kill you. But at 6'9", 330 pounds, I bet you he was a shot caller.Jim: Oh, yeah. What we're trying to do here is paint y'all a picture of how intimidating this guy is before you even know even a shred of his criminal record. Now, you may wonder what's that look like. Well, get ready for this. Woody: Well, in 2006, Casey White was arrested on a domestic violence charge. But, Jim, it wasn't his wife. Domestic violence doesn't mean it's your spouse. In this case, he was arrested for beating his mama's ass. His own mother. Four years later, in 2010, he pled guilty to attacking his brother, another domestic violence, with an axe handle, and was sentenced to six years in prison.And, y'all, in December 2015, Mr. White went on another crime spree where he tracked down and tried to kill his ex-girlfriend. The rampage spanned both Alabama and Tennessee as he held victims at gunpoint, shot one woman in arm, killed a dog, and carried out a home invasion and staged multiple carjackings before he was finally captured in a dramatic police chase. Now, this spree unfolded on the morning of December 1st, 2015, when he broke into a home and stole two guns. Later that night, he turned up at his girlfriend's house armed with the stolen guns and opened fire on her and two men inside the home.Jim: Didn't even hesitate.Woody: He had it on his mind. After that, White then broke into another home and stole a man's car and another gun. Around an hour later, he shot another woman in the arm in an attempted carjacking in Tennessee before carjacking another person at gunpoint.Jim: This is all the same freaking weekend.Woody: He's just rolling. I mean, he's just straight up thug life. White was finally captured in a dramatic 100-mile-an-hour police chase that ended in a standoff back over the border in Alabama. Now, he's in a standoff. And during the standoff, he demands to speak to the sheriff and threatened to shoot himself in the head. He asked for a pack of Marlboro cigarettes and a Sun Drop soda before he surrendered. Jim: [laughs] Got to have them Marlboros. Woody: Got to get me them reds. Jim: That's crazy.Woody: Got to get that voice right. Well, he knew he was going back to prison. In 2019, White was convicted on multiple charges over the rampage, including attempted murder of his ex-girlfriend, and he got 75 years in prison. Jim: So, that's what kind of guy we're dealing with here. Woody: Real winner.Jim: I guess you could say, walks the walk and talks the talk when it comes to it. Woody: When you tat yourself up with Swastikas and shit, you're pretty much not going to get a job as a whatever, as an accountant. I mean, you're in for the thug life. He's proven it, and he has total disregard for the law and anything going on with it.Jim: Yeah, so he's right where he belongs. And while serving this 75--Woody: He's the reason they build Bloody Angolas. Jim: Yeah, that's right. While serving this sentence of 75 years, he's also awaiting a trial for the 2015 stabbing and murder of a 58-year-old mother of two named Connie Ridgeway. Now shortly after he got locked up for that 75-year stint, he provided a confession for that particular murder. Now, she was found stabbed to death in her apartment. This was in Rogersville, Alabama on the 23rd October of 2015. The case went unsolved for five years until White sent a letter to the Lauderdale County Sheriff's Office confessing to the crime. During a subsequent interview with authorities, he allegedly gave details about the crime that had not been made public which only the killer, y'all, would have known. Prosecutors say he was paid to carry out that hit. Woody: Got to make a living. Jim: Got to make a living. Look, his whole life, that's how he generated money, I'm sure. In 2020, he was charged with two counts of capital murder. Now, after confessing to the murder in which he initially pled guilty, he changes his plea to not guilty by reason of mental illness. Woody: See how that works out for him.Jim: Yeah, primarily because they were going for the death penalty if he was convicted in that case. So, there's no way at that point he's going to plead just straight up guilty. Now, if that's not enough to paint a picture of how evil this guy is, there's also the mysterious disappearance and death of his 2008 girlfriend. Casey White's then girlfriend, back in 2008, Christy Shelton, was shot in the chest by a sawed-off shotgun inside an Alabama home belonging to White's mother. Woody: The same mother he beat the shit out of. Jim: Same one he beat the shit out of. Ms. Shelton, who was 31 at the time, died at the scene. Now, White was in the home with her at the time of the shooting, but somehow, Woody, was ruled out as a suspect. Woody: Ah, look at that.Jim: That was his history. Back then, officials ruled the 31-year-old