Podcasts about genomes project

Play Episode Listen Later Feb 12, 2025 29:47

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.

Jillian Hastings Ward, Dr Karen Low and Lindsay Randall: How can parental insights transform care for rare genetic conditions?

Play Episode Listen Later Jan 15, 2025 29:26

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.

tv university uk care impact quest unique transform rare ward conditions nhs parental genes genetic swan hastings dla ppi decipher ddd coinciding bristol university chief investigator ehc kbg genomics england genomes project bill griffin disability living allowance karen thank

Dr Rich Scott and Adam Clatworthy: Reflecting on 2024 - A year of change and discovery

Play Episode Listen Later Dec 18, 2024 48:52

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.

Major Red Flags: FDA Approves Bird Flu Self-Amplifying mRNA Vaccine Trial w/ Dr. Clare Craig & Jessica Rose – Ask Dr. Drew – Ep 428

Ask Dr. Drew

Play Episode Listen Later Nov 25, 2024 77:14

The Defender reports “Arcturus Therapeutics announced earlier this week that the U.S. Food and Drug Administration (FDA) issued a “Study Can Proceed” notification for its investigational ARCT-2304 vaccine candidate.” Jessica Rose PhD says there are “major red flags.” The Defender also reported that “In clinical trials for the self-amplifying COVID-19 vaccine offered in Japan, “five deaths occurred among the injected in study phase 3b. Injected participants experienced a 90% adverse event rate (74.5% systemic, 15.2% required medical attention) after the first dose in study phases 1, 2, and 3a combined…” Dr. Clare Craig, BM BCh FRCPath, is a diagnostic pathologist, author, and co-chair of HART (Health Advisory and Recovery Team). She studied medicine at Cambridge and completed clinical training at Oxford. After 15 years in the NHS, she became pathology lead for the cancer arm of the 100,000 Genomes Project at Genomics England. She is the author of “Expired: Covid the Untold Story” and advocates for public education on COVID. Find more at https://hart.org and https://x.com/ClareCraigPath Dr. Jessica Rose is a Canadian researcher with a Bachelor's in Applied Mathematics and a Master's in Immunology from Memorial University of Newfoundland. She holds a PhD in Computational Biology from Bar Ilan University and completed postdoctoral research in Molecular Biology at the Hebrew University of Jerusalem and Biochemistry at the Technion Institute of Technology. Her recent work focuses on descriptive analysis of Vaccine Adverse Event Reporting System (VAERS) data. Find her at https://jessicasuniverse.com and https://jessicar.substack.com 「 SUPPORT OUR SPONSORS 」 Find out more about the brands that make this show possible and get special discounts on Dr. Drew's favorite products at https://drdrew.com/sponsors • CAPSADYN - Get pain relief with the power of capsaicin from chili peppers – without the burning! Capsadyn's proprietary formulation for joint & muscle pain contains no NSAIDs, opioids, anesthetics, or steroids. Try it for 15% off at https://drdrew.com/capsadyn • FATTY15 – The future of essential fatty acids is here! Strengthen your cells against age-related breakdown with Fatty15. Get 15% off a 90-day Starter Kit Subscription at https://drdrew.com/fatty15 • CHECK GENETICS - Your DNA is the key to discovering the RIGHT medication for you. Escape the big pharma cycle and understand your genetic medication blueprint with pharmacogenetic testing. Save $200 with code DRDREW at https://drdrew.com/check • PALEOVALLEY - "Paleovalley has a wide variety of extraordinary products that are both healthful and delicious,” says Dr. Drew. "I am a huge fan of this brand and know you'll love it too!” Get 15% off your first order at https://drdrew.com/paleovalley • THE WELLNESS COMPANY - Counteract harmful spike proteins with TWC's Signature Series Spike Support Formula containing nattokinase and selenium. Learn more about TWC's supplements at https://twc.health/drew 「 MEDICAL NOTE 」 Portions of this program may examine countervailing views on important medical issues. Always consult your physician before making any decisions about your health. 「 ABOUT THE SHOW 」 Ask Dr. Drew is produced by Kaleb Nation (https://kalebnation.com) and Susan Pinsky (https://twitter.com/firstladyoflove). This show is for entertainment and/or informational purposes only, and is not a substitute for medical advice, diagnosis, or treatment. Learn more about your ad choices. Visit megaphone.fm/adchoices

Helen White, Professor Ian Tomlinson, Claire Coughlan and Dr David Church: Can genetic discoveries revolutionise bowel cancer care?

Play Episode Listen Later Nov 20, 2024 34:21

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.

Adrianto Wirawan: What does 'no primary findings' mean?

director dna primary nhs findings genomic genomics england genomes project

Play Episode Listen Later Nov 13, 2024 3:57

In this explainer episode, we've asked Adrianto Wirawan, Director of Bioinformatics Engineering at Genomics England, to explain what the term 'no primary findings' means. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you've got any questions, or have any other topics you'd like us to explain, feel free to contact us on info@genomicsengland.co.uk. You can download the transcript or read it below. Florence: What does ‘no primary findings' mean? I'm joined by Adrianto Wirawan, Director of Bioinformatics Engineering for Genomics England, to find out more. So firstly, Adrianto, when we speak about findings from genomic tests, what does this mean? What are we looking for when we do a genomic test? Adrianto: Our DNA is made up of a long sequence of letters that act like instructions for your body. Genomic testing analyses these letters to see if there are any unusual patterns or changes that might change your health. You can imagine your DNA as a book full of recipes for your body. Every recipe tells your body how to make proteins that keep you healthy, and sometimes there might be a typo in the recipe, like missing an ingredient or mixing up the steps. This could result in a health problem, just like how a changed recipe can lead to a bad dish. On average, we would expect about 5 million out of our 3 billion DNA letters to be different. And each of these, we call them a genetic variant. Genomic testing is designed to examine some of these variants to help inform our healthcare. So, for example, in understanding why certain health problems happen and in choosing the best treatment based on our unique genetic makeup. Florence: And what do we mean by primary findings? Adrianto: Primary findings mean that in a patient's genomic testing, we identified a set of variants that is linked to the patient's condition. The variants that we have makes us who we are. However, not all of them cause a disease or contribute to a health problem. our bioinformatics pipelines will automatically prioritise variants of potential relevance to the patient's conditions. Using this data, the NHS clinical scientists will then determine whether any of these prioritised variants are linked to the patient's condition and whether a genetic diagnosis has been identified, which would explain why certain health problems happen. Florence: So, then what happens when there are no primary findings? Adrianto: When no primary findings are found, that means that no genetic diagnosis has been identified. As developments are made and our knowledge of the variance improves over time, additional findings might be identified in the future. The clinical team responsible for a patient's care may request reanalysis of data according to the national guidance, following a change in the patient's clinical status to inform reproductive decisions, or after significant new disease gene associations have emerged. In addition, Genomics England also provides the diagnostic discovery pathway where we focus on uncovering new diagnosis, where the participants of the 100,000 Genomes Project, as well as the patient's sequenced through the NHS Genomic Medicine Service This is meant to be more equitable as we don't rely on the clinical teams to raise individual separate requests. Florence: And finally, what do we mean by secondary findings? Adrianto: Secondary findings are additional findings not related to the conditions in which the patient was recruited for. For example, if a patient was recruited for one type of cancer, but perhaps we found variants linked to a different condition. We explored secondary findings for the 100,000 Genomes Project but we do not do secondary findings for the Genomic Medicine Service. Florence: That was Adrianto Wirawan explaining what we mean by ‘no primary findings'. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.

Öznur Özkurt, Mathilde Leblond, Rebecca Middleton and Sandra Igwe: How has design research shaped the Generation Study?

Play Episode Listen Later Oct 9, 2024 24:02

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.

Dr Rich Scott and Helen White: How can we work in partnership towards a new era of genomic medicine and research?

Play Episode Listen Later Jul 17, 2024 44:56

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.

Professor Sir Jonathan Montgomery, Dr Latha Chandramouli and Dr Natalie Banner: Why do we need to consider ethics in genomic healthcare and research?

Play Episode Listen Later May 15, 2024 42:41

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.

Shaun Pye, Sarah Crawford, Sarah Wynn and Naimah Callachand: Shining a light on rare conditions

Play Episode Listen Later Mar 27, 2024 42:26

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.

Lisa Beaton, Dr Celine Lewis, Jana Gurasashvili and Louise Fish: Hope for those with "no primary findings"

director nhs clinical lead genetic counseling genomics england genomes project

Play Episode Listen Later Mar 14, 2024 44:12

There are a range of outcomes from a genomic test. The results might provide a diagnosis, there may be a variant of uncertain significance, where a genetic variant is likely the cause of the condition, or there might be no particular gene found that is linked to the phenotype or clinical condition - also known as a "no primary finding" result. In this episode, our guests explore the impact of a "no primary finding" result on families, discussing the common experiences and expectations of parents and patients who undergo that genetic testing, and the role that hope plays in the experiences of children with rare and undiagnosed conditions. Today's host, Lisa Beaton, member of the Participant Panel at Genomics England is joined by Dr Celine Lewis, Principal Research Fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a Genetic Counsellor, and Louise Fish, CEO of Genetic Alliance. "I think it's also really important to add that hope isn't necessarily lost when you don't get a diagnostic result. And in a sense, what can be really helpful is for genetic counsellors to reframe that hope...sort of giving it a different context." For more information on the SWAN UK project which supports families with children that have been through genetic testing but have not found a result following that genetic testing, visit the website. Read more about the study by Jana Gurasashvili and Dr Celine Lewis: The disequilibrium of hope: a grounded theory analysis of parents' experiences of receiving a "no primary finding" result from genome sequencing. You can read the transcript below or down it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Hope-for-those-with-no-primary-findings.docx Lisa: Hello, welcome to the G Word. Lisa: I think in the back of my mind, subconsciously, I had hoped that when we eventually got a diagnosis, it would – I don't know, bells and whistles, balloons going off, fireworks, etc. And then the experience of a letter thumping on the doormat, and I recognised the postmark quite quickly, and it was at that moment I suddenly thought, “Oh gosh, I haven't buried all these feelings of hope.” Because I opened that letter with quite trembly hands, and then this diagnosis or lack of diagnosis, you know, nothing had been found, and it was a bit… I don't know if it's been described as like a nail in the coffin experience, because I really hadn't realised I was still clinging to this hope all that time, and then again it was, you know, another, “No, nothing's there. Lisa: My name is Lisa Beaton and I'm a member of the participant panel at Genomics England. On today's episode, I'm joined by Dr Celine Lewis, the principal research fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a genetic counsellor, and Louise Fish, the CEO of Genetic Alliance. Today we'll be discussing the impact on parents with children with rare conditions, who received a no primary findings result after diagnostic whole genome sequencing. If you enjoy today's episode, we'd love your support. Please like, share and rate us on wherever you listen to your podcasts. Can I ask all of us here present to introduce themselves, please? Celine: Hi everyone, I'm Celine, I'm a behavioural scientist in genomics at UCL Institute of Child Health, and I currently hold an NAHR advanced fellowship to look at the implementation of WGS, or whole genome sequencing, in the NHS. Jana: I'm Jana Gurasashvili and I'm a genetic counsellor at Northwest Thames Regional Genetic Service, and prior to that I was at Great Ormond Street, involved with consenting families to the 100,000 Genomes Project, and I also have an ongoing interest in the lived experience of patients and parents of genetic counselling and rare disease. Louise: Hi, I'm Louise Fish, I'm the chief executive of Genetic Alliance UK, and we are an alliance of around 230 charities and support groups that work with patients and families who have particular rare conditions. We also run a really longstanding project called SWAN UK, and SWAN stands for syndromes without a name. And the SWAN UK project supports families with children that have been through genetic testing but have not found a result following that genetic testing. So, it's clear they have a genetic condition, but science hasn't quite advanced far enough yet to tell us what that means and what that will mean for their child, and what that will mean for their family over the coming years. Lisa: And I personally can attest to the wonderful support that SWAN UK can offer because, as the parent of a still undiagnosed child, I have been involved myself with SWAN UK since my daughter was around the age of three to four years old. It's brilliant being a part of my big SWAN UK family. We first realised that there were some – I suppose something wrong with our daughter when she was around two weeks of age, but it wasn't something I could specifically put my finger on. I couldn't at that point have taken her to a doctor and said, “I don't know what's wrong but there's something wrong.” I just knew in my heart of hearts, probably because I have three elder children, that there were issues, and things weren't developing as they should. She cried a lot, she screamed a lot, she never seemed to be comfortable in any position when you held her, when she was asleep, when she was upright. It didn't seem to matter what you did, she was just a rigid, stuck child, for want of a better word. And all my mum senses were screaming, but it completely sounded ridiculous to take her to a doctor saying, “She feels wrong.” And I think that's quite a SWAN UK experience, from chatting to other families with similar situations. The parents just know that there's something not right, but it can be very isolating not to be able to identify kind of where that starts and what it is. In our case, it wasn't until our daughter was nine weeks old that things became much more obvious, that there were developmental concerns physically and medically, and at that point we went from my sort of mutterings that there was something wrong but I wasn't sure what it was, to a sudden hospital admission with quite a shocking turn of events. From something that had started out quite normally, as a routine visit to the baby clinic, to suddenly being seen by a troop of different paediatricians, and doctors coming in and out constantly, asking different questions, and sending us off all over the building for different tests and x-rays and imaging. And being given a partial diagnosis that our daughter had a condition called arthrogryposis, but it was clear that there was much more going on than that, and we would need referring to many more different fields. And that day really our diagnostic odyssey, for want of a better word, began. So actually, in terms of that diagnostic odyssey, many parents of children with rare undiagnosed conditions experience this, and when we agree to have genetic testing, we feel that we are going to get these answers straight away, and that every appointment that you go along to is going to be the one that brings you the answers. But certainly in our experience kind of 15 years on, that's not been the story at all. Celine, can I ask you to explain what the words no primary findings actually mean when a parent receives that regarding their child? Celine: So, there's a range of different possible outcomes from a genomic test. So, the results might provide a diagnosis to that patient and family, or other situations, there might be a variant of uncertain significance, so we don't necessarily know if the gene that we found, a genetic variant is the likely cause of the condition, or we might find no particular gene at all that we think is linked to the child's phenotype or clinical condition. So, that's what we mean really when we're sort of saying no primary finding. Lisa: Louise, would you be kind enough to explain what you think the impact of no primary findings means to families like my own, parents who don't have a genetic likelihood cause, just a gene thrown up to diagnose their child? Louise: Yeah, I think it's a huge challenge for families, and you'll obviously know that from your own experience. People go to have genetic testing hoping it will give them some answers, first and foremost, just to kind of understand, you know, what condition their child has and what the likely impact that's going to be on their child and on the child's life, and on the family's wider life. And I think one of the things that we really ask genetic counsellors and geneticists to do is help people understand before the genetic testing takes place that there may be nothing found from it, so that that kind of expectation is built in. Because people hope that they will get a diagnosis that will give them answers about what the impact of the condition will be on their lives. In a best-case scenario, access to a particular treatment that might be a huge help for their child, but at the very least, access to a range of services and support for their child. So, that kind of diagnosis is often seen by families as the key to unlocking a range of services and support that will help them and their families at what is the beginning of a lifelong journey. And I think when families get no diagnosis, there's a real concern on behalf of families, a, that they don't understand how their child's going to be affected by the condition. What we're really careful to say to families is, “Just ‘cos you don't have a diagnosis with a name, your child is still the same person they were before. They still have exactly the same bundle of needs as they had before, and you will still need to work with the NHS and with wider services to make sure that they can access speech and language therapy, and physiotherapy, and all of the services that they are going to need and you are going to need to help them live their lives to the full.” But I think that moment of not getting a diagnosis is when people feel I think real – the uncertainty continues, and uncertainty, we know, is a really hard thing to live with, and the lack of clarity about which services you'll be able to access. So, I think psychologically it's a massive impact on the family not to have the answers that they were looking for, or the key to the services that they were hoping would be there. Lisa: Thank you, Louise, yeah, I would definitely agree with that. We had a no primary findings result in I think it was 2019. It was a really bittersweet moment because my daughter's list of various different conditions kind of – by this point, named parts of difficulties for her spans over sort of two pages of A4, and yet on the letter back from the genomics service, it just says that, you know, nothing causative has been found. And so part of you is left wondering, well, how can there be all these different conditions or difficulties, and yet there's still nothing there? And I know personally, I had comments when she was much younger, every time a test came back, where people would say things like, “Oh well, that's great news,” and to some extent it was great news that something hadn't been found, but also if that hadn't been found, what was still out there? And that fear of kind of the unknown was extremely difficult. And also paradoxically, there was a sense of some very well meaning people saying things like, “Oh well, if they haven't found anything then there can't be too much wrong.” But yeah, I have a child who is tube fed and on multiple different medications, and cared for basically for 24 hours a day, so that doesn't really fit in with the picture of there not being very much wrong from a personal perspective. And I think it can make you as a parent/carer feel perhaps there's a tendency to downplay that there is an issue and that perhaps, you know, you're making it up, for want of a better word, and that sense of isolation around that can certainly be problematic. Celine, if I can come to you, that diagnostic odyssey, what are the common experiences and expectations of parents and patients who undergo that genetic testing from your perspective? Celine: Well, I think sort of parents go into genetics testing for a whole range of reasons really, and Louise has already alluded to many of these. Ones that I've come across in my own work include wanting to know why their child has a particular health problem, so that that child can access the most suitable treatments or therapies, or even access clinical trials. Even relief from guilt for many parents, a validation that the parents hadn't done anything wrong during their pregnancy to cause the child's condition, and that's hugely important really, to try and get that relief from guilt. Also to know whether future children might be affected by the same condition, and then more social reasons really, for example, making contact with other parents through support groups, or access to social and educational support. And I think there's also a drive from many parents to feel that they're doing everything absolutely possible for their child. I mean, particularly with something like the 100,000 Genomes Project, it was really a sort of first of its kind project, where patients were on a significant scale able to access this new whole genome sequencing technology. So, many of the parents taking part in that project felt like pioneers, and there was really a lot of expectations around whole genome sequencing in delivering a diagnosis for those parents who'd previously not been able to get hold of one. Lisa: Yes, I strongly can resonate with a number of the points you made there, particularly the feelings of guilt. I must have asked myself a thousand times whether, you know, something I did do, something I didn't do, something I thought of, something I hadn't thought of [laughter], all those questions that swirl around, particularly in the small hours of the night when you feel particularly alone. And yes, I can completely relate to that. And also although SWAN UK is primarily for children and parent/carers whose children don't have a diagnosis, actually a number of the parent/carers on there will have children with diagnoses that are so very rare that absolutely, you know, very, very little is known. They might be the only parent – the diagnosis, for want of a better word, they may have received may just be a series of kind of numbers and genetic dot-dashes, forgive my layman's terms there, but it may not actually help them any further along in terms of feeling that they know anything further or the direction of, you know, where that will lead their children, and that can feel very, very isolating, I'm sure, probably just as much for those of us who don't have that diagnosis. Louise: Yeah, just to add to that, I think that's absolutely right, Lisa, and I just want to give a shoutout – at SWAN UK, we tend to support families who don't have a diagnosis at all, or, as you say, a small number of families who do but have been part of the SWAN UK family for so long that we're very happy to keep them because of the support they're finding from other parents. We work really closely with another of our members, Unique, who are a charity that support parents in exactly the situation you've talked about, where people have finally got a diagnosis and it's that kind of relief of having a name, but it's a super long name, and you find out you're one of only three families in the world with that diagnosis. And so although there's a real I think comfort for people, perhaps if you have a five year old and you're meeting a family who have a 13 year old and a family of a 19 year old, then you start to see a little bit about how your child might develop, but there's not enough kids affected that you can be really certain about that. So, it gives you a little bit more information, but not the kind of wealth of information you were hoping for about how your child's going to be impacted by a particular condition, and what the future might hold for you and for them. So, SWAN UK and Unique very much work alongside each other to kind of support families on whichever part of that journey they're on, because there's still a huge amount of uncertainty for families with those super rare conditions, as you say. Lisa: Definitely, and I'm sure you'll be familiar, Louise, yourself if you get time to go on the online communities and seeing the question that pops up quite regularly when somebody has received a diagnosis of, “Can we still remain part of the SWAN UK family?” And they very much use that word, family, because I think they do feel that, although all our children are different, there are children with physical, medical, cognitive, a combination of all the above syndromes, conditions, etc, they feel that kind of embrace of all being in a collective club of rare and unique and undiagnosed, and that's very comforting to the members. Louise: Absolutely, yeah, I think that sense of belonging and being able to reach out to other families that you've been on that journey with for many, many years. You know, many of our families join when their children are like one or two, and they're still with us when, you know, their children are 26, 27 [laughter], and that sense of having that community and that family and that belonging is really, really important to people, I agree. It makes a big difference psychologically to be part of a community you can reach out to and ask the questions that perhaps you can't ask to other people. Lisa: Celine, can I ask you how many patients for the 100,000 Genome Project have had a no primary findings diagnosis back? Celine: Well, back in 2021, there was a paper published in the New England Journal of Medicine, which reported that, in the initial pilot for the 100K, a diagnosis was found for around 25 percent of rare disease participants, and other studies looking at the diagnostic yield of whole genome sequencing have put the number anywhere between 25 percent to 55 percent, depending on the clinical indication. And we know that even already from the 100,000 Genomes Project, this pioneering project has led to more than 6,000 diagnoses being identified, and that number will obviously continue to go up as they explore the data and gather new insights. However, that still obviously leaves a significant number that won't get a result from whole genome sequencing, as many as half of those rare disease patients, and that was really the basis of the study that Jana and I worked on. So, we felt that there had been so much research really looking at the experience of parents who do receive a genetic diagnosis, and that a lot of attention rightfully does focus on the amazing successes of the 100,000 Genomes Project and genomic medicine more broadly, but actually that there is a considerable number of patients and parents and families who don't get a result, and we felt that it was important that we also focus on those parents and patients, and try and understand their experiences. Lisa: Yes, you can feel, if your child, for example, is under multiple different care specialists, that it can be quite hard, when you've just got this list of different names of things that are wrong, that you feel very much still out on the limb and forgotten about. But it's clear that, from your work, you're identifying that and pointing that back to the specialists, the consultants, to remind them that these parents and these children are still finding their ways through. Can I ask you, Jana, the study that was conducted, what would you say the main things from that study told us? Can you describe some of the emotions experienced by the parents, and what challenges that they have faced along that receiving the no primary findings diagnosis? Jana: Yes. So, many participants really felt very strong disappointment and sadness on receiving that no result, and for many, it kind of reflected the feelings they had had when they first realised they had a child and there was no diagnosis for their condition. And as Celine said, this was such a new technology that people had invested a lot of hope in, and so many felt that it had been their last chance of finding a reason for their child's condition, and that they'd come to the end of the road with that no primary finding result. And, well, one person described it as another door shut. And people talked about the actual toll taken, the emotional and physical toll, and one person described feeling low for several weeks following the result. And some talked about the timing of the result. Somebody got it as a letter just before Christmas, and so their whole family holiday that they'd prepared was marred by getting that news just before Christmas. And it often seemed to leave parents feeling isolated and unable to contribute to normal parental roles, such as going to parent groups, etc, because they felt that other mothers particularly - as it's mothers we were speaking to, other mothers, their experience of motherhood was so incredibly different to their own, and they felt a lack of support. And one parent actually talked about wanting to lock everyone in the house just to escape the feeling of judgement and pity from outside the front door. And some parents talked about finding it hard when other people would post on support groups that they had got results from the 100,000 Genomes Project, which was very difficult. And some talked about hope as finding it hard to keep hopeful but needing to keep hopeful. So, they talked of hanging onto a little bit of hope, as though that was quite an intense thing, which I think, Celine, you'll agree, that made us able to kind of identify that hope was really part of a coping mechanism for this whole process of going through this diagnostic odyssey. Celine: Yeah, people sort of talked about not wanting to let go of hope and the importance of hope, and that without hope, there was no sense of wanting to continue this journey of trying to find a diagnosis, and that it was still very important to people. And I think that parents did understand that, even though a no primary findings result now, that doesn't necessarily mean that they won't get a diagnosis at some point in the future. So, there's obviously the opportunity to do future reanalysis of the genome, particularly as we understand more about the function of different genes, and as new genes are added to many of the panels that we're using in whole genome sequencing. So, I don't think not finding a result means that there is no hope in these circumstances, but for many parents, they did talk about hope being too painful, and not wanting to be let down again, and really preferred to focus on the here and the now rather than necessarily focus on the future. Lisa: Yes, I can only speak from my own experience here, but I think I primed myself to actually forget about going on the 100,000 genomes sequencing because, having undergone genetic testing for certain conditions that they were quite convinced my daughter had from around the age of four months through to around the age of three years, I'd gone to so many appointments and thought, “Oh, this'll be the time that I turn up and somebody will tell me this is what is the diagnosis.” And when I then joined the 100,000 Genomes Project in 2015 with my husband and my daughter, the genetic experience, the discussions that we had at the time were very helpful in that it was made quite clear to me that potentially we wouldn't get a finding, and actually that any information that did come forward was perhaps unlikely to be hugely beneficial to our family at that point. So, I was quite clear what potential finding would mean to us. But I think in the back of my mind, subconsciously, I had hoped that, when we eventually got a diagnosis, it would – I don't know, bells, whistles, balloons going up, fireworks, etc. And then the experience of a letter thumping on the doormat, and I recognised the postmark quite quickly, and it was at that moment I suddenly thought, “Oh gosh, I haven't buried all these feelings of hope.” Because I opened that letter with quite trembly hands, and then this diagnosis or lack of diagnosis, you know, nothing had been found, and it was a bit… I don't know if it's been described as like a nail in the coffin experience, because I really hadn't realised I was still clinging to this hope all that time, and then again it was, you know, another, “No, nothing's there.” And I think because of the work I've undertaken with SWAN UK as a volunteer, and being quite involved in wanting to sort of educate myself and learn more, I did understand that, even though we had no primary findings, it didn't mean that the study, everything was closed to us. It didn't mean, you know, that things won't still be looked for. But equally, at the same time, it just meant that we had nothing yet to pin anything on at that point. And I think it's quite hard to pick yourself up and dust yourself off again, to be like, “Okay, we're still here, we're still circling that drain,” as it were. I think actually that takes us on quite nicely really, about what role hope has in the experiences of a child with rare and undiagnosed conditions. And again if I can just say that there's hope and there's realism, and somewhere along the way, if you've been on the journey for quite a long period of time like ourselves, you have to try and find a way of living with that hope and realism all at the same time. So, we're still hopeful that one day we might get some answers, but we're realistic that day to day we need to focus on the difficulties or the experiences that my daughter has, so that we can manage to give her the skills to live her life to the very best of her abilities. Certainly, that's our experience. And also I think if I'd let myself dwell forever on not having a diagnosis or a pathway specifically for that, it would have been quite difficult to carry on, pick ourselves up every day. What would you think about the role of hope there, Louise? What would you say your experience is from chatting to fellow parent/carers? Louise: Yeah, I think you've described it really eloquently and better than I'll be able to do, but when we talk to people, the phrase I always have in my head is kind of hope for tomorrow and help for today are the two things that people are looking for. So, making sure that that hope for tomorrow's still there both in terms of, you know, the NHS being really clear that it will provide support for individuals without a diagnosis, and there may be opportunities for reanalysis in the future as science makes future progress. And, you know, there is progress being made so fast at the moment in genomics and that's really welcome. So, making sure that people who've already had whole genome sequencing but not found anything continue to have access to that potential reanalysis I think is really important. As you've rightly said, Lisa, as well, thinking through in terms of hope for tomorrow, the opportunity to take part in clinical trials and to make that as easy as possible where treatments are being delivered, to have the opportunities to take part in trials for non-condition specific treatments, whether that's for epilepsy, which affects people across a whole range of conditions, or sleeplessness, which affects people across a whole range of genetic conditions. You know, there are both trials that only people who have a particular condition can take part in, and trials that are open more broadly, so making sure those opportunities are available as well, so that people have that kind of hope for the future. But alongside that, I think it's really important for the NHS to be clear with people about what help for today will continue to be available, and so we are working really hard with the NHS to emphasise the fact that when no diagnosis is possible, the NHS still needs to be clear to people about how they will be supported, whether that's through the genetics team or a particular discipline, perhaps the one that is the closest fit for their child's biggest need, whatever that may be, that they can still access more joined up care. So, you know, who is the person in the NHS, if you don't have a diagnosis, who's going to help you secure referrals to speech and language therapy, to physiotherapy, to learning disability nurses, and to the package of care that your child may need. Who is the clinician, if you don't have a clear diagnosis, who's going to be the person with the authority and the confidence to lead the multidisciplinary team, maybe up to 30 healthcare professionals who are going to support your child. You know, who is going to be the lead clinician that's going to pull that multidisciplinary team together and make sure that your child's not being prescribed stuff that's contraindicated, or that's going to help one element of their condition but make another element worse. So, we are really trying to work with the NHS to make sure they're thinking through, where will that support be for the family in terms of their healthcare. And alongside that, you know, many wider services like schools or social care or employers welcome the chance to talk to a geneticist or a genetic counsellor or nurse to understand what adjustments they might need to make for someone who clearly has a genetic condition but doesn't have a clear diagnosis. And so we're trying to kind of make sure the NHS is both focused on the kind of science side and making sure that the hope for future findings is there, but also the help side, and making sure that the right package of care is still available for families who clearly have a genetic condition. Lisa: Actually Louise, yeah, you've really summed it up excellently there, and whilst I am hugely grateful to the NHS and the various services, I can say, hand on my heart, my daughter has a huge number of professionals involved, both from the health side of things and social care side of things, and actually the person that kind of holds all that together is myself. And because we're under multiple different teams, every time a new medication, for example, is prescribed, I need to go back to our lead team, which in this case happens to be neuromuscular, and check that, for example, if gastroenterology have prescribed a medication, that it's not contraindicated from a neuromuscular side of things and so forth. It's all a bit like having sort of interlocking parts of a jigsaw, but perhaps no picture to follow [laughter], and that can be quite an isolating experience. And certainly, having chatted to fellow parent/carers, I know that's their experience as well. And I imagine, Celine and Jana, you found sort of similar experiences when conducting the research. Celine: Yeah, so my PhD actually was focusing on the sort of journey for parents as they go through the diagnostic process, and one of the things that came out really strongly from that body of work was how the parents were really carving their own care pathway, how they had to sort of push and fight to access services, but at the same time were the gatekeepers for their child's health. Having to make sure all the various teams and clinicians were kept up to date with all the different tests that they had and all the results. And, you know, at times, this could be really frustrating for a lot of parents, ‘cos they had to keep repeating their story over and over again, particularly ‘cos they didn't have a diagnosis. So, these parents really were having a very different parental experience to many of their friends and family, because their experience of being a parent to a child with an undiagnosed condition was really sort of as being a patient advocate, and as having to push and fight to access services. Lisa: Yeah, it's quite a unique experience. You are the specialist for your own child in that sense, I think would be the way I'd describe it. And I suppose over the years, I've got so used to sort of trotting out different medical explanations in terms that you can almost sound like you know what you're doing [laughter]. And a few times when I've been at medical appointments, and perhaps we've met a new specialist or consultant, they've said, “Oh, what's your field? What's your area of expertise?” And actually you just think, “No, I'm just a specialist in my own child” [laughter]. But that's quite an empowering feeling actually, so I guess that plays back into the feelings around hope and expectation, even with having an undiagnosed child. Lisa: When I was recruited to the 100,000 Genome Programme, we didn't actually as a family receive genetic counselling specifically, and I know that this is something that is incredibly important to many families, and how that can support you sort of going forward. We were quite lucky in our experience in that we knew that our daughter was definitely going to be our last child, so we didn't have the thoughts and insecurities around potentially what it might mean for any future children that we had. But certainly as my daughter has got older and she's asking her own questions, and our older children are at a stage in life where they're looking at potentially having families in the future, I know that those things have come up, and we're just still exploring what that will mean in the bigger picture. But can you tell us, Jana, really what can genetic counsellors do to help parents feel less isolated and better to cope with the uncertainty surrounding their child's condition? Jana: Yes, well, I'm sorry to hear you didn't have any genetic counselling prior to going on the 100,000 Genomes Project, because that consent conversation right at the beginning, before the whole genome sequencing, is really important. It's important to know what the range of outcomes may be, so that it may be that you might get a result, you might get a variant of uncertain significance, or you might get no result. And parents in our study did suggest that their sense of isolation when they got a no primary finding result would have been alleviated if they'd known how many were not getting results. So I think in the longer run, it's 40 percent perhaps received a result, so that's 60 percent that didn't receive a result, so those parents were not alone, but they felt very alone. And some suggested if they'd just had a leaflet really explaining that, and explaining that they'd still contributed to research and that that had been, you know, a good outcome in a sense, then they would have felt better about it. So, a lot of work can be done before the testing really, to explore how you might feel on that range of results, and then that way sort of prepare parents for how they're going to feel, and perhaps that helps them to have things in place, to know that it might be a vulnerable time with that letter, although that was particular for the 100,000 Genomes Project, to get the result in a letter in that way, and as you described, after such a long time, that you'd been able to forget that you'd been on the project. But to actually be a little bit prepared that it make take its toll on you might actually help with preparing oneself. It also might be helpful to include ways of promoting ways to enhance health and wellbeing for parents in terms of practical support, such as those things that you're already attempting to access, like the respite services, school support, support groups, and thinking about psychological wellbeing and ways of managing stress, psychological support for parents, and possibly spirituality based resources as well. And focusing maybe on what is known about the child's condition even without a diagnosis, so what's likely to be beneficial, and support parents in actively coping, such as what research they might be able to access, and continued medical support. And also actually having a named person within the genetics service, so they have someone to go to for any follow-up that has a name, and so they don't feel isolated from the genetic service. And signposting to those external resources, such as SWAN UK, can be very important as well, of course. Celine: I think it's also really important to add that hope isn't necessarily lost when you don't get a diagnostic result. And in a sense, what can be really helpful is for genetic counsellors to reframe that hope, if you like. So, one thing that we talk about in our paper is that it might be useful for health professionals to ask a question such as, “In light of the new information that we now have from the whole genome sequencing result, what are you hoping for now?” So in a way, it's sort of reframing that hope, sort of giving it a different context. Lisa: Definitely, and I think one of the things as well is that, because potentially for when parents were first recruited to a study such as the 100,000 Genome specifically in this case, that it might be quite a length of time between that initial recruitment and when the actual result comes out. And of course, in that time, with the advances in genetics, it's sort of somewhat of a Pandora's box really, isn't it, in that we're almost kind of finding the information out quicker than we actually know how to process it and what it potentially means. So actually if there's a genetic counsellor available to speak to those parents, or for those parents to be signposted to somebody who can say, “Well look, since you were recruited, actually this is happening, that's happening,” or, “These research projects are happening,” personally, I can say that is going to be really helpful and handy, and would have been really useful. I just know that for myself anyway and my family, that if there was a leaflet or something that had given me a way of knowing how I could contact somebody in the future, that would be really helpful. What ways do genetic counsellors use in maintaining a delicate balance between not creating false hope but also providing meaningful support to parents? What would you say around that, Jana? Jana: I think as we've already touched on, it's that managing expectations from the outset when the test is offered. So, not generating too much hype or excitement, but setting those expectations, giving that information about the diagnostic yield. Also, informing parents that what people do experience has been described as a rollercoaster of emotions. It's normal. You might also want to explore people, not only what they're hoping for, but also the outcomes that they might be fearing, and giving them a chance to voice those, because they can be very powerful things as well. A diagnosis might not be what you want to hear, so there can be a lot of ambivalence around wanting a diagnosis when it might actually be a life limiting condition, that you didn't really want that certainty. And also helping parents to explore how not receiving a result might feel, so that they've actually rehearsed it a little bit, and where they might go to when they need a bit of extra support. So, they already know, “I go and talk to my friends, that's where I get my support from,” so that they're kind of ready for it, and that might help them with that sense of isolation, but also validating these feelings. So, it's okay, it's okay to have that dip, it's okay to feel, that it's something that many people experience. And creating a safe space for people to feel that, so if they want to talk to a professional or a friend, that those feelings are validated. And in that way, kind of with that pre-counselling really, helping parents to develop their own set of resources, so they've got those to draw on. And as you've mentioned, Lisa, it's like having your own resources also helps generate that feeling of empowerment and control. And as Celine has said, it's really facilitating parents through that passage of reframing what you're hoping for, reframing what the future looks like, if you had one picture of a future. You need to become comfortable with the future you're now looking at. Lisa: Thank you, Jana. Louise, if I can ask you really, we've already touched on the role that SWAN UK can play for parents dealing with undiagnosed rare conditions, but perhaps if you could home in on that and explain in more detail the main focus of SWAN UK, and what that can do for parent/carers. Louise: So, what SWAN UK primarily does is bring together parents who are in a similar situation. So, we have a team of amazing parent representatives, who Lisa is one, who help us shape the support that SWAN UK can provide, and really make sure that it's based on a really strong understanding of what it's like to be a parent of a child with an undiagnosed genetic condition, and an understanding of that kind of expertise that parents who have been on that journey themselves will bring. So, we have a series of Facebook groups. Some of them are for different regions, so people come into contact with other parents in their area who are going through similar circumstances. Some of them are more around age. So, you know, we have Facebook groups for parents who are waiting for a diagnosis or have got a new diagnosis, and then we have a group called SWAN Graduates, which is for children who are older and over 18, so their parents can come together and share their experiences. So, it's really to help parents be able to talk to one another, to share their experiences, to support one another, and often to ask for advice. They're often kind of practical questions about, you know, “My child needs this kind of wheelchair, has anybody been able to source that from somewhere?” “My child's having real difficulties eating at the moment, can anyone give some advice on this particular challenge?” “This thing someone else has faced, how did you approach it? Where did you reach out for support?” So, that peer to peer advice and support is really at the heart of SWAN UK. And then what we try and provide around that is access sometimes to information events, where there's particular issues that are affecting a lot of SWAN families. So, we hope over the coming year to have a series of information events targeted at families with children who don't have a diagnosis, and some of it is just trying to have social events and bring people together again. We've had, for example, an active dads group in Wales, who've been bowling and wanted to go axe throwing, and really they just want to come together with other dads who are in the same situation, and being able to talk to one another and provide emotional support to one another. So, that's kind of the nub of SWAN UK and what we do, and then alongside that, that kind of fits in with Genetic Alliance's wider goal, which is much more around campaigning for improved services. So for example, the Genetic Alliance UK team has worked really closely with commissioners in Wales, who actually commissioned the first SWAN clinic, which is in Cardiff. That was a two year pilot, to see what support could be provided both to help SWAN families get a diagnosis, but far beyond that, to make sure that the care for families who don't have a diagnosis is better joined up. And that we feel has been a real success. Again, there hasn't been a really high diagnostic yield, there have been very few new diagnoses, but the support provided to the families who are in contact with that clinic, in terms of helping them access better joined up care both from the NHS and from services more widely, has been brilliant. And we're currently working with NHS England in the UK, who are exploring an opportunity to commission two SWAN clinics in England. So, that trying to kind of improve services, and then the third aspect of that is just working generally with the new genomic medicine service alliances as they emerge across England, to try and make sure they are thinking through what support they will need to continue providing to families who've gone for whole genome sequencing in future, not through a research project like 100,000 Genomes, but just through routine clinical practice and routine clinical diagnostics, what support will they need to provide for families who go through that process and don't get an answer. And that won't change the support they will need from the NHS. It will just mean that perhaps that clinic needs to play a more active role in helping them access those services. So, all of that kind of campaigning to have better services for family who have an undiagnosed genetic condition continues as well. Lisa: So, I think one of the things really just to finish off today, is of course looking at the future. Considering advancements in technology, would you say that future reanalysis of the 100,000 Genome Project is going to yield additional insights? Celine, can I ask you to comment on that? Celine: Yes, absolutely. As we understand more about the role and function of different genes, and as new genes are added to the panels, we will definitely be able to provide a diagnosis for more parents and more families. But I think we don't yet necessarily know exactly what that reanalysis will look like, and it's not really clear yet how this will work in practice. Lisa: And Louise, would you have anything else to add to that at all really? Louise: No, I think it is just that hope for the future and kind of help for today. I think the NHS needs to be equally clear about, you know, there's some amazing investment by the UK government in genomic research, and that's brilliant and we want that to continue, but equally we want the investment to be taking place into routine clinical services and diagnostic services, so that we can talk to people both about the hope of potentially getting a diagnosis in future, but making sure that the help continues to be available for as long as they don't have a diagnosis, and that help for families who don't have a diagnosis is going to be just as important. And what we try to ask for is both real clarity around what the NHS can provide, and really clear signposting to organisations like SWAN for families that continue to not have a diagnosis. And again, just to give an equal shout out to Unique, who are able to support families who have an ultrarare diagnosis, where perhaps they're the only person in the country with that particular diagnosis, or one of a handful of families around the world. Signposting to that peer to peer support will continue to be a really important part of the process as well, so that families can help one another, learn from one another, and just give each other support that they are kind of sharing that same journey and walking alongside one another on that journey as it continues. Lisa: And bringing this podcast to a close, can I just ask you really, any final thoughts, anything that you would sum up from your experience of researching the no primary findings and where we now are today? Celine: I think the main thing for me is just to sort of make it clear to parents that a diagnosis isn't necessarily a magic wand, even though it is obviously very important to a lot of parents. But that even without a diagnosis, we still have the opportunity to manage patients' symptoms, and often a diagnosis doesn't make a substantial difference, because parents are sometimes left with a lot of uncertainties and a lot of unanswered questions. So I think, and as Louise and Jana have said before, it's really sort of on focusing what we do know, and thinking about what we can offer and what support we can provide to parents and families even without a diagnosis. Lisa: Thank you very much to our guests today, Jana Gurasashvili, Celine Lewis and Louise Fish, for joining me as we discussed the impact of a no primary findings result. If you'd like to hear more like this then please subscribe to the G Word on your favourite podcast app. Thank you for listening. I've been your host, Lisa Beaton. This podcast was edited by Mark Kendrick at Ventoux Digital, and produced by Naimah Callachand.