deaths as a suicide and the case was closed. So, he probably made it look like a suicide somehow. Ms. Shelton's family, of course, always doubted that version of events and it was never solved. That is the crimes, Casey White was convicted of and the ones he still faced justice for in 2022 when the incident we're about to tell you about took place. Woody: It's just a long, long storied history of being a piece of shit. Jim: His whole life. Woody: A hardcore piece of shit. Jim: Start out beating his mother and his brother. Woody: I mean, he's just the gift that keeps on giving. But again, that's why we build prisons, for murderers and pieces of shit like this. Let me tell you about the other side of this story. And that is about Ms. Vicky White. Now listen, they have the same last name, y'all, her and Casey White, but they're not related at all. They weren't married, not blood related, nothing. Just chances, I guess. White is a pretty common name. But Vicky White was a total opposite of Casey. At 56 years old, Vicky White was almost getting ready to retire from her career as a correctional officer. Rick Singleton, the sheriff in Lauderdale County, Alabama, was quoted as saying she was a model employee in all her coworkers. All the employees in the sheriff's office, the judges and all had the utmost respect for her. Now, Vicky White was a widow with no children and never had so much as a speeding ticket in her entire life. She was clean as a whistle. She is 5'5" and weighed 145 pounds. Now, we told you about him, 6'9", 330.Vicky, in 1997, she joined the Lauderdale County Sheriff's Office and she went on become the office assistant director of corrections. That's something special for a female. I mean, that's a big deal. In 2002, she and Tommy White got married. Now, that's not Casey White, y'all. That's her husband. They got married and she was six years younger than him, and they raised cattle on a farm. She later left him when his drug problems got out of hand in 2006 and she divorced him. But she was so respected and well liked. In fact, between 2015 and 2022, her peers voted her as supervisor or employee of the year four times.Jim: Wow.Woody: I mean, she was just jam up. After her divorce with her husband, Tommy, she remained friendly with him. In January 2022, he died from complications related to Parkinson's disease. She's getting ready to retire. She's 56 years old. She's put in almost her 30 years. She's risen as high as she can get in corrections, sans a warden, I guess. Then, she's liked by everybody. Jim: Yeah. Just a stand-up citizen in all--Woody: All aspects. Jim: Total opposite of the other guy. Now, I know you're wondering, you're probably saying to yourself, "What happened? How the hell did these two completely different individuals just get intertwined?" Well, in 2020, while serving down his sentence at the William E. Donaldson Correctional Facility, which is in Jefferson County, Alabama, Casey White came into contact with Vicky White. Let me tell you how they came into contact. He was at a state prison, but they would transfer him to her jail whenever he would have court appearances. He'd get transferred to the jail, he'd see Ms. White and he wanted to get him a little something-something, probably wink at her or whatever. Look, this is a big dude now. He ain't blended in nowhere. Woody: Yeah. I'm sure he started out, he floated her a little wink or something and she didn't reject it. So, that opens up his can of worms. Like, "Every time I'm going down, I'm going to try to lay a little smackdown on this girl."Jim: That's right. Woody: If can be honest with you, I'm totally confident in my sexuality, I could say this. But I think you look at a 6'9" guy that's 330 pounds, and you think everything is big on that dude. [laughter] Woody: He probably got 14-- [crosstalk] Jim: An anaconda in his pants? [laughs]  Woody: At 14, his anaconda, but he don't fold it in half for anybody. [laughter] Jim: Indeed. And I'm sure she was thinking the same thing at the time.Woody: She's 56 and [crosstalk] husband for a while. That's still cracker. Jim: So, they would see each other. Speculation now is that the flirting started, and she started calling him. She would call him at his state prison, and they just shoot the breeze. Look, this became a two-year thing.Woody: Yeah. Once I submit to you on that first phone call, it's going to be a shitty--Jim: Yeah. "What are you wearing?" That was what that question was on that first phone call. "Is it red panty night?" [laughs] [crosstalk] Woody: That may have been the second phone call. The very fact that he got it across that line of calling me-- now, I'm sure they say, "This is a collect call from an inmate at correctional center, da, da, da," she had to take the charge. Jim: That's right. They start this kind of phone thing and visiting thing, and it becomes a two-year ordeal. As a matter of fact, during the next two years, they formed a relationship and other inmates-- and look, inmates talk and inmates after the fact, after all the dust settled and this case became obvious, they came forward and said he would get extra food and special privileges from Vicky White every time he was at that jail. And they were pissed. They're not going to rat out the 6'9", 330-pound beast for sure. Now,in the months and weeks leading up to what will become his escape from prison, aided by Vicky White, and of course, unbeknownst to officials, Vicky was preparing. Vicky announced plans to retire on April 29th, 2022, which incidentally, y'all, was the same day of the escape. She sold her home on April 18th of 2022 for $95,550. Now, that's important because it was well below the market value of $235,000.Woody: Yeah. She wanted that quick money. She had plan.Jim: She wanted that quick money. Yeah. First person looked at it, "What if I charge you 95,000?" They were like, "Okay." She ended up selling it for a third of its value. She then moved in with her mother, Pat Davis, for about five weeks after selling that home. She started taking money out of the bank. She had a number of different banks. She was taking cash out of everywhere. So, she was preparing. She even went shopping for men's clothing at a local department store, Woody Overton. Then, she goes to the adult store.Woody: The men's clothing, she had to look in the big and tall section. Jim: Oh, yeah. You had to get probably some special stuff there. She goes to the adult store even and buys lingerie and sex toys. Woody: We had to put on the kinky.Jim: Yeah. Woody: [crosstalk] Jim: Yeah. This is all going on the weeks before the actual escape, and she even purchased, which would become an important point, a 2007 Ford Edge that was orange under a false name. Woody: Right. Now, we set it up for you. You know who he is, what he's about. The two faces that she put on, the professional face and now she's got-- well, they had a common face. She's lining it all, and he's telling her to do all this. But I think $95,000, we can get by, have some good times on that. On April 28th, 2022, Vicky White stayed at a Quality Inn hotel in Florence, Alabama. It was this day that she positioned the orange Ford Edge at a parking lot about 10 minutes from the detention center.On the day of the escape, at 09:30 AM, Vicky White told another deputy that she planned to take Casey White to a mental health evaluation in court and then would seek medical attention because she wasn't feeling well. While the jail policy states that inmates are always accompanied by two deputies, because she's who she was, Vicky White, and everyone loved and trusted her, no one even second guessed her decision. That's really using your power and your authority and your reputation.Vicky White then took Casey White, who's wearing an orange jumpsuit and shackles, and put him in a patrol car, and she drove away. As they left the prison, Florence City Council member, Bill Griffin, was outside shooting a commercial for his council district, and he saw Vicky drive past him with Casey White in the backseat. Well, not unusual. Griffin knew White and waved at her, and she waved back to him twice before driving off. Just a day at the office. She drove the patrol car from the detention center to a nearby shopping center parking lot and left the vehicle there. They then got into the orange Ford Edge that had been left there the night earlier and drove away. The patrol car was found abandoned in the parking lot around 11:00 AM by someone on a lunch break. Imagine that, right? Jim: Yeah. Woody: When we say patrol cars, even every jail or prison, especially sheriff's offices, they have jail units. It looks just like a patrol car, like a uniform deputy patrolling in. But they have jail units that they can transport one inmate or time or go do whatever jail functions they need to do. That's what she did in this case. Officers at the jail became concerned and tried to call her but her phone kept going straight to voicemail. Then, they realized that Casey White had not been returned to the jail. The Ford Edge was found locked and abandoned in the middle of the road in Williamson County, Tennessee, about a two-hour drive north of Lauderdale County. Unaware of its origin, a tow truck driver, Robert Keynes, transported the vehicle to a local tow lot. At about 03:30 PM, officials realized Vicky and Casey White were missing. Now y'all remember when she bought the Ford Edge, she did it under assumed name so it's not tied to her. Once they realized that Vicky and Casey were missing, the Lauderdale County sheriff's office put out an alert on their Facebook