christmas ceo uk england phd medicine fish unique wales primary nhs swan cardiff ucl findings genomics new england journal genome a4 child health beaton nhs england nahr ucl institute wgs g word principal research fellow genome project great ormond street genomics england genomes project lisa yeah lisa yes lisa so lisa thank

Genomics England Clinical Lead for Genetic Counseling - Amanda Pichini

Once Upon A Gene

Play Episode Listen Later Feb 29, 2024 43:25

ONCE UPON A GENE - EPISODE 219 Genomics England Clinical Lead for Genetic Counseling - Amanda Pichini Amanda Pichini is a genetic counselor from Genomics England, here to share their initiatives and mission. EPISODE HIGHLIGHTS What is your role at Genomics England and how did your career develop? I work at Genomics England as the Director of Clinical Implementation and I'm responsible for the strategic clinical leadership for our products and services, ensuring research, diagnostics and clinical programs we support are in line with the latest healthcare standards and research. Prior to joining Genomics England, I worked as a genetic counselor, a profession I was interested in for a long time. When I started studying biology, I was keen to do something that allowed me to communicate and speak to people, but still be immersed in science. While my role isn't patient-facing now, I bring my genetic counselor skills to understand the complexities of genetics in healthcare and how we communicate to various audiences to design and deliver our programs. What are the current initiatives at Genomics England? Since the 100,000 Genomes Project, we are focused on working with the NHS to provide genome sequencing as a standard clinical test. We've worked hard to ensure healthcare professionals understand how to help families through the process, manage their expectations and potential results of genome sequencing. We're also focused on looking at different types of sequencing technology we can use to enhance the testing and care for cancer patients, and also a newborn genomes program which is part of a large-scale national research study called the Generation Study. This study will sequence the genomes of 100,000 newborn babies with a goal of understanding if sequencing in the newborn period can help identify rare conditions earlier in life, with the ideal goal of improving the quality of life and outcomes for the babies identified as having a rare condition. Can you talk more about the newborn screening? Like in the US, we do a heel prick when a baby is about 5 days old at the parent's discretion. We recommend it as public health and to look for rare conditions that could be treated if found early. We currently test for 9 conditions, but the Generation Study is an optional screening in addition to standard newborn screening. It will be available to parents at different hospital sites, a baby doesn't already need to be ill and parents don't have to have a known history to participate. At birth, a small amount of cord blood will be taken and that sample used to carry out genome sequencing and to look for around 200 rare conditions that we feel would have an early intervention option if found through screening. We will follow up on every test, with much closer monitoring and follow-up where a condition may be positive. LINKS AND RESOURCES MENTIONED Genomics England https://www.genomicsengland.co.uk/ Genetic Alliance UK https://geneticalliance.org.uk/ Genetic Alliance US https://geneticalliance.org/ CONNECT WITH EFFIE PARKS Website https://effieparks.com/ Twitter https://twitter.com/OnceUponAGene Instagram https://www.instagram.com/onceuponagene.podcast/?hl=en Built Ford Tough Facebook Group https://www.facebook.com/groups/1877643259173346/

Dr Nirupa Murugaesu and Professor Sir Mark Caulfield: Providing tailored care for cancer patients through whole genome sequencing

Play Episode Listen Later Jan 17, 2024 33:39

In this instalment of The G Word, our guests engage in a compelling discussion centred around a recently published paper that supports the integration of whole genome sequencing into standard cancer care. Our guests shed light on the transformative potential of combining health data with whole genome data. Discover how this innovative approach empowers doctors to deliver more personalised and effective care. Our guests delve into the findings of a landmark national study, unravelling the significance of identifying inherited cancers for patients and their families. The episode explores not only the scientific advancements but also the real-world impact on individuals facing a cancer diagnosis. Our host Naimah Callachand is joined by Dr Nirupa Murugaesu, a Consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the Principal Clinician for Cancer Genomics and Clinical Studies at Genomics England. And by Professor Sir Mark Caulfield, a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as Chief Scientist for Genomics England and was instrumental in the delivery of the 100,000 Genomes Project. "In cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients. So this is a real opportunity to create precision cancer care." You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Whole-genome-sequencing-in-cancer-care.docx Naimah: Welcome to the G Word. What does it mean if we can test for inherited genes? Nirupa: It can influence how their cancer is treated. So it means that there may be certain types of therapy that are available if they have a specific inherited cancer gene, number one. It also can impact in terms of preventing further or other cancers related to those genes, and it may impact the type of surgery they have, and also the type of overall cancer treatment. And then finally, if they have got an inherited cancer, then, as I mentioned before, it may impact in terms of testing and screening for their family members. Naimah: I'm your host Naimah: Callachand. Today, I'm delighted to be joined by Dr Nirupa Murugaesu, who's a consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the principal clinician for cancer genomics and clinical studies here at Genomics England. And Professor Sir Mark Caufield, who's a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as chief scientist for Genomics England and was instrumental in the delivery of the 100,000 genomes project. Today, Mark and Nirupa are going to discuss key findings from a recent paper that's just been published in Nature. If you enjoy today's podcast, we'd really love your support. Please like, share and rate us on wherever you listen to your podcasts. Now, let's get into the interview. So first of all, Mark, I wondered if you could give me a bit of background on the 100,000 genomes project? Mark: So the 100,000 genomes project started in July 2013 following an announcement by the then prime minister, David Cameron, that the UK would be the first health system in the world to sequence 100,000 whole genomes, which is as much as you and I can read of the genetic code. In the case of cancer, which we focused on here, in cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients. So this is a real opportunity to create precision cancer care. Naimah: And Nirupa, can you tell me what the 100,000 genomes project meant for these patients with cancer? Nirupa: I think, firstly, we're very grateful for all of the participants in the programme, because what it's allowed us to do is to look at the data as a whole, and having all of that sequencing data alongside clinical information has been incredibly valuable, it has also developed the infrastructure for testing. And really I think for patients with cancer, they participated in this programme as a research project, and unusually for a research project these results were returned back to treating clinicians to clinical teams, if there may have been a result that would impact or change their management. But I think, importantly, what it enabled is the implementation of standardised cancer testing in the NHS, and really enabling that for a wider range of patients, not just those that participated in the project. And because of patients participating, this then allowed all of the data to be stored in a single place, and this has been incredibly valuable for clinical academics and researchers. Naimah: And can I ask what specific types of cancer that were looked at in 100,000 genomes project? Nirupa: Again, the project was set up such that we allowed a number of different types of cancers to be sequenced and, therefore, very permissible, because we also wanted to ensure that some of the less common and rarer cancers were also sequenced and, as you would expect, more of the common cancers as well. In addition, I think the opportunity to sequence paediatric cancers, as well as haematological malignancies, or blood cancers, was also key as part of the cancer programme. Here, we focus on the solid cancers, but obviously there was a much wider range of cancers that were sequenced. Naimah: And next, can we move on to talk about the findings of the study? Nirupa: I think, firstly, by undertaking sort of a pan-cancer analysis, it really gave us an overview of the number of target and genes that were found to be actionable. And what I mean by that is that they have a, well, clinically relevant, and we can see that in certain cancer types, such as in brain cancers, in colon cancers, lung cancers, there were within the genome sequence more than 50% of these cancers had something that was what we would call actionable. So there was a mutation in a gene for which this would influence treatment. And as we started to look more across the entire cohort of patients, you can really get an idea of the fact that the more that we sequence, and the more comprehensive the testing is, the number of different types of mutations that we were able to discover. Naimah: And when you mentioned that these findings were actionable, what does that mean? Nirupa: So what that means is that has an impact in how the patient will be managed and treated. It may influence, firstly, the type of surgery they have, it may influence the type of cancer treatment that they receive. And all of this, I suppose, comes back to the point that Mark mentioned, of precision oncology, so we more precisely treat patients based on their individual cancers. Naimah: And could you give me some examples of maybe some of these genes that were found in the study that were actionable? Nirupa: Yes, so the types of genes also matter, or the type of mutations. So some of them were in known cancer genes, and if you have, for example, a mutation in lung cancer, in a gene called the EGFR gene, we know that there are cancer therapies that can be provided that target specifically this mutation. So that's one example, and this is quite well characterised and understood in oncology care. But what we were also able to do with whole genome sequencing, is identify different types of mutations that are harder to characterise routinely. And these are often included things that we call pan-genomic markers, where we can see what the mutational landscape is of the cancer, the different patterns of mutations can be gleaned from this, and often this can then give you an idea of the underlying biology of the cancer. But importantly, in certain types of cancers, such as high grade serious ovarian cancer, it highlights which patients may have a particular marker that means they may or may not benefit from a particular type of therapy. So in this particular case, the class of therapy is called PARP inhibitors. Naimah: And how did the study compare to other similar stuff studies in the genomics area? Nirupa: That's a really good question, and I think we looked at this from other large sequencing endeavours, such as the ICGC, TCGA, so these are big studies where have been whole genomes sequencing. Also within the Hartwig Institute in the Netherlands, they've also undertaken whole genome sequencing for cancer patients. And what we were able to identify is that the patterns of mutations were as expected, we found, you know, a lot of similarities. I think the difference, the main difference is not just identifying the type of mutations across the different cancers. But the fact that we were then able to look at the longitudinal outcome, and correlate some of these genomic markers with outcomes related to both therapies, as well as survival impact of having certain mutations in terms of prognosis. Naimah: Mark, do you have something you'd like to add there as well? Mark: Yeah. So one of the things that we did in the 100,000 genomes project, was to evaluate the best way of measuring the whole of your or my genetic code. And we discovered that very early on that if you expose the tumour to a preservative, which is called formalin which keeps the tumour preserved, that actually you could get quite a number of misleading findings. And so to address that, the distinctiveness from former programmes, such as Nirupa mentioned, like the Cancer Genome Atlas, is that all of the tumours that we studied in this paper were actually produced under fresh tissue conditions, and have not been exposed to a preservative. And that means that what we have is a really accurate reflection of the variation within the tumours. And the other thing about this particular resource is it's the biggest resource. We were able to look at 13,000 people with solid tumours, but we also had blood cancers and other cancers which also feature of this paper. And a further remarkable thing about this is early on, Nirupa and the team and I decided that we would longitudinally life-course follow the patients and by accruing data from multiple sources in the health system. So, every attendance at the hospital, what chemotherapy was had, we've been able in this paper to recapitulate signatures that clearly show that certain mutations are harmful. And many of the findings that we've made are absolutely, if you look at the survival of patients particularly, you can see almost identical patterns to those in clinical trials. What this means is that by the really rich data set which is now many billions of clinical data points on these patients, we can actually look for long-term signals of benefit and harm that perhaps would not be detected by a clinical trial that might last for six months or a year. So this is a really valuable resource, and the really great thing is we can use what's called real-world data, which is where we take routine health data, and we can recapitulate the findings from tightly controlled clinical trials. And I think that's quite an important finding. Naimah: That kind of brings me onto the next question, Mark, where I want to talk about the value and benefit of genomics sequencing for cancer patients. I wondered if you could expand? Mark: Well, what we know from one of the genomics medicine centres which were regional hubs, is that they use the information that we return, that Nirupa outlined earlier in a report, for 25% of their patients. Which means that they concluded having evaluated that as the clinical team locally, that there was something the patients could benefit from. Now, what we think is this makes the case for certain cancers being part of the national genomics test directory whole genome sequencing, but it's still the case that the majority of testing for cancer is now very large focused panels that are focused on specific gene features. But in some measure, this work is also able to reassure us that those gene features are the right ones to focus on, so this work has been very useful in that respect, even where the NHS today cannot make the financial or clinical case for using whole genomes in specific cancers. So I think the programme's made a massive difference. The biggest thing it's done for patients, which Nirupa was very actively involved in, is it's allowed us to create a national genomics test directory. So when we started this, cancer genomic testing was completely random and would vary from one postcode to another, one hospital to another. And what Nirupa and the cancer team created is a national cancer genomic test directory, which now means that standard of care, that's the basis for reimbursement, and it's available across the landscape of 56 million people. And given that one in two of us will have cancer, this is a massive advance. Naimah: Yeah, you've really highlighted the impact of having access to such a large database. And I just wanted to ask as well, what are the challenges associated with implementing routine whole genome sequencing into clinical care? Nirupa: I think as with all of these things when implementing something new within a healthcare system, it requires a level of education, upskilling and also, as Mark has touched on, how we handle the tumour tissue, so that it's handled in a genomic-friendly way to enable the best results if you like, because we want to ensure that their DNA is not damaged so that we can get accurate read-outs on the results. So there are challenges and there is also cost implications in weighing up the pros and cons. And I think what we were able to show, and by undertaking this sort of pan-cancer analysis, is where there are those cancer type where there is a real need for whole genome sequencing, or where it can be justified, because there are a number of different types of mutations both within the tumour. And also from a blood sample that is also taken, so this is your constitutional DNA, so this is if there is a risk of an inherited cancer. So we are able to pull together all of this information, and obviously that's important, not just for the patient, and their management, but also for family members. So I think really what this shows is that where you have to identify many of these different types of mutations, whole genome sequencing enables that through a single test. Naimah: Mark, would you like to add something else there? Mark: One thing I think which Nirupa's very much part of, is the distinctiveness of the Genomics England approach has been to involve the NHS at every stage. Now, what that means is we estimate that at the peak of the 100,000 genomes project, 5,000 frontline NHS staff touched the project at some point in their working week. What that does mean is that Nirupa and the cancer team could realign the cancer tissue handling pathways. But it also meant that we were able to upskill the frontline workforce, such that at the end of the programme, when we produced a genomic test directory, they were really up for it because they did not want all the hard work they'd put in to stop. And so what we've done is produce the national test directory within five years of starting, that wasn't a deliverable for the project, but it was nonetheless obvious to all of us working in it, including NHS England, that there needed to be service transformation, and we've managed to effect it. Now, if you look at other settings where perhaps Nirupa and I might have a research team, we might do it some distance from the health system, it would be in the health system, but not with the health system, then it takes between nine and 16 years to get these things into clinical practice. And that was achieved here in five years. So there is a lesson from this, the cancer programme particularly, because the cancer programme testing was very limited when we started, but you can take an entire workforce on a journey and leave them with the legacy of an entirely transformed system for patients. And thankfully because we got, Nirupa and I, the NHS to agree to reimburse for the testing directory being used, we have eliminated a lot of randomness that was in the system previously. So it's quite an important advance in that respect, and it really does show in the beautiful work that Nirupa was describing exactly how you can use this information to change an entire system. And the NHS is not the easiest system to change in the world. Naimah: Nirupa, you mentioned the findings show that there was potentially inherited genes. Can you tell me what does that really mean for patients, if we're able to diagnose these inherited genes sooner in life? Nirupa: It can influence how their cancer is treated, so it means that there may be certain types of therapy that are available if they have a specific inherited cancer gene, number one. It also, can impact in terms of preventing further or other cancers related to those genes, and it may impact the type of surgery they have, and also the type of overall cancer treatment. And then, finally, if they have got an inherited cancer, then, as I mentioned before, it may impact in terms of testing and screening for their family members. And that's really key as well, because this means that their cancer can be diagnosed, if they do develop a cancer, because they're being monitored, because it's much more targeted, their approach in terms of screening for a particular type of cancer, they can potentially have their cancer treated much earlier. Or even better, before it becomes what we call an invasive cancer but at the pre-cancerous stage. So this has huge implications, and what we're finding actually with more and more testing – and this is not just... our study was consistent with other studies that have been published – is that when you undertake more routine testing, then you are able to identify this. It is not common amongst the population, but in those patients where it is relevant, it really can impact their care. Naimah: Mark, do you have something to add there? Mark: Well, I think Nirupa's just highlighted a really important point. So to bring that into a little bit more ways of which people listening to this can relate to it, we have a family where there was a women who had no family history of breast cancer, she developed breast cancer, and in the tumour we found that she had a BRCA 2 mutation. We also found that she'd probably acquired that or inherited it, we don't know. That for her meant that she could enter the Olympia trial, which was running at the time, which Nirupa alluded to earlier, was a study of PARP inhibitors. But without that genetic makeup she'd never have got into that trial, and she probably wouldn't have been tested for BRCA at that time in the NHS because she had no family history, I think that's probably right, Nirupa. And then there was a family-wide consequence for that, because she had a brother and son, and she also had a daughter, and the daughter was under 30 at the time and underwent BRCA testing and was BRCA 2 positive. But she has the opportunity now to enter intensive breast screening from the age of 30, and that's what's happened. And her brother, and this is the lady who had the breast cancer, her brother and her son may be at risk of prostate cancer, so they can consider testing. So Nirupa makes a really important point, that when people have inherited a previous disposition to cancer, that can have a family-wide impact. And one test in one family member can open the doors to opportunity for others to understand their risk and to be screened more actively and intensively, hopefully with meaning that if they do develop cancer it will be detected very early, or maybe we can just prevent it altogether. Naimah: Thanks, Mark, a really good example of the impact that this testing has had. I just wanted to touch back on your point, Mark, that you'd made about real-world data. And I wondered actually, Nirupa, if you could kind of explain to me why it's important to link real-world data to the genomic data? Nirupa: Yeah. So I think the work we've done here really does emphasise this, because when we refer to real-world data, we're talking about different types of healthcare data across the population. And we had the opportunity to link the genomic data to a number of key data sets that are curated by the cancer registry, the national cancer registry database. And this includes things like all of the population base systemic anti-cancer therapy, so we know that for each of the participants the type of cancer therapy they receive, and also, as Mark has mentioned previously, the hospital episode. So when patients needed to be... we can see their data in terms of admissions, investigations, and so on. And these are really valuable data points, because you get an indication of when patients may have had to then have further testing, or if there is a risk of recurrence and importantly survival data, because a lot of this has been, in terms of a lot of the cancer genes have been well characterised and tested. But what we were able to do here at a pan-cancer level on a large cohort of patients over a period of time, is to look at if you had a particular mutation, what is the impact of that in terms of outcome for a particular cancer type, and even more broadly, on a pan-cancer level? And actually, as this type of data accumulates, I think the real value, and if you've got a larger number, you know, what is the value for patients who've participated in this programme going forwards, is that as that data accumulates and the numbers go up, we are able to then ask more detailed questions. What is the impact of a particular type of mutation, or a particular type of variant within a gene? And, importantly, what happens when you get a different sequence or a combination of genes? And how does that impact? And this, I feel, is the way that we are going to move more towards precision oncology, because we are beginning to understand the cancer in more detail, how it is going to behave, and then try and tailor therapies accordingly. Naimah: And Nirupa, I wondered if you could tell me as well if the findings from this study have benefited directly those patients that were involved in the 100,000 genome project? Nirupa: It has benefited some of the patients because, as Mark has mentioned, there are findings that we weren't expecting in terms of potentially inherited cancers and, therefore, this has had implications. The way that the project was set up from the outset, is that we were obtaining tumour samples from patients who had not received any previous cancer therapy. And what this meant is that this was predominantly in patients, so they were treatment naïve with early stage disease that were having surgery to treat their cancers. And as such, what we know is that fortunately most of those patients did not require further therapy, because their cancers were treated successfully with surgery. But what it did tell us, and what it's really highlighted, is the number of important genes that were identified. And so whilst it may not have impacted patients directly, it's enabled us to study the biology of the different types of cancers, how they behave, along with the longitudinal clinical data. But what it is doing now, is through the national test directory through the genomic medicine service, is enabling testing for patients that unfortunately now have more advanced cancers, but where these genomic findings are more likely to impact directly in terms of therapy. So, for instance, as we've mentioned, the ability to have whole genome sequencing for patients with high grade serious ovarian cancers, means that this will impact the type of treatment they have. And this also was the tumour type where we found the highest number of patients with BRCA mutations, so we have a potential inherited risk of a cancer as well. So now what we have learnt and the infrastructure that we have developed has enabled this to have a real impact, not just for patients in the project now, but wider within the NHS. Naimah: Mark, would you like to add something else there? Mark: I think Nirupa's encapsulated it very well. There were a range of benefits, so I mentioned earlier that in one centre 25% we have evidence got a benefit for their treatment for their cancer in some way shape or form. So an example to what there might be is that some people got a medicine they wouldn't have received from routine care, and that might have been licensed for the treatment of that tumour, but it wouldn't have been the first line treatment choice. Some people got medicines that they wouldn't have got because we don't normally associate using that medicine with that cancer, but they had a signature that showed that they were very likely to benefit. Quite high numbers got an opportunity to get into a clinical trial, which is really important because if you look, over 50% of global oncology trials now have some kind of biomarker or diagnostic, or something like this alongside, what better than to have a comprehensive inventory of the variants and the cancer, and to be able over time to use that library to understand better the treatment course of that patient. And that's what I think a whole genome adds, rather than the single, look at a single part of the genetic makeup. And then finally, some had lots of mutations, really high rates of mutations, and maybe they should receive specific advance therapies, like immunotherapies. Or alternatively, they had a feature in their genetic makeup which it looks like they inherited, as Nirupa absolutely correctly said earlier, these people need to be followed-up and they need more intensive screening, because this is how you detect cancer at an earlier stage. And the final way people benefited is we could detect genetic changes in their DNA that meant that if they were exposed to certain medicines, they were likely to suffer harm. And there's a particular, two medicines, 5-fluorouracil capecitabine, where possibly about 5% of people will need either a reduced dose or a completely different medicine, because it will be very harmful. And so this is about getting the right medicine to the right patient first time, and getting the right outcome for that patient downstream. And I think, you know, Nirupa's encapsulated it perfectly, there's a whole range of benefits that the patients can accrue from this. And I think we should probably, Nirupa, say that people were quite cynical when we started, about what it would be that you would get over and above, for example, the cancer genome map that's at the international cancer genome consortium. And, you know, I'd had leading cancer scientists in Britain say, "Oh well, we've discovered it all, there's nothing to find here." And I think what this paper shows is that's not entirely true. Nirupa: I would agree with that Mark, but I would also probably add that it highlights the value of having a large data set alongside that clinical information. And what we were also able to do, is whilst we very much talked about what were the gene targets that had a direct impact or genomic markers that impact care now, for which there is an approved therapy. What we've also been able to do through this analysis, is actually highlight the number of mutations that have been identified for which there is a licence therapy in another cancer type, but not in that particular cancer type. And what that means, is that specially now, as we have more and more biomarker-driven therapies, I mean, if we look at that compared to when the project started and now, that has increased dramatically. And what that means is then there are sort of licensed medications that actually can be used in non-licensed indications via a clinical trial, via these very, you know, these basket studies which are across cancer types and are actually based on different types of molecular markers. And really, we're able to show this at a pan-cancer level across the 13,000 tumours through the results from whole genome sequencing. Naimah: You've both kind of touched on this throughout and, you know, we've talked about the development of personalised medicine. And where do you see the future of cancer treatment in the next five years? Maybe, Nirupa, we can go to you first? Nirupa: That's a very good question. I think and what I hope is that with more comprehensive and equitable and standardised testing for patients, especially within the NHS, that this will enable more personalised and targeted therapy alongside, you know, systemic chemotherapy. And as well as that, better selection of patients that are likely to benefit from the newer immunotherapies. And also where sequencing is very exciting, is that once we begin to understand more about the individual tumours, you know, going forwards there are a number of cancer vaccine trials, and the aim of those are to have specific vaccines that are going to target an individual's tumour. So I think in the next five years, this is I think a very exciting space, I hope so, because we need to keep doing more in the space for our patients to try and improve therapy and precision oncology for them. Naimah: And Mark, do you have anything to add to that point? Mark: I think Nirupa's right, that there are new therapy extractions coming on, vaccination's one way. But I think that what will become clear is whether we can use any molecular mechanisms for early detection of cancer. The battleground here is that we all too often detect cancer late, when it's already outside of the organ it originated in and may be spread in other parts of the body. It's very hard to effect a cure, almost impossible in that setting. But what if we could detect cancer earlier? And then what if we could place a whole genome or detailed molecular characterisation alongside that? And then, as Nirupa suggested, give someone a vaccine tailored to their tumour that would eliminate it. The real problem is all too often we detect cancer late, so maybe some of these new molecular diagnostics, such as cell-free tumour DNA will usher in an era of early detection. And one of the things, and particularly before we did this project but also up until the beginning of the last decade, there were very few good biomarkers of cancer that were usable in the health system. So we have for the first time opened the vista of having early detection, if we combine early detection with detailed molecular characterisation, possibly a whole genome, possibly another test, then I think we really can usher in the era of precision medicine. And so I think Nirupa's absolutely right, there will be new treatments, there always will be, but what we have to do is to get detection at an earlier stage. Naimah: We'll wrap up there. Thank you to our guests, Dr Nirupa Murugaesu and Professor Sir Mark Caulfield for joining me today. If you'd like to hear more about this, please subscribe to the G Word on your favourite podcast app. Thank you for listening.