page just before 6 o'clock in the evening. Jim: Wow. You can imagine the panic, y'all. This guy was a stone-cold killer. He just escaped your jail. I mean he is the worst of the worst. There's probably going to be violence at some point. Now in addition, you're assuming Vicky is a victim. Nobody is thinking at this time Vicky helped this guy escape. They're all thinking he must have overpowered or got out of his handcuffs or something. So, you call the cavalry. And that's just what they did. On May 1st, the US Marshals offer up to a $10,000 reward for information leading to the capture of Casey White. Vicky White was described as missing and endangered.Woody: In case you don't know, anytime there's an escaped inmate or convict, the US Marshals, they have a specialized division just in tracking down escapees. Everybody else would have been looking for them also, the sheriff's office and all the state police. But when you call in the US marshals, this division, all they do is eat escapees. Jim: Yeah. As Woody said, they start investigating and they figured out, and they figured out pretty fast. As a matter of fact, by the next day, they figure out that Vicky White was somehow involved in aiding him in this escape. On May 2nd, a warrant is issued for Vicky White, charging her with permitting and facilitating escape in the first degree. So, something happened. Woody: I'm sure they figured out that he actually didn't have doctor's appointments. She made all that shit up. Jim: Absolutely. And some other things. Actually, she and Casey White were caught on camera as well, which in reality, look, that was going to happen sooner or later. People don't realize it, but all of us are on camera. An average, y'all, you, whoever's listening right now, all of you, you're on camera an average of 70 times per day, whether it's going in and out of stores, pumping gas, sitting at red lights, whatever. Woody: Considering the Chinese spy balloons. Jim: Yeah, that's right. [chuckles] The particular video of the two that kind of tied it in for them shows Vicky White driving the patrol car straight from the detention center to the parking lot where it was found. She made no stops in between and that was an indication to police that there was some planning involved. On May 3rd, the Marshal service releases images of the orange Ford Edge that the fugitives were last seen driving, what they picked up in the parking lot. They left the patrol car, they got in the orange Ford Edge and the marshals added a $5,000 reward for information leading to the capture of Vicky White. So it's up to 15,000 now. The subject should be considered armed and dangerous and may be armed with an AR-15 rifle or a shotgun, the marshal's office also reported.Woody: And that would have been out of the marshal unit, y'all, the jail unit, they keep them in the trunk. Jim: It was at this point and still not discovered by police that Casey and Vicky ditch the Ford Edge and they pay $6,000 cash for a Ford F150. It is also at this time that they purchase a Cadillac, and they continue their escape with one following the other into Indiana.Woody: Interesting.Jim: Yeah. Look, this was actually well planned. Just to set the scene for, y'all, there's panic now. This guy is as bad as they get. He's on the loose. Now, you've got a former employee on the loose with him, because I'm sure she got fired quick. Casey and Vicky White drive that car into a car wash in Evansville, Indiana.Woody: That's a long ways from Alabama. Jim: Yeah, that's right. Their last location before that that was known was Tennessee, a place called Williamson County, which was 175 miles north or south of Evansville.Woody: And then, to Indiana is a long ways from there.Jim: Yeah. Period. Woody: He's smart. They're putting in miles. The more miles in, the less news coverage and all that. Jim: There you go. So, they pull into that car wash. They leave the F150 sitting in the car wash stall, and they get into the Cadillac, and they drove away from the car wash. Now, at this point, law enforcements still assume they're in that orange Ford Edge. Woody: Right. Well, what they did not know was that tow truck driver had towed the Ford Edge two days earlier after it was left in the middle of a roadway. When he saw a news report on May 5th looking for that vehicle, he recognized it, and he called the cops and told him what tow yard it was in, and he brought them to it. The US Marshals found the Ford Edge in the tow lot and confirmed it was the one used by Vicky and Casey White.On May 8th, a few days later, another big break in the manhunt took place when investigators were notified about the Ford F150 abandoned at the car wash and its possible connection to the fugitives after the curious car wash attendant viewed surveillance video to try to find out who left the truck in his car wash and then recognized the fugitives. Jim:  Naturally. Woody: And they're pretty easy to recognize. Remember, it's anaconda and shorty. [chuckles] Woody: So, on May 9th, US Marshals release images dated May 3rd from the Evansville car wash surveillance camera of a man believed to be Casey White in the Ford F150. Y'all, they're also established in what direction they're headed, basically and that they're swapping vehicles. And the car wash surveillance video showed the suspects leaving the F150 and getting into that Cadillac. Jim: So now, they know what they're driving, at least at that point. Woody: Right. At this point, the Evansville police, where the two were last seen, had the Cadillac burned into their brain and they were looking everywhere for it. An Evansville police officer spotted the Cadillac vehicle at a Motel 41 and alerted other investigators. They began the surveillance of the motel and observed Vicky and Casey White exiting the motel and getting into the Cadillac. Police began to pursue the Cadillac and the fugitives fled north on the US Highway 41 in Evansville in the Cadillac. In the pursuit, Casey White and Vicky White drove onto a grassy field and parking lot near an industrial area of the city. A law enforcement officer rammed a vehicle into the car, flipping it onto its side in a ditch. It's like movie shit. You can't make this up, right? Jim: Yeah. And this was the Evansville, Indiana police. Woody: That's called a PIT maneuver. And maybe they didn't do it correctly. They flipped a Cadillac, dude. Officers reached the duo in the car, and they took Casey White into custody and found Vicky White with a gunshot wound to the head, and what investigators believed the time to be a self-inflicted or suicide y'all. She died in the hospital that night from her injuries. The Indiana coroner's office ruled the death as a suicide. During the arrest, Casey White referred to Vicky White as his wife and said he did not shoot her. They were not believed to have been married, talking about Vicky. Jim: Yeah, he just called them. They weren't legally-- Woody: Hell, he might have got an ordained minister through the thing or whatever, he might have married them in the hotel room. It's funny, it's not the Motel 6. It was the Motel 41. Jim: Motel 41. Only the best for that guy. Woody: Investigators found four handguns, a semiautomatic rifle, three magazines. That's not GQ magazines. People commonly refer to them as clips, magazines with bullets. They found wigs and about $29,000 cash in the vehicle. Casey White spoke for a lengthy period with investigators and said that they had planned to have a shootout with the police. The fugitives had been staying at the Motel 41 in an attempt to lay low for a while and had paid for a 14-day stay after paying a homeless man $100 plus the room cost to book the room for them. So, they had somebody else book it for them. Jim: Yeah. A homeless man at that. Woody: Now let me tell you this, anytime I had a BOLO for somebody that might be in my area, guess where I'm going to check first? The Motel 41 or whatever the local one is. In Albany, it was the Albany or whatever. I mean, you're going to cruise those places first. What they didn't know was cops had the Cadillac. If they didn't have a Cadillac, they'd have got away with it. If they didn't have the Cadillac on video like you're talking about, we're all on video so many times. Jim: That's right. That was a big key. There were a lot of questions to be answered, especially in regard to Vicky's death. We're going to play the 911 call for you now. One thing we didn't tell you in what we just told you was that right before the Cadillac got rammed, Vicky placed a 911 call. However, the operator picks up and she doesn't respond to the operating. They pick up, they say, "911, what is your emergency?" Normally, someone would say, "I'm in a chase with the cops," or something. "We don't want them shooting at us." She doesn't respond to that. It sounds like someone that would have dialed the phone in their lap and just left it sitting there so that the operator could hear what was going on. This is my impression, but I'm going to kind of let you gather your own impression. Right now, we're going to play that audio for you. This is Vicky White calling 911.Vicky: Hi. Operator: Evansville 911. Vicky: Oh, my Good. Operator: 911.Vicky: Please stop, the airbags are going to go off and kill us. Operator: Hello?Vicky: Casey. Oh, God. Airbags are going off. Let's get out and run. We should've stayed at the fucking hotel. [screams] [police sirens going off] [background noise] Operator: Hello?