Dr. Clare Craig: These Beliefs About Viral Covid Are NOT Supported By Evidence – Ask Dr. Drew – Ep 301

Ask Dr. Drew

Play Episode Listen Later Dec 23, 2023 79:43 Very Popular

Dr. Clare Craig is the author of “Expired: Covid the Untold Story” and a Diagnostic Pathologist who worked in the NHS. She studied medicine at Cambridge University, moving to Oxford for her final three years of clinical training. After qualifying, she practiced in the NHS for 15 years, specializing as a diagnostic pathologist and becoming a fellow of the Royal College of Pathologists. She was the day to day pathology lead for the cancer arm of the 100,000 Genomes Project, and led research and development projects at Genomics England. She is co-chair of the Health Advisory and Recovery Team (HART.org) who are a voluntary body of professionals educating the public on COVID issues. Follow Dr. Craig at https://x.com/ClareCraigPath 「 SPONSORED BY 」 Find out more about the companies that make this show possible and get special discounts on amazing products at https://drdrew.com/sponsors • GENUCEL - Using a proprietary base formulated by a pharmacist, Genucel has created skincare that can dramatically improve the appearance of facial redness and under-eye puffiness. Genucel uses clinical levels of botanical extracts in their cruelty-free, natural, made-in-the-USA line of products. Get an extra discount with promo code DREW at https://genucel.com/drew • COZY EARTH - Trying to think of the right present for someone special? Susan and Drew love Cozy Earth's sheets & clothing made with super-soft viscose from bamboo! Use code DREW to save up to 40% at https://drdrew.com/cozy • THE WELLNESS COMPANY - Counteract harmful spike proteins with TWC's Signature Series Spike Support Formula containing nattokinase and selenium. Learn more about TWC's supplements at https://twc.health/drew 「 MEDICAL NOTE 」 The CDC states that COVID-19 vaccines are safe, effective, and reduce your risk of severe illness. You should always consult your personal physician before making any decisions about your health. 「 ABOUT THE SHOW 」 Ask Dr. Drew is produced by Kaleb Nation (https://kalebnation.com) and Susan Pinsky (https://twitter.com/firstladyoflove). This show is for entertainment and/or informational purposes only, and is not a substitute for medical advice, diagnosis, or treatment. 「 ABOUT DR. DREW 」 Dr. Drew is a board-certified physician with over 35 years of national radio, NYT bestselling books, and countless TV shows bearing his name. He's known for Celebrity Rehab (VH1), Teen Mom OG (MTV), The Masked Singer (FOX), multiple hit podcasts, and the iconic Loveline radio show. Dr. Drew Pinsky received his undergraduate degree from Amherst College and his M.D. from the University of Southern California, School of Medicine. Read more at https://drdrew.com/about Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr Rich Scott: Reflecting on 2023 - A year of podcasts and a decade of progress

Play Episode Listen Later Dec 20, 2023 30:07

As we approach the conclusion of 2023, we reflect on a year that not only signifies our 10-year anniversary but also marks another chapter of The G Word. Throughout the year, guests have joined us fortnightly to share their research, stories, and aspirations for the future of genomic healthcare. In this special end-of-year episode, Naimah Callachand sits down with Dr Rich Scott, Interim Chief Executive Officer at Genomics England, to look back on the last decade of Genomics England. Tune in as we revisit memorable moments from the 2023 podcast episodes through key quotes, reflecting on the transformative journey of Genomics England. Join us for this insightful recap and a glimpse into the exciting future ahead! Below are the links to the podcasts mentioned in this episode, in order of appearance: Adam Rutherford, Laurence Hurst, Cristina Fonseca and Vivienne Parry: Public views on genetics - what have we learnt? Dr Jack Bartram: Can genomics improve our understanding of childhood cancers? Helen Webb, Lizzie Mordey, Kirsty Russell and Prabs Arumugam: How can advances in genome sequencing support patients through their sarcoma journey? Vivienne Parry and David Bick: Which conditions will we look for initially in the Generation Study? Dr Nicola Byrne: What are the challenges of data governance in the digital age? Chris Wigley: The journey to the Human Genome Project and beyond with Dr Francis Collins “We're also looking to the future where, as I say, we're proud of the impact that there already has been, and the NHS Genomic Medicine Service is the first national healthcare system to offer whole genome sequencing and that is extraordinary. Thinking about how we can broaden our impact is a really important part of that, and that's thinking about how we can be supportive of genomic technologies broader than just whole genome.” You can read the transcript below or download it here: Reflecting-on-2023-transcript.docx Naimah: Welcome to the G Word. Rich: We're in an extraordinary time. The power to analyse genomic data has changed enormously. These are big changes in terms of the, sort of, analytics that AI could bring and the potential to work not just within the UK but with other countries and other big initiatives to make sure that we're answering the questions as best we can. Naimah: I'm your host Naimah Callachand and today we'll be hearing from Rich Scott, Interim CEO for Genomics England. He'll be sharing insights with us from the last year, and we'll be revisiting key moments from earlier podcasts in the year featuring some of the voices that have shaped our discussions. If you enjoyed today's episode we would love your support, please like, share and rate us on wherever you listen to your podcasts. Now let's get into the interview. So, this year we celebrated our ten-year anniversary and as 2023 comes to a close we want to reflect on our achievements not just in the last year but over the last ten. So, Rich first of all can you talk us through where we started in 2013 and where we are now? Rich: It's amazing really to think about how much things have changed in terms of genomics in clinic and in hospitals and then for us as Genomics England over the last ten years. So, actually thinking back ten years ago was only ten years after the Human Genome Project was completed, and when one thinks about what one could do in clinic and those questions you could answer using genomics in clinic. We could see what was coming, we could see these new technologies, next generation sequence in coming, but it was much more dependent on very targeted testing. And now with, you know, our founding project, the 100,000 Genomes Project that Genomics England was founded to deliver in partnership with the NHS we asked the first big question if you like which was how can whole genome sequencing play a role in routine clinical care. And that's now played out where evidence from the project, what we've learnt, the infrastructure we've built, and also evidence from around the world that through the NHS Genomics Medicine Service has now put that into practice and we're working in partnership to help them deliver it. So, it has gone from an idea where we could see this new technology, this potential, to a position where now patients in the NHS with cancer or with rare conditions have whole genome sequencing as a routine part of their clinical care where that's in that national genomic test directory that NHS England have set up. Naimah: Earlier in the year we heard from Dr Adam Rutherford, geneticist, author and broadcaster who commented on how the public perception of genetics and science has evolved over the last few decades. “I've been doing this a long time and I think that when it comes down to it, genetics which is a relatively young science and really in a sophisticated way, you know, a mere few decades old, but what is it at its absolute core, it's thinking about families, it's thinking about inheritance and it's thinking about sex. And these have been the major preoccupations of humans for thousands of years, and it's only really in the last century, really only in the last 30 years or so, that we've had a sophisticated understanding of how these things work, if indeed we have had at all.” Naimah: Let's get back to Rich. Rich, I've already touched briefly on it, but can we dive a bit deeper into the 100,000 Genomes Project and can you tell me a bit more about how it started. Rich: Yes, so the 100,000 Genomes Project as I said was there to ask what role can whole genome sequencing play in understanding medical conditions, you know, is it ready for clinical prime time. And also how can we link routine clinical care to research so that we're not just asking questions with today's knowledge, but we can continue to build that knowledge for the future. So, the 100,000 Genomes Project was driven by that idea that people realising, the government realising and the NHS forming a partnership with us Genomics England to explore that question in real depth. And it's not just about the clinical aspects and the scientific questions, it has also been working with participants and the public to understand how we could do that. And through the 100,000 Genomes Project we worked particularly with patients with cancer and rare conditions to see how we could help make diagnosis and improve care. And also with their consent make their data available in our secure, trusted research environment so that researchers could continue to look for answers that we couldn't answer today, and we continue to do that work for those participants now. Naimah: Next we're going to hear from an interview with Dr Jack Bartram, a Consultant Paediatric Haematologist at Great Ormond Street Hospital for Children. He spoke about the significance and impact of integrating genomics into routine clinical care in diagnosing cancer in children. “If I look back and if I reflect on the last three years, you know, we could probably accurately say at least a quarter of patients it has given us additional information which is either aided in diagnosis or like I had said help risk stratify a patient or potentially reveal a target for a therapy that we didn't know of before. And what this has led to and what we've seen over the last three years or so is that we have actually changed management of patients based on this. So, definitely we've got examples where we scan clarify the diagnosis, we've changed the risk category, or we've identified for example that an unexpected cancer predisposition in a family which has then led onto screening for the family which can then give the family the knowledge to try and do things to either modify the risk of cancer in the family or at least screen for it so they can detect things early to prevent things presenting too late.” Naimah: Okay, now let's talk a little bit about some of the initiatives at Genomics England. Can we talk about how they've progressed and what they might look like in the future. Rich: Yeah, so we really are on a journey both as an organisation but with all of those partners that we work with across the UK system. And one of the great things I think about genomics and genomics in the UK is that the ecosystem that we're in and the strong partnerships that we can form to ask these really big questions. So, if you like when we formed as an organisation we had the questions that we're asking around diagnostic use of whole genome sequencing in the 100,000 Genomes Project. And if you like in our second chapter as we've moved on to support the NHS in delivery of life clinical care we also have been thinking about the other big questions that we need to address. And those have played out and we've been really fortunate to gain the funding and to work in partnership with the NHS and others on these big questions. So, firstly our newborn genomes programme, secondly our diverse data programme and then our cancer 2.0 initiative. And each of them have big questions behind them so that we're saying, you know, where could genomics better support healthcare and move forward and improve care for everyone. Our vision at Genomics England is a world where everyone can benefit from genomic healthcare and each of them is pushing those boundaries, asking those questions in different ways. For the newborns programme the big question is should every newborn baby be offered whole genome sequencing driven particularly by that potential to identify more treatable severe genetic conditions at birth, and if so how should we do that. Again, developing evidence in and around really broadly across the clinical and scientific aspects, but also engaging and understanding public attitudes how we might do that. And really understanding how that might impact on the healthcare system, how it might be delivered in clinical care. For the diverse data initiative we recognise the challenges historically that there have been because of the inequity in terms of the communities who have been engaged with and included in genomic research. And the diverse data initiative aims to both understand where we are today but also to make sure for example the national genomic research library is at least representative of the UK population so that we can work towards again that word that's in our vision, everyone, a world where everyone can benefit from genomic healthcare. And in the cancer 2.0 initiative we've been exploring two really promising areas in terms of cancer genomics. Firstly, exploring different sequencing technologies and in this case partnering with the NHS to work on the Oxford Nanopore technology which we think is really promising in terms of use in diagnostics to speed up and better diagnose and treat cancers. And also looking in our multimodal element of our cancer 2.0 initiative at bringing in a broader range of data alongside the genomic and clinical data that participants in our programme consent to us holding in our trusted research environments. And bringing in image data, images of their tumours on the histopathology slides that are looked at traditionally down a microscope but scanning those at very high resolution and with uniformity between participants working with NPIC to do that. And also bringing in imaging, so radiology type imaging, of tumours so that that data is there to drive new discovery. And working in partnership with academics and with industry for example insitro to understand how we can both bring that data together usefully, put the right tools next to it and then allow that discovery so that our participants know that we're looking not just on what we know today but to improve things for the future. Naimah: Rich mentioned some of our initiatives here at Genomics England. And now we're going to hear from some G Word guests on how these programmes can make a difference for those with a genetic diagnosis. We spoke to Lizzy Mordey, a clinical trials co-ordinator, whose husband Steve sadly passed away last year after receiving a sarcoma diagnosis. Lizzy commented on the pivotal role whole genome sequencing can play in receiving a quicker diagnosis on the identification of suitable treatments for patients with sarcoma. “Personally, I would hope for quicker diagnosis, and I know that's super hard to do and I think as we've discussed before on this call it's such a rare thing and it, kind of, often doesn't fit the standard clinical pathway and that's one of the reasons why it's so frustrating. So, anything that we can do on that front that I think would be hugely valuable to anyone experiencing a journey like what me and Steve went through, and yes advances like genome sequencing are really amazing in supporting that. Yes, as I mentioned as well any information about types of treatment, you know, the diagnosis is important but then the other aspect of getting a diagnosis and a specific diagnosis is understanding what's most likely to help.” Naimah: Next we're going to hear from David Bick who is a principal clinician for the Newborn Genomes Programme at Genomics England. He spoke about the generation study which is being delivered in partnership with the NHS. “I'm doing this because I imagine a day when all over the world we will find and treat children before they get ill. This is one of the most wonderful programmes to be involved with because I can see that future. I want there to be a healthcare system. I really want to help children stay healthy and really live their best lives, that's what's so exciting for me.” Naimah: Now let's get back to the interview with Rich. You mentioned all of the partnerships there and also one important one is with the NHS. As you know the NHS also celebrated its 75th anniversary year as well as our tenth anniversary. And I wondered if you could tell me a bit more about that relationship with Genomics England and the NHS and how we're working together. Rich: Our relationship with the NHS is absolutely critical. So, as we're thinking about what we can do to enable better genomic healthcare we're so fortunate in this country to have a national healthcare system. And for us and for our work at Genomics England it's absolutely critical to work hand in hand with NHS England both in supporting their live clinical services so we enable their national whole genome sequencing service through the Genomic Medicine Service and also as we work through all of our patient facing research. So, as we did for the 100,000 Genomes Project, as we are for our Newborn Genomes Programme and so forth co-designing these programmes so that the evidence that we're able to generate is relevant in the UK for our healthcare system but also that national scale is just so extraordinarily powerful. And I think we're really lucky for many reasons, the UK genomics ecosystem, it's richness, the investment that has come from government and from the NHS in genomics and the recognition of its importance and from funders, and then that ability to ask questions at national scale. And when you look internationally I think that's the piece that people are often most jealous of in terms of the power of the questions that we can ask together with the NHS so that we can do exactly what we want to do which is transform care so that it's better in the future. Naimah: Rich highlighted the importance of our relationship with the NHS in transforming patient care. Louise Fish, CEO of Genetic Alliance UK commented on the importance of joined up care following diagnosis to support them throughout their lives. “So, there is a lot more we need to do to work with the NHS to make sure that the care from the health service is joined up and co-ordinated for people. And then beyond that how does the co-ordination reach out to education, to housing, to benefits, to social care. The bit that almost should be simplest is if the NHS has someone who understands your child's condition. But it should be possible for their school to be in touch and to find out how that condition is going to affect them and what support the school might need to put in place through an education health and care plan, but those links out to the other services aren't there either. So, for us there is a lot of work to do that's not just around the diagnosis but it's about ensuring that lifelong care and support is delivered in a co-ordinated way. And as more people are getting genetic diagnosis through this amazing, kind of, clinical advances how do we make sure there is also investment into the clinical services that are going to support people throughout their lives.” Naimah: One of the key factors in supporting Genomics England to deliver this important work and all of our initiatives is the participants and the trust that they have in us. I wondered if you could share a bit more on this, so how Genomics England works with their participant panel. Rich: Yes, so I think one of the things I'm proudest about at Genomics England and it was established about the time I was arriving at the organisation is the participant panel who are a group of our participants who represent a broader participant across the national genomic research library. And they're a part of our governance, which governance sounds like a boring word, our relationship with the participant panel and their role in our governance is absolutely critical. They are the people whose data we are the custodians of, and we have a responsibility to them to live up to their expectations and also to make sure that they're driving the decisions that we're making. An example is how we setup the access to data for researchers. So, I mentioned that the way the national genomic research library works and a model that we developed through engagement with the public and with the input of our participants is that people can visit the de-identified data in our trusted research environment, but they can't take it away. They come and look at the data, they carry out their research which is on approved projects that is exploring healthcare questions. Those researchers have to go through an access process overseen by an independent access review committee that has our participants on it. So, they are making the decisions about the sort of research that they are comfortable with and that they want to be done on their data, and I think that's really critical. It has also been a real pleasure to work with our participants as we design future programmes either on for example finding further answers or looking for better treatments for people who are already in the national genomic research library, already a part of our participants or to help us design future programmes, for example our Newborn Genomes Programme. Our participants as well as engagement with potential future participants and the public more broadly has been absolutely critical in guiding us on how we do that. It's a team sport what we're doing in many different ways. That's with our broader ecosystem, it's with our participants, and that means this isn't about some people going away and sort of thinking up what sounds like the right programme and using all of their knowledge and expertise and producing something which is set in stone. This is about dialogue and engagement and using that to understand the right way of us approaching the questions we are and responding to what we hear. And our participant panel are absolutely critical in that. Naimah: And maybe it would be good now to discuss a bit about the new challenges that we're currently facing such as AI and issues with data sharing and data protection. Can you comment a bit on that. Rich: Yeah, so genomics is a fast moving area. We're really proud of the impact that we've had already, but we also recognise that at the moment we can only use genomics in a particular number of clinical situations. And even within those we can only help a certain proportion of patients. And what our participants say to us is that we need to be restless if you like and not accept where we are today. I think it's quite easy to merely celebrate progress but it's really important to also then ask where we need to be going next. I'm always guided by our participants thinking about what the new technologies are and what the different ways of approaching these scientific questions is critical. We're in an extraordinary time, genomic technology has changed enormously. The power to analyse genomic data has changed enormously. These are big changes in terms of the sorts of analytics that AI could bring and the potential to work not just within the UK but with other countries and other big initiatives to make sure that we're answering the questions as best we can. That brings with it as with all of these areas questions about how you best do things and how you balance the importance of privacy, data privacy, with the benefits of being able to look across larger number of research participants to find answers that you just wouldn't otherwise. Likewise with AI there is the potential for us to both speed up current processes but also ask broader questions that we can't yet using some of these technologies. Doing that in conversation with our participants and the public to understand how to best balance the different benefits and also clarify where there are, sort of, very clear expectations that we shouldn't exceed is really important. And I think that's one of the things that puts us in such a strong position is that confidence that our participants are guiding us and often, and speaking as a doctor myself, it's interesting the medical community is often quite paternalistic, quite cautious and quite narrow in what they might think their participants would want. What we like to do is be driven by what our participants want and expect, and I think that has been really important for us in our history up to now as an organisation and increasingly in the future. Naimah: Yeah, and I think you've really highlighted how Genomics England were trying to keep the participants at the heart of everything that we do. Dr Nicola Byrne, the National Data Guardian for health and adult social care in England spoke about challenges with sharing health data and the importance of transparency and accountability in how data is used to support better outcomes from health and care services. “So, it's absolutely important that people feel that they can share that information and then feel confident that any information they do share is going to be used in ways that are safe, appropriate and ethical. Whether that's for their own care or thinking about the benefit of other people in future through research, innovation and planning.” Naimah: Well, let's get back to the interview for some final reflections with Rich. So, we've been looking back at our achievements over the last ten years, and I'll be keen for us to look at what's next. So, we've touched on it, but let's take some time to reflect on the research that has taken place across the global genomic landscape for example and, you know, what we've done here at Genomics England. Rich: The world has changed a lot in ten years. We've learnt a lot ourselves as an organisation and the researchers that work with our participants data and the national genomic research library have done extraordinary work. So, to give you a flavour of the sorts of things that I guess have changed in terms of what we can enable them doing in terms of research and research work. When participants data enters the research library they're consenting to their genomic data sitting there alongside deidentified clinical data from their longitudinal health records. As I said through our multimodal cancer initiative we're also now able to bring in image data for our cancer participants. And increasingly, and this is something that Matt Brown, our chief scientist, was talking a lot about at our research summit in September, was bringing in additional modalities of data alongside that. So, for example, in our rare disease participants bringing in proteomic, transcriptomic and long read data alongside the current sets of data. It means that that resource becomes even more powerful and able to answer a broader set of questions and able to ask questions across a broader set of data in terms of what might be useful for improving the understanding of medical conditions and improving clinical care. So, for example, there has been amazing work over the last few years on cancer and the mutational signatures that are there in tumours. For example, Serena Nik-Zainal's group understanding the patterns of mutation that are there in tumours driven by the underlying biology, not just because it helps us understand how things have happened, but also because it helps us understand about prognosis and how to treat conditions. We've got really exciting early insights from the work on the image data, that multimodal data, working as I said with academia and also looking at the work that insitro are doing. Recognising patterns between you can see down the microscope of a tumour and the genomics. To understand some of those processes that we've just not been in a position to explore before. And I think one of the really powerful pieces of work that is ongoing and will continue to is the ability for researchers and teams within Genomics England to continue to look for answers as our knowledge improves. So, some of the research work that we're doing is discovering some new fields if you like of understanding. We also know that each year literally hundreds of new genes linked to rare conditions are identified. So, enabling research that allows us to go back and look in our existing participants data to see if that new knowledge, that new knowledge about gene to condition links or better understanding of genomic variation means that we can keep looking for and finding things relevant to people who at the moment are research studies, 100,000 Genomes Project, or the Genomic Medicine Service initial testing with today's knowledge or the knowledge of today or whenever their test was couldn't identify because of the limitations of knowledge. Now we can go back and identify through by sharing likely insights of clinical importance with NHS laboratories. We can then pass those findings back to participants and that has been the case in more than 2,000 of our 100,000 Genomes participants already and it's enormously powerful. I think as we think about the direction of travel in the future, I think thinking about how we make sure that the breadth of questions that can be addressed for our participants in the national genomic research library is even broader, is really important. And that's, as I say, something that's particularly bringing in other types of data alongside has been a really important part of. We're also looking to the future where as I say we're proud of the impact that there already has been, and the NHS Genomic Medicine Service is the first national healthcare system to offer whole genome sequencing and that is extraordinary. Thinking about how we can broaden our impact is a really important part of that, and that's thinking about how we can be supportive of genomic technologies broader than just whole genome. So, for example, panel and exome data and thinking about some of those other modalities of data like transcriptomes is really important as well for us. And that's something that we're exploring at the moment how we best do that, how we might do that. Also thinking about the range of settings that genomics is currently playing a role and we can see a future in five to ten years' time where rather than genomics being something where it plays a role in a small proportion of healthcare encounters where it could be impactful, over a much larger proportion, perhaps even up to a half of all healthcare encounters through, for example, pharmacogenomics potentially. And our Newborn Genome Programme is developing evidence that will help us understand whether that whole genome sequencing should be offered to all newborns. Potentially in research studies like Our Future Health are asking questions around the value of integrated or polygenic risk scores. Through those sorts of elements we can see genomics playing a role much more broadly both in terms of the number, proportion of clinical settings where it's relevant, much more towards it being a routine part of healthcare, but also across the lifetime at different stages and thinking about the value of genomic data if you like through the life course as something that can be looked at repeatedly increasingly without requiring specialist knowledge from the clinical teams so that it can have the impact it can. And thinking about how we might play a role in developing that evidence but also supporting the infrastructure through our expert knowledge in the management of coherent national genomic data sets. And also having that dialogue in public about how genomic data might be used and working out how we generate evidence that can drive policy change. I think there is enormous potential in the future and we in the UK I think remain uniquely placed to explore those sorts of questions. Naimah: So, we'll wrap up there and that brings us to the end of our podcast for 2023. Thanks to Rich Scott for sharing his reflections on the last ten years of Genomics England and his aspirations for the future. Moving into the new year we'll leave you with a powerful quote from our podcast with Dr Francis Collins who is renowned for his landmark discoveries and leadership in the Human Genome Project. “My dream Chris is that we come up with in the next decade a scalable approach to every genetic disease where you know the mutation.” You can find all of the podcast episodes mentioned in this podcast plus many more on our website www.genomicsengland.co.uk or on your favourite podcast app. We look forward to bringing you some new episodes with more exciting guests in the New Year but do get in touch if you have any topics you would like us to cover. I've been your host Naimah Callachand, and this episode was edited by Mark Kendrick at Ventoux Digital. Thank you for listening.

Rebecca Middleton, Professor Dame Sue Hill and Dr Rich Scott: Transforming the NHS with genomic testing

WIRED Science: Space, Health, Biotech, and More

Play Episode Listen Later Nov 22, 2023 42:35

This year as we celebrated our 10-year annivesary, the NHS celebrated a significant milestone of 75 years. In this episode we reflect on our journey over the last 10 years, including the impact of embedding genomic testing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. Host Rebecca Middleton, Vice Chair of The Participant Panel at Genomics England is joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England in this special episode of the G Word. "To date, we've had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they've been given or make treatments available. That is a real positive benefit from that pipeline to individual patients." Listen to the other episodes in our 10-year series: Shelley Simmonds, member of the Participant Panel at Genomics England, speaks to Louise Fish, CEO of Genetic Alliance UK, and Amanda Pichini, clinical lead for genetic counselling for Genomics England as they reflect on how the patient journey has changed over the last 10 years for those living with rare conditions. Dave McCormick, member of the Participant Panel at Genomics England is joined by Jenny Taylor, a valued member of our research community, and Professor Matt Brown, our Chief Scientific Officer, discussed the last decade of genomic research at Genomics England. Transcript You can read the transcript below or download it here: Transforming-the-NHS-with-genomic-testing.docx Rebecca: Hello and welcome to the G Word. My name is Rebecca Middleton and I'm the Vice Chair of The Participant Panel at Genomics England. On today's episode, I'm joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England. Today we'll be reflecting on the last ten years of genomics, including the impact of embedding whole genome sequencing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. If you've enjoyed today's episode, we would love your support. Please like, share and rate us on wherever you listen to your podcasts. Thank you, Sue and Rich, for joining me today as we look back at how genomics has developed in the NHS over the past decade and impacted tens of thousands of lives. It all started with the creation of Genomics England and it's first groundbreaking initiative, the 100,000 Genomes Project, which sequenced around 85,000 NHS patients affected by rare conditions or cancers and led to groundbreaking insights and discoveries for so many families. I'm one of those rare condition patients and my genome sits in the National Genomics Research Library besides thousands of others. Along with the project, I've been on a journey over the past ten years and I'm still hopeful that through time and further scientific discovery, my family and many others will get the answers they need for the future. Today is a chance to reflect back over the progress of the past ten years and to look forward about what's next for genomics, for genomic science, the genomic service, and for the patients and families it impacts. Sue, welcome. If we can come to you first, and it's a very big ask coming up, but can you briefly sum up your critical role in genomics over the past ten years and talk us through how you've shaped the service in the NHS to date? Sue: My role in genomics in the NHS has actually been much longer than ten years, because particularly genetic services have been part of the NHS journey since it was formed in 1948. As Chief Scientific Officer for England, part of my responsibility since I was first in that post in the Department of Health at that time and now subsequently in NHS England, but still with a crosscutting health and social care role, genetics and genomic services actually sit under the remit of the Chief Scientific Officer for England. Shortly after the 100,000 Genomes Project was announced and that the NHS would be a major contributor to the 10,000 Genomes Project, I was asked to lead the NHS contribution to the 100,000 Genomes Project. My role has been both of leading the NHS contribution to the 100,000 Genomes Project, and then as Senior Responsible Officer for Genomics in the NHS in introducing the NHS Genomic Medicine Service to the NHS and its subsequent role in delivery and in supporting research and other initiatives. Rebecca: Rich, over to you. Ten years ago I believe your role was very different and you were in clinic, so how has it changed over the past decade as genomics has embedded itself into the NHS? Rich: That's right. As you say, I'm a doctor by background and ten years ago I was consultant in clinical genetics at Great Ormond Street, where I still practice, I still do one clinic a month, but my role is primarily sat there meeting families with a child normally with some symptoms or some problems which people thought might be those of a rare condition and thinking about how we did that testing. At that time I was beginning to think about how we use in Great Ormond Street some of the newer technologies that were coming along. Using, for example, gene panels to help diagnose children who had epilepsy of early onset. Eight years ago, I joined Genomics England, where I could see the work of Genomics England and the partnership with NHS to deliver the 100,000 Genomes Project was something where at national scale we could do something, which at that stage I was just thinking about within one hospital setting. That's really changed things for me in clinic, but also my role in that has changed. I joined Genomics England originally as the clinical lead for rare disease, so bringing that specialist clinical expertise to give advice on how we establish the rare disease component of the 100,000 Genomes Project. More recently, in my role as Chief Medical Officer, I'm actually now as interim CEO thinking about how we've made that transition from the learning that we've gained through the 100,000 Genomes Project to working in partnership with the NHS and Sue and team to play our role in supporting their NHS Genomic Medicine Service. The next phase, if you like, or questions for us to make sure that we are still thinking in a forward looking way about how genomics can do what we believe it can do to be really there in the mainstream for everyone in terms of healthcare. Rebecca: And it really has been quite a journey over these past ten years, moving from a research project with 100,000 Genomes Project to a live clinical service and all the challenges that that must bring. Sue, what are you most proud of, what are those challenges that you've had to overcome and how do you see genomics medicine service moving forwards so it can help even more families? Sue: I think in answering your question, first of all, the Genomic Medicine Service is much broader than the whole genome sequence service that is delivered in partnership with Genomics England, and I'll come back to that. In terms of what I'm most proud of, I think when we started the 100,000 Genomes Project there was a view that we shouldn't involve the whole of the NHS in recruitment and in feedback to participants. I pushed really hard to have the whole of the NHS involved, recognising that if we were going to enter into a transformative project particularly for the use of cutting edge technologies by whole genome sequencing and the analytics that went alongside that, if we only started with a small number of centres we wouldn't get the transformation that was required within a whole health system. I'm really proud of the NHS contribution because the number of patients that were recruited over the period of time where we didn't start active recruitment until 2013 and then we completed early in 2019, to deliver this from routine care in the NHS in terms of recruitment and then for feedback I think is something that is unsurpassed by many other research projects, let alone research initiatives in genomics across the world. So while this is a world leading project, it's also I think a world leading contribution from the NHS from its routine care position. I was also proud myself to be a participant in the 100,000 Genomes Project within the cancer arm of the project and being able to speak at different public events around the benefits of sharing data through the National Genomics Research Library, in that it's a benefit that is much broader than you as an individual and has the potential to impact on thousands of people. The other thing I'm most proud of is introducing the NHS Genomic Medicine Service because we still remain in the NHS world leading. Of course, a key part of that is that we have whole genome sequencing now available within routine care, within the NHS for patients with rare and inherited disease and cancer. Obviously not for all of those patients, but for the group of patients that fit within those broad-brush clinical groupings where there is the most need, but also the ability to deliver a diagnosis compared to what we could do from standard of care testing. I think it's those two halves for me with myself being a participant and being part of the NGRL right in the middle. Because, of course, from the NHS Genomic Medicine Service, which is what many other countries are grappling with, as soon as you introduce a whole genome sequencing service within a health system, how do you also continue to support research and continue to populate a research database that can be accessible, access is approved and in a safe data environment, how can you continue to support that? Rebecca: Over to you now, Rich, on what you're most proud of for yourself, but also for Genomics England and being the custodian of people's data, that people have given their data through the 100,000 Genomes Project and they continue to give their data through the GMS. If you could pick up also on the research side, so the role that Genomics England has played in the development of the Genomics Medicine Service and the genomics within the NHS, but also in the wider ecosystem as well in terms of driving discovery and driving answers for the many families and for many patients out there who are still looking for those answers. Rich: I think really there is one word that I come back to quite a lot which is the word together, where the journey that we've been on as Genomics England, me playing my role at Genomics England, but all of those involved across the ecosystem, that key partnership that we have with the NHS and with our participants, but also broader than that into the other people involved in delivering a live clinical service now that we support the whole genome element of. Also, collaborators in research, whether that's in academia or industry, this is a team sport. What I'm proud of most is the impact that we've had together and recognising that when this journey started there was a real vision about the potential that genomics could bring in the coming years because of the changes that came. For example, the next generation sequencing technology, but also the changes in ability to hold and analyse data at scale. I think rightly no one would have pretended to know what the journey was. I think the thing I'm most proud of is that we have navigated that together. In a way, we've continued to learn and we've learnt from the challenges that we have encountered, whether it's through delivering the 100,000 Genomes Project or our work since, because there always will be challenges. The reason that we're so proud of the impact that there has been is because we recognise it's hard to do. I think that point particularly of linking healthcare and research is absolutely key. That's something that we're working with Sue and the teams across the NHS are absolutely committed to and recognising that this is an ongoing learning area. That means learning how we do every element of it, but it also means that marrying clinical care and research is absolutely critical to getting the best outcomes for the system as a whole and for participants/patients individually. We've learnt how to set up a system that works in that way. We've worked through the consent models that patients in the NHS receiving routine care are comfortable with. The models of presenting data de-identified for researchers to use for purposes that those participants are comfortable within, as we call it, a trusted research environment, is a model that comes with challenges in terms of the data access for researchers but is one that is really broadly accepted and we can get to work at scale. I think it's that ongoing learning and that we've now I think shaped an approach to genomics across clinical care and research which no one would say is perfect, but we definitely understand that we've learnt about a model that we can keep iterating on and, crucially, we'll keep learning for participants present and future. So that, as you say, Rebecca, one example of that situation is where families have had a test, whether that's through 100,000 Genomes Project or more recently through the NHS Genomic Medicine Service, if today's knowledge can't find the answer in terms of a rare condition diagnosis, we know that one really important element of that research offer is that researchers will continue to look for answers. If something is found that is relevant, that can be fed back to the clinical laboratories to look at. If there is something that is clinically actionable, that can be reported. Rebecca: Thank you, Rich. I suppose, Sue, we've had a decade of navigation, a decade of learning and a decade of adapting to really take us from the 100,000 Genomes Project to the NHS Genomics Medicine Service. There have been challenges along the way, no less we've had COVID to deal with, a global pandemic. What other challenges have you had to overcome to embed a workable world class service within the NHS, how have you navigated that with your partners such as Genomics England? Sue: What's been really important is actually understanding the challenges. I see the challenges more in the sense of the transformation that we need to drive rather than them actually being challenges. Some of the transformation that was driven through the 100,000 Genomes Project we've actually baked into the Genomic Medicine Service. For example, during the 100,000 Genomes Project we understood the importance of clinical leadership; particularly if genomics was going to be embedded across the NHS for patient benefit, then it would involve more clinical specialties than clinical genetics. Through the 100,000 Genomes Project, we really drove leadership and engagement across multiple clinical specialties. We also drove this whole model that Rich talked about earlier about data sharing for broader benefit, and that benefit has then transferred over into the Genomic Medicine Service. We also recognise that if we were going to hold genome sequence a number of the processes, technical processes that happen within now our genomic laboratory hubs, needed to be standardised with quality and also external quality assurance at the core. That's right from taking a sample from a patient, extracting DNA, the sequencing methodology, whatever that is, whether it's whole genome sequencing of the type of testing within the NHS, so large gene panels, whole exome sequencing, or even smaller gene panels and other types of testing, that had to be consolidated and standardised. When results are returned we needed a standardised approach to results and interpretation. Across all of those areas if we're trying to drive a national approach as we were in the 100,000 Genomes Project and we're now in the Genomic Medicine Service is having an external quality assurance process that can look externally at each of those components that has been an important learning from the 100,000 Genomes Project into the Genomic Medicine Service. A key other element of transformation, and I hope you'll agree with this, Rebecca, was the involvement of members of the public and also participants. So right through the 100,000 Genomes Projects from Genomics England establishing The Participant Panel, through to the involvement of patients and public throughout the national programme for the 100,000 Genomes Project in NHS England, through to the genomic medicine centres that we created at that time, all of that has now been reproduced in the Genomic Medicine Service. So, patient and public involvement is a key part of the delivery mechanism. Finally, we've had to change and continually adapt and develop the underpinning data and digital infrastructure in the NHS. Initially in the 100,000 Genomes Project we standardised the data that was collected for rare disease. We introduced the use of terms called human phenotype ontology system that enabled individual patients and their presenting characteristics to be classified; that's continued on into the Genomic Medicine Service. But still more work to do in the 100,000 Genomes Project, we have to get multiple informatic systems to talk to one another. As we moved into the Genomic Medicine Service, we've both with Genomics England had to develop the analytical pipeline. We've had to develop a system that's enabled whole genome sequencing, for example, to be ordered and then to be returned after sequencing and the semi-automatic analytical pipeline in Genomics England to generate a report that could then be looked at and interpreted in the genomic laboratory hubs and returned to patients. What's been a key part of that has also been the establishment of genomic multidisciplinary team meetings that came out of the 100,000 Genomes Project, but now is embedded into the Genomic Medicine Service. Of course, the difference between the 100,000 Genomes Project contribution and now in the genomic medicine service is to ensure there's equity of access across the country in terms of the testing that is provided. A key part of the way in which the testing is offered is that introduction of the National Genomic Test Directory that sets out the standardised offer that will be funded by NHS England. That's across where an inherited disease or cancers, as well as common diseases and some other pharmacogenomic applications. The challenge always is standardisation, equity of access, and the infrastructure and leadership that makes this happen, together with developing a workforce that is genomically enabled so that it can spread out beyond that clinical genetics specialty into those multiple specialties to make sure that it's embedded. So remain in terms of some of the challenges around making sure that we change clinical pathways where genomics means that we can do things much earlier on in a patient pathway and get a definitive result and intervene. This is particularly important in cancer, but it's not just cancer, it's also in rare disease. Secondly, it's about how do we develop the whole of the NHS workforce. We have 1.3 million people that are directly employed by the NHS. There are another 600 that actually are associated with the NHS through the contracts that they hold. It's a huge task that we still have to undertake to make sure that genomics is available to all. There are two other elements, one we have to continue to take the public with us, and I think we've learnt from COVID that the public does understand now the importance of molecular tests. But there's still more to do as we use genomic information more broadly across the NHS and to drive treatment decisions that might mean that a patient thought they were going to get one cancer drug but they're going to get another because their genomic mutation says treatment B might be better for them than treatment A. We have and will continue to have a number of ethical issues that will arise as we consider whether it's some of the research initiatives that are undertaken or whether it's some of the decisions that might be made within the NHS Genomic Medicine Service or for the use of genomics. That's just a few, but it pulls it together from what we've learnt from the 100,000 into the GMS, what else the GMS is doing, and what some of the challenges are that remain. Rebecca: And a great deal has been done. There are a number of key challenges ahead. As you say, it's been a learning process, it's been a navigation process, but it's been driven by the people, by systems, by people, and they have played a critical role and will continue to play a critical role in ensuring the success going forward. I sit as the Vice Chair of Rare Conditions on The Participant Panel. Rich, if I can come to you next, how has the patient voice, how has The Participant Panel but the wider patient voice been heard and how are their view, their needs being reflected in addressing these four big sort of buckets of challenges and how are we learning these lessons going forward thinking of the new projects? For example, the newborn genome project, The Generation Study, could you give us some examples of how that learning is going forward and we're learning from the past but preparing for the future? Rich: I think it comes back to one of the really key words here is transparency and transparency in a number of ways. One of those is about the fact that this is a journey we're all on together. So, one of the things that was there right from the beginning of the 100,000 Genomes Project before I arrived was putting participants absolutely at the centre of project and the design and then in time that came for us in Genomics England wider in terms of our organisational governance. Establishing The Participant Panel on which you're a co-chair I think was really important for us early on to make sure that participants whose data it is we hold, it's no one else's data, it's our participants' data, are there driving and at the centre of the decision-making process, for example, through our Access Review Committee around who accesses the data. Participants sit on various of our governance groups and that's a template which I think is one that people have seen in various fields as working really well. It's one that Sue has touched on as being looked at and has provided useful input as to how patient and participant involvement has been set up in the Genomic Medicine Service. I think recognising that much of this is us all collectively finding the right path forward is how we approach every question that we tackle. Sometimes that's around really very practical questions. So, for example, Rebecca, you will know we often come to you guys about how we phrase a letter that might go out to participants, because recognising that from the inside of an organisation you see things one way but you might not recognise some of the nuances that are really important. Through to thinking about the really important questions around how we should set up access and safeguards around access that are there and, again, having participants sat on our Access Review Committee is crucial. And on to finding our way in new areas where the Newborn Genomes Programme I think is a really nice example where in many ways it's quite similar to the 100,000 Genomes Project in that it's a research study and it's delivered in partnership with the NHS. It's asking big questions around whether genomics can be used in a particular setting and if so, how could we use it? I think a really critical part of that and one that's been, as you know, sat in a number of the different strands and in the overall governance for the programme, Rebecca, having participants guide us, whether those people who like yourself are already part of the national genomic research library or whether they're people who might join the study themselves, or whether they're people with a different perspective that is important to include, including that engagement work as well as just with the broader public as part of the study is absolutely crucial. Before we even started the design of the study we set out with a public dialogue around attitudes to do with genome sequencing in newborns jointly with the National Screening Committee to understand where public views were to allow us to do a bit of a deep dive, not just a superficial vox pop view on what's your attitude to a one-liner question, but really to work with people on understanding some of the nuances here. There's a lot of nuance in most of the questions that we're engaging with, and then through the programme into different elements, whether that's designing the materials for consent or whether it's understanding how to practically design the process for contacting families or feeding back findings as part of the study, making that part of the process rather than a separate endeavour I think is really crucial. One of the words that I often hear people use when talking about challenging questions around how we make advantages in medicine is around explaining what people are doing. I actually think that's a really interesting word which I don't like. Most of the time this is about dialogue and it's about discovering together what we are doing and it's not people sit in with the best of intentions and with great expert knowledge in a closed room to decide what's the best approach, which is often an easy way to think about how to design a research study, for example, but this needs to be an active process where there's genuine dialogue and we learn and find our ways together. Rebecca: Some great examples there, Rich, of how powerful the participant and the patient is in the designing future services for even more patient and participants going forward and ensuring how needs and views are reflected. But, Sue, it doesn't just happen in Genomics England, there are patients and participants across the GMSAs as well, which is fantastic to see and I sit on the panel at the East GMSA as well. How important was that for you to establish that as part of establishing the Genomics Medicine Service? How important was that for you to ensure that the patient and participant view was there locally as well? Sue: So, I think we learnt from the 100,000 Genomes Project about the importance of patients and participants being part of the research element of the 100,000 Genomes Project and how that was designed, how the different pathways were put in place. In NHS England the patient is at the centre of everything when we come to our services. In all of our major programmes we have patient representatives, patient for an ongoing discussion with patient groups. This was both building upon what we'd created together with the Genomics England Participant Panel in the 100,000 Genomes Project, but then making sure that it fitted with the new genomic medicine service infrastructure that NHS England commissioned from 2018 onwards. It was making it a key part of that, making sure that coproduction with patients and families and really having a temperature check on an ongoing basis about the experience of patients and families of the genomic medicine service that they were experiencing has been a key component of our infrastructure and how we've put the infrastructure together. I always think there is more we can do, there's more we can do to monitor the experience particularly of services. That having been said, we will continue to drive forward the involvement of patients and families in the future iteration of services, whatever that might look like. I think if you put patients and families at the centre, that actually helps you determine the type of services that need to be commissioned nationally, the type of concerns that people have of the service and the experience that's feeding up, but it makes sure that patients and public representatives are part of all the important governance groups. For me, that's where the conversation needs to happen, it needs to happen both at an individual service level but through all the levels of governance that actually govern a service that is commissioned by the NHS in England for the population that is being served. Even if we haven't got it totally right, I hope that we've got it as a key component of all of the services and set out in commissioning specifications such that it's a requirement as is having the technology in place to deliver a bunch of genomic tests. Rebecca: Thank you, Sue. The Genomic Medicine Service is unique in the way that it provides a clinical outcome that is an answer for a patient, and also includes the option of joining the research library which supports further discovery. What are the benefits of this? Sue: The positive benefit of having the National Genomic Research Library has been through the researchers, scientists who've been granted access to the data. To date, we've had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they've been given or make treatments available. That is a real positive benefit from that pipeline to individual patients. But also the evidence that's generated enables us to evolve the genomic test directory. It enables us to add to genes if new genes have been discovered to the test directory, changes in eligibility criteria, so it's this continuous evolving learning system. From patients providing samples and their consent for their data to be used to the research library, to the feedback loop back into the NHS that influences both individual patient care, but also the type of tasks that get offered in the genomic medicine service overall. In conjunction with Genomics England we have also been working on an NHS Genomic Medicine Service research collaborative that's enabled us to look at the projects and initiatives that industry or other researchers would like to undertake, would like to have access to samples or to data, and to consider that on the basis of would this support the overall national endeavour in genomics, would it add to the National Genomic Research Library and create that learning system? Is it something that we need to do nationally rather than just locally in a research project? It's making the infrastructure available for those research projects over and above the ones that are part of Genomics England spending review initiatives or NHS England's Genomic Networks of Excellence. But enabling us to work with industry and researchers to support their research endeavours in a way that is contained and make sure that we create and continue to create and add to the National Genomics Research Library and this overall learnings infrastructure. Rebecca: And Rich, anything further to add there? Rich: I think that creation, that word, that learning infrastructure is the key thing there. I think the process that has taken us here where we've worked out how to integrate clinical care and research is so valuable, both for the individual patient and participant and also for the system as a whole, often making the choices that allow us to arrive in the direction actually all point together towards doing the same thing. It's really constructing things around that central vision and I think that is so important. Rebecca: Thank you so much. We've had a whistlestop tour of genomics over the past decade which and improved and informed the lives of thousands of patients and families. But to finish, let's look forward. What is your one hope for the future of genomics within the NHS? Rich, perhaps we could start with you? Sue: I think my wish is a relatively simple one, which is that we maintain this momentum that we've got and we've built together. We're on a journey and it's momentum towards genomics being absolutely part of the day-to-day, the mainstream of healthcare so that wherever you are in the country, whoever you are and often potentially without the clinical teams needing to feel they're doing anything very genomicsy, if you like, genomics is there and bound into the routine care that one has to deliver. I think when we look and we compare ourselves to other countries, because of that link that we've made and that partnership between clinical care and research, we are in a really strong position. It's therefore about maintaining that momentum and getting us to that place where genomics is just a routine part of everyone's care. Rebecca: And Sue, finally over to you, what is your one hope for the future? Sue: What I'm looking for when we put the patient at the centre is that we adopt all of the genomic technologies that would really enable us both to diagnose a genomic cause for patients that of presenting symptoms, or to inform their more preventative or inform their treatment such that genomics becomes part of everyone's pathway of care in the NHS, and that we really maintain the NHS Genomic Medicine Service as the most advanced service within the world and that it continues to work to populate a National Genomic Research Library with Genomics England such that patients can benefit from ongoing analysis and interpretation of their data. That we really become the leader across the world of this learning ecosystem and we give as many patients as possible a diagnosis and that we inform as many patients as possible treatment pathways. I believe we're in the next wave of genomics following the discovery of DNA in 1953, and now it's how do we make genomics available to everyone across where an inherited disease, across cancer, across common and acquired disease and in pharmacogenomics. Rebecca: Thank you to our guests, Professor Dame Sue Hill and Dr Rich Scott, for joining me today. It's been great to talk to you and understand the journey so far and what's ahead for genomic healthcare. Happy 10th birthday, Genomics England, and happy 75th birthday, NHS. Here's to the next decade of supporting patients and more scientific research and genomic discovery to drive home. If you'd like to hear more like this, please subscribe to the G Word on your favourite podcast app. I've been your host, Rebecca Middleton. This podcast was edited by Mark Kendrick at Ventoux Digital and produced by Naimah Callachand. Thank you for listening.

Dr Clare Craig - EXPIRED: The Untold Story of COVID, Media Attacks and Questioning the Existence of Viruses