[police sirens going off][background noise] Jim: You hear things in that audio like, "Wait," "Stop," "Airbags are going to go off and kill us." Soon, you hear a loud noise. Now, the first of at least four loud noises to happen in about 15 seconds. It's unclear in each instance what the noise represents and it's kind of unclear from the audio when the car was rammed, when it rolled over and when the gun was fired. You do hear a woman, which is Vicky, saying, "God, airbags are going to go off. Let's get out and run." And she even mentions a hotel. The second noise you hear, you hear kind of shriek. And at least two more noises follow, followed by another shriek. You can hear sirens in the background. But this is the question I want y'all to ask yourselves, and that I certainly asked was if you're about to kill yourself, you're not worried about airbags going off, you're certainly not worried about getting out and running. So, I kind of call bullshit on that.Woody: And you wouldn't have dialed 911. Jim: And you wouldn't have dialed-- yeah, I call bullshit. Woody: I personally think what you're thinking is at some point in her pursuit, she realized, "Holy shit, he's going to kill me. I want 911 to at least be able to listen to it." Basically, what you just played is Vicky, a voice from the grave saying-- naturally, she knew she was culpable in all this, and at some point, she realizes, "Holy shit, he's going to kill me." Jim: Yeah.Woody: Jim, you may be 100% correct, but while Casey has not been charged with pulling the trigger against Vicky, he is being charged with felony murder in connection to the death of Vicky White and he's been indicted. The indictment says Casey White is responsible for Vicky White's death because it happened during Casey White's escape. Well, I get that, and that's a whole lot easier to prove than the fact that he killed her in a car. But I'm saying that he killed her in the car. Y'all want to read you a news release from the Lauderdale County Alabama's District Attorney. This news release is titled "Casey Cole White indicted for the felony murder and the death of Vicky White, July 12, 2022." On July 6, 2022, a capias warrant was issued for the rest of Casey Cole White for the offense of felony murder regarding the death of Vicky White. The warrant was issued based on the grand jury indictment. White, who is in the custody of the Alabama Department of Corrections serving a 75-year sentence due to the convictions from Limestone County, was served with the warrant yesterday at Donaldson Prison. He is also charged with capital murder for the 2015 murder Connie Ridgeway. The felony murder indictment alleges that during the course of an in furtherance of committing escape in the first degree, White caused the death of Vicky White, who died from a gunshot to the head. As are all criminal defendants, White is presumed innocent of the charge. No further information will be released by this office at this time. Chris Connolly, Lauderdale County District Attorney." Jim: That's pretty interesting because even though they're still saying that she killed herself, they're saying because of his involvement with her, that was almost the cause of it.Woody: It's the same thing. I go to rob a bank and you're driving a car and I kill somebody inside the bank, you're getting the murder charge also. In this case, because of the pursuit and whatever, she wouldn't have been in that situation.Jim: Right. Very interesting. One thing I will throw in here is a little caveat and a fun fact for y'all. The Motel 41 that you brought up, get this. Six months after that murder, tt was completely booked up. The same room that they stayed in for all that time. Woody: Yeah. Jim: Yes, people love it. "Yeah, I want Casey White's room." They could actually say that they slept in Casey White's room at the Motel 41. Woody: That's crazy. Jim: So, Motel 41 was loving it. [laughs] Woody: They're probably still loving it. Jim: Probably still loving it.Woody: They're going to love it after this episode. Jim: Yeah. Go check out the Motel 41. Maybe they'll sponsor Bloody Angola. [laughs] Woody: Yeah. Right. They can give us a free room when [crosstalk] Casey White room. We do a TikTok. Jim: The Casey White honeymoon suite. Woody: Very unique story. Jim: It really is.Woody: It happens every day. Think about all the ones, especially Angola, where these people, 6000 of them, certainly a certain percentage have to be masterminds and master manipulators. I've dealt with a lot of them. Like David Constance. He's not as dumb as he looks. He looks like a little troll, but the dude's a genius. Not formally educated, but he's a genius on playing people. It happens. Correctional officers are begging inmates, correctional officers are the largest reason that inmates get contraband, whether it's cell phones or dope or whatever. You can get more dope in prison than you can on the street. And it's probably