Hearts of Oak Podcast

Play Episode Listen Later Jul 27, 2023 58:58 Transcription Available

Show notes and Transcript Dr Clare Craig has become known to many of us over the last 3 years for her medical wisdom and common sense shared on her Twitter account. For 15 years she worked in the NHS so her subsequent time in pathology and clinical data puts her in a perfect position to make sense of the Covid data bombarding us all. Clare joins Hearts of Oak to discuss her first book that was recently published titled 'Expired: Covid, the Untold Story'. She goes through 12 beliefs or assumptions we were all told as fact which she debunks in a clear and systematic way before discussing the media attacks which she has faced, including from so called 'friendly' media. We finish by looking at a new train of thought, that maybe viruses don't even exist, and Dr Craig eloquently puts forward the case to dismantle this argument. Dr Clare Craig BM BCh FRCPath studied medicine at Cambridge University moving to Oxford for her final three years of clinical training. After qualifying she practised in the NHS for 15 years specialising as a diagnostic pathologist and becoming a fellow of the Royal College of Pathologists. Subsequently she was the day to day lead for pathology and clinical data in the cancer arm of the 100,000 Genomes Project and worked in A.I. cancer diagnostics. From May 2020, she has worked full time, pro bono, on covid research, distilling the evidence for a lay audience. Since January 2021 she has co-chaired HART with Dr Jonathan Engler. HART (Health Advisory and Recovery Team) is a multi-disciplinary body of experts who have provided an independent source of information on covid issues. Despite attempts to smear her (supported by government) she has continued speaking out and remained a consistent voice of reason and calm throughout the covid era. 'Expired: Covid the untold story' available from Amazon in paperback, audio-book and e-book https://www.amazon.co.uk/gp/product/B0C9FNHYTV/ref=dbs_a_def_rwt_hsch_vapi_tkin_p1_i0 Connect with Dr Craig... TwitterX: https://twitter.com/ClareCraigPath?s=20 HART Group: https://www.hartgroup.org/ Interview recorded 19.7.23 *Special thanks to Bosch Fawstin for recording our intro/outro on this podcast. Check out his art https://theboschfawstinstore.blogspot.com/ and follow him on GETTR https://gettr.com/user/BoschFawstin and Twitter https://twitter.com/TheBoschFawstin?s=20 To sign up for our weekly email, find our social media, podcasts, video, livestreaming platforms and more... https://heartsofoak.org/connect/ Please subscribe, like and share! Subscribe now Transcript (Hearts of Oak) Hello Hearts of Oak and welcome to another interview coming up in a moment with Dr. Clare Craig. I had the privilege of meeting Clare at a Workers for England Union conference earlier this year and she has for the last three years spoken boldly truth on COVID and on Twitter. Not one of her impersonators is the tagline and she's obviously got a medical background, studied Oxford, Cambridge, 15 years in the NHS and she joined us to talk about a book she has just had published her first book, Expired, Covid the Untold Story, and she goes through 12 of the lies, the myths that we were given, and systematically takes those apart. Very well written. And then we look at HART, the Health Advisory and Recovery Team that she has co-chaired since the beginning of 2021, why that's needed, the attacks they have had from the mainstream media, but also more surprisingly the attacks from the so-called friendly media, those that supposedly were on side with us, that often are the most vicious. Dr. Clare Craig, it is wonderful to have you with us today. Thank you so much for joining us. (Dr Clare Craig) Thanks for having me on Peter. No, great to have you on and can I just point out that she is not one of her impersonators. Do you know that tagline, that stuck with me and I knew what your tagline was before I knew who you were and I kept saying, what's this not one of her impersonators? Who is this person and then I delve deeper. So I love that little tagline you have on it. Actually, my daughter persuaded me to remove it this week, so why do you say that, it's so embarrassing. And actually I haven't had an impersonator for a while, so I did take it off this week, so now I'm just me. Just you, all good, all good. And obviously, @ClareCraigPATH on Twitter, the best place to find you and then all the links out from there. And your background, obviously medical, studied medicine at Cambridge University before moving to Oxford. You were in the NHS 15 years, and then you worked a lot on the cancer side. That's possibly for another time. That's an intriguing side, just that, but we'll park that aside. We're going to get on to your book, which has just come out at the end of last month, expired. Get on to heart why, that was started, what that's for and then a couple of the stories that you have been highlighting as you have been doing for the last three years. But Claire if I can ask you first, just give us a little bit of your background and also your medical background because that actually gives you the, legitimacy to write a book which you've written. Okay, so yeah I'm a fully qualified doctor, I qualified in 2000 and you know I was a junior doctor on the hospital wards back in the day, but I went and specialised in diagnostics because it always struck me that that was the most important thing really, you've got to get that bit right and I also never had enormous faith in all that pharmaceutical companies told me about their drugs, and didn't particularly want to be a drug peddler. So I went down the diagnostics route from early on. And also that fascinated me because you get the full breadth of medicine and you get all the kind of scientific backing of it. And so it really felt like the meat to me of the subject. And so when I first started down the kind of COVID path, it was with that diagnostics hat on. So it was in summer of 2020. And as somebody who knows about medical testing, there were issues that were really clearly going on with how we were testing for COVID in that period. And there were clearly testing errors being treated as if they were real disease. And I didn't have time to dig into it at the time. So I had been home-schooling four children. And then it was the summer holidays. And so during the summer holidays, I was like, I can't wait for them to go back to school because I really want to get some data out and have a look at what's going on here. And so it was September when I did. And what I tried to do was check that hypothesis that there was a problem by looking at whether the people who are being diagnosed or in hospital and dying with a COVID label in the summer had the same characteristics as the ones in spring. Because there were certain things about COVID that were quite unique, like it killed 60% men in the spring of 2020. And there were far more Black people in ICU. And there were more diabetics and hypertensive. And there's all sorts of things that tell you that this is COVID without the test. So you can compare those and see how well the test is doing. And so I did that and it didn't look like it was doing very well. And I thought, well, what do I do with this? And I wasn't on social media or anything like that, really not my cup of tea, that kind of thing, nor is being on these sorts of shows, by the way, but I'm doing it anyway. But that, so you've grown your Twitter to a sizable following really on the back of you speaking truth on COVID. Yeah, I've kind of just tried to do that and you know I have just told people what the evidence is showing and there does seem to be an appetite for that because it's not being provided by mainstream sources and yeah that really is all that I have done. It's been a very odd journey really, the whole social media thing, because I remember getting stage fright repeatedly at particular points. The number of followers would go up to a hundred and I'd think, oh god, now that feels like I'm speaking to a lot of people and then it'd be a thousand and I'd have the same thing and I'd just go quiet for a while. I'd hit each of the landmarks and then it got so big that I just couldn't actually visualize it anymore and then just carried on. But yeah, every now and again I do, I'm astonished by how many people are listening to what I'm saying. But it is a huge responsibility and I think all of us who are speaking out, you're speaking out, as a real expert, a true expert, but there are many commentators and we really do, you do others, you have a responsibility in what we put out because there are a lot of people watching that and observing and taking that as fact and that is, that is pressure. Yeah, absolutely and, you know I have made mistakes along the way and so I have tried to always acknowledge that but there's this awful thing that happens where, if you make a mistake, especially when it's something that, like the it's more likely to be a mistake if it's something slightly shocking, something surprising. So you'll make a mistake and that will go really far and then you'll try and correct it if it's wrong and then that doesn't get picked up and so there's always that it's really really difficult because you can't go wrong. If you go wrong you can't really pull it back and you know I've learned that lesson the hard way. I think I've touched wood, it's been a while since I made a mistake that I've had to try and pull back on. But I was doing that earlier on and, you know, had to really learn that the hard way around. And the thing is that I'm going to make mistakes, right? That's the problem. And that's the whole problem with the way that free speech is approached at the moment, is that people seem to have this idea that you should be allowed to speak as long as you get everything right. Well, nobody. That means that nobody can speak, because everybody knows they're going to make mistakes at some point about some things. And so as soon as you're told that you're going to be cancelled if you make a single mistake, then you're basically silencing everybody. Yeah, 100%. Before we get on the bit, what point was it? Many of us were looking on at the information coming out. At daily death totals and I'm trying to make make sense of it and I've always found intriguing talking to those in the medical community because I want to hear kind of where they came from, what they were looking at, what they were suspicious about, how they viewed it. What was it for for you? Was there a point where you thought, hmm, this doesn't seem right. Yeah, so I was really bought into the whole thing in spring 2020, and I think that the Diamond Princess story stopped me worrying about me and my husband and my children, but I was still worried about the system collapsing, and I was still worried about my parents, you know, I was still watching BBC, looking at the counts. I remember that, I really vividly remember actually, the time when it was about to peak and like the amount it had risen each day had slowed and every day you'd kind of say well has it fallen yet, has it fallen yet, and there was about a week before the death toll finally fell. But in that period you know I was completely bought into the whole thing and worried about the staff on the front line, volunteered myself to help but was never contacted and really it wasn't until the summer and that sort of testing issue that I started to properly question what was going on and then having you know put my face and my name online saying there's a problem here, really naively I expected one of two things to happen I thought either they're going to say oh no no no you've got that wrong you've looked into it and it's x y z or they'd say, oh yeah, you're right, we'll see what we can do to fix it. I really thought those were the two scenarios I was facing. But what actually happened was that I got attacked, and people tried to cancel me and then other people got in touch and introduced themselves and said, actually, you know, I've had this concern about my area of expertise. And so I was then kind of thrown into this world of scepticism with a lot of people who sounded genuine but who were clearly minorities in their field, as no one else in their field was saying this, it was just a few of them, or just them. I thought, well I can't just believe all these people because that's not rational. And so I had to sort of go back to first principles and try to figure out what they they were saying each time. And it took ages. And I wasn't working, so I could do it. But I was literally all hours of the day trying to figure out what was going on. And I always said it took about six months to figure out what was really happening. But I mean, that's not really true, because I've continued to learn about it since. I mean, it's been a huge amount of work to try to figure out what's going on. And that was part of the reason for writing the book, actually was, if I've just gone through all this complexity to try to get a handle on it, other people can't be expected to do that, you know, I want a shorter journey for other people. And obviously a lot of people have taken that journey independently and are where we're at, But what I really wanted for the book was to aim for people who are at the beginning and want to, well not necessarily the beginning, hopefully appeals to everyone. I learnt loads writing it and I think there'll be, you know, I think even though you know loads about it Peter, I hope you'd enjoy reading it because there's brilliant stories in there, there are new little bits of information you might not know. But the style I wanted to write it in was to avoid anyone running away, sticking their fingers in their ears, feeling foolish. I didn't want any of that and ultimately there's some brilliant books already out there for our side of the argument. But the titles are very off-putting to say the least to someone who's on the other side. And there's a lot of anger, understandably, in those books. And to be honest, there's a bit of anger in my book, too. But I've tried to keep it towards the end. Because I think if you're going to explain to people what's happened, the problem we had when I started out writing this in 2001 is that when you were speaking to someone about it face-to-face, You might take some little part of the puzzle, and you would explain that to them, and they'd understand it. And then they would be in cognitive dissonance because it didn't fit with all the other parts of the puzzle as they understood it. And so next time you met them, you'd be back at square one. And so I thought the only way to actually teach people about this is to have their attention for a considerable period of time, because you have to explain all the different facets in order to understand the whole. And so that was why I thought I'm going to have to write a book because otherwise people won't get it. So the book isn't really, it's not my Twitter feed. It's not the kind of maths and graphs and science, but that I could have written. And maybe one day I will write because I wanted it to really have a purpose, which was to be able to, you know, get through to people who maybe just now starting to get curious, who just now the fear starting to ebb, they're able to actually think rationally again, I want to talk to them. Well, I'll bring it up. Obviously there have been so many. Some look at the political failure. Ed book looks at the excess deaths that's happening. Others look at the media. Laura Dodsworth book looking at how fear was used in the media. And there are so many aspects of it. Here is, let me bring up, here is Expired, COVID, the untold story. And it's a large book. How, so you spent quite a while, I assume, working on it. What was that like? I've never written a book. I've talked to others who, big things have happened and they said, I have to put pen to paper and I have to put my thoughts down. Did you ever feel you were never going to get it finished because there's so much to cover? What was your kind of, was a narrow focus? Did that become wider? Were you concerned you, you know, you never get to covering everything? What was it like for you as someone writing the first book? So, I mean, all of the things that you just said, really. So, I set out to take each of these beliefs around COVID and start with where people were at and explain to them why they believe what they believed and then sort of show which parts of that story aren't very true. And I kind of came up with quite a few beliefs because there are all sorts of beliefs around COVID that are flawed. And then I thought, actually, that's not going to really be enough. So what I need to do is also explain to people, the psychology of belief, why we believe what we believe, what we take on trust, why we change our mind, how important authority is, how important fear is, because otherwise you haven't really understood why you've believed it all. So I put that bit in. And then it became also a little bit about sort of almost pseudo-religious aspects of it, the way we have these false prophets and the high priests and Puritans with their zero COVID claims. And so there was that theme running through it too. And actually at one point it was, got really too big. And so I pulled out the vaccine. I just thought, right, let's just do a book about the virus and how it spreads. And so the vaccine is gonna be book two and the treatments and the origin. So all the kind of slightly meatier topics. And actually the book two is also more about the witch hunts. And it's just like it's step two of the whole thing. So step one is the mild introduction version. And then it really ramps up. And so having done that, it was a more reasonable size. And then it sort of grew again. And so what was helpful about it taking? It really did take a lot of work. And I read loads of nonfiction. And whenever I read a nonfiction book, I always think, wow, that must have been so much work to do. And it is. It's so much work to do. But what I was hopeful about taking a long time is that It didn't change. So, you know, I'd written this story, I've explained everything in this way, and you think, well, over time, other things might be revealed, which would mean that you, might have to rewrite bits, or you might have emphasised things wrongly, and it didn't change. That was really reassuring, that after sitting on it, well, it wasn't sitting on it, but you know, after the editing and the typesetting, all the processes you have to go through, I didn't feel like it needed to be changed. It's the same story it held for that length of time. And, you know, it's also a brilliant reference book. So whilst doing it, it was really helpful to me because I knew where to go for all the different key bits of information because it was all there and referenced in the document I was working. You go, you break down, you go through different, you call them beliefs. And you say, well, this is one belief and wasn't correct. COVID only spread through close contact or COVID would likely kill me or everyone's susceptible. And you go through each of them and disprove it. You even say, how does Scientists get things wrong? Wow, that's a break with tradition in this day and age where everything we are told from someone who has an educational background must be true because they've learned it in a university somewhere. What, as you were going through, tell us about, yeah, putting all those in and how you, I guess, how you went about refuting it because it is, we've all had these debates with friends, family, colleagues, and sometimes you feel as though you're hitting a brick wall And they're just saying, but the BBC told me. And you're like, no, let's think through. How did you feel just trying to break down these positions and nullify each of them. So, I mean, this was, like, the thinking behind it, I can't say this all 100% mine. You know, I've been talking to people about this stuff for a long, long time, and, you know, the people in HART in particular, and trying to figure out what was going on. And that took us on all sorts of different journeys. So sometimes where we ended up was in the history books 100 years ago, we're thinking, well, where did this come from, this idea? So the idea, say, of asymptomatic transmission. That's been around a long time, and it's never been based on anything more than it was a really good explanation for why some of the other myths don't look right in the real world. So there was this guy called Charles Chapin, who was a public health officer in Providence in Rhode Island. And he wrote a book in 1910, which became the textbook of public health medicine. And sure, he's a perfectly pleasant guy, but it's quite clear from his writing that he's got an issue with germs. He talks about how he has to touch things that people have touched on public transport, and the windowsills are all dirty, and people lick the pages of a book he might touch. So he's got this real issue with it. And he is absolutely passionate about close contact transmission. And he's passionate about it because he's living in an era where there's still a bit of a hangover from miasma theory. So the germ theories won the argument 50 years before him. And the miasma theory was discredited and was over. But people still talked about things being spread through the air. And they talked about, he calls it the sewer gas fogie, this idea that the smells from the sewer have got disease in them and you want to avoid it. And he thought this was completely wrong and that it was only spread through close contact for every disease except TB. He had an exception for TB because people had done this experiment where they put hamsters in cages at the top of a TB ward and the hamsters caught TB. So he thought, well, we'll exclude TB, but he basically grouped every other infectious disease, the same. So TB was different, but everything else must spread the same way. And he talks about mouth spray and how it's coming out in mouth spray. And so you have to be in close contact to somebody for a spread to occur. And he did some good things. Well, probably did some good things. So one of the things that made him so passionate about this was that there was evidence at the time that in infectious disease wards in the hospital, if you separated the beds a bit more, disease spread less in that ward. And so he thought, well, this is proof that it must all be from bodily fluids. And therefore, you know, we've got to really, we've got to make sure people are all doing this. And so that's what he was really evangelical about. And I think probably he was right that spreading out the beds reduced infection in hospitals. But it wasn't because of mouth spray. It was because of a variety of reasons, depending on the disease. And for respiratory diseases, it was largely because aerosols are at a much higher concentration than they are to a person that you are. But they can spread a long, long way. And anyway, so he had this theory. He wrote up his book. And towards the end of the book, he says, well, the real problem with my theory is influenza, because we know that it appears overnight, just rapidly, all across the world. And we get these massive surges that are too fast for it to be spread person to person. So he said, the only way to explain this is a symptomatic transmission. It must be that all of these people that are apparently healthy are the ones giving it to you. And then, at the end of the book, he says, probably wrong on most of this, but you know. So he kind of does this disclaimer where he says, obviously, this is just based on what we know today. There's bound to be more that we find out along the way. And I'm very happy to keep learning and accept that some of this is going to be wrong. And that bit obviously always gets completely ignored. And everyone bought into the close contact spread idea and bought into the asymptomatic transmission idea. And it doesn't really seem to have been questioned properly since. And the close contact transmission story has been questioned a lot by physicists who do work on aerosols. So often they were experienced in air pollutants and how they move. But the physics is the same for aerosols from people. And so they knew all about how aerosols could spread and how they'd go long distances. And we're saying this at the beginning of the pandemic, as it were, inverted commas, and they were shut down and ignored. They were called misinformation spreaders by the WHO. And what's interesting about that particular group though, is that they have always tried to go along with the narrative. So that they would always, in their writing, they'll say, well, we know that it's not droplet spreading it, which masks might be able to stop because a big droplet of saliva would be stopped by a mask. We think it's aerosols, but that means you need to mask more with better masks. So they kind of use that, I think. Well, I don't know if it's deliberate or subconscious, and maybe they do believe it. So that's a way in to the medical literature, is to say what your findings are, and then you sort of recite the scriptures of the public health high priests, and then you get published. It's ridiculous, but if you look at it, you can see that this has happened again and again throughout the last few years, where people will show a result that actually contradicts the scriptures, but in the abstract introduction and the discussion, they'll repeat the scriptures, and then they get published, and then they're through. And so that's what these people were doing as well, but I think they do believe it because they continue to talk about the importance of respiratory masks to reduce aerosol transmission. But do you think, so looking at this, usually with any business you assess what you're doing, you assess your relationship with the customer, you assess how you're growing and you keep looking at that and want to do things better and you get rid of things that aren't working. My huge worry, is that no one in position of authority seems to have learned anything. No one is willing to say actually we really screwed up on this in this area or that area. It's no no no we we did our best and if something happens again we'll probably do something similar. How is it that those in authority, I mean the medical, media, government. They're not learning from mistakes. It's weird. It's very, very weird. So they sort of do these kind of goalpost shifts, don't they? So with the vaccine, the goalpost was, well, it starts off with, we're going to get herd immunity and COVID is going to go away. And I think that was said repeatedly by all sorts of people. That was how it was sold at the beginning. And that was a justification for no one is safe until everyone is safe, which actually that phrase is still being used, still up on the WHO website. And then the evidence came out that actually that was not the case. These vaccines do not stop infections. And so they started saying, well, but they stop hospitalisations and deaths and emphasise that more. But at no point have they said, no, they don't stop infections. And so we still, and even in June, the Department of Health was still pushing adverts, last chance to get your first dose aimed at people like me who haven't had one. Because for good reason, and it's not bad to go and get one, but the reasoning can only be, to stop an infection. And they're still now justifying giving it to children, because the child lives with someone who believes that they are at risk. That's frightening. That's completely unethical and yet that justification is ongoing. But in the meantime, we've had good evidence since that actually it's worse than nothing. It's not that it's not stopping infection, the people who've had the most doses are the ones most likely to be infected. And that message is obviously being massively suppressed, but there's good evidence for it. And where there was sort of public health data sources that were showing this shifting trend that with Delta, the infections did appear to be more in the unvaccinated relatively. Over time that reduced, reduced, reduced, and then it went the wrong way and it became more in the vaccinated. And then that data source got pulled and that happened again and again across the world. And those data sources have not been put back up. And you think, well, what are we meant to think about that, guys? That's just the biggest signal that there's a terrible issue going on here. And so they might suppress this big, cleave-in study with 45,000 health care workers being tested repeatedly. Which clearly shows a dose dependency. But if they're not showing the real-world data either, you're like, well, you're just hiding this problem that you've created now. And we don't know where that problem's going to go. We don't know what that means longer term. And there seems to be a belief that almost everybody holds at the moment, which might well be right, that COVID's basically over now. It's done. But I am not 100% sure that is right. So if you look at wastewater sampling, which is obviously are pretty, that measure isn't affected by how often people are tested and all that kind of thing. It's just a straightforward measure over time. And it's starting to creep back up in the southern states of the USA, which at this time of year start to get COVID again. And it may be that it'll just come and go, but I'm not completely convinced by this story that everyone's had it. We're told repeatedly everyone's had it, based on blood donor samples, looking at antibodies, and they say, well, you know, we've traced it all through, and we've seen it rise and rise and rise, and now everybody's had it. But I'm not very sure that that data is right, because when you ask people, which I've done repeatedly, albeit on Twitter, but you know, samples of 20,000 people, and I've done it over time, every few months, and I'm always getting around the same answers, and it changes over time. But we're still at a point where about 40% of both vaccinated and unvaccinated people say they've not had this thing. You think, well that's a huge chunk if we're, you know, if it's working its way through the population, we've got some way to go yet. Where does that put the public in terms of trust in the health profession, because now I think actually I really don't want to go and see my doctor. Not that you can anymore, because you have to go through four phone calls and have a full assessment by some person somewhere before you even see a doctor, but that's a separate issue. Simply, I think that if I go and see my doctor, all they're going to do is give me a load of drugs that they're probably making money on. And it's the last place. I mean, anyone who tells me that, oh, yes, you're sick because you don't have any symptoms. So if you have no symptoms, that means you're sick. That's great. Or because you've had a a box that's made in China and therefore that tells you, I mean it's, we used to not trust when I said made in China, now actually we have trusted our lives literally with that. But what from your assessment is, as someone who has worked in the health industry all your professional life, what's the damage this has done to the profession and to doctors and to the public going to see their medical professional. So for a long time I was really distraught about the damage this had done to the medical profession and the inability of my peers to see it. They couldn't see the harm that they each individually were causing and that's the thing isn't it, that because they're in the majority, because they're in the group, they sort of think, well I'm I'm doing the right thing. It's not me. It's not on me, any of this. But of course it is, because you didn't speak out. You didn't say the difference. You didn't show. You didn't question it. You didn't speak to your colleagues and say, we can't be doing it like this. Anyway, over time, I've come to not only be reconciled with the loss of trust, but actually, I see it in a completely different way. I think there was too much trust in doctors. There was too much. And I absolutely think that every patient who's properly sick needs a doctor that they can trust, a trusting relationship with their doctor. And that's absolutely what I would want if I was sick. But I think that trust has to be earned. And it shouldn't just be there just because of a white coat. That's not a good place to be. Because when you're acutely ill and anxious, of course, you want to just be able to put all of your faith in medicine. But that isn't probably where faith belongs. And, If it means that people are a little bit more questioning, a little bit more careful, a little bit more cautious about the advice, wanting to check what it really means and understand it for themselves, a little bit more careful about preventing having to ever see a doctor, if you can do all those things to keep yourself healthy so that you're not in front of a doctor. Then actually that's a good thing. I think all of those are good things. And I think as a society we perhaps have become more unhealthy because of this faith in the medical profession, being able to just solve all your ills. And very often in reality, I mean medicine's done some brilliant stuff. I mean I'm a really big fan of some aspects of Western medicine. We have testicular cancer used to kill young men and now almost all young men, if they're diagnosed early enough, they're going to be cured. It's a brutal treatment, but they get to live the rest of their life. And that's a phenomenal thing that is a really exciting achievement of the way that science has developed and taught us things. So I'm not anti-medicine in any way. But on the other hand, I know lots of people who take far too many drugs. And doctors are not very good good at stopping people taking drugs. And my father is one of the people that it brings to mind. But he actually died last year. But in the lead up to his death, it felt like he was consuming more pharmaceuticals than food. It was just the balance was completely wrong. And I'd been fighting for some years to get him off certain drugs that clearly weren't appropriate. And I couldn't get the doctors to stop it. And I didn't want to be the one that stopped it. His relationship was with his doctor, not with me. And I think he was sceptical about some of them, too, but didn't want to rock the boat. And that's not healthy, right? We need to have a medical profession that thinks as often about stopping this into starting them. because... That every medicine has a side effect, you know, they all have side effects and some, you know, if you get the dose right, hopefully it makes not much difference, but over time you might find that a side effect becomes a problem and then you're going back to the doctor and you're getting a drug to treat the side effect and these quickly enter a bit of a vicious cycle that we need to avoid if we want to have a healthy population. Can I, I want to ask you about HART, Health Advisory Recovery Team that you have co-chaired since the beginning of 2021 and I'm sure writing this book will not do your medical career in the UK any good and I'm amazed at people's willingness to speak truth despite the personal cost it is for them and I know to people like you I think wow if only we had more people like yourself in all different fields who would actually stand up and speak what they believe is right as opposed to following the line. But tell us about HART. I've read a lot of the information HART has put out. Is that a collection of those working in the medical profession that are questioning? Just tell us about that and what people can find on the website. So HART is a group of professionals but we're not all medics by any means. We've got other healthcare professionals including lots of psychotherapists who you know obviously they were very, concerned about the fear propaganda and the impact that everything's had on mental health. But we've also got other professionals including economists and ethicists and lawyers and all sorts of skill sets, because really it's not about just medicine. And so a good chunk of those people were speaking out independently and were being dismissed as being outliers or lone wolves and attacked as individuals. And so the person who set it up said, we've got to bring you guys together so that you can't be attacked like that and that you're speaking as one, which is why we did it. And we actually started off authoring different articles. We started off with a big review of the evidence, sort of going through different aspects of the narrative that didn't make sense based on conventional science. So there's something very interesting about how this played out in that if you have something new discovered in science. What happens is that the person with this sort of new hypothesis will say, Look now, I found this thing. And they might have to argue their case against the sort of established authorities who've got their evidence base where that didn't fit. So you've got this sort of new thing, new evidence up against the old guard and this old body of old beliefs. So that's where the battle lies. But with Covid, we had the authorities taking on a new belief system. And so in HART, we had the whole body of established scientific knowledge that we could rely on to say, well, this is actually what's going on. And so that's what was happening. It's we were writing based on decades of knowledge, saying, well, what they're saying there isn't right. And so what the benefit of that was, that a year on, we went back to that evidence review and we said, which of it did we get wrong? Because it's been a year, we've bound to got some of it wrong. Let's go back and review each of those things and update it. And when we did that, there wasn't very much we'd got wrong at all, because it was just common sense and broad understanding of how the world works compared to some really very strange new beliefs that had been introduced but had been bought by the whole population. So from that, we went on to writing weekly bulletins. So we've kind of tried to give an evidence-based review of things that have been happening in the world that mainstream media aren't covering. Largely around COVID, almost entirely around COVID. And so we have now this huge, this website's full of information, which again stacks up over time. You know, it hasn't really, all of it still works. And there was a time, in fact, it was in the summer of 2021, when we were quite badly under attack. And I had already been attacked brutally back in January 21 by Neil O'Brien, who was an MP. And at the time, he was a minister in the Justice Department. And he did this sort of Twitter shaming of me, where he pulled out tweets that I'd said and was essentially saying, oh my god, she said this. Look at this. She said this. And for some of them, I'd got it wrong. And so by all means, tease me, shame me. I made a mistake. But for quite a lot of them, I was just stating facts. I was saying things like the number of A&E attendances in this period was less than the period the year before. And that was something that didn't fit with what you'd expect, because that was during January 2021, when we were in the middle of the COVID wave. We're going to get overwhelmed. And so somebody who was reading the BBC and thinking we're about to be overwhelmed might read that and think, well, that's not true. It can't be true. But it was true. It was true. And I was being shamed by a minister saying, oh, my God, she said this. Can you believe it? What is this person? Call yourself a doctor. She's saying there's fewer attendances. There were fewer attendances. So it's a bit hard. It's really odd to know how to defend yourself. When someone's like calling you out for telling the truth, what's the defence there? Anyway, so that happened. And then in the summer of 2021, HART were using this kind of conversation software. So we were sort of sharing conversations with each other online, and it got hacked. So we were sort of illegally hacked, and the content of those conversations were shared. And within 24 hours of being hacked, a company called Logically AI contacted us and said, we're about to publish all of your chat logs, do you want to, you know, write to respond as if they're, as if they're journalists, right? So you're like, oh my God, what the hell is this? And we did actually give a response and they did print that response. But it turns out this company was a tiny setup that was formed by a 27 year old on his own who's still the only named shareholder director in the company, was given 1 and 1⁄2 million pounds by the government. And this is what they did. And if you go back now, actually, I just wrote an article recently for HART. You can find it on the website, where I went back to reviewing what they said about us in June 2021. And basically, the way they were trying to smear us was saying, these people say lockdowns don't work. These people say masks don't work. So they were literally saying that because our beliefs, well, our knowledge was conflicting with their beliefs, that was enough to be smeared. And so I went through in the Tweets and the article all the things that they were using to discredit us, to show that absolutely those have stood up over the course of time. And the one thing that was slightly more controversial was the last one, where people in the HART chat group we've been having a conversation about how certain people after their injections seem to have magnetism in their arm at the injection site and that sounds bonkers but actually there was really good evidence of that and people did Kind of Vox Pox type videos where they were out in the street with people, complete strangers, asking them if they've been vaccinated and trying it out and half the time there was nothing there at all. But, you know, like 40% of the time, these magnets were sticking and you could feel the pull and it wasn't just, you know, it was only in that particular point in the arm, it wasn't in the other arm, it wasn't sweat, it was really clearly there was something going on there. But, you know, that is obviously quite an odd thing to be talking about. And we talked about it in the chat log in private saying, what do we do with this? What do you think about this? Because actually, that's how science works. You get to discuss things. And we didn't talk about it in public. But I did in this article that I just wrote just now, because I think this was a real phenomenon. I don't think it was microchipping and all that nonsense that people sort of, you know, but I do think it was a real phenomena. And the fact is that. So some, although we don't know all because it's all secretive, but some of the manufacturers who are making this product use magnetic beads to separate out the nucleic acid. So what happens is you have all sorts of stuff, sort of cellular machinery that's being used to make the product, and you have to go through purification steps along the way, otherwise you're gonna be injecting all sorts of gubbins. And so one of the ways to purify is to use magnetic beads that have antibodies on them that hold on to the bits that you're trying to separate out. And then you wash them clean. And then you use electric forces to get the magnets to release it. And then you've got what you need. But we know now that there were all sorts of contaminants in these vaccines. So we have DNA from the bacterial plasmids of being used that got into the vaccines. There's endotoxin from bacterial cell walls that seem to have got into some of the vaccines. So the idea that these magnetic beads never made it, never got sucked out along with the rest, is just, of course, they would have done sometimes. And so we can't prove how many of the manufacturing lines had magnetic beads. But the idea that some people have magnetic beads in them, having been injected with something that wasn't very pure, Yeah, I completely buy that. Yeah, that whole thing on different batches is a massive area. And just two things I want to ask you, one was the attacks. You've had friendly fire attacks. I mean, that article spiked, I think, that had issue. And the attacks are either calling you out for speaking truth or throwing names at you. Those are the two tactics, the truth. Yeah, that is what I said, or you're anti-vaxxer, flat-earther, whatever it's going to be. Has that surprised you, coming from angles that you think, actually, I thought we were kind of on the same side here. I've never been called a flat earther. But yeah, I do get called things by people who were supposedly on the same side as me. And probably not as much as some people, because I kind of don't do anything dramatic ever. So I never quite get the same attention that some of them. I mean, I don't know if this is right, right? I'm not criticizing here. I really strongly believe that having a whole range of voices over a spectrum of beliefs is what free speech is about, and it's really, really important that all voices are heard. But my voice is a bit boring. You know, if there's a sort of level of evidence that you've got, you've sort of got a bar, and I will always go a bit below that bar to say, well, this is what we know. We have some flamboyant characters who engage in this, I know. Particularly, it's really interesting, the kind of cultural divide with the US. Because the US always, they go a bit above the bar. And I don't think that that's wrong. I think that's just a cultural difference. In the UK, you say, we've got proof of sort of this. And you under-exaggerate, and people believe you. Whereas in the US, if you're not going over the bar, they think you're talking about something else, because they have that, they just that's how they communicate about risk and about harm. And anyway, so there is that difference. But I have these days, the attacks I get it's friendly fire, it's all around the virus not existing. So there's a lot of people who think that there is no such thing, and I'm not one of them and they get upset by that and you know I think they've probably been shut down more than most and I don't think that's helpful. As I said I think it's really important to hear all voices, but I'll just go through the arguments for why I think virus exists, if you like. So, I believe there was a new illness with characteristic symptoms. They're not completely unique symptoms, because there's only so many symptoms a body can have, right, but they're fairly characteristic. So, actually, one of the polls that I did was trying to work out, you know, who's who's had this thing, and I was talking to people who think they'd had it before testing was widely available, and comparing their answers to people who had it when testing was widely available. And basically, you could tell you had it because of how long it lasted, and because even if you didn't have characteristic symptoms, someone else who cohorted around the same time as you did. And, you know, so there were ways of telling without any testing at all whether or not, you'd had it and I've had it and I've had some weird symptoms. I had eye pain, I couldn't look sideways without my eyes really hurting and actually that's other people have reported that as well. So you know I think you can kind of tell if you've had it. So I think there was this disease with characteristic symptoms and I think it would have been noticed regardless but it would have probably been called a nasty flu if we'd had no molecular biology. And we know that there were instances of spread where groups of people caught it at the same time as each other in a particular place. So there was some kind of environmental factor that is responsible for the symptoms, right? And then we know that these people with these symptoms that caught at the same time as each other, are much more likely than other people to have this particular sequence of RNA when you test their orophants, right? And the sequence of, you know, the testing's not perfect, but the chances of these people testing positive compared to random people is massively different. So there was definitely something there and it's a very specific sequence. And then these same people also test positive for the proteins that that sequence produces. So you can say, well, look, you know, this is the sequence that codes for these proteins and that these people also have these proteins in them. And then they develop antibodies to those proteins over time, right? So you've got a whole sequence of things that say there is a virus. All of that to me says there is a virus. Now. The no virus people seem to be in various different camps, so some of them seem to think there's no viruses at all ever, which is ridiculous, because we've got biological systems which work based on replication of nucleic acid, and any system that's working based on, code is going to be susceptible to viruses, because why wouldn't there be a virus that can interact with that code? It's almost that's the harder thing to believe, is that you could have a system like that where there isn't such a thing as a virus. Now where I have some sympathy with the no virus people is that there are bits of evidence that don't completely fit with this narrative of scary virus out to get us, breathe it in, you get sick, you know there's all sorts of aspects of that that are wrong. So part of it's around the fact most of us aren't susceptible to any one variant, and parts of it's around the fact that our immune systems are developed such that they learn from other foreign material what apparently novel things would look like because it's only ever looking at shapes, it's not ticking off nucleic acid sequences on a list. And one of the things that I have sympathy with them over is that if you look at hospital COVID. You could come up with, based on the narrative, you'd come up with this theory. You'd say, OK, so we had this disease in the community. And over time, there'll be, after it's peaked in the community, you'd expect to see a peak of people coming through A&E, which is what happened. Coming through A&E, also testing positive, because they've been sick in the community and they've now got so sick they've got to come to hospital. And then you're going to have, after that, a peak of people in hospital who are breathing out the virus. And so the peak of people catching it in hospital should be after that. You've had a peak of virus, and then you get a peak of people who've caught it in hospital because you've got that sort of incubation period of a few days, and then it would all die away. But when you look at the data, that's not what happens. So what actually happens is that the peak of people testing positive in a hospital setting happens at the same time as it happens in the community. So there's something that's causing people, whether they're in hospital or in the community, to be susceptible in this wave-like manner that peaks and falls. And then some people get really sick following that. And I'm not suggesting the hospitalized population only had as much COVID as the community. They didn't. They had substantially more. But there you've got people who are, their immune systems, you know, are either very busy with something else or really not working very well at all because they're sick people. So of course you have a higher rate of spread among sick people than you do in the community. But the point is that there is something causing waves of susceptibility that we don't understand. And this has been talked about for a long, long time, but never really acknowledged. So there's a GP called Dr. Hope Simpson who worked in the, well, in the 30s, he set up as a GP and shortly afterwards, he turned his cute little Cirencester cottage, this 18th century cottage, into the epidemiological centre for influenza research. Well, I can't remember the exact title, but he gave it this very, very impressive sounding name. And he studied influenza and he studied it in a really holistic way. So he's got all sorts of evidence based on old parish death records going through his local area, what happened over time. And a lot of his work was based on people developing antibodies to influenza. And he showed that only 10% to 15% of people are susceptible to any wave. And he talked about this susceptibility. And he called these surges and what happened after them. He said that they were caused by a seasonal trigger. And I think that's a really useful term because there is a seasonality to it. It doesn't mean it's once a year, but there is definitely a predictable timing of these seasonal triggers. But we don't know what causes them. And actually, one of the things he reports in his book on influenza is that when you're working in a lab with animals on influenza and you're trying to infect the animals, and people have done this with all these careful experiments where they're looking at different temperatures and humidity and other environmental factors. And what they find is that, regardless of those factors that they're controlling carefully in their experiments, it's much easier to infect them in the winter. Well, that's kind of interesting, isn't it? There's something going on there that we don't understand. And I think that the way the susceptibility isn't just around how likely you are to catch it. I think it's also how sick it makes people. Because we saw that the hospital fatality ratio, which was hard to measure at the very beginning because there wasn't as much hospital testing. But over time, by the time you get to April, May, there was actually plenty of hospital testing. And you see it fall quite dramatically, and then rise again with the next wave and fall again. You think, well, there's something to that, that there's more than. And it kind of makes sense to have. It makes sense of a lot of things, because we know that we've got variants in the community now. And we've had them every summer and yet it doesn't spread. And so, well, you know, how come this one that was around all summer not spreading. When people suddenly become susceptible to in the autumn and the winter, I think, why were none of them catching it in the summer? You know, it was around. And, you know, I get the idea of the mass of the spread, that it might start off slowly. And then, but actually, when you do the maths, the timing is not like it would be with close contact spread. So the all the modelers at the beginning, when Neil Ferguson et al, when they looked at their models of, you know, this person gives it to this person, gives it to this person, then they were anticipating a peak in July of 2020. That's when it should have peaked. And so that's why they believed lockdown had worked, because it peaked earlier than that. But, you know, it peaked, it peaked at the time of year that these things peak. So it wasn't, and we've seen so many ways subsequently, haven't we, across the world, across years now. And in this country, we see peak deaths in January, in April, in July, and then in sort of end of October, beginning of November. And it's been like that, sometimes it's not every single one of those every time, but those are the times when it might peak. And so people, the fact that people still, after three years, are claiming that the earlier peak was to do with lockdown and the second peak was to do with vaccination. Wow, really? Really? And all the subsequent peaks were natural ones. But those two, those two were different. Yes, it's bonkers. And if I could just leave people with the book, Expired: Covid, The Untold Story, you can get it as a paperback, you can get it as an e-book, you can get it as an audiobook, and Dr. Clare Craig will read that to you. It is her herself, so that is an extra treat. I always love when authors put in the time, and there's a lot of time, talking to many of them, of spending hours and hours recording that. So Dr. Clare Craig, thank you so much for joining us today. It's been great having you with us. Thank you very much for having me, Peter.

Dr Clare Craig Talks About Her New Book "Expired: Covid The Untold Story" Which Debunks 12 Covid Beliefs

Doc Malik

Play Episode Listen Later Jul 23, 2023 102:38

Please support the show so that I can continue to speak up by choosing one or all of the following options - ⁠Buy me a coffee⁠ If you want to make a one off donation. Join my Substack To access free and paid additional content. ⁠Support the show⁠ and have access to exclusive contents and perks. To sponsor the Doc Malik Podcast contact us at ⁠hello@docmalik.com⁠ About this interview: Dr Clare Craig is a qualified pathologist, who worked in the NHS and reached consultant level in 2009. She specialized in cancer diagnostics including diagnostic testing for cancer within mass screening programmes. Clare was the day to day pathology lead for the cancer arm of the 100,000 Genomes Project. She was clinical lead for the data team and led on research and development projects at Genomics England writing national guidance and helping build bespoke software. Clare has been a tireless voice, on and offline, over the past several years in advocating for evidence based policy around Covid issues, and the importance of upholding basic medical ethical principles including informed consent and bodily autonomy. Clare is Co-chair of the Health Advisory and Recovery Team (HART) who are a voluntary body of professionals educating the public on covid issues. Her first book, Expired - Covid the untold story, is out now on Amazon - click here for book This is a must read book, which documents the Covid era policies and debunks 12 beliefs of what became almost a religion. Links - HART ⁠Website Twitter Clare Craig About Doc Malik: Orthopaedic surgeon Ahmad Malik is on a journey of discovery when it comes to health and wellness. Through honest conversations with captivating individuals, Ahmad explores an array of topics that profoundly impact our well-being and health. You can follow us on social media, we are on the following platforms: ⁠Twitter Ahmad⁠ | ⁠Twitter Podcast⁠ | ⁠Instagram Ahmad⁠ | ⁠Instagram Podcast

covid-19 amazon beliefs new books nhs untold stories expired genomics england genomes project clare craig ahmad malik

Genomics Are a Lifesaver for Patients With Rare Diseases

Play Episode Listen Later Jun 8, 2023 3:20

The 100,000 Genomes Project has a massive database to help doctors and patients solve baffling medical cases and diagnose cancers. Read this story here.

patients genomics rare diseases lifesaver genomes project

Dr Clare Craig - The TRUTH About Covid Vaccines, Lockdowns, Big Pharma and More | Reg Podcast #75

The Radical English Gentlemen

Play Episode Listen Later Jun 1, 2023 104:38

In this week's episode I talk with the incredible Dr Clare Craig about everything to do with Lockdown, Covid vaccines, and so much more. She explained why the government acted the way they did, the approval of the covid vaccines, the trail data, real world data and a lot more to do with the vaccine. This was such a powerful conversation as she went into specifics about the WHY and WHAT happened the past three years. Uncovering the lies, deception and everything else surrounding it, not to mention the attacks and brutal things she has been through for simply speaking out as a concerned doctor. Hope you enjoyed, love you all! (00:00) - Introduction (05:00) - The lies of Covid (19:50) - Were most doctors and scientists scared of Covid? (29:30) - The harms of the Covid vaccine (47:30) - The false reality of the Covid vaccine (01:11:00) - The harms of the Covid vaccine on the heart? (01:26:00) - How many people have been vaccine injured in the UK? Follow her - (https://twitter.com/ClareCraigPath) Follow me - (https://www.instagram.com/regpodcast/?next=%2F) Who is she? Clare has been a pathologist since 2001 working in the NHS and reaching consultant level in 2009. She specialized in cancer diagnostics including diagnostic testing for cancer within mass screening programmes. She was the day to day pathology lead for the cancer arm of the 100,000 Genomes Project. She was clinical lead for the data team and led on research and development projects at Genomics England and wrote national guidance and helped build bespoke software, working closely with NHSE. Subsequently she has worked on artificial intelligence for cancer diagnostics.

covid-19 uk lockdown uncovering nhs covid vaccines lockdowns big pharma subsequently truth about covid genomics england genomes project nhse clare craig

Helping Undiagnosed Patients Who Experience Symptoms of Rare Diseases Find Answers with Free Genetic Testing in a Matter of Weeks with Probably Genetic CEO Lukas Lange

Once Upon A Gene

Play Episode Listen Later Apr 6, 2023 42:21

ONCE UPON A GENE - EPISODE 181 Helping Undiagnosed Patients Who Experience Symptoms of Rare Diseases Find Answers with Free Genetic Testing in a Matter of Weeks with Probably Genetic CEO Lukas Lange Lukas Lange is the CEO and Founder of Probably Genetic. They seek to give genetic testing to families who are experiencing symptoms of a rare genetic disorder. Go to probablygenetic.com, fill out a survey, and see if you qualify for a free genetic test so we can get more patients diagnosed who have been in buckets and under umbrellas for too long. EPISODE HIGHLIGHTS What led you to specialize in rare disease? I became fascinated by genetics, knew it was a field I wanted to be involved in and two professors I worked with were rare disease icons. One of them built the 100,000 Genomes Project, which is the largest rare disease study on the planet. How was Probably Genetic born? When I was working on the 100,000 Genomes Project as a PhD student, I needed patients' phenotypes in a structured format so I could figure out what was causing their disease when I analyzed their genome. The idea I had was that if we could develop an algorithm, we could flag undiagnosed patients and share that insight with their doctor for further testing. With re-energized inspiration from a parent, our core idea shifted to develop phenotype technology which parents or patients would contribute to, and couple that with a telemedicine genetic testing service so undiagnosed patients receive a test kit and subsequent clinical lab report to share with their provider. Can you talk about the first survey on autism? The mission of the company is to diagnose 200 million rare genetic disease patients. We think there are about 40 million people on the planet who have a rare disease, and at least 50% of them aren't diagnosed. There are many rare diseases for which autism is part of the phenotype, but there's a large underdiagnosis rate. Children with an autism diagnosis often don't have genetic testing, but for a lot of conditions that present with autism symptoms, we have a good chance at finding rare disease through testing. What is the most rewarding aspect of starting Probably Genetic? It's really hard to build the type of technology and service we're building. It requires raising a lot of money, recruiting really smart people, and understanding compliance constraints so that you can make the service safe for people. It took a long time and took a real toll on my personal mental health also. We eventually got to this point where, as a team, we had a huge sense of accomplishment realizing we made a difference in a life based on this crazy idea we had. In this particular case, this patient had an ultra rare mitochondrial disorder that comes with very severe muscle weakness where patients lose their ability to breathe independently. This person saw an ad for our service on Facebook while they were hospitalized on a ventilator. It was bittersweet-- the sweet side of it being that we were able to find this person, get them an answer and get them a clinical lab report. It was great proof of concept for us, but also unbelievable that no one initiated genetic testing for this patient before then. LINKS & RESOURCES MENTIONED Seattle Rare Disease Fair & Summit 2023 Registration https://app.smartsheet.com/b/form/14aefca977cd43548885a2d1b4f1f2d5 100,000 Genomes Project https://www.genomicsengland.co.uk/initiatives/100000-genomes-project The Disorder Channel https://www.thedisordercollection.com/ Probably Genetic https://www.probablygenetic.com/ Email Lukas lukas@probablygenetic.com CONNECT WITH EFFIE PARKS Website https://effieparks.com/ Twitter https://twitter.com/OnceUponAGene Instagram https://www.instagram.com/onceuponagene.podcast/?hl=en Built Ford Tough Facebook Group https://www.facebook.com/groups/1877643259173346/ Interested in advertising on Once Upon a Gene? Email advertising@bloodstreammedia.com for more information!

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The Participant Panel: What are you doing to keep my data safe?

ceo director head data safe panel vice chair clinical director genomics england genomes project

Play Episode Listen Later Jan 18, 2023 40:42

What is the impact of the participant data from the 100,000 Genomes Project? Rebecca Middleton and Jillian Hastings Ward explore these questions and discuss how the science has evolved at Genomics England with our CEO, Chris Wigley, Head of Translational Genomics, Dr Suzi Walker (a.k.a. the gene detective!) and Clinical Director and Director of Quality, Dr Ellen Thomas. We are taking you back to the Reanalysis Webinar for Participants, where Jillian, Chair of the Participant Panel, and Rebecca, Vice Chair of the Participant Panel, asked Chris, Suzi and Ellen questions that the participants had about Genomics England's approach to reanalysis. Hear directly from participants of the 100,000 Genomes Project! You can read our transcript here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Reanalyis-Webinar.docx ''What should I do? Should I have another test? If so, what test should I have? What should be my next steps?'' The Participant Panel at Genomics England is currently looking for new members. Email us at participantpanel@genomicsengland.co.uk to apply and find out more.

18: NHS England - A world leader in genomics (Professor Dame Sue Hill)

Play Episode Listen Later Dec 8, 2022 20:47

The buzz around the potential of Precision Medicine continues as new technologies, more powerful computing and our ability to store, share and interpret Big Data increases. On these podcasts Steve Coldicott and Scott Buckler chat about all aspects of the industry with patients, healthcare industry and research professionals about creating personalised medicines for each and every one of us. This is a bonus episode, dedicated to the 10 year anniversary of Genomics England's 100,000 Genomes Project, featuring Professor Dame Sue Hill. Sue is the Senior Responsible Officer for Genomics in NHS England, leading developments in this area, having previously established the NHS Genomic Medicine Centres and led the NHS contribution to the 100,000 Genomes Project. She is a respiratory scientist by background with an international academic and clinical research reputation. See more about Sue here: https://www.england.nhs.uk/author/professor-sue-hill/ Thank you to Devyser for their support with this special episode: https://devyser.com/ For more content, and to see many episodes of this podcast in video form, please visit our website: https://precisionmedicineforum.com/

professor dame nhs big data genomics world leaders precision medicine nhs england genomics england genomes project sue hill

The last 10 years and the next...

head england nhs public engagement genomics england genomes project

Play Episode Listen Later Dec 7, 2022 29:49

This week we are celebrating the 10-year anniversary of the announcement of the 100,000 Genomes Project. To mark this ground-breaking project, our Head of Public Engagement, Vivienne Parry OBE, is joined by two guests who have played a critical role over the last 10 years: Professor Sir Mark Caulfield, who led the strategic oversight and delivery of the project, and Jillian Hastings Ward, Chair of the Participant Panel at Genomics England. Jillian and her family joined the project in 2015, in search of answers for her young son who is severely disabled. Tune in to hear Jillian and Mark discuss their highlights over the last 10 years, how Genomics England has grown as an organisation and what they think the future of genomics holds. “Thanks to the 100,000 Genomes Project, Sam was the first person diagnosed in the mainstream NHS in England with a GRIN1 genetic disorder. That's been wonderful for us to know, as a family, who else we can find around the world with the same condition. But also, I'm really delighted that GRIN1 genes were added to the gene panels that the teams were using to diagnose more people as a consequence directly of the 100,000 Genomes Project. That's meant that we've been able to find a lot more since then, who shared the same condition. Hopefully, in due course, we'll have enough people that we can get more researchers interested and make real progress together." You can read our transcript here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/10-years-of-100K-Project.docx

17: Patients supporting patients and genomic research (Jillian Hastings Ward)

research project patients ward big data hastings precision medicine genomic genomics england genomes project

Play Episode Listen Later Dec 7, 2022 27:11

The buzz around the potential of Precision Medicine continues as new technologies, more powerful computing and our ability to store, share and interpret Big Data increases. On these podcasts Steve Coldicott and Scott Buckler chat about all aspects of the industry with patients, healthcare industry and research professionals about creating personalised medicines for each and every one of us. This is a bonus episode, dedicated to the 10 year anniversary of Genomics England's 100,000 Genomes Project, featuring Jillian Hastings Ward, the Chair of the Participant Panel. Her family joined the Project in 2015, in search of answers for her young son who is severely disabled. Find out more about the panel here: https://www.genomicsengland.co.uk/patients-participants/participant-panel Thank you to Devyser for their support with this special episode: https://devyser.com/ For more content, and to see many episodes of this podcast in video form, please visit our website: https://precisionmedicineforum.com/

16: Collaborations and homebrew assays (Devyser: Dan Hauzenberger & Turid Sundin Carlsson)

big data collaborations homebrew precision medicine carlsson sundin assays turid genomics england genomes project

Play Episode Listen Later Dec 6, 2022 39:20

The buzz around the potential of Precision Medicine continues as new technologies, more powerful computing and our ability to store, share and interpret Big Data increases. On these podcasts Steve Coldicott and Scott Buckler chat about all aspects of the industry with patients, healthcare industry and research professionals about creating personalised medicines for each and every one of us. This is a bonus episode, dedicated to the 10 year anniversary of Genomics England's 100,000 Genomes Project, featuring Dan and Turid from Devyser. They talk about the importance of collaborative work, 'homebrew assays', and a future with preventative heatlhcare. Thank you to Devyser for their support with this special episode: https://devyser.com/ For more content, and to see many episodes of this podcast in video form, please visit our website: https://precisionmedicineforum.com/

15: 100,000 Genomes Project - The impact and the future for Genomics England (Chris Wigley)

ceo big data precision medicine wigley genomics england genomes project

Play Episode Listen Later Dec 5, 2022 43:59

The buzz around the potential of Precision Medicine continues as new technologies, more powerful computing and our ability to store, share and interpret Big Data increases. On these podcasts Steve Coldicott and Scott Buckler chat about all aspects of the industry with patients, healthcare industry and research professionals about creating personalised medicines for each and every one of us. This is a bonus episode, dedicated to the 10 year anniversary of Genomics England's 100,000 Genomes Project. It's a set of 4 shows released during this week as a celebration. It features a chat betweem Scott Buckler and Chris Wigley, the CEO of Genomics England. Find out more about the project and it's impact here: https://www.genomicsengland.co.uk/initiatives/100000-genomes-project Thank you to Devyser for their support with this special episode: https://devyser.com/ For more content, and to see many episodes of this podcast in video form, please visit our website: https://precisionmedicineforum.com/

#208 The 100,000 Genomes Project with Dr. Julian Barwell

Razib Khan's Unsupervised Learning

Play Episode Listen Later Oct 28, 2022 Very Popular

In 2012, the 100,000 Genomes Project was announced, the same year we started this podcast!Back in 2015 we did an episode about the 100,000 Genomes Project so we're excited to revisit this massive project today with Dr. Julian Barwell, who is a clinical geneticist and has countless titles but today's most relevant one is the operational clinical lead of the 100,000 Genome project.After finishing his Clinical Genetics training (2001-2007) at Guy's, St George's and the Royal Marsden from the University of London; Dr. Barwell started as a consultant in Clinical Genetics in Leicester. He runs specialist clinics in inherited cancer susceptibility; non-alcoholic fatty liver disease and susceptibility to hepatitis, cirrhosis and hepatocellular carcinoma; Von Hipped Linda syndrome and Neurofibromatosis type 2. He has over 60 publications and helped coin the internationally known phrase, the 'Angelina Jolie effect' on referrals to inherited breast cancer clinics. He also developed the first YouTube channel for Clinical Genetics that has been viewed in over 100 countries and developed the Supporting Families with Cancer projects in association with the Genetics Education Centre (GENIE) at the University of Leicester. He is the clinical lead for the delivery of Paediatrics, Obstetrics & Gynaecology, Non-Malignant Haematology and Clinical Genetics national portfolio research studies (CRN) in the East Midlands. He is the rare disease lead for the 100,000 Genome Project in Leicester and the public and patient involvement clinical lead for the East of England Genomics Medicine Centre with the aim of reducing inequality of access to Genomic Medicine. He is the designer of the genome project eligibility criteria wheels for Health Education England and is on the Genomics England committee for patient involvement and access to genomics for black and minority ethnic groups. He is a national clinical advisor to the National Hereditary Breast Cancer Helpline and helped develop the award winning Prostaid male health App and is clinical lead of the United Against Prostate Cancer project, establishing tumour BRCA testing. He is joint clinical lead of the Paediatric and Genetics Clinical Research Facility at the Leicester Royal infirmary and is establishing a fragile X syndrome research group and patient self-navigation App project with the Genomic Medicine Service Alliance. He is a senior author of the newly commissioned book, Clinical Genetics and Genomics at a Glance as well as a children's book on DNA. On This Episode We Discuss:Ten years of the 100,000 Genomes Project (2012-2022)Advantages of using digital pedigrees tools such as the one developed by TrakGeneWhy it's important to have genomes from various ancestries representedImportance of utilizing digital pedigrees How the 100,000 Genome Project is going to change the role of genetic counselorsReclassifying variants as data is continuously being analyzedIf you want to learn more about what it's like to be a clinical geneticist, check out this article which follows Dr. Barwell through a day in the life, and you can find a list of Genomics England's publications here.To learn more about TrakGene, the pedigree drawing tool and clinical genetics database software company that we mentioned in this episode, you can head to their website or follow them on Twitter, Facebook, LinkedIn, and YouTube. You can also follow Dr. Barwell on Twitter and Facebook!Don't forget to enter our upcoming giveaway via social media next week for a lifetime subscription to TrakGene and a copy of “The Patient Will See You Now” by Dr. Eric Topol. You can also use code “DNATODAY” for a year free trial for TrakGene. Stay tuned for the next new episode of DNA Today on next Friday, November 4th, 2022 where we'll be defining quality genetic tests with Blueprint Genetics! In the meantime, you can binge over 205 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com.

Rare-X Wants to Build the Data Infrastructure for Rare Disease Research

MoneyBall Medicine

Play Episode Listen Later Jul 19, 2022 57:20

For people with common health problems like diabetes or high blood pressure or high cholesterol, progress in pharmaceuticals has worked wonders and extended lifespans enormously. But there's another category of people who tend to get overlooked by the drug industry: patients with rare genetic disorders that affect only one in a thousand or one in two thousand people. If you add up all the different rare genetic disorders known to medicine, it's a very large number; Harry's guest this week, Charlene Son Rigby, says there may be as many as 10,000 separate genetic disorders affecting as many as 30 million people in the United States and 350 million people worldwide. That's a lot of people who are being underserved by the medical establishment.Rigby is the head of a new non-profit organization called Rare-X that's trying to tackle a systematic problem that affects everyone with a rare disease: Data. In the rare disease world, Rigby says, data collection is so inconsistent that each effort to understand and treat a specific disease feels like reinventing the wheel. For longtime listeners of the show, that's a familiar story. Time and again, Harry has talked with people who point out the harms of storing patient data in separate formats in separate silos, and who have new ideas for ways to break down the walls between these silos. Rare-X is trying to do exactly that for the rare disease world, by building what Rigby calls a federated, cloud-based, cross-disorder data sharing platform. The basic idea is to take the burden of data management off of rare disease patients and their families and create a single central repository that can help accelerate drug development.Harry talked with Rigby about the challenges involved in that work, how it gets funded, how soon it might start to benefit patients, and what it might mean in a near-future world where every child's genome is screened at birth for potential mutations that could lead to the discovery of rare medical disorders.Please rate and review The Harry Glorikian Show on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to The Harry Glorikian Show podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3. Scroll down to find the subhead titled "Ratings & Reviews."4. Under one of the highlighted reviews, select "Write a Review."5. Next, select a star rating at the top — you have the option of choosing between one and five stars. 6. Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7. Once you've finished, select "Send" or "Save" in the top-right corner. 8. If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9. After selecting a nickname, tap OK. Your review may not be immediately visible.That's it! Thanks so much.TranscriptHarry Glorikian: Hello. I'm Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.For people with common health problems like diabetes or high blood pressure or high cholesterol, pharmaceuticals has worked wonders and extended lifespans enormously.But there's another category of people who tend to get overlooked by the drug industry.And that's patients with rare genetic disorders.By definition, rare diseases are rare, meaning they might only affect one in a thousand or one in two thousand people. But here's the thing. If you add up all the different rare genetic disorders known to medicine, it's a very large number.My guest today, Charlene Son Rigby, says there may be as many as 10,000 separate disorders affecting small populations.And if you count everyone who has these conditions, it may add up to as many as 30 million people in the United States and 350 million people worldwide.That's a lot of people who are being underserved by the medical establishment.And Rigby is the head of a new non-profit organization called Rare-X that's trying to fix that.Now, there are a lot of rare disease organizations that are looking for a cure for a specific condition.Rigby actually came to Rare-X from one of those, the STXBP1 Foundation, which is searching for a treatment for a rare neurological condition that affects Rigby's own daughter Juno.But Rare-X is a little different. It's trying to tackle a systematic problem that affects everyone with a rare disease. The problem is data.Rigby says that in the rare disease world, data collection is so inconsistent that each effort to understand and treat a specific disease feels like reinventing the wheel. For longtime listeners, that'll be a very familiar story.Time and again I've talked with people who point out the harms of storing patient data in separate formats in separate silos, and who have new ideas for ways to break down the walls between these silos. Rare-X is trying to do exactly that for the rare disease world, by building what Rigby calls a federated, cloud-based, cross-disorder data sharing platform.The basic idea is to take the burden of data management off of rare disease patients and their families and create a single central repository that can help accelerate drug development.I talked with Rigby about the challenges involved in that work, how it gets funded, how soon it might start to benefit patients, and what it might mean in a near-future world where every child's genome is screened at birth for potential mutations that could lead to the discovery of rare medical disorders.Here's our full conversation.Harry Glorikian: Charlene, welcome to the show.Charlene Son Rigby: Thanks. Nice to be here, Harry.Harry Glorikian: So I've been reading about what you guys are doing. I mean, all of it sounds super exciting. I'm, you know, been looking into this space for a long time from a rare disease, but many different angles of it. But can you just start off, tell us a little bit about yourself and how you got active in this world of rare disease research?Charlene Son Rigby: Yeah, thanks for that question. So I've spent most of my career building scalable software solutions for analyzing big data, and that's been both in health care as well as enterprise software. And so I'm now the CEO at Rare-X where we're building a platform to analyze rare disease data cross-disorder. And prior to being at Rare-X, I was the chief business officer at a company called Fabric Genomics, where we developed artificial intelligence approaches to speed diagnosis of patients through genomics. We had a considerable focus on rare disease and contributed to projects like the 100,000 Genomes Project and also the work that Stephen Kingsmore is doing at Rady Children's with diagnosing critically ill newborns in the NICU. And so when I started at Fabric, my daughter Juno was ten weeks old. She's my second child. And it was kind of a fortuitous timing, in some ways kismet, because at when I started at Fabric, I didn't know that she was going to start experiencing issues with her development. But at around four months she started missing milestones. And that started us on a three and a half year journey to find an answer to what was going on with her. And so during that time, we went through many, many tests, including genetic tests, MRIs, all kinds of all kinds of things, and everything kept coming back as negative or inconclusive. And so I was working at a genomics company, and so I kept pushing for whole exome testing, which at that time was still not, not readily available clinically and by insurance was still considered experimental. So we were denied three times, until we finally were able to get authorization in 2015. And so in early 2016, we got my daughter's diagnosis and she has a mutation in a gene that's involved in communication between neurons and the genes called STXBP1.Charlene Son Rigby: And so it's very rare. Thirteen kids born a day somewhere in the world. So thinking about Juno and thinking about this from a science standpoint, that it was pretty interesting that when she was diagnosed because she didn't have a classic phenotype for STXBP1. So most kids, 90% of the kids have seizures. And she has more of the symptoms around developmental delay, low muscle tone, cognitive issues and delayed walking and motor issues. And, you know, this this kind of challenge around these atypical phenotypes, I think, is actually becoming much more common in disease generally, so in rare disease and also more broadly in more common conditions as we're really starting to understand kind of the true breadth of patients. So in terms of your original question about my journey through rare disease, so I went on to co-found the STXBP1 Foundation to accelerate the development of therapies for kids like my daughter. And then coming to Rare-X was really a kind of joining of my software background with my passion for rare disease and really wanting to do something more broadly for the rare disease community.Harry Glorikian: I have to tell you, like what you said, three and a half years, I'm like, oh, my God. Like, I would be I have so many stories. And like when I was at Applied Biosystems and, you know, we're doing all this work. It just boggles the mind that some of these things are not really readily available to help get over that diagnostic odyssey for especially parents, because you're going to do anything to help your child. I'm glad it's actually moving theoretically faster these days. I'm not sure if insurance has actually kept up, but we're, on the technology side, I know we're everybody's pushing the envelope now. But when we talk about rare disease and you did some of the numbers but we hear about these rare diseases, I think a lot of people think of like there's an n of 1, right? They assume that this disease only affects a tiny number of people. Right. Maybe just one or a handful worldwide. But I mean, the fact is, if you add up all these different rare genetic diseases that exist in the human population, the number of people is actually pretty big. I mean, can you sort of. Put that into some sort of scale for us in what you've seen.Charlene Son Rigby: Yeah, you're absolutely right. You know, rare disease is by definition rare. And so it's easy in some ways to be dismissive of a rare disease because, oh, it's only affecting a few people. And it's true that a single rare disease can affect a very small number of people, even down to the n of 1 case that you talked about. From a definition standpoint, so, in the US, rare disease is defined as a disease affecting fewer than 200,000 Americans. And in Europe, in the EU, it's defined as affecting no more than one in 2,000 people. So we even though for ultra rare or n of 1 diseases, we can be talking about a small number of people, or like in my daughter's disorder, we can be talking about low thousands, there are still thousands of rare diseases and the traditional number that we hear a lot is 7,000. So 7,000 rare diseases. Rare-X is about to come out with some research that indicates that there are over 10,000 individual rare diseases, and this is really due to our growing understanding of genetics. So previously we might have grouped together a set of disorders based on what the symptoms were like. But now we understand that those actually are due to a different genetic etiology or different cause at a genetic level. And so if you aggregate all of those people up, across those 10,000 rare diseases, you know, what we're looking at is one in ten, potentially one in ten people in the world. And so in the US that's about 30 million people and in total 350 million people worldwide. So it's really a huge number of people. And from an impact standpoint, it's staggering when you look at the impact from a health care standpoint and from an economic standpoint.Harry Glorikian: Yeah, I mean, if you can diagnose, I mean, if there is a way to treat someone, then you get to it faster. And the economic impact is huge and unfortunately, if there isn't, maybe it spurs a pharmaceutical company to, you know, start working on it or figure out a way to treat that patient better. But at least you, I always tell people, the better the diagnosis, the better the next step. I see people sometimes, it seems like they're throwing a dart, you know, and they're it's an educated guess, but it's not, you know, the accurate diagnosis that you'd like to have. So. But how and where, when was sort of Rare-X born and what are you trying to do with the organization? What do you want to fix?Charlene Son Rigby: Yeah. So Rare-X was a pandemic baby. The organization was started in early 2020 and I just joined the organization last year. But, you know, it's really been quite a journey being able to have the, launch the platform during COVID. And I know we can talk about that in a little bit, but the unsolved problem that we are working to address is really around collecting data for rare disease. And one might ask, well, why is this an issue? I'll give an example. From the early days of the STXBP1 Foundation. W e assembled our scientific advisory board and we got together for our first scientific meeting. And we were going to develop our roadmap so that that would guide our priorities in terms of scientific development. And we were all very focused on therapies. So my expectation going into the meeting was we were going to talk about all the mice models we were going to build. What did we need to do in the lab? How are we going to get to that first therapeutic candidate? And the number one priority that came out of that meeting was to build a prospective regulatory-compliant natural history study. And so it was a huge learning for me because if you look at the kind of canonical steps in terms of drug development, it's always preclinical and then you move into clinical. And what I think that kind of simple model misses is this foundational layer around the data that you need and the real kind of understanding of the symptoms and the disease progression that is critical to building effective therapies, developing effective therapies.Charlene Son Rigby: And so that's really what Rare-X was started to do, was to enable the gathering of this data, the structuring of this data and enable it to be shared and to do this at scale. So, cross-disorder. And there are several problems today that that make this challenging. And so maybe I can talk a little bit about that. There are three or four of these significant challenges. So today some of this data does exist, but it's often kind of trapped in data silos. So it was generated in an individual project that might have happened in academia or industry. And then the data is often really only accessible to the group that collected it. And in rare disease where we don't have that many patients, it really makes it challenging to create a kind of more comprehensive understanding and picture of the patients if that data is trapped in these individual silos. Charlene Son Rigby: Another challenge that that we've seen is the lack of usable data. So individual studies may not include the key data that's needed to drive drug development forward. So some of these data repositories, they might either be a symptom specific. So they're looking at a specific organ system that might have been of interest to that researcher. So they're an incomplete picture. Or some of these repositories or these registries were started by passionate parents. You talked about that, the urgency that one feels as a parent, that I feel as a parent. And the registry may have been structured or the questions may have been structured in a way that isn't necessarily immediately usable by researchers because of the fact that it was started by a parent who, like you, you might not have had a statistical analysis background, you might not have had a survey methodology background. And we so those can be challenges in terms of having the data be robust and usable later. Charlene Son Rigby: And then the other thing that can be challenging and probably is often the most challenging is, is especially in these very, very new diseases, there's no data, and it takes quite a bit of funding to start data collection. Often, often passionate parents are going around trying to get researchers interested in their disorder. But it's often that you have to have a little bit of data to get a researcher interested. And so this is a huge challenge in terms of implementing data collection. And the other thing that kind of underlies this is that patients often are not empowered in this process. And so that was a fundamental piece of the way that we've structured Rare-X and the way that we collect data and the way that we enable patients to participate in the process to power data collection.Harry Glorikian: Yeah. I mean, it's, you know, they make movies out of this, right? People trying to push this boulder up a hill. So, what are the new ideas that say Rare-X is bringing to the table? I mean, your organization has called for like, you know, the largest data collection and federated data system and analysis platform in rare disease. So, I think unpacking that statement because it's a big statement, right, of, you know, what are you doing to improve data collection? What do you mean by federated, for those people that are listening? And why is it important? A nd how will the platform enable better analysis of this rare disease data?Charlene Son Rigby: Yeah. Great question. From a design perspective, the one of the things that we wanted to do was make sure that the platform was cross-disorder. So a lot of registries are started for an individual disorder. And what we really wanted to be able to do was given that number of 10,000 diseases, how do we scale to support so many disorders to accelerate therapies? And so a fundamental design principle was to do that cross- disorder. The other piece of this is that we are focused on patient-reported data. So typically a participant will join the research program, create an account on the platform and they are either a patient or a caregiver of a patient and providing information on their symptoms. There is a lot of other data out there in the ecosystem that could come from other related registries, or it could come from clinical data, it could come from many different types of studies. And so we really want to enable the aggregation of or federation of that data. So you asked me to define that term. It really means bringing together multiple different data sets in a way that enables those data sets to be analyzed together. And I think, again, going back to this theme that for any individual rare disorder, there aren't that many patients. And so analyzing that data, kind of individually, we are really missing the opportunity to maximally use the data that's been contributed by rare disease patients. And I would even argue that it's a moral imperative for us to do that as a rare disease community, because we urgently need to move these understanding of these disorders forward in development of therapies as well.Harry Glorikian: I almost wish I could take all the companies I know doing this and put them there so the n goes up for everybody. But I know that there's all sorts of reasons that that doesn't happen. But, you know, when you were saying we're pulling in patient-reported data, you know, the first thing, and we talk a lot about this from different groups on the show is, you know, would a wearable or one of these other devices that are now available give you more granular, real- time information that might be valuable to this sort of study. And have you guys considered things like that?Charlene Son Rigby: T he short answer is yes, because the our desire is to really continue to expand the types of data that are collected. And the I think that the nice thing about mobile, mobile devices, wearables, is that it makes it very easy to collect that data. And so we have a partnership with Huma. They do work in the mobile space. And we're definitely continuing to evaluate where we can develop partnerships there. I mean, our goal overall is to de- burden patients and so that the, if we can do that in a way that additive to an overall body of research, then we're huge proponents of it. And I think that it's also important that we're really trying to create an open system. So our partnership model is a very, very open partnership model in terms of who we can work with.Harry Glorikian: Yeah, I had a really extensive conversation with the head of data sciences at WHOOP yesterday and you know, they're pulling in somewhere between 50 and 100 megabytes of data per patient per day. I shouldn't say patient -- per individual per day. Right. I was like, that's a lot of data. And she was, you know, the kid in a candy store because they're she's like, we can really see what's happening with people. And you can ask questions at a scale that you couldn't ask before. Like she was saying, you know, the last one of the things that we're working on publishing is 300,000 people. You couldn't imagine that in the world of, say, a clinical trial of 300,000 people are just going to, you know, and you have all the data, almost 24/7 on this person that's delivered by this device, which is sort of interesting, you know, place to be. So, you know, I know that you don't have 300,000 people in one in one area, but it'd be interesting to have that sort of 24/7 data available from these kids if you could, you know, get a device that would lend itself to that. But what stage is the company at in building the platform and you know, I guess the killer question is, when will drug developers or other researchers be able to start using it? If they already are, do you have any early success stories you can share?Charlene Son Rigby: Yeah, yeah. It's really a very exciting time at Rare-X. So the platform launched last summer and we have over 25 communities on the platform. And those encompass several hundred participants already. So we're really starting to see some exciting numbers in terms of in terms of participants. So we are launching our researcher portal at the end of Q2. So very soon. And at that point, any researcher, so academic researchers, pharma researchers, will be able to access the data and be able to utilize analytical tools to really interrogate the data. I'm excited that we also have launched our first sponsored program, and that's with Travere. They're supporting the homocystinuria community to start data collection, to start a registry. And we just launched that at the end of February.Harry Glorikian: So I want to. Jump back, like just talking through some of the biggest technical challenges along the way. I mean I know one of your goals is like interconnecting all these disparate data sources. But one of the issues that always comes up is how do you clean up that that existing data so that you can store it all the same way. And then obviously that enables somebody to then do the analytics right after that. But the biggest issue that I hear from a lot of people is, man, it takes a lot of effort to make sure that that data is cleaned up and put in the right place.Charlene Son Rigby: Yes, the data munging. Yeah. I mean, I think that that is really the, a significant challenge, because creating research-ready data and then harmonizing data sets is a huge amount of upfront work that has to happen before you can actually do any of the analysis and the data mining. So what we have done with the core data that's being generated within Rare-X is that we have mapped it to data standards. So we utilize standards like the human phenotype ontology, OMIM, HL7, so that the data that we're producing already is mapped to all of these generally utilized standards. And then we would if we were working on a federation project, the same thing would need to happen with these other data sets to really enable that type of integrated that type of integrated analysis. And you're right, it's it can be a very brute force effort in terms of doing it accurately. And that's why I think that it's really important from a from an industry perspective to really start adopting these standards and putting them into the base model, you know, for assuming just making the assumption up front that the data is going to be federated and utilized downstream. I think that kind of traditional studies, a lot of the scope was more really looked at in terms of what are we doing with the data today? And we need to be really thinking about from a lifetime perspective, how is this data going to be used?[musical interlude]Harry Glorikian: Let's pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that's leave a rating and a review for the show on Apple Podcasts.All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but you'll be doing a lot to help other listeners discover the show.And one more thing. If you like the interviews we do here on the show I know you'll like my new book, The Future You: How Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.It's a friendly and accessible tour of all the ways today's information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.And now, back to the show.[musical interlude]Harry Glorikian: Now if we go one step before like getting that data, I mean. I have to imagine there's a huge political, bureaucratic or organizational challenge when it comes to who controls that data. And I think I have to assume, part of your job is convincing them to share it, right, despite its potential as intellectual property. Right. So how do you get on the phone and say, “Why don't you press send and shoot that over to me and so that we can take the next steps with it?”Charlene Son Rigby: Yeah, well, this is a really significant challenge, and I think that we're in a time of change in terms of attitudes around this. And part of it is what's been happening in terms of national programs to collect data. And people are starting to see the benefit of being able to share and really utilize these larger data sets. But the reality today is that in terms of the status quo, researchers control the data, and that's because the data was generated in a specific project that might have happened in academia or in industry. And there's a challenge with alignment of incentives. So on the academic side, I think that if one were to ask a researcher, do they want to hoard data, they don't want to hoard data. But the reality is, is that we still have this challenge with academic tenure and needing to publish or perish in that environment. And so researchers are still rightly concerned because of that paradigm that they have to write their paper and get their paper in before they can feel comfortable with allowing others to access the data. And so something really needs to happen there to that incentive system. Charlene Son Rigby: And in pharma, interestingly, I think that that's also an area where there has been a feeling that data is almost akin to intellectual property. But I think that especially in rare disease, there has been a growing understanding that accessing natural history data is not going to, at the end of the day, enable pharma to win because they're going to win on the quality of their therapeutic pipeline and how quickly they can get those therapies through to a successful market approval. And so what we've been really working to do is position natural history data as pre-competitive and for rare disease, frankly, it's too expensive to build these data sets, you know, alone. They're, as we scale to all of these disorders it's going to become untenable to for each company to build their own data set. The thing that we need to do and what Rare-X has been working to do with our collaborators is to transform the way that research has been done and initiated and break down these barriers and just show that the model of building these pre-competitive collaborations can work, both from a how does the business model work and then how is the data shared? And so I think that Rare-X being a nonprofit and a kind of neutral third party is really additive in terms of building those relationships so that this, this kind of public-private partnership model can really serve as a way to drive this type of change.Harry Glorikian: Now. Okay. So we've talked about industry sharing data, but I always I mean, especially in the last maybe 5 to 10 years, I keep thinking about, you know, how much of this comes directly or will come directly from patients, right? If they have control or access to their data, they have the ability, theoretically, the ability to then share that data. Right. And it could be just for the research in general as opposed to, not specifically to find a cure for a specific disease. So how do you get that data or convince patients to share it?Charlene Son Rigby: Yeah, well, I think that in in rare disease patients are typically highly motivated. You know, there are many rare diseases that can be pretty devastating in terms of the symptoms and the disease progression. And so overall, there is a a good portion of the rare disease population that is motivated to provide their data. And so what we do there and I think that that your points about the paradigms and thinking about it, that the patients are sharing their data, is really important. Because I think that that gets lost a lot. You know, a patient, and we've all signed up for some research study in our lives. You go and you fill out a survey or you contribute a blood sample or something, but oftentimes the patient contributions get forgotten because it becomes part of the researcher's data set. And so the what we're really trying to do is turn around that kind of paradigm with a core principle that patients are the ones who own their data and they're contributing their data. And so we enable them to, through an innovative consent process, we enable them to basically say that, yes, they're willing to share their data for these types of projects, and they can change that at any time. And we really feel that that changes the paradigm and allows them to have a real seat at the table. And then I wanted to also talk about, because obviously not everyone is — there is this proportion of folks who are motivated and trust and that's part of the reason that they will be willing to share their data — but there is also a portion of the population that might not be as motivated. And so it's important for us to be able to reach those populations and to build trust in the approach that we're taking and the value of it in terms of really being able to drive research. And so patient education is an important component of our model patient education, patient engagement. So we work directly with patient advocacy organizations and patient advocates to educate their communities on the value of data collection, how it really spurs and supports research. I think that that's a critical component to this as well.Harry Glorikian: Well, hopefully people will listen to this podcast worldwide and me that may spur someone to search you guys up on the web. But I noticed that another principle of the company is you don't sell patient data, right? Does that mean you're giving it away? And if that is true, what's the criteria of doing that? And do your data partners that you're giving it to have to meet certain standards?Charlene Son Rigby: Yeah, this is a great question because monetization models around data are very, very common today. Some companies have built significant valuations around data monetization. And for from a Rare-X standpoint, and this is part of the reason why we were started, is that the question was asked like, is that the right thing to do, especially for diseases where we're in the very early stages of understanding a disorder, and so I talked about this a little bit earlier, that if you have no data, getting any researcher interested is already then a huge challenge. And so we're here really to break down barriers to advancing rare disease research and encourage that research. And so I say sometimes that it's really important that we free the data. So we don't sell data at Rare-X. And we have an open access model for researchers to access the data. Charlene Son Rigby: And so there it is not, “we open the doors and anybody can come, come and access the data.” It's done in a responsible way. So one of the key things is that the data is de-identified. And so it is it is critical to do that, because we want the data to be utilized for research. It doesn't need to have identifiable information in it to drive that research forward. You know, the second thing is, is that researchers need to submit information on their project, and then that's reviewed by a data access committee. And the idea behind this data access committee is not to slow down things. It's a streamlined and efficient process. But the idea is that there is a review process. The researchers need to specify whether there's an IRB with whether that protocol has gone through an institutional review board review, and patients can opt to only have their data. As an example, patients can opt to only have their data shared with projects that have gone through IRB review. So there's really kind of a, since this is in many ways a two sided platform, there's really a way that patients can actively engage in terms of who's accessing their data. And then the researchers also in terms of the types of projects that they're that they're going to put forward.Harry Glorikian: Okay. So now you're giving away the data. Remember, I'm a venture capitalist, so you're giving away the data, right? First question somebody like me asks is, how do you pay for the operations? I mean, you're building this fairly sophisticated system that is, you know, you've got to clean the data, you've got to make it available. You're trying to talk to all these people. I mean, are you funded by let's say, I mean the typical stuff, grants? Is it member donations? Is it major gifts from individuals? You know, those are all the questions that that would cross my mind.Charlene Son Rigby: Yeah, absolutely. So frankly, it took me some time to get my arms around this, because my whole career has been in tech and venture backed companies. And so so I took some time to really think about this and think about this scalable model from a scalability standpoint before joining. So we get our funding largely through pharma and industry, as well as some grants. And the way that that funding happens is, it's basically platform investment. And I think that this is a really key thing from my perspective of, of thinking about the, the platform as something that is, if you will, a social good. Because they're investing in expanding the platform. They might invest, like Travere did, additionally to help to onboard specific groups or expand our capabilities in terms of being able to gather data in a particular disease area. But the funding that they're providing is to make the platform and the research program more robust. The data at the back end will be open in the way that we've we have talked about it. We have a unique ability to do that and create that kind of model as a nonprofit. And you're right that what we're doing, we're kind of blending this health tech company with this this nonprofit tmodel. But I think that there are some good examples out there of public private partnerships that have been very successful in the long term in doing this. And that's the model that we're really pursuing.Harry Glorikian: This area is small. I feel like I've been in and around it for a long time because of, you know, being in and around genomics. But there's a small but sort of growing infrastructure of support for rare disease, you know, patients in the world, sort of nonprofits, NGOs, patient advocacy group. Tthere's Global Genes, right? There's the Rare and Undiagnosed Network, RUN. There's the Undiagnosed Disease Network Foundation, and then there's the n-Lorem Foundation. And so many others that I don't want to leave out, right, the long list. But how does your, or, does your group overlap with these? I mean, I was reading a press release that this summer you guys will launch a collaboration with RUN and the Undiagnosed Disease Network Foundation to launch something called the Undiagnosed Data Collection Program. I mean, if you could sort of talk about what that project is about. Is your real ambition to be the data infrastructure sharing platform for the entire community of rare disease patients and families?Charlene Son Rigby: Yeah, well, I love that you call it infrastructure because I think this is critical from a concept standpoint. Rare disease should not be a model where each rare disease is doing it on its own. That was one thing that really struck me, thinking again about my daughter's disorder, where we were looking at ways to ladder up to that prospective natural history study. And we were trying to do something. I talked to a few other genetic neurodevelopmental conditions that were kind of our cohort, if you will, and we were all doing it in different ways. And it's such an opportunity cost to be figuring out the model new each time. And so these groups like Global Genes, amazing organization, actually, the Rare-X founder, Nicole Boyce, was also the founder of Global Genes. And we were, the STXBP1 Foundation used every single resource possible that came out of Global Genes. You know, that there's this broad this really broad education and enablement that needs to happen for people who want to become rare disease advocates. And that Global Genes has really done that in a tremendous way for so many organizations and so many individuals. And so we partner with them in terms of, and are very complementary, in terms of providing that infrastructure where Rare-X is focused on this area of how do you accelerate research through data collection, and then we use that.Charlene Son Rigby: It's great that you saw the announcement on the work that we're doing with RUN and the UDNF. I'm particularly excited about this because Rare-X, we talked earlier about ultra rare diseases, about n of 1 diseases. The reason why Rare-X is able to collect data across all of these disorders is that we have a fundamental assumption in the way that we collect data, which is that we don't assume that anybody does or does not have any symptoms. So we start out with a very high level, head to toe type of set of questions that if you say yes to any of them, it leads into a more detailed set of questions to collect data on particular symptoms. And so this is really ideally suited to situations where there isn't a lot of characterization around or understanding of the symptoms in a disorder and where you don't have a diagnosis. Because then what we're really enabling an individual to do is to gather robust data about their individual symptoms and disease progression that then can be utilized for research. And so we're very excited about being able to work with and support RUN and UDNF in in that effort. Charlene Son Rigby: And so do we have, you asked about ambition? You know, do we have a goal of being the only data sharing platform? I would say that our goal is to be an incredibly robust comprehensive cross- disorder platform. We believe that the way that we are approaching things really is enabling us to support all rare diseases. And we're really focused on de- burdening patients. So we're enabling patient communities to get started very quickly. And they don't have to become experts in protocol development, they don't have to become experts in creating clinical outcome assessments, etc. At the same time, the world is large and that they're going to be groups who decide that they need specific solutions. They may want to take on the role of being a principal investigator, as an example. And so I think that that's also the reason why federation is an important component of what we're really bringing forward as a as a way to bring all of that data together.Harry Glorikian: So again, you know, being on the venture side, right. You can lead a horse to water, but you can't make them drink, right? So you can do a lot. You can improve clinical trial readiness. You can make sure the data is better about rare disease patients, and that it's available. But you can't force the drug discovery companies or the drug makers to sort of develop a cure for a specific disease. Right. How do you think about that as part of a rare disease problem? Is that is that part of the work that Rare-X is,are you making it less risky so that they are willing to take that next leap?Charlene Son Rigby: You're right that pharma is going to be making, I would say, rational business decisions based on commercial drivers. And the challenge with a lot of rare diseases is that no one knows about that individual rare disease, and there isn't much data on it. And so anything that can be done to de-risk that process for a pharma company is huge in terms of increasing their interest or generating interest for them and then increasing their interest. And those things can include knowing that there's an activated community, you know, because if you have a clinical trial and nobody wants to participate in the clinical trial, that's going to be a huge problem in terms of being able to get that drug through an approval process. And so Rare-X, by building a very robust data set, is able to de-risk that process in terms of that investment, of trying to understand what the disorder is and also trying rto understand disease progression. And going back to that point about activation of the community, we're also able to help to demonstrate the activation of the community because of the number of people participating in the in the data collection.Harry Glorikian: I know it's not science fiction. I think it's right around the corner, hopefully, but I think, isn't an ideal future where we do either whole-exome or preferably whole genome on every newborn and scan for these genetic changes that are associated with rare diseases. I mean, I'm assuming that would really push this area much farther along. And if that is true, if that statement is true, how long do you think it'll take for us to get there?Charlene Son Rigby: Wow. You're reminding me of the Gattaca movie, but hopefully that's not the real future for us, you know. Winding things back. So my daughter was born, my daughter Juno was born in 2013. So that's nine years ago. And it took three years for us to get a diagnosis. And, you know, that's like an entire other podcast. But I think that the really, if we fast forward to 2022, we have groups like Stephen Kingsmore's group at Rady Children's where they're diagnosing newborns who are in the NICU, in less than 24 hours. And even standard exome testing, which it took us three months to get our results, the standard exome testing results are now returned in less than two weeks. You can also get it faster if you have an urgent testing and we have the tech. Illumina has long been dominant and continues to be dominant in the clinical area. But you have these new entrants with Oxford Nanopore, Element, Singular, and there are others that are entering now. And so these costs are coming down and this is really going to be a transformative in terms of becoming, I do think that this is going to become standard of care and it's closer than we think. I think that it's probably going to be in the next ten years, less than ten years.Charlene Son Rigby: We already have some analogs to this in terms of or precursors, I should say, in terms of newborn screening. And so what I think is going to happen is that genomic sequencing is is going to become a core newborn screening tool. And the interesting thing is that there are applications, not just in rare disease, but also in common conditions and the value of genomic sequencing. So today, 5% of rare diseases have a therapy, but there are right now hundreds of gene therapies that are currently in preclinical and clinical pipeline. So this picture is going to change enormously in the next five years. And so because the value of is going to grow, because there are therapies, the other important thing is therapeutic windows. So therapeutic windows are when we can intervene to have the most impact on a disorder. And so that's often when someone's young before the symptoms present or start or very early in that process. And so I think that this is going to become a reality in the next decade. And frankly, I think it's a very exciting time. I have always been a big believer that knowledge is power. And this is this is one of those great situations where we have the ability to do something because we know.Harry Glorikian: Yeah, I talk about some of this in my book and there's some, you know, interesting stories and it's a fascinating time. And when I think back, you know, to when we first started sequencing and people would say, why would you want to sequence anything? And now it's the complete opposite. And the price is coming down. It's becoming easier and faster. And I mean, at some point, I think the price is going to be low enough between the actual sequencing and then the analysis, that as my friend says, it's going to be a nothingburger. I mean, it's just going to be like, yeah, we should just do that because it gives us the information we need for the next step, which is sort of going to be interesting.Charlene Son Rigby: Yeah, absolutely. I think that the that is the challenges that I talked about, cost of sequencing. But you're right that, you know, the analysis is still quite expensive today. And that's something that we're also going to need to need to improve. I mean, AI and the growing knowledge bases is really going to help to address that. Yeah. And but that's a huge component of it as well today. Absolutely.Harry Glorikian: Yeah. I'm looking at a company that in this particular area of oncology, they've gotten the whole genome analytics down to about $60. So it's, you know, it's coming to a point where you're like, why wouldn't you do that? Like, what's stopping you from doing that? So it's been great having you. Great conversation. I wish you guys incredible success. A nd I'd love to keep up on how things are going with the organization.Charlene Son Rigby: That'd be great, Harry. Really enjoyed it today. Thanks.Harry Glorikian: Thank you.Harry Glorikian: That's it for this week's episode. You can find a full transcript of this episode as well as the full archive of episodes of The Harry Glorikian Show and MoneyBall Medicine at our website. Just go to glorikian.com and click on the tab Podcasts.I'd like to thank our listeners for boosting The Harry Glorikian Show into the top three percent of global podcasts.If you want to be sure to get every new episode of the show automatically, be sure to open Apple Podcasts or your favorite podcast player and hit follow or subscribe.Don't forget to leave us a rating and review on Apple Podcasts. And we always love to hear from listeners on Twitter, where you can find me at hglorikian.Thanks for listening, stay healthy, and be sure to tune in two weeks from now for our next interview.