cleaner, less fentanyl. But the sex part, everybody is here because two people screwed. Everybody on this earth, they just happen to find the vulnerable ones. Jim: That's right. Woody: And do what they do. Jim: You may wonder what's next for Casey White. I mean, he lived. He's back in jail. Well, in August of this year, 2023, he'll finally go on trial for the 2015 rampage that we told y'all about.Woody: Yeah, he should get death penalty.Jim: In that particular instance, he's charged with killing two people. As Woody discussed earlier in this podcast, he will most assuredly spend the rest of his life, if not get the death penalty for that.Woody: Some people just don't-- a rabid dog need to be put down because if he gets out-- he's proven, if he ever gets out, he's going to kill and maim and do whatever. This dude's definitely living for the moment. They found $26,000 out of the $95,000 something she sold her home for. He's living for the moment in the end. He planned on shooting out with cops anyway. He's like, "I'm going to be the--" [crosstalk] Jim: He told them that in interviews after.Woody: "I was going to shoot it out with y'all. I was going to kill as many of y'all as I can." Basically, he wanted to get killed too. Jim: That's right. Woody: He wanted to be that bad ass motherfucker, right? Jim: Yeah. The thing is, Woody, he's even said many times that had the vehicle not been flipped, he would have had that shootout. He just couldn't get out. He was pinned in.Woody: So, that 6'9", 330-pound anaconda. [crosstalk] Jim: Monster, man.Woody: Big dude. I don't know if I've ever met anybody-- Well, Shaq, I think it's a little taller than that, but that's a monster of a dude. Think about this, y'all, for every extreme case like this where they help him escape and all that, think about all the correction officers that are getting laid every day by convicts that never get found out. Jim: Never get found out. And you mentioned Shaq. Look, we're going to deviate just a second because I got a good Shaq story for y'all that I'm going to tell y'all, you may like. For those of you that may not realize, we record out of Baton Ridge, Louisiana area. And, of course, Shaquille O'Neal, Shaq played for LSU and back when he was in his college ball days, he was very well known around here. And much like Casey White, and it's worth pointing out those sized people stand out no matter where they're at. So, the first thing that I wondered with Casey White was he never would have been able to ever, ever, ever go in public anywhere for the rest of his life anyway because he stands out like a sore thumb. Just look for the guy that's 6ft 9in tall with tattoos. Woody: With swastikas.Jim: Yeah, I mean, it would have been obvious in that situation. But back to my Shaq story. I was in the mall and at the time, I was dating a girl and she was like 5ft tall, literally. I was probably 17 at the time. He might have been a sophomore at LSU. We're walking through a mall in Baton Rouge, and there he is. He's like looking at watches like in the breezeway there. I was coming out of Dillard's with my girlfriend. I asked the lady for a paper bag and a pen. So, she gives it to me. I told my girlfriend, I said, "Go get Shaq's autograph." She walks up to him and gets it but, y'all, Shaq is like 7'2". Standing next to my girlfriend, he's signing this thing, this is before cell phone cameras, sadly, but I saw it in person, it was like a two-year-old standing next to a full-grown adult. That was the size difference between those two.Woody: I got a couple I'll throw on you real quick. The same time, Shaq and Chris Jackson and all of them [crosstalk] I was at LSU. Reggie's, which we talked about on the last episode of Real Life Real Crime Daily, it's where Madison Brooks got overserved, that used to be called the Tiger. I lived in the first apartment right behind the Tiger. I'd go to the Tiger every night. Shaq, he was in the bar, and I went up, stood beside him, he was like a mountain of a man. Jim: Yeah. And Woody's tall. Woody: Yeah. I'm 6'2". But fast forward, I don't think anybody knows this. Shaquille O'Neal was a commissioned officer with the Killian Police Department. Jim: I forgot.Woody: Now I am going to tell you why. Not only did he have a house down there, but he is a big diver, scuba diver. He bought all the scuba diving equipment and the boat and everything for Killian Police Department. They're on the water down there on the [unintelligible 00:46:52]. He was instrumental in funding the dive rescue team and recovery team. Jim: Really? Woody: Killian Police Department. Yeah.Jim: I didn't know that.Woody: And he's [crosstalk] with them. Super, super cool guy, down to the earth. He's getting up there in age like me. But it is what it is. One of the best. Now, how we