Sir Walter F. Bodmer: from R.A. Fisher to genomics

Play Episode Listen Later May 19, 2022 66:51 Very Popular

Three of R.A. Fisher's Ph.D. students remain active today, C. R Rao at age 101 and A. W. F. Edwards, and W. F. Bodmer, both 86. Bodmer was not only a student of Fisher, the cofounder of both population genetics and modern statistics, he was also mentored by Joshua Lederberg, the 1958 winner of the Nobel Prize in Medicine for his work in bacterial genetics. With more than 60 years in science, Bodmer joins Razib on this episode of Unsupervised Learning to discuss everything from his recollections of Fisher, Lederberg and Cavalli-Sforza, to the recent cancellation controversy around his Ph.D. advisor. Over the course of the hour, they go on to discuss what has surprised Bodmer about the trajectory of genetics over the past few decades (he thinks the recent “completion of the human genome” is a bit overhyped), his continuing passion for the HLA loci (which are notably difficult to map genomically), the People of the British Isles Project, as well as his current interest in cancer genomics. Bodmer's massive public record spans the history of much of modern genomics, from work on linkage and recombination in the 1960s to being part of the 1000 Genomes Project in the 2010's.

medicine edwards nobel prize genomics hla walter f genomes project razib

Powering a New Era of Genetic Medicine

RARECast

Play Episode Listen Later Apr 28, 2022 39:05

Genomics England is working to embed genomics into healthcare, enable research, and improve the diagnosis and treatment of patients. In 2018, it completed enrollment of its first initiative—the 100,000 Genomes Project—and is working on a new initiatives to explore the benefits and challenges of sequencing and analyzing the genomes of newborns. We spoke to Ellen Thomas, clinical director and director of quality for Genomics England, about the outcomes from the 100,000 Genomes Project, its Newborn Genomes Programme, and the potential for genome sequencing to alter the diagnostic odyssey for people with rare disease

new era powering genetic medicine genomics england genomes project

Amanda Pichini: Genetic Counselling

g word genomics england genomes project genetic counselling

Play Episode Listen Later Mar 23, 2022 35:09

“It's not just talking about a genetic test, testing parents to see if they're carriers after their child's been diagnosed or talking about reproductive options when people want to have another child - it's a lot more than that. It's navigating those difficult decisions in a situation where there's a genetic risk or someone has been diagnosed with something and they need to know if it's going to have an impact on their life and future.” In this week's episode of The G Word, Chris Wigley is joined by Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England. They discuss genetic counselling, The 100,000 Genomes Project and uncertainty in genomic medicine. They also discuss the impact of genomics on young people and her early career.

1. Genomics in the NHS with Dame Sally Davies

Genomics Unravelled

Play Episode Listen Later Mar 6, 2022 21:56

In this episode, we are joined by Dame Sally Davies. Dame Sally was the Chief Medical Officer for England and Senior Medical Advisor to the UK Government from 2011-2019, during which time she oversaw the 100,000 Genomes Project and the launch of the NHS Genomic Medicine Service. We chat about her time as Chief Medical Officer, the intersection of genomics and antimicrobial resistance, and the future of genomics within the NHS. --- Send in a voice message: https://anchor.fm/genomicsunravelled/message

england dame nhs chief medical officers uk government genomics sally davies genomes project

#172 PhenoTips: Advances in Rare Disease Diagnosis

Play Episode Listen Later Feb 18, 2022

DNA Today's host Kira Dineen is also one of the hosts of the PhenoTips Speaker Series. This monthly live webinar focuses on relevant genetics topics by featuring discussions with thought leaders and experts in genomic medicine. In this podcast episode we are sharing an installment of the PhenoTips Speaker Series, “Advances in Rare Disease Diagnosis”, which is hosted by Kira's colleague, Dr. Pawel Buckowicz.With over 6,000 rare diseases, reaching diagnosis is a long and arduous process for the 300 million people worldwide affected by rare disease. Advances in technology, collaboration, bioinformatics and more hold the promise to end or reduce this diagnostic odyssey. To address these advancements, PhenoTips invited Dr. Stephen Kingsmore, Dr. Marshall Summar, and Dr. Ellen Thomas.Dr. Stephen Kingsmore, the inaugural President & CEO of the Rady Children's Institute for Genomic Medicine, previously held roles as Director of the Center for Pediatric Genomic Medicine at Children's Mercy Hospital, President & CEO of the National Center for Genome Resources, and Chief Operating Officer of Molecular Staging Inc. Dr. Kingsmore's rapid genome diagnosis was ranked as one of the top 10 medical breakthroughs of 2012 by TIME magazine, and his 26-hour genetic sequencing garnered him the Guiness World Record for the fastest genetic sequencing in the world.Dr. Marshall Summar is the Margaret O'Malley Professor of Genetic Medicine and Chief of the Division of Genetics and Metabolism at Children's National Hospital. In addition, he launched and directs Children's National's first clinical Rare Disease Institute, the largest clinical division of its kind treating over 8,000 rare disease patients per year. Dr. Summar currently chairs the National Organization for Rare Disorders' Scientific and Medical Advisory Committee as well as Co-Chairing the Research Committee for the Rare Disease Diversity Coalition. His research focuses on adapting knowledge from rare diseases to mainstream medicine.Dr. Ellen Thomas is Clinical Lead for Rare Disease and Clinical Safety Officer at Genomics England, Clinical Advisor to the Genomics Unit at NHS England and Improvement, and a Consultant in Clinical Genetics at Guy's and St Thomas' NHS Trust. As part of the Genomics England Science Team led by Professor Sir Mark Caulfield, she has worked on delivery of the 100,000 Genomes Project, and now focuses primarily on Genomics England's contributions to the Genomic Medicine Service, as well as supporting the interface between research and clinical care for participants and researchers within the National Genomic Research Library.In this panel discussion moderated by Dr. Pawel Buczkowicz, leading rare disease clinicians and researchers address:The latest technological advances helping to reduce the diagnostic odyssey for patientsThe greatest challenges faced by patients and clinicians and methods to overcome themThe role of bioinformatics in the analysis of large datasets generated from sequencingThe role of rare disease diagnosis in precision medicine.Tune in for the next PhenoTips Speaker Series with our host Kira Dineen! Join us live on March 23rd from 11 am – 12:15 pm EST, for the 18th installment of PhenoTips' Speaker Series, “Future of Hereditary Cancer Genetic Counseling”. The Future of Hereditary Cancer Genetic Counseling is a panel discussion and interactive Q & A with Jill Stopfer, Associate Director of Genetic Counseling at the Dana Farber Cancer Institute, Jessica Corredor, Senior Genetic Counselor at the University of Texas MD Anderson Cancer Center, and Emily Nazar, Lead Cancer Genetic Counselor at Genome Medical. Register for free here. Stay tuned for the next new episode of DNA Today where we wrap up our rare disease month celebrations with Keith McArthur from Unlocking Bryson's Brain podcast! New episodes are released on Fridays. In the meantime, you can binge over 170 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com. Preparing for a career in genetics? Keck Graduate Institute in Claremont, California, is a recognized leader in healthcare and biotech education and offers two master's programs ideal for those looking to impact the genetics field. The master's in human genetics and genetic counseling will train you to become an innovative, collaborative, and caring genetic counselor. The master's in human genetics and genomic data analytics will give you hands-on experience with the technologies and information revolutionizing the future of medicine. Learn more about KGI's innovative programs by visiting kgi.edu. (SPONSORED)PerkinElmer Genomics is a global leader in genetic testing focusing on rare diseases, inherited disorders, newborn screening, and hereditary cancer. Testing services support the full continuum of care from preconception and prenatal to neonatal, pediatric, and adult. Testing options include sequencing for targeted genes, multiple genes, the whole exome or genome, and copy number variations. Using a simple saliva or blood sample, PerkinElmer Genomics answers complex genetic questions that can proactively inform patient care and end the diagnostic odyssey for families. Learn more at PerkinElmerGenomics.com. (SPONSORED)

Empowering Women: A Celebration of the International Day of Women and Girls in Science

Play Episode Listen Later Feb 9, 2022 35:28

“Although there is this sense where you don't really find as many women in science, and when we get missed out of science, I think we have been really lucky and fortunate to work with incredible women in large numbers. We're quite lucky to find the experiences that we have.” […] “Life is so precious, we really shouldn't be spending any time doing things we don't enjoy.” In this week's episode of The G Word, Dr Ellen Thomas, Clinical Director and Director of Quality at Genomics England, is joined by Arzoo Ahmed, Ethics Lead of the Newborn Genomes Programme, and Cassandra Smith, Senior Bioinformatician, both at Genomics England. Ellen worked on the delivery of the 100,000 Genomes Project and Cassie did her PhD using bioinformatics to study parts of mitochondria before joining the operations team at Genomics England. Arzoo completed her MPhil in Mediaeval Arabic Thought before moving onto the Nuffield Council on Bioethics and then joining the Ethics Team here at Genomics England. In this discussion, these three brilliant women talk through their roles and what inspired them to pursue a career at Genomics England. In celebration of the International Day of Women and Girls in Science, they also discuss the challenges they have faced along the way and how being a woman has impacted their career.

women director science phd girls celebration empowering women clinical director international day bioethics women in science mphil g word girls in science genomics england genomes project cassandra smith nuffield council

Serena Nik-Zainal: Personalised treatment for cancer patients

Play Episode Listen Later Feb 2, 2022 41:21

“I hope it will happen in our lifetime, that we will start to learn how to use the totality of information that's available on tumours. And I don't just mean genomics, I mean any of it - including all the bits around the tumour, the microenvironment, the immune system. In the last 10 years alone, cancer research has grown phenomenally. It's been extraordinary to be involved in all of it. It's a very real privilege to be to be in this space.” In this week's episode of The G Word, Chris Wigley is joined by Serena Nik-Zainal, a consultant in clinical genetics, a Cancer Research UK Advanced Clinical Scientist at the University of Cambridge and an Honorary Consultant in Clinical Genetics at Addenbrooke's Hospital in Cambridge. She was the first woman to win the Josef Steiner Cancer Research Award in 2019. Serena discusses sharing data, personalised treatment for cancer patients and the impact of the 100,000 Genomes Project. She also talks about the involvement of participants, cancer research and the need for genomic data diversity.

university hospitals treatments cambridge cancer patients g word addenbrooke clinical genetics honorary consultant genomes project personalised treatment

Umstrittenes Geoengineering zurück in der Klimadebatte

Wissenschaftsmagazin

Play Episode Listen Later Nov 13, 2021 27:17

Und: Maschinen analysieren Affenverhalten. Zudem: Bessere Diagnosen für seltene Krankheiten (00:00:45) Umstrittenes Geoengineering zurück in der Klimadebatte: Die Idee von einem Sonnenschirm aus Staubpartikeln zum Schutz der Erde vor Wärme ist alt und umstritten. Aktivisten warnen vor dem radikalen Eingriff in die Erdatmosphäre. Nun will eine Gruppe von Forschenden die heftige Debatte mit neuen Vorschlägen vorantreiben. (00:06:44) Aktuelles aus der Woche: Patentstreit um Coronaimpfstoff zwischen US-Behörde und Moderna – Was Wildbienen futtern – Graupapageien mit Impulskontrolle. (00:13:19) Maschinen auf Feldforschung: Wissenschaftlerinnen haben eine künstliche Intelligenz entwickelt, die erstaunlich präzise typische Verhaltensweisen von wilden Schimpansen erkennen kann. Das System basiert auf einem künstlichen neuronalen Netzwerk und könnte auch den Artenschutz voranbringen. (00:18:19) 100'000 Genome für seltene Krankheiten: Etwa 10'000 Krankheiten gelten als selten. Meist sind sie genetisch bedingt. Das «100'000 Genomes Project on Rare Diseases» hat sich 2013 in Grossbritannien auf den Weg gemacht, um diese Krankheiten dereinst präziser diagnostizieren zu können. Erste Auswertungen zeigen: Es funktioniert.

EP 43 - ENGENHARIA GENÉTICA

Quina do Mundo

Play Episode Listen Later Oct 13, 2021 93:29

Novamente Quina do Mundo esbanja ousadia e fala de mais um tema do qual não entendemos absolutamente NADA: Engenharia Genética! Mas para isso contamos com nosso amigo, o biólogo Rafael Alves! Conversaremos sobre temas hereditariamente estimulantes, como: Bioinformática, Sequenciamento do Genoma Humano, 1KGP (1000 Genomes Project), LGPD, Apartheid Genético, Eugenia, Designer Babies, NIPT, Junk DNA, Questões Éticas, Virar Jacaré, Mini Velociraptor Caipira, CRISR-CAS9, Biohacking, Padre do Balão, Genomas Sintéticos, Bioterrorismo, Testes Genéticos de Ancestralidade, GMOs (Transgênicos), Terminator Seeds (Sementes Suicidas), Ozônio, Transhumanismo, Pantropia, Seleção Artificial, Mensagem de Arecibo, Carl Sagan fodeu o Brasil, etc. Quina do Mundo é André Gomes, Paulo Jabardo e Tiago Januzzi Chave PIX: apoiaquina@gmail.com https://linktr.ee/quinadomundo https://apoia.se/quinadomundo @quinadomundo Música tema por Rafa Almeida (@rafalemosalmeida) e Tiago Januzzi (@tjanuzzi). Produção por Januzzi Podcasts https://linktr.ee/januzzipodcasts --- Voice Of Eternity by Keys of Moon | https://soundcloud.com/keysofmoon Music promoted by https://www.free-stock-music.com Creative Commons Attribution 3.0 Unported License https://creativecommons.org/licenses/by/3.0/deed.en_US

Scientists Completed the First Human Genome 20 Years Ago. How Far Have We Come, and What's Next?

Singularity Hub Daily

Play Episode Listen Later Sep 28, 2021 8:17

If the Human Genome Project (HGP) was an actual human, he or she would be a revolutionary whiz kid. A prodigy in the vein of Mozart. One who changed the biomedical universe forever as a teenager, but ultimately has much more to offer in the way of transforming mankind. It's been 20 years since scientists published the first draft of the human genome. Since its launch in the 90s, the HGP fundamentally altered how we understand our genetic blueprint, our evolution, and the diagnosis and treatment of diseases. It spawned famous offspring, including gene therapy, mRNA vaccines, and CRISPR. It's the parent to HGP-Write, a global consortium that seeks to rewrite life. Yet as genome sequencing costs and time continue to dive, the question remains: what have we actually learned from the HGP? After two decades, is it becoming obsolete, with a new generation of genomic data in the making? And with controversial uses such as designer babies, human-animal chimeras, organs-in-a-tube, and shaky genetic privacy, how is the legacy of the HGP guiding the future of humanity? In a special issue of Science, scientists across the globe took a deep dive into the lessons learned from the world's first biomedical moonshot. “Although some hoped having the human genome in hand would let us sprint to medical miracles, the field is more an ongoing relay race of contributions from genomic studies,” wrote Science senior editor Laura Zahn. Decoding, reworking, and potentially one day augmenting the human genome is an ultramarathon, buoyed by potential medical miracles and fraught with possible abuses. “As genomic data and its uses continue to balloon, it will be critical to curb potential abuse and ensure that the legacy of the HGP contributes to the betterment of all human lives,” wrote Drs. Jennifer Rood and Aviv Regev at Genentech in a perspectives article for the issue. An Apollo Program to Decode Life Big data projects are a dime a dozen these days. A global effort to solve the brain? Yup. Scouring centenarians' genes to find those that lead to longevity? Sure! Spitting in a tube to find out your ancestry and potential disease risks—the kits are on sale for the holidays! Genetically engineering anything—from yeast that brew insulin to an organism entirely new to Earth—been there, done that! These massive international collaborations and sci-fi stretch goals that we now take for granted owe their success to the HGP. It's had a “profound effect on biomedical research,” said Rood and Regev. Flashback to the 1990s. Pulp Fiction played in theaters, Michael Jordan owned the NBA, and an international team decided to crack the base code of human life. The study arose from years of frustration that genetic mapping tools needed better resolution. Scientists could roughly track down a gene related to certain types of genetic disorders, like Huntington's disease, which is due to a single gene mutation. But it soon became clear that most of our toughest medical foes, such as cancer, often have multiple genetic hiccups. With the tools that were available at the time, solving these disorders was similar to debugging thousands of lines of code through a fogged-up lens. Ultimately, the pioneers realized we needed an “infinitely dense” map of the genome to really begin decoding, said the authors. Meaning, we needed a whole picture of the human genome, at high resolution, and the tools to get it. Before the HGP, we were peeking at our genome through consumer binoculars. After it, we got the James Webb space telescope to look into our inner genetic universe. The result was a human “reference genome,” a mold that nearly all biomedical studies map onto, from synthetic biology to chasing disease-causing mutants to the creation of CRISPR. Massive global consortiums, including the 1000 Genomes Project, the Cancer Genome Atlas, the BRAIN Initiative, and the Human Cell Atlas have all followed in HGP's steps. As a first big data approach to medicine, before the internet was ub...

Augusto Rendon: Bioinformatics at the Heart of Genomics England

genomics bioinformatics rendon engagement officer g word chief communications genomics england genomes project

Play Episode Listen Later Jul 29, 2021 35:04

"Within the wider framework of personalised medicine, trying to identify treatments, diagnosis, prognosis, that is about a personalised individual. Genomics plays a really important role because our genomes are unique. Bioinformatics is there to try to identify how those genomes are unique and what they tell us about the consequences of those differences." In this week's episode of The G Word #sciencepodcast, Anna Tomlinson, the Chief Communications and Engagement Officer at Genomics England, is joined by Augusto Rendon, the Chief Bioinformatician at Genomics England and the architect and facilitator of our bioinformatics infrastructure. Augusto has a wealth of experience in deploying whole genome sequencing in healthcare. He is a research scientist with a vast background in computational biology and statistical genomics and he coordinated the delivery of various bioinformatics and analytics solutions for the 100,000 Genomes Project. Today, Augusto talks about the use and anonymisation of data, the role of bioinformatics at Genomics England, personalised treatments and the multidisciplinary aspect of bioinformatics.

Jillian Hastings Ward: The ladder of participation

ward ladder participation hastings g word genomes project

Play Episode Listen Later Apr 28, 2021 35:33

"How do we climb the ladder, from the participant representation side? How do we demonstrate that we are partners who would be worth working with, from the view of those in power? And whose ladder is it anyway?" In this week's episode of The G Word, Chris Wigley is joined by Jillian Hastings Ward, who is Chair of the Genomics England Participant Panel, a founding board member of the CureGRIN Foundation, and a participant representative on the National Genomics Board. Jillian's son, Sam, has the very rare genetic disorder GRIN1, which was diagnosed through the 100,000 Genomes Project. Today, Chris and Jillian discuss the 8 rungs of the ‘Ladder of Citizen Participation' - from the group of users being told to what will happen to them, to them having a role in decision-making.

Shelley Simmonds: The first place you turn to is Dr Google

google fraser first place simmonds dmd snowdon duchenne muscular dystrophy dmd genomes project

Play Episode Listen Later Apr 7, 2021 34:54

"At first, it's all a big whirlwind and you can't process the big bombshell that you've been given. Suddenly, it turns out the life you had mapped out is not going to be like that at all. Almost overnight, you become a geneticist, you become a physiotherapist, you become a nurse, you become a dietitian. You are now the expert." Shelley is mum to Fraser, whose medical journey has been tough because he didn't have typical symptoms for any known conditions. But genetic testing found he had an alteration in one of his genes, leading to his diagnosis of Duchenne Muscular Dystrophy (DMD). As a family they later joined the 100,000 Genomes Project to find out why Fraser's non-textbook symptoms meant he didn't fall neatly into a faster DMD diagnosis. In this episode, Chris and Shelley talk about the lived experience of families managing a rare disease, climbing Snowdon, and being active in supporting disability rights.

Dave McCormick: Embedding the patient voice

Jerm Warfare: The Battle Of Ideas

Play Episode Listen Later Mar 10, 2021 32:51

“This is about developing a balance between quantitative and qualitative perspective, it isn't just about the data - the data is important, of course it is - but it's also the lived patient experience. Both are key.” In this week's episode of The G Word, Chris Wigley is joined by Dave McCormick, who has been a member of the Genomics England Participant Panel since 2017 and became a participant in the 100,000 Genomes Project due to his rare sight condition. Dave is also an Advisor on the MSc in Genomic Sciences at The University of Manchester, and a Patient Representative in North West GLH Clinical Advisory Group. In this episode, Dave and Chris discuss why is it so important for people studying to become bioinformaticians or clinical scientists to embed the patient voice, getting healthcare professionals and scientists to talk to people in lay language and DIGVIP (Digital Inclusion on Genomics with Visually-Impaired People), a webinar series launched to try to bring research and patients closer together.