got on that from Bloody Angola, I don't know. Jim: [laughs] Well, we're talking about height and how these people stand out and that was just a few little for me and Woody, but just an enormous human. Woody: You're right. They absolutely would stand out like that. But this dude took it-- I'm talking about Casey White, took it to the whole next level, on getting tatted up with racist tats. Who's going to come up to him and say shit? Shaq might have said something to him but anyway.Jim: He is, Woody, the prime example that you can point to as someone who never, ever needs to be out of prison, ever. Woody: Yeah. Absolutely. Jim: Just a horrible human.Woody: They build prisons for that dude. Jim: They build prisons for them. Woody: Patreon members, thank you so much. Jim: Couldn't do it without them. Woody: I couldn't do it without you. Y'all, if you want to be a Patreon member, there's a ton of episodes locked up and get commercial-free early releases. Jim: And let me say this, Woody. I had a few people reach out, and I just want to explain this. They were asking with the regular episodes weren't dropping them every week. I just want to explain, and we appreciate all of you. Look, I love it when people say, "Where's the next episode?' I love that. I want everyone to understand, when you're a patron member, you don't miss any weeks. We're going to give you something, whether it's just Woody, whether it's just me, whether it's both of us, you're going to get extra and you're going to get bonus stuff. Sadly, this stuff is not free. And it is expensive for us to produce this podcast. It requires a lot of time, a lot of research. And so, with the regular feed that is just absolutely free, we unfortunately have to limit what we can put out there. If we were to a point where Nike would sponsor us or something, look, we're all over it. But if your Patreon member is $10 a month for the starting tier, and you get episodes every week.Woody: Even the higher tiers, I came in yesterday to record, you had a stack of packages that were going out. Jim: The Warden Team members. Woody: Warden Team members. I'll be looking for those. [crosstalk] Jim: I've got some good little swag this time. Woody: We give you a lot of benefits in that, and that's just a way to help us keep going and we give back, whether it's in the form of the commercial-free episodes or the episodes that nobody else is getting, the ones that are locked up. Look, some of those, I consider to be my favorite, the ones that are locked up haven't been released to the public. Jim: That's right. We've got probably about 10 of those now. If you're not a patron member yet, look, you can go to Patreon right now. It's $10 a month for that opening tier, and you got 10 episodes in there you ain't never heard.Woody: And you get commercial-free early releases. Basically, you get episodes if we have weeks of not dropping them.Jim: That's right. Don't forget about the other things we do. Woody, Real Life Real Crime Daily, Real Life Real Crime.Woody: Real Life Real Crime Daily. I would have let the cat out of the bag here first. Real Life Real Crime Daily has been such a success, about to take it from three days a week to four. Jim: Boom. Woody: Starting-- that's next week.Jim: Big deal, y'all. That means you're going to get either a Real Life Real Crime original or a Daily every day of the week. Woody: Five days a week. And Bloody Angola. It's a lot of recording, it's a lot of time. But you know what? The numbers don't lie. Y'all are the best fans in the world, and we appreciate you. Jim: That's right. We love doing it. Woody: And we're blessed. Jim: Yeah, don't forget about the app. Bloody Angola. You can get episodes straight through the app. Woody: That's the Real Life Real Crime community app. Jim: The Real Life Real Crime community app. So, you can download that on Apple Podcast. You can also do it on whatever Google's-- for Android. Woody: Yeah. Jim: Google Play Store. Woody: Yeah, just go you go to the App Store and download it. Jim: Yeah. So, that makes it easy, y'all, you can get it there. Woody: Respond to everybody in one place. We just have so much other social media, it's almost impossible now. Jim: That's right. Woody: It's a good problem to have, Jim. Jim: Yeah. [crosstalk] Woody: Y'all are a great problem to have. We love you. Jim: We love you very much. And until next time, I'm Jim Chapman. Woody: And I'm Woody Overton.Jim: Your host of Bloody-Woody: -Angola.Jim: A podcast 142 years in the making. Woody: The Complete Story of America's Bloodiest Prison.Jim and Woody: Peace. Our Sponsors:* Check out Factor and use my code bloodyangola50 for a great deal: https://www.factor75.com/ Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

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