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Is this pandemic a social experiment?

Play Episode Listen Later Nov 30, 2020 80:11

Is this pandemic about a virus? Are we in the middle of a huge social experiment? What is fact and what is fiction? Nick Hudson is an actuary and founding member of PANDA (Pandemic Data & Analytics). Dr Clare Craig is a consultant pathologist, working in the NHS (Britain), and later on the cancer arm of the '100,000 Genomes Project', and more recently, medical AI. PANDA's website: https://pandata19.org

ai pandemic panda social experiment nick hudson genomes project

Is this pandemic a social experiment?

Jerm Warfare: The Battle Of Ideas

Play Episode Listen Later Nov 26, 2020 80:08

ai pandemic panda social experiment nick hudson genomes project

Modern Humans from Adam and Eve? You Bet!

Biblical Genetics

Play Episode Listen Later Oct 20, 2020 23:00

The idea is that all humans came from a first couple. Many people don't think this is possible, but Dr C demolishes one common argument against Adam and Eve: the thought that you can't get millions of rare variations in the genome if you start with just two people a few thousand years ago. In fact, not only are Adam and Eve an excellent fit for the real-world data, but computer modeling tells us the biblical scenario is a better fit to the data than the evolutionary one. Links: Sanford J, Carter R, Brewer W, Baumgardner J, Potter B, and Potter J. 2018. Adam and Eve, designed diversity, and allele frequencies. In Proceedings of the Eighth International Conference on Creationism, ed. J.H. Whitmore, pp. 200–216. Pittsburgh, Pennsylvania: Creation Science Fellowship. An audio recording of this presentation is also available. The Non-Mythical Adam and Eve! Refuting errors by Francis Collins and BioLogos. Carter RW. 2019. A successful decade for ‘Mendel’s Accountant’, Journal of Creation 33(2):51–56. 1000 Genomes Project

journal pittsburgh accountant adam and eve creationism mendel whitmore refuting francis collins biologos modern humans in proceedings genomes project

October 7, 2020

The COVID-19 LST Report

Play Episode Listen Later Oct 13, 2020 2:31

In today's episode we discuss: —Climate: An article in Nature highlights concerns among the scientific community about current COVID-19 vaccine trials being run by AstraZeneca, Pfizer, and Moderna. In light of two reported cases of transverse myelitis in trial participants, some scientists urge for more transparency from the companies leading trials, others are concerned about public opinion of vaccine safety and worry about political pressure on the trials, especially during the U.S. election season, and some question the vaccine trials' goals of reducing cases of symptomatic COVID-19, and instead suggest focusing on reducing incidence of severe disease. —Epidemiology: Members of the Max Planck Institute for Evolutionary Anthropology in Germany conducted a genetic analysis investigating previous findings of an association between severe COVID-19 disease (hospitalization and respiratory failure) and a six-gene region on chromosome 3 (49.4kb), asserting that the region has been inherited from Neanderthals, following analysis using the 1000 Genomes Project. The anthropologists report this haplotype is seen in 50% of South Asians and 16% of Europeans, which they believe directly contributes to increased susceptibility to severe disease. —Understanding the Pathology: A review by molecular biologists found a higher prevalence of the G614 variant of SARS-CoV-2 is related to increased prevalence of chemosensory dysfunction due to expression of a spike protein with higher receptor binding domain affinity to h-ACE2 receptors, leading to enhancement of SARS-CoV-2 binding in the olfactory epithelium and increased chemosensory deficits. —Adjusting Practice During COVID-19: Increased risk of COVID-19 infection among patients with a history of or current gynecologic cancer has led to the development and implementation of an algorithm for less invasive and more cost-effective surveillance with telemedicine-based, risk-stratified surveillance and a shared-decision making program for patient follow-up, suggesting the potential for reconsideration of healthcare delivery for these patients. --- Support this podcast: https://anchor.fm/covid19lst/support

covid-19 germany nature european pfizer increased moderna astrazeneca sars cov neanderthals max planck institute south asians evolutionary anthropology genomes project

Features of Functional Human Genes.

PaperPlayer biorxiv bioinformatics

Play Episode Listen Later Oct 10, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.10.334193v1?rss=1 Authors: Cooper, H. B., Gardner, P. P. Abstract: Proteins and non-coding RNAs are functional products of the genome that carry out the bulk of crucial cellular processes. With recent technological advances, researchers can sequence genomes in the thousands as well as probe for specific genomic activities of multiple species and conditions. These studies have identified thousands of potential proteins, RNAs and associated activities, however there are conflicting conclusions on the functional implications depending upon the burden of evidence researchers use, leading to diverse interpretations of which regions of the genome are "functional". Here we investigate the association between gene functionality and genomic features, by comparing established functional protein-coding and non-coding genes to non-genic regions of the genome. We find that the strongest and most consistent association between functional genes and any genomic feature is evolutionary conservation and transcriptional activity. Other strongly associated features include sequence alignment statistics, such as maximum between-site covariation. We have also identified some concerns with 1,000 Genomes Project and Genome Aggregation Database SNP densities, as short non-coding RNAs tend to have greater than expected SNP densities. Our results demonstrate the importance of evolutionary conservation and transcription for sequence functionality, which should both be taken into consideration when differentiating between functional sequences and noise. Copy rights belong to original authors. Visit the link for more info

copy functional genes gardner snp rnas biorxiv genomes project

Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs

PaperPlayer biorxiv bioinformatics

Play Episode Listen Later Aug 14, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.249839v1?rss=1 Authors: Lu, T.-Y. T., The Human Genome Structural Variation Consortium,, Chaisson, M. J. Abstract: Variable number tandem repeats (VNTR) are genetic loci composed of consecutive repeats of short segments of DNA, with hypervariable repeat count and composition across individuals. Many genes have coding VNTR sequences, and noncoding VNTR variants are associated with a wide spectrum of clinical disorders such as Alzheimer's disease, bipolar disorder and colorectal cancer. The identification of VNTR length and composition provides the basis for downstream analysis such as expression quantitative trait loci discovery and genome wide association studies. Disease studies that use high-throughput short read sequencing do not resolve the repeat structures of many VNTR loci because the VNTR sequence is missing from the reference or is too repetitive to map. We solve the VNTR mapping problem for short reads by representing a collection of genomes with a repeat-pangenome graph, a data structure that encodes both the population diversity and repeat structure of VNTR loci. We developed software to build a repeat-pangenome using haplotype-resolved single-molecule sequencing assemblies, and to estimate VNTR length and sequence composition based on the alignment of short read sequences to the graph. Using long-read assemblies as ground truth, we are able to determine which VNTR loci may be accurately profiled using repeat-pangenome graph analysis with short reads. This enabled measuring the global diversity of VNTR sequences in the 1000-Genomes Project, and the discovery of expression quantitative trait loci in the Genotype-Tissue Expression Project. This analysis reveals loci that have significant differences in length and repeat composition between continental populations. Furthermore, the repeat pangenome graph analysis establishes an association between previously inaccessible variation and gene expression. Taken together, these indicate that measuring VNTR sequence diversity with repeat-pangenome graphs will be a critical component of future studies on human diversity and disease. Copy rights belong to original authors. Visit the link for more info

dna disease alzheimer's disease copy variable graphs tandem populations profiling variation biorxiv genomes project

SVCollector: Optimized sample selection for cost-efficient long-read population sequencing

PaperPlayer biorxiv bioinformatics

Play Episode Listen Later Aug 6, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.06.240390v1?rss=1 Authors: Ranallo-Benavidez, T. R., Lemmon, Z. H., Soyk, S., Aganezov, S., Salerno, W. J., McCoy, R. C., Lippman, Z. B., Schatz, M. C., Sedlazeck, F. J. Abstract: An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g. microarrays, exome capture, short-read WGS), from which a few individuals are selected for resequencing using a more comprehensive approach, especially long-read sequencing. The subset of individuals selected should ensure that the captured genetic diversity is fully representative and includes variants across all subpopulations. For example, human variation has historically been focused on individuals with European ancestry, but this represents a small fraction of the overall diversity. To address this goal, SVCollector identifies the optimal subset of individuals for resequencing. SVCollector analyzes a population-level VCF file from a low resolution genotyping study. It then computes a ranked list of samples that maximizes the total number of variants present from a subset of a given size. To solve this optimization problem, SVCollector implements a fast greedy heuristic and an exact algorithm using integer linear programming. We apply SVCollector on simulated data, 2504 human genomes from the 1000 Genomes Project, and 3024 genomes from the 3K Rice Genomes Project and show the rankings it computes are more representative than widely used naive strategies. Notably, we show that when selecting an optimal subset of 100 samples in these two cohorts, SVCollector identifies individuals from every subpopulation while naive methods yield an unbalanced selection. Finally, we show the number of variants present in cohorts of different sizes selected using this approach follows a power-law distribution that is naturally related to the population genetic concept of the allele frequency spectrum, allowing us to estimate the diversity present with increasing numbers of samples. Copy rights belong to original authors. Visit the link for more info

european cost copy selection population efficient notably mccoy schatz optimized salerno sequencing lemmon lippman wgs biorxiv vcf longread soyk genomes project

Genetics Shambles 2: A guide to the human genome

Genetics Unzipped

Play Episode Listen Later Jul 23, 2020

The Human Genome Project has been referred to as one of the great feats of scientific exploration and discovery in human history. But what was it, and, more to the point, what is the human genome and why was sequencing it such a big deal? And in 2020, some 17 years after it was deemed completed, what has it helped us with in the fields of biology and medicine, and what is there still to discover?Robin Ince is joined by three experts in the field. Geneticist, broadcast and author of a number of best selling books on the subject, Dr Adam Rutherford, one of the founders of the Human Cell Atlas Group and the Head of Cellular Genetics at the Wellcome Sanger Institute, Dr Sarah Teichmann and co-chair of the 1000 Genomes Project and founder of Genomics plc, Professor Gil McVean.To view previous episodes in the Genetics Shambles series head to Cosmicshambles.comFollow us on Twitter @GeneticsUnzip

head guide genetics genomics shambles human genome project geneticists human genome robin ince adam rutherford wellcome sanger institute genomes project professor gil mcvean

Coronavirus R number, genome study of Covid-19 survivors and using aircraft messages to assess aviation

BBC Inside Science

Play Episode Listen Later May 14, 2020 32:35

R seems to have found its way into the newspapers and on Radio 4 as if it’s a word, or a letter, that we should all be familiar with and understand. As part of the government’s briefing on Sunday, it appeared in a pseudo-equation, the infographic - 'COVID alert level = R + number of infections' - the Government called R the 'Rate of Infection', but it is commonly known as the 'Reproduction Number'. So what exactly is R, and what does it do? Mathematical Biologist, Kit Yates, from the University of Bath, clears up the confusion, and explains how R was first calculated for covid-19. And one of the scientists tracking R in the UK is Petra Klepac, who is Assistant Professor in Infectious Disease Modelling at the London School of Hygiene and Tropical Medicine. She explains how crucial R is in tracking the pandemic and how it’s now being used to shape the way we get out of lockdown. There are so many variables about who will survive Covid-19 and who, unfortunately, will not. Many people will only experience mild symptoms, but a minority will have a severe or even life-threatening response. Whilst some of the difference can be explained by age, or underlying health conditions, the reasons why men and some ethnic minorities and a number of apparently fit younger people become so ill, is one of the great puzzles of this pandemic. Some of the uncertainly is down to environmental effects. But a lot of the variability could be down to our genomes. To try and find out, this week Genomics England announced funding for a study - The GenOMICC - COVID Genomics UK (CoG-UK) Partnership for Severely Ill Patients to sequence the whole genomes of 20,000 severely ill and 15,000 asymptomatic or very mild patients. Led by Genomics England, these genomes will be compared with those held in the 100,000 Genomes Project dataset. The coronavirus pandemic is really highlighting the need for fast, accurate ways to analyse data on a global and national scale. Be that data on the number of people dying or track and trace data from various apps. But do we realise how much data we leave about ourselves online even in normal times? This is something Professors Tobias Preis and Suzy Moat in the Data Science Lab, at the Warwick Business School get very excited about. They use rapid analysis of big data to try and understand our behaviour as a way to rapidly inform economists and policy makers on how the world works. They have been looking at alternative data sources to give us quicker estimates of what’s happening in the world – travel patterns, economic indicators, how many people have a given disease. This is going to become invaluable both during and in the aftermath of the pandemic, when understanding the economic fallout will be key to helping the economy recover. Take their latest work – where they’re gathering much quicker estimates on the contributions of air travel to the UK’s GDP. Presenter – Marnie Chesterton Producers – Fiona Roberts and Beth Eastwood

Communicating Genetic Risk

Risky Talk

Play Episode Listen Later Mar 1, 2020 53:32

Personal genetic risk information is set to be become part of everyday healthcare. But is some unhelpful, even dangerous? What psychological impact does it have on patients? And do doctors know enough about genetics to effectively guide patients and inform treatment decisions? Joining David to discussing what genetic risks should be communicated and how, we have: Professor Robert Green, Director of the Genomes to People group at Harvard Medical School. Dr Gemma Chandratillake, Course director of the Genomic Medicine Programme at the University of Cambridge Dr Saskia Sanderson, a UCL psychologist working on the impact of genetic information With a special contribution from Jillian Hastings Ward, Chair of the participant panel for the 100,000 Genomes Project. Views to share? Get in touch on Twitter @RiskyTalkPod or email riskytalk@maths.cam.ac.uk. Risky Talk is produced by Ilan Goodman for the Winton Centre for Risk and Evidence Communication at the University of Cambridge.

director university personal risk cambridge views communicating harvard medical school genetic ucl genome genomes project evidence communication

Episode 66: The Story of Vivienne Parry OBE and Tomorrow's World

The Healthtech Podcast

Play Episode Listen Later Feb 6, 2020 67:59

If you want to know what Prince Charles says to you as you're appointed Order of the British Empire (OBE), how a liver surgeon and a paediatrician put an ear on a mouse's back with a 3D cell 'car park,' or what the future of precision medicine and genomics might be... then incredibly, you're in the right place. This week, James is joined by the inimitable Vivienna Parry OBE. Vivienne is a writer and broadcaster. A scientist by training, Vivienne hosts medical programmes for BBC Radio 4, writes widely on health, presents films, facilitates many high level conferences and trains young researchers. She has a part time role as Head of Engagement at Genomics England which delivered the 100,000 Genomes Project. She also sits on the board of UK Research & Innovation which is responsible for the strategic spend of the UK's £7 billion research budget. Many will remember Vivienne from her role as presenter of the BBC TV science programme Tomorrow's World between 1994 and 1997 when she was part of iconic technology breakthroughs that were displayed all around the world. Not short of an anecdote or two, James and Vivienne discuss Vivienne's career, from breaking thousands of pounds worth of equipment at UCL, through learning her trade women's health organisations, changing tack to broadcasting (blagging an interview with zero experience) and now into precision medicine and genetics. This episode is a must-listen! For more information and content, check out our website www.hs.ventures. You can follow us on Twitter @HSVenture, on Instagram @hs.ventures, on Linkedin at HS. and you can email us at info@hs.live You can get our host, Dr. James Somauroo, at www.jamessomauroo.com and you can follow him on Twitter @jamessomauroo, on Instagram @j_soms and on Linkedin at james-somauroo

head world uk innovation 3d engagement bbc radio hs ucl prince charles parry bbc tv uk research british empire obe tomorrow's world genomics england genomes project james somauroo

S1/EP1 - RARE OPPORTUNITIES AND HOW WILL THE 100,000 GENOME PROJECT CHANGE HEALTH CARE?

RARE/D Conversations

Play Episode Listen Later Dec 29, 2019 32:34

In our first (pilot) episode we talk with Professor Bill Newman from Manchester about Rare opportunities and how will the 100, 000 Genomes Project change health care?Professor Bill Newman is Professor of Translational Genomic Medicine in The Manchester Centre for Genomic Medicine at the University of Manchester and Honorary Consultant at Manchester University NHS Foundation Trust. He is also Director of the Greater Manchester Genomic Medicine Centre for the 100,000 Genomes Project.Our RARE/D conversations are hosted by Nichola Garde and Mariangels Ferrer, and aim to stimulate and capture public conversation about one of the biggest changes in how we think about health – what does it mean to have a rare disease and how we all may become “RARE” when genomics becomes part of mainstream healthcare. This project will focus on the psychological, ethical and economic debates and in turn show how social science is helping to shape the health care of the future.

director university opportunities professor healthcare manchester rare genetics genomic medicine genome project honorary consultant genomes project

#38 Issues in legacy genomes with Luke Anderson-Trocmé

the bioinformatics chat

Play Episode Listen Later Oct 22, 2019 61:13

In this episode, Luke Anderson-Trocmé talks about his findings from the 1000 Genomes Project. Namely, the early sequenced genomes sometimes contain specific mutational signatures that haven’t been replicated from other sources and can be found via their association with lower base quality scores. Listen to Luke telling the story of how he stumbled upon and investigated these fake variants and what their impact is. Links: Legacy Data Confounds Genomics Studies (bioRxiv, Molecular Biology and Evolution (paywall)) (Luke Anderson-Trocmé, Rick Farouni, Mathieu Bourgey, Yoichiro Kamatani, Koichiro Higasa, Jeong-Sun Seo, Changhoon Kim, Fumihiko Matsuda and Simon Gravel)

evolution genome molecular biology luke anderson genomes project

Professor Dame Sue Hill joins Dr Christian & Alex

Second Opinion with Dr Christian

Play Episode Listen Later Jun 16, 2019 34:22

Dr Christian and Alex are privileged to be joined by Professor Dame Sue Hill, the Chief Scientific Officer for England to talk all about genetics. This is a fascinating episode, looking at the power of genetic research and how it affects all of us. Sue is the Senior Responsible Officer for Genomics in NHS England, leading developments in this area, having previously established the NHS Genomic Medicine Centres and led the NHS contribution to the 100,000 Genomes Project. See acast.com/privacy for privacy and opt-out information.

england professor dame nhs genomics chief scientific officer nhs england genomes project sue hill

008 - Getting ready for genomic medicine

Genetics Unzipped

Play Episode Listen Later Mar 4, 2019 35:56

This is a special edition of Genetics Unzipped, in association with the Genomics Education programme - part of Health Education England. We’ll be finding out how genomic medicine is coming into the NHS, and what it means for everyone working in the health service.Since the publication of the draft sequence of the human genome back in the early noughties, researchers and doctors have been working hard to harness the secrets within our DNA in order to benefit human health. Progress was slow for several years, due to the high cost and slow pace of sequencing technology. Everything changed with the advent of Next Generation Sequencing in around 2009, making it possible to read the entire sequence of anyone’s genome at low cost and high speed.To realise the potential of this technology in healthcare, the 100,000 Genomes Project was launched in 2012 aiming to sequence - as you might have guessed - 100,000 genomes from people affected by cancer and rare diseases within the NHS. The next chapter began in October 2018, when NHS England launched a brand new Genomic Medicine Service, using insights and information from the new era of large-scale DNA sequencing, known as genomics, to improve the nation’s health. The service is aiming to sequence 500,000 whole genomes over the next five years, as part of the UK government’s broader aims to reach five million genomic tests by 2024.More information and show notes online at Geneticsunzipped.com

dna united kingdom progress nhs getting ready nhs england genomic medicine next generation sequencing genomes project

#99 Coriell Institute on Biobanking

Centre for Personalised Medicine

Play Episode Listen Later Mar 1, 2019 29:50

Two leaders from the Coriell Institute for Medical Research join the show to discuss biobanking. Nahid Turan, Chief Laboratory Officer, and Alissa Resch, Chief Scientific Officer, lead separate aspects of the Institute scientific efforts.Coriell is known for its impact in the world of biobanking. If you’ve ordered biological materials in the past for research, there’s a good chance you’ve ordered from them before. In its 65 year history, Coriell has partnered with many federal, private and nonprofit organizations, offering expertise in the collection, processing, storage and distribution of biological materials, and in the process built one of the most diverse and important collections of biomaterials in the world. It’s because of their collection that endeavors like the Human Genome Project were possible and that the science of personalized medicine thrives today.On This Episode We Discuss:Definition of Biobanking and ProcessSample Tissue and Species TypesNumber of SamplesDisease RepresentationApproach to Finding Specific SamplesResearch Access and ShipmentOrganizations, Institutions and Projects SuppliedIncluding the Human Genome Project and the 1,000 Genomes Project!Managing Big Bio DataTo learn more about Coriell head over to their website, specifically their biobanking page. Stay updated with their latest news by following them on Twitter.Stay tuned for the next new episode on April 5th, 2019. This will be the 100th episode of DNA Today! To celebrate I interview Carl Zimmer, a popular science writer for the New York Times and has also contributed to The Atlantic, National Geographic, Time and Scientific America. He has won the Stephen Jay Gould Prize Among many other honors for his journalism. Zimmer teaches science writing at Yale University. His books include Parasite Rex, Evolution: The Triumph of an Idea, Microcosm and his latest, She Has Her Mother’s Laugh which we will be discussing on next month’s episode. So tune back in on April 5th to hear the interview!New episodes are released on the first Friday of the month. See what else I am up to on Twitter, Instagram, Facebook and iTunes. Any questions/inquiries are welcome and can be sent to info@DNApodcast.com.

time new york times institute idea atlantic laugh national geographic yale university institutions zimmer chief scientific officer medical research human genome project microcosm carl zimmer dna today scientific america biobanking genomes project she has her mother

Putting our genome to work

Pod Academy

Play Episode Listen Later Jun 21, 2018 36:38

This podcast is drawn from a Progress Educational Trust (PET) event called Putting Your Genome to Work: For the NHS, for Industry, for the UK Post-Brexit Chair: Sarah Norcross, Director of PET Speakers: Dr Eliot Forster, Chair of MedCity Dr Edward HockingsFounding Director of Ethics and Genetics Dr Athena Matakidou, Head of Clinical Genomics at AstraZeneca's Centre for Genomics Research, and Consultant in Medical Oncology at Cambridge University Hospitals Dr Jayne Spink, Chief Executive of Genetic Alliance UK We are at the beginning of a biomedical revolution built on the promise of genomics. The British government has put this at the heart of its post-Brexit industrial strategy. So what is the potential of genomics, what is the journey we are setting out on, and what are the pitfalls? The British Government's Industrial Strategy White Paper Building a Britain Fit for the Future sets out an ambition for the UK to 'be the world's most innovative economy' and play a leading role in a 'fourth industrial revolution... characterised by a fusion of technologies that is blurring the lines between the physical, digital and biological worlds'. The White Paper argues that 'the government, the NHS and charities can all contribute to make the UK an attractive location for businesses to invest and for patients to benefit'. According to the first in a series of Sector Deals published in the wake of the White Paper, the Life Sciences Sector Deal, 'a new genomics industry is beginning to emerge... with UK companies like AstraZeneca, Cambridge Epigenetix, Genomics plc and Congenica working with Genomics England'. The Sector Deal discusses investments from and agreements with a variety of companies, involving the whole genomes of around 70,000 participants in the 100,000 Genomes Project and around half a million participants in UK Biobank. GSK and others have committed to sequencing the whole genomes of the latter, while a separate consortium coordinated by Regeneron Pharmaceuticals will sequence the exomes (partial genomes) of these same participants in the shorter term. Health Secretary Jeremy Hunt says the Sector Deal 'proves that life science organisations of all sizes will continue to grow and thrive in the coming years, which means NHS patients will continue to be at the front of the queue for new treatments'. However, there remains a degree of public unease about the involvement of commercial interests in health. This unease may be intensified at a time when how best to fund and manage the NHS, how best to approach Brexitand who can be trusted with health-related data are all matters of ongoing concern. Issues discussed at the event included: What are the benefits of genomics for patients? How can we ensure that the NHS, and its patients, derive reciprocal benefit from scientific and medical advances that involve people's genomic data? How can we address the view that there is, or should be, a clear partition between public and private involvement in health, when the development of medicines and diagnostics has always been led by the private sector (and now the Industrial Strategy involves closer collaboration)? What can we learn from the world of direct-to-consumer genetic testing, where consumers often consent to their data being used in research (to the commercial benefit of the testing company)? Finally, can we learn anything from proposals by a US company to treat members of the public neither as patients nor as consumers but rather as 'data owners', who will use blockchain technology to make their genomic data accessible (or inaccessible) to whomever they wish? Photo: PLOS One Pyhlogeny Comparative genomic DNA hybridization and in silico comparison of gene content within mobile elements of bovine and human SA isolates

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Ethical Issues in Research in Reproductive Medicine

Play Episode Listen Later Nov 24, 2017 44:18

Filmed at the CPM's event 'Personalised Medicine in Practice: Advances in Reproductive Science' on 7th March 2017, Michael Parker gives his talk 'Ethical Issues in Research in Reproductive Medicine'. Professor Michael Parker is the Director of the Ethox Centre and of the newly established Wellcome Centre for Ethics, Innovation, Globalisation and Medicine. Both Centres are located in the Big Data Institute Building at the University of Oxford’s Old Road Campus. Michael is also the Chair of the Genomics England Ethics Advisory Committee and one of the Directors of the 100,000 Genomes Project. His main research interest is in the ethical issues arising in the clinical and research uses of genomics. Together with partners at the Wellcome Major Overseas Programmes in Kenya, Malawi, South Africa, Thailand and Vietnam, Ethox has a Wellcome Strategic Award to build ethics capacity and conduct research on the ethical issues arising in global health research. This collaboration also has a focus on the ethics of global health research involving genomics and data-sharing.

Episode #44: Lyme Genomics with Dr. Bob Miller, CTN

BetterHealthGuy Blogcasts

Play Episode Listen Later Sep 18, 2017 94:37

Why You Should Listen: In this episode, you will learn genetic variants that are prevalent in those with chronic Lyme disease. About My Guest: My guest for this episode is Bob Miller, CTN. Bob Miller, CTN is a Certified Traditional Naturopath specializing in the field of natural health, including genetic-specific nutrition, homeopathy, stress reduction, detoxification and education. He earned his naturopathic degree from Trinity School of Natural Health and is board certified. In 1993, Bob Miller opened the Tree of Life practice and he has served as a traditional naturopath for 20+ years. For the past several years, he has been engaged with genetic variants and related research. Working with many clients, he is astounded at how many peoples’ health concerns are related to the genetic issues. For Bob, following a natural approach to health is personal. It was during a personal health crisis in 1993 that Bob experienced first-hand the profound effects of natural remedies as a solution to regain his health. His passion to help others and to learn more catapulted his desire to obtain knowledge in the natural health and wellness field. He is committed to educating others, empowering them to have more control over their health care and their lives. He feels the naturopathic philosophies of working with the mind, body and spirit in a natural approach to be the best way to help others. Recognizing that there was not a nutritional supplement line on the market comprehensive enough to address all of the possible genetic variants, he began working with a national company, Professional Health Products, to formulate an Epigenetics line of products for use by health care providers. Bob lectures at nationwide seminars to educate physicians and health care practitioners about genetic variants and nutritional supplementation for achieving optimal health, and has created an online certification course in genetic nutrition for health professionals. He has created a propriety software program, MethylGenetic Nutritional AnalysisTM , which he uses in his practice to assess, analyze and design support for his clients based upon their personal genetics, lab work and presenting symptoms. To support his growing genetic research efforts, Bob founded the NutriGenetic Research Institute in 2015 to research and publish reports on the relationship between genetic variants and labs and presenting symptoms. His first research project on genetic variants and Lyme disease won an award for research at the International Lyme Conference held in Helsinki, Finland in June 2016. Key Takeaways: - What genetic patterns are more common in those with Lyme disease as compared to the 1000 Genomes Project. - Are today's health challenges more of a genetic issue or an epigenetic issue? - Why is supporting methylation not always a good idea? - Which genes impact iron absorption at higher levels in Lyme patients and lead to hydroxyl radical production? - What are KEAP1 and Nrf2 and how do variants in these genes lead to some of the sickest patients? - What is MTOR and autophagy and how do we shift these to be more supportive of improved health? - When are things like vitamin C, ozone, glutathione, NAC, glutamine, GABA, and arginine potentially not a good idea? - What tools can we use to mitigate these issues? Connect With My Guest: http://nutrigeneticresearch.org http://www.tolhealth.com Related Resources: http://www.methylgeneticnutritionclasses.com (Practitioners) https://dnasupplementation.com (Practitioners) Interview Date: September 15, 2017 Disclaimer: The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.

tree finland genetics practitioners lyme helsinki epigenetics genomics natural health gaba nac mthfr mtor trinity school bob miller ctn nrf2 related resources genomes project nutrigenetic research institute certified traditional naturopath professional health products

The 100,000 Genomes Project

Surgical Grand Rounds Lectures

Play Episode Listen Later Apr 10, 2017 39:54

Ms Jennifer Whitfield talks about the 100,000 Genomes Project, which aims to establish a new genomic medicine service through the NHS by sequencing the entire genomes of around 70,000 people with rare inherited diseases or cancer. This is an NHS transformational programme, working with hospital Trusts through each of 13 Genomic Medicine Centres around the country (of which Oxford is one) to deliver the project at a local level. This includes developing pathways for identifying and recruiting patients, engaging and training clinical staff and setting up the necessary infrastructure, processes and systems, both clinical and diagnostic, to be able to continue the service once the project is over. Further information about the project at national level can be found here: http://www.genomicsengland.co.uk/ Ms Jennifer Whitfield is the Training and Education Lead for the Oxford NHS Genomic Medicine Centre.

training cancer oxford surgery nhs genetics surgeons trusts genome rare diseases education lead genomes project

#62 Charlotte Keith on Cytogenetics

uk dna scotland edinburgh scotland cytogenetics genomes project

Play Episode Listen Later Feb 3, 2017 34:08

Cytogenetics is the field genetics at a cellular level, which means looking at chromosomes (bundles of DNA). Clinical Cytogeneticist, Charlotte Keith, discusses the areas of testing; acquired and constitutional, which is broken down into prenatal and postnatal. She explains how balanced and unbalanced rearrangements work and talks about a case that explains the concept. Charlotte gives us an UK view of how genetic counseling is incorporated into their genetic testing process and just how complex “informed consent” is when it comes to genetic testing as incidental findings do happen. Direct-to-consumer testing becoming more popular and Charlotte adds in her opinion on these companies and the science behind them. Check out the website Charlotte recommends for understanding chromosome disorders, http://www.rarechromo.org, it has resources for countless syndromes with downloadable pdfs outlining information in laymen’s terms. She also mentions the Deciphering Developmental Disorders (DDD) project and the 100,000 Genomes Project. Charlotte Keith is a Clinical Cytogeneticist from Edinburgh, Scotland. She works for the South East Scotland Genetics Service, providing diagnostic and prognostic genetic testing for NHS (National Health Service) patients.

Cracking the Genetics of Rare Diseases through Crowdsourcing

RARECast

Play Episode Listen Later Oct 16, 2015 19:31

Genomics England, as part of its 100,000 Genomes Project, is turning to crowdsourcing to help develop gene panels to diagnose some 130 rare diseases. PanelApp, as the tool has been dubbed, creates evidence-based gene panels for rare diseases that can be downloaded and viewed by anyone. By calling on rare disease experts from around the world to review the panels, Genomics England hopes to validate and standardize the genes used to diagnose specific rare diseases. We spoke to Ellen McDonagh, lead scientific curator at Genomics England about PanelApp, why the organization has decided to use this crowdsourcing approach, and what it ultimately hopes to accomplish.

genetics cracking crowdsourcing rare diseases genomics england genomes project

Going Beyond the $1,000 Genome with Mark Gerstein

Mendelspod Podcast

Play Episode Listen Later Sep 17, 2015

Though recent guests at Mendelspod say we're not quite to the $1,000 genome, we're close enough to use that benchmark in genomics discussions. But what are we getting for that almost $1,000? Mark Gerstein is the co-director of the Yale Computational Biology and Bioinformatics program where he focuses on better annotation of the human genome and better ways to mine big genomics data. He has played a big role in some of the large genomics initiatives since the first human genome project, including ENCODE and the 1,000 Genomes Project.

going beyond genome bioinformatics encode gerstein genomes project

#23 100,000 Genomes Project