Podcast appearances and mentions of patrick wallace

In this episode of Behind the Genes, we explore how personalised cancer vaccines are being developed, and how genomics and AI could help make these treatments more precise.  Our host, Florence Cornish is joined by:  Dr Victoria Goss, Associate Professor of Early Diagnosis and Translational Research at Southampton Clinical Trials Unit and head of the Southampton Clinical Trials Unit Cancer Vaccine Launchpad team  Professor Lennard Lee, Associate professor at the University of Oxford, Consultant Medical Oncologist, NHS  Ali Richards, a participant who took part in a cancer vaccine clinical trial  Together they discuss how cancer vaccines train the immune system to recognise cancer, how genomic information can help identify the unique features of an individual's tumour, and how AI could help researchers analyse genomic data and accelerate the development of new cancer vaccines.   “The reason I said yes was because my treatment really was punishing. It was so many side effects to it. The cancer never made me feel sick, but the treatment made me really sick. So I said yes because I just wanted to help other people not have to go through what I went through.”    Transcript [00:00:00] Florence: What if a vaccine could help treat cancer? Hello and welcome to Behind the Genes, the podcast that brings you the stories, research, and innovations shaping the future of genomic healthcare. Today, we're going to be talking about cancer vaccines, how they're being developed with the help of AI, what role genomics has to play, and what it could mean for patients.  [00:00:23] Florence: I'm Florence Cornish, and joining me today we have Dr Victoria Goss, who leads cancer vaccine research at Southampton Clinical Trials Unit; we have Professor Lennard Lee, who is a medical oncologist and Associate Professor at the University of Oxford; and Ali Richards, who took part in the Southampton Cancer Vaccine Programme.  [00:00:45] Florence: I think before we get into cancer vaccines specifically, it might be good to start with the basics. So vaccines are something most of us have heard of and probably experienced as well, but we don't always necessarily understand how they work. So Lennard, can I come to you to explain what a vaccine actually is, how it works with our immune system, maybe at the most basic level for those who might not have a scientific background?  [00:01:19] Lennard: Thanks, Florence. What's a vaccine? Very, very simply, something that protects your body from disease. We've had a few when we were younger, like which protects you against meningitis or hepatitis or different types of infections that can affect children.  [00:01:36] Lennard: And it really does show that your immune system is really powerful. Every day, it looks around trying to work out what's there which shouldn't be there and takes care of it. And ideally, your immune system just works in the background without causing any problems. And so what a vaccine does is it really helps the body understand something that's abnormal.  [00:01:55] Lennard: And the vision here is that you can use this technology to hopefully patrol against cancer, because half the people out there will never get cancer. They are the maybe the lucky ones or maybe the ones with a good immune response. And so a vaccine is basically giving your immune system a wanted poster:  [00:02:11] Lennard: "This is what threat looks like. This is what you need to control".   [00:02:16] Florence: And I think you mentioned some great examples there. There are lots of common examples of vaccines people might have heard of. I think maybe the flu vaccine is probably a common one that people are thinking about in the wintertime. I think another one is maybe the HPV vaccine.  [00:02:29] Florence: Lennard, could you explain a bit more to our listeners about the HPV vaccine? What it is, how it works? I think people often think of it as a type of cancer vaccine, but actually it's targeting a virus. Is that right?   [00:02:41] Lennard: Yeah, that's correct. So this is now a vaccine which has been rolled out across the NHS, and it's actually worked really well to get rid of a few cancer types, which is incredible.  [00:02:51] Lennard: And why is that important? Well, cancer can be caused by many, many different things. Sometimes it's because you've done things like smoking or weight plays a role or just bad luck or the genes that you've inherited. But some cancer types are caused by viruses. And so many people nowadays are getting the HPV vaccine to stop cancer types like cervical cancer, hopefully head and neck cancer, and many of the rarer cancer types.  [00:03:21] Lennard: And so again, what you're doing here is you're taking the immune response, telling it the body shouldn't get this virus and hopefully prevent some of the bad consequence of getting this viral infection, like cancers.   [00:03:33] Florence: Thank you. That's really helpful to understand. So we've talked about how vaccines can be used to treat viruses, and I think most of us, when we hear the word ‘vaccine', we probably do associate it with something that stops us from getting ill.  [00:03:46] Florence: Victoria, could you tell us about how vaccines could be used to treat cancer?   [00:03:50] Victoria: Yeah, absolutely, and it is great to be here today. Thank you. So Lennard's already sort of spoken about preventative vaccines, and when we think about cancer vaccines, we're thinking about therapeutic vaccines. So we're thinking about training the immune system to recognise the cancer as something that needs to be dealt with because cancer is really tricky because it's our own cells that have gone wrong, if you like.  [00:04:16] Victoria: But that means it also is very good at evading those signals which tell the immune system that it needs to be cleared. So the analogy that Lennard has already given of a cancer vaccine sort of creating a wanted poster sort of builds on an analogy from one of your previous podcasts where they described the immune system as like the police almost trying to catch criminals, which are the cancer cells.  [00:04:41] Victoria: And the cancer vaccine analogy builds on that. So you've created a wanted poster which is training and giving the police more information about what those cancer cells look like. And then when we think about building on that with sort of personalised cancer vaccines, which is an incredibly exciting step when we think about the development of how cancer vaccines can be used, sort of really individualised therapy going forward, that wanted poster gets even more specific.  [00:05:07] Victoria: It's almost like giving a phone number or an address for that specific cancer type that is very specific to that patient. So the therapeutic vaccine is, is targeting the immune system. It's training our immune system to recognise the cancer as something that needs to be dealt with.   [00:05:26] Florence: It's funny you mentioned that analogy because I was just about to point listeners to that episode. If anyone wants to learn more about cancer vaccines specifically, you can check out our previous Genomics 101 podcast episode called ‘What Are Cancer Vaccines?' So Ali, I think I'd love to bring you in at this point because you have experienced this from the patient side of things.  [00:05:49] Florence: Could you tell us a little bit about your journey, your cancer diagnosis and treatment, and maybe more about the clinical trial you were part of, if you feel comfortable sharing that?   [00:05:57] Ali: Yeah, sure. Hi, Florence. It was Christmas 2015, and I felt a lump in my neck. And maybe because I'm a woman and we're always taught to treat lumps seriously, in the January I made an appointment with the GP, and she very quickly fast-tracked me through to the hospital.  [00:06:19] Ali: And January 2016, I got a diagnosis. It was a tumour on the base of my tongue at the left, and I was told it was caused by a variation of the HPV virus. So yeah, that was all a bit of a shock. I was shocked and I was scared, but I was also really angry because I look after myself. I eat well, all those things.  [00:06:45] Ali: It's just bad luck that it was a virus that my body couldn't deal with. I just, I felt guilty as well because of what I was gonna put the family through. So I had various scans and tests. I had an operation to remove my tonsils, although we soon discovered there weren't any left anyway. And they took a biopsy, which I didn't know at the time, but turned out to be important later on for the trial.  [00:07:15] Ali: Then I had to have a whole load of prep beforehand because of the impact of the treatment. So I had to have restorative dentistry, audiology tests. I had a PEG fitted, that's a feeding tube, in my stomach, and I thought, "Surely it's not going to be this bad." But that PEG, that feeding tube was a blessing in the end.  [00:07:40] Ali: And I had a mask made, and the mask fits you and basically pins you down to the radiotherapy table so you don't move when... because it's very precisely targeted at your tumour. So yeah, I went on to have five sessions of chemo, which felt quite easy. The radiotherapy was the really, really tough part. I had, uh, seven weeks of it, 35 sessions.  [00:08:08] Ali: So that was, yeah, that was a challenge.   [00:08:11] Florence: Thank you, Ali. Thank you for sharing that. I think it's always really valuable to get that patient perspective when we're talking about things like this. Lennard, I wanted to come back to you now to talk about the different types of vaccines that exist and which ones are being used specifically in the treatment of cancer.  [00:08:30] Lennard: Um, thanks, Florence. And Ali, are you 10 years now down the line since your diagnosis?   [00:08:34] Ali: Yeah, it feels good.   [00:08:37] Lennard: Congratulations.   [00:08:38] Ali: Yeah, yeah. It feels good. I really valued the follow-up checks that I had, both from my oncologist, but also I got some through the trial, and it really helped restore some confidence in myself and my body to deal with things and to be able to move on as well.  [00:08:56] Lennard: Oh, well done. That's fantastic because you telling us that story just really brings it to life about how scary this can be and also the fact that you had to go through all those sessions, thirty-five sessions and, um, and now you're 10 years down the line and still talking and giving hope-   [00:09:11] Ali: Yeah ...   [00:09:11] Lennard: that new technology still comes, so thanks, Ali.  [00:09:13] Ali: That's a pleasure.   [00:09:14] Lennard: Um, yeah, so Frances, this is what's really exciting. What types of vaccines are there? Well, first thing to say is that we're really good in this country about vaccine research. If you look around the world, what are we good at? Well, everyone knows that we developed the pandemic vaccine, and actually that technology is something that we can control.  [00:09:31] Lennard: We're world leaders at. It's quite cheap technology, and it's something that we are really good at bringing to patients. And Ali's our testament where she got on the trial, she helped test it and really pioneered new ways of research. So what types of vaccines are there? Well, I think we talked to the first bit where Victoria taught us that some of them can treat cancers and some of them can maybe prevent cancers.  [00:09:53] Lennard: And the HPV's one which is maybe be able to do both one day, which is brilliant. What would like... what else do people know about? Well, people might know that there are different types of technologies. So if we think back a few years now, back to 2020, there are some which are viral-based, and some which are mRNA based.  [00:10:12] Lennard: Both of these were new technologies which the whole population of the world came together to create and some of them are peptide-based. So there's probably three different types here. The protein ones or peptide one, which you always had, and then in the last five years, it's an incredible time to be alive, where new vaccine technology comes through, it's more effective and safer.  [00:10:32] Lennard: These are the viral ones and mRNA ones, and everyone's now pursuing all of these to try and make sure that we can maybe treat cancer in future.   [00:10:41] Florence: Can I possibly pick your brain a little bit more about the mRNA ones specifically? I think as you mentioned, lots of people might have heard of those during COVID.  [00:10:50] Florence: Could you maybe explain a little bit more about those and how they work?   [00:10:53] Lennard: Yeah. So this is going to take us all the way back to GCE biology now. If you remember - and we are Genomics England, so we, we got to work out why genomics is important, and we'll probably get to this. But remember, genes make RNA, which then makes protein.  [00:11:11] Lennard: And so if you're trying to reprogramme the immune response, you could give your body a protein, the back end of it. You can maybe give it an RNA, which is a blueprint too. And so what an mRNA vaccine is, it's a way of giving the blueprint or the instructions to the body of what to recognise, what the cancer looks like, um, um, or what the virus looks like, and target it.  [00:11:32] Lennard: If you want the analogy, well, for those people who had the pandemic vaccines, the ones which was mRNA based was, uh, the Pfizer one, and that worked really, really well. Cheap to make, easy to produce, and, uh, it's just a jab. And so people are now exploring that for cancer treatment now. Take new technology, which has only been developed five years ago, technology, which is just a blueprint, cheap to make, easy to update, and now we're targeting cancer.  [00:11:59] Lennard: Um, so that's basically what an mRNA vaccine is, giving the body the blueprint or the instruction of what a cancer looks like and trying to target that cancer.   [00:12:08] Florence: And you kind of alluded to it a little bit in your answer, but, um, it would be good to know more about where genomics comes into all of this. You know, why is it such an important part of developing vaccines?  [00:12:18] Lennard: And that's a great question, and really comes back to our second strengths, which is that we're really good at vaccine research, and yet we are also world leaders at genomic research. It's a really exciting time because, um, when Victoria and me and Ally at school, we would-- we, we learnt about that race to sequence the first human genome.  [00:12:38] Lennard: It was really exciting because for the first time, we can see every single genetic base in every human, and that used to cost billions of pounds to do that, and it would take many months or years to do that Fast-forward a few years, and then now Genomics England delivered the next success for humanity.  [00:12:57] Lennard: I think it was about 2015 to 2017 where they, they did 100,000 Genome Project, where the UK led the world in sequencing 100,000 people, including people with cancer, to try and understand what caused their cancer, what the risk factors are. And why is that relevant now? Well, it's because if you know what a cancer looks like, then you know what the abnormality is, well, then you can vaccinate against it.  [00:13:22] Lennard: So we've now gone from this amazing arc of discovery here, where when we were at school, we worked out what the human genome looks like. We can sequence it end to end and see in all its detail. Then a, an amazing organisation came out the ground called Genomic England, which shows that you can run it in the NHS.  [00:13:39] Lennard: 100,000 people could do it. And now we're making the next big jump now, which is it's not just going to give you a diagnosis, but maybe becomes a drug and a vaccine in future. And actually, probably it already has because Ali's that example, a success example of it happening.   [00:13:54] Florence: Yeah, I wanted to actually ask you about that, Ali.  [00:13:56] Florence: So just as you were saying, Lennard, it kind of... The cancer vaccine sounds quite futuristic, but as you said, it's, it's sort of already happening. So Ali, do you remember kind of how you first heard about the cancer vaccine trial?   [00:14:11] Ali: Yeah. I had a bit of an unfortunate time because after all that radio and chemo, my cancer still hadn't gone, and I had to have an operation to remove lymph nodes.  [00:14:22] Ali: But my oncologist at Poole Hospital, who's a fantastic woman, she had been involved, unknown to me, in the some of the thinking behind the trial, and particularly that she could recruit people because they were sat in her office. So she asked me if I'd like to take part, and without knowing anything, I said yes.  [00:14:49] Ali: And the reason I said yes was because my treatment really was punishing. It was so many side effects to it. The cancer never made me feel sick, but the treatment made me really sick. So I said yes because I just wanted to help other people not have to go through what I went through. I didn't really understand it, if I'm perfectly honest.  [00:15:16] Ali: I didn't really know what was going on, but then I'm not, you know, a super brain like Lennard and Victoria. I knew that I just wanted to do something to help people going forward, not having to deal with the same. So yeah, I put my hand up and there I was on the trial.   [00:15:37] Florence: So you mentioned there the, the really horrible side effects that you got from your original treatment. Did you have, um, what was your experience with side effects with the vaccine? Was it similar? Was it different?   [00:15:47] Ali: Oh, no, the, the vaccine was like a holiday compared to the treatment. Absolutely. At, at worst, in the first few treatments, you felt a bit like you had a cold, bad cold coming on, maybe slightly flu-y, but you took, you were given Ibuprofen at the same time as you had the vaccine.  [00:16:10] Ali: So no, it, the treatment with the vaccine was an absolute breeze. Which is kind of like, yes, this is what I want for people. You know, not, not the radiotherapy, not the chemo. So yeah, it was, it was really very easy by comparison.   [00:16:29] Florence: Oh, I'm so glad to hear that that was your experience. I'm just curious now also, was there anything that surprised you about the trial?  [00:16:35] Florence: You said there that you didn't really, like, have an understanding of cancer vaccines. You, you agreed to it straight away. Was there anything that maybe, like, you weren't expecting or surprised you?   [00:16:45] Ali: I think it surprised me that it was really quite easy.   [00:16:48] Florence: Yeah.   [00:16:49] Ali: Uh, I was delighted to have the team I had looking after me because they were fantastic. It all felt very simple.  [00:16:59] Ali: And how nice that was. You know, if I could've had that instead of all my previous treatments, um, it would've, it would've made everyone's life so much easier. And I guess, I don't know about the cost of drugs, but I guess the cost to the NHS would've been less because I wasn't in and out of hospital, I wasn't having to have all these extra things done, and all this extra support like dieticians and so on because I had to have my feed tube replaced.  [00:17:35] Ali: So all of that is impacts on the NHS, whereas this was very simple.   [00:17:40] Florence: I wanted to come to you now, Victoria, and ask you about the outcomes of this trial that Ali took part in or other trials like it, and whether we know yet what the broader implications of, of these advances might be.   [00:17:55] Victoria: So I think what we need to think about when we're thinking about developing these treatments and sort of evaluating the treatments at each stage is that it goes through a very clear pathway of progression, and Ali was involved in one of the, the earliest stages of that progression.  [00:18:09] Victoria: And it's, it's always amazing to me to hear your story, Ali, and to know that patients are willing to take part in the research and that's what allows us to develop these treatments. So the trial that Ali was part of has now gone on to develop into a, a larger scale study which will be evaluated again.  [00:18:27] Victoria: And that all starts to form the evidence for how these treatments can be shown to be effective, and also how they can show... Also, you know, Ali's already touched on there about the cost implications, so how we can show that that can be beneficial as well. And then we can start to think about how they can be taken up and become part of routine standard of care for patients like Ali, as she was describing.  [00:18:50] Victoria: And all of that evidence comes together, which then gets evaluated and then it, and then it moves forward through that progression. But it's-- we have very clear, um, you know, a, a route that each new, new treatment has to go through, um, to be able to, to become part of standard of care.   [00:19:07] Florence: And Victoria, you also play a key role in the Cancer Vaccine Launchpad.  [00:19:12] Florence: For any listeners who might not be familiar with the Cancer Vaccine Launchpad, could you maybe tell us a little bit more about it?   [00:19:18] Victoria: Absolutely. So in its simplest terms, the Cancer Vaccine Launchpad is designed to help find patients who might be eligible to take part in trials like the one that Ali was part of.  [00:19:30] Victoria: It's an incredible project. Cancer Vaccine Launchpad is quite long, so we tend to abbreviate it to the CVLP, which I'll do from now on, if that's okay. The CVLP to me really demonstrates the power of collaboration because it's brought together so many different teams that have been necessary to make sure that, that what we're trying to achieve, so finding as many patients as possible for these trials, is possible.  [00:19:52] Victoria: We deliver this project on behalf of NHS England. I know that Lennard was involved right from the start as well. The reason that we need the CVLP is because one of the biggest challenges in research of these new treatments is finding the patients who might be eligible. So one of the reasons for that is because when we are running the trials to test these new treatments, there's a lot of different infrastructure that's needed to support the delivery of those trials.  [00:20:19] Victoria: So you need special pharmacy services, special research nurses. All of that has to come together to be able to deliver trials of new treatments. And actually, that means that actually those studies can often only take part in a small number of hospitals. So historically, you only had the opportunity to take part in those trials if you lived near one of those hospitals, which is, you know, like Ali did.  [00:20:42] Victoria: So what the CVLP is, what, what it has done, it has created a formalised network which enables referrals to happen from ... we're opening 83 hospitals now across England. We've just expanded out to the devolved nations as well, which is a really exciting development, and it creates that, that network which allows patients who might live further away from a hospital delivering one of those vaccine or immunology trials to be able to be referred in to see if they might be eligible.  [00:21:09] Victoria: So essentially, it's a bit like creating a big funnel. So you're finding all of the potentially eligible people that could take part in that trial, and you're funnelling them into the trial site to find those patients who are eligible.   [00:21:22] Florence: And what impact do you hope that this could have for the NHS and also for, like, individual patients as well?  [00:21:29] Victoria: So we've seen such positive results from the CVLP so far. The first study that we worked with was for a colorectal cancer vaccine trial. Before the CVLP started working with this trial, only 17% of the eligible patient population in England had the opportunity to take part because they lived near one of those hospitals delivering the trial.  [00:21:52] Victoria: After the CVLP started working with it, we had increased that to over 60% of the eligible patient population. So you could really see how it has expanded out access, and that's just a fantastic opportunity to be able to bring, to bring patients. We also were able to show that the UK was screening, so looking for patients at three times the global average.  [00:22:14] Victoria: So we really were able to see how the CVLP is supporting and accelerating recruitment to those trials I think the key thing for me has been the patient enthusiasm that we have seen though. So when we open up to a new trial where, that the CVRP is working with, we are always inundated with people who contact us to find out how they can be part of this network because they want the opportunity to take part.  [00:22:40] Victoria: We know that some patients have travelled for two hours to a trial site to find out if they could be eligible because actually they want the opportunity. So the CVRP has really sort of enabled that patient choice, which is a fantastic thing to be able to do. But it also builds on what Lennard was talking about earlier, which is the UK is really good at this research and actually what the CVRP is then doing is showing how we can really support recruitment to these trials to accelerate these trials and that only brings more trials to the UK which again creates more opportunities for patients which is exactly what we're trying to do.  [00:23:14] Victoria: We're trying to create more and more opportunities for patients to take part in these studies if they want to.   [00:23:20] Florence: Yeah. That's really incredible. Thank you for sharing that with us. I wanted to ask you a question now, Ali, because I think when we were talking about trials and projects like this, as Victoria said, we often think about kind of the high level impact, but also it's an opportunity to create connections as well between patients and families and, and I know that you, you had a patient's family reach out to you about advice as to-- about whether they should take part in a trial. Is that right?   [00:23:47] Ali: Yeah. I think it was the wife of a guy up in Liverpool who had throat cancer, and, um, she must have done some really good research on the internet. I'd done various bits of publicity both for Southampton Uni and cancer research around the trial. So she obviously found me and then stalked me on Facebook , which was absolutely fine.  [00:24:13] Ali: I didn't have a problem. So her husband was down to go on the trial, which is the next stage that Victoria had spoken about, and she just wanted to know, would I recommend it, would-- what was it like, that kind of thing. So I said to her, "I would absolutely recommend it, of course," and told her what my experience was.  [00:24:35] Ali: I couldn't guarantee his would be the same, of course, because things might have moved on. But it was a really, it was a kind of a nice feeling that I could say to her, "Get him to have it done because it's got to be the best outcome." I think his stage was much further on than me. So yeah, it had to be the way as far as I could see for him. And as far as I know, he went on the trial. Which is great.   [00:25:05] Florence: How, how did it feel to kind of make that human connection, maybe not something you were expecting to come out of a trial?   [00:25:13] Ali: No, it was really, it was really nice. I am a bit of a, a fangirl for, for Lennard and Victoria and all the team at Southampton.  [00:25:22] Ali: If anybody asks me about vaccines and cancer vaccines, I'm like, "Oh, yes." And you-- So yeah, I'm, I'm a bit of an evangelist. So to, to have somebody real-   [00:25:33] Florence: Mm ...   [00:25:34] Ali: ask me about that was great feeling.   [00:25:37] Florence: I think that's a, a really great example of how research can have impact far beyond, uh, one individual. And I think another great example of this is also artificial intelligence or AI as a potentially transformative force in, in healthcare.  [00:25:54] Florence: Lennard, when we come onto this topic, I wanted to hand over to you because I know that you've recently received funding for a project exploring AI, and how it could support cancer vaccine development in particular. Could you tell us a bit more about this project?   [00:26:08] Lennard: Thanks very much, Florence. And I also want to add, I feel very proud about what Ali did just there, where she's able to bring through opportunity for other people, too, which is amazing.  [00:26:19] Lennard: The NHS is there to not just do the technology of today, but also be one of the best healthcare systems in the world to bring through new technologies. And it's just really exciting about people wanting to help the NHS, advocating for new technologies to be tested, and actually that's what Genomics England i there to do, make sure the NHS gets new technology in there so that patients will get new treatments.  [00:26:41] Lennard: I just wanna just reflect what Victoria noted In the NHS, in their Cancer Vaccine Launchpad, patients are getting in at three times the rate of other countries.   [00:26:51] Ali: Mm-hmm.   [00:26:52] Lennard: That's really special. And also she's increased coverage to, uh, did you say 60% of population? That's 42 million people have potential access to this.  [00:27:01] Lennard: So that is huge, and I think it's really a passion project for so many people out there, PICT trials units, the research nurses and doctors, and also patients who make this all happen. So it is quite impressive. It is very impressive. Oh, yes, and AI. I probably should cover that too. Just beyond what's special about the NHS and Genomics England.  [00:27:22] Lennard: Well, AI I think is changing everything. I went to a garden party, and actually everyone's talking about how they're using AI to make their lives simpler, make them do things that they've never been able to do before, get the information instantaneously there. And I think that there's technologies which come through every so often in our lifetimes, which changes how we think, how we communicate, and actually makes us better in many ways.  [00:27:47] Lennard: And so the great opportunity here is what happens if we take that third strength now? So we've already said we're really good at vaccine research in the UK. The UK invented vaccines. We also are world leaders at genomics. We did the 100,000 Genome Project. What happens if we use this new technology now?  [00:28:06] Lennard: And what's a problem that we can solve? Well, let's say we did a whole genome sequence on someone, which is what Genomics England does every day for the NHS. Well, that creates a lot of data. Um, I tried to do the calculations before we went online. It's about 100,000 photos. You know, when you take on your phone, that's a lot of data.  [00:28:25] Florence: Wow. Yeah.   [00:28:26] Lennard: And that's a miracle what's happening in the NHS and Genomic England, and we need to make a cancer vaccine out of that. And so you need to process that. So that's time-consuming. It could be automated. And so what AI could do now in future is that we could use the supercomputer we built in the UK.  [00:28:43] Lennard: In fact, we are doing this already. We've built supercomputers in the UK, and we're going well beyond other tools out there and designing cancer vaccines. And the AI scientists which can do that can do it at weekends, at nights, and help design the drugs. And so what it does is it heralds a future where every patient can contribute into a model that's created in the UK, stored safely in our supercomputers.  [00:29:07] Lennard: It can now be made into drugs, and the UK will start to make things again, which will hopefully change cancer care across the world. We can deliver that legacy whereby our three strongest strengths come together - vaccines, AI, and genomics. It then super powers the NHS and everything that Victoria's done in the Cancer Vaccine Launchpad, so many millions of people around the world can get access to trials.  [00:29:31] Lennard: And people like Ali can also help hold up the NHS even further. So people once again look back to us and say, "If you want to get things done, come to the NHS because it provides world-class care for patients." And so that's a big initiative now. Use AI to make better drugs, safer drugs, more effective, more precise in the UK. And it's only possible because of everything that we've built here with our funders, ARIA, MRC, Cancer Research UK, people raising, raising money through cake bake sales to make this happen.  [00:30:02] Lennard: So it's very exciting.   [00:30:04] Florence: Yeah. I think AI can be a topic that people often have very strong opinions about. When it comes to AI in, in your line of work, are there any misconceptions you think people might have, or are there any benefits to using it that maybe people might not be aware of?   [00:30:21] Lennard: Oh, that's a tricky question, isn't it? I think you're right. Any tool that comes through can be used for good things and, and things that people will question because maybe we don't want to cross those boundaries. And yet I think what we're doing here is really special because we want to - as long as your heart's in the right place - we want to give more people like Ali hope so that she knows that one day the drugs in the NHS will be much safer so you don't get all those side effects, much more effective, much more precise.  [00:30:52] Lennard: And on top of that, people like Victoria will be able to bring even more trials in the UK which will change lives and change practices around the world through an amazing working launchpad. So I think that's the right use of AI, make people's lives better. I think there are other uses of AI which I probably scratch my head and say, "Well, should we be doing that?"  [00:31:10] Lennard: And that's what I think it's really special that we do think about these and talk about these things here, and then bring the public with us because I know that people reach out, and Ali's been reached out in the past before, and I think we need to have this discussion here. Is AI right to develop cancer drugs using capabilities from Genomic England to go through the NHS Cancer Vaccine Launchpad?  [00:31:31] Lennard: I say cautiously, yes, and we should do more of this. And I think the most important thing is there's a lot of people starting to use AI for benefit, and you know my views, Ali, and I don't know if they're right. Um, I'll be a bit cautious, but I do want to ask you, Ali, is this the right use of AI? Should this be what we develop?  [00:31:50] Lennard: I don't know what you're going to say.   [00:31:52] Ali: For me, I think it is. I do think AI is a bit if you put rubbish in, you get rubbish out. But if you- If you ask the right questions, if you give it data analysis and experts like you have set up the protocol in the first place and it makes everything faster and reliable, then it's got to be the right thing.  [00:32:16] Ali: It gets used and abused for things, that isn't what AI should be doing, in my opinion. It should be used to do-- to help us, to supplement the work that we're doing, uh, and make it even faster than you're already making it.  [00:32:38] Florence: Well, we've covered so much today from how vaccines work to the role of genomics, NHS trials, and of course, what all of this could lead to. So before we wrap up, I have two final questions for each of you. What do you think is the most important thing for listeners to understand and take away from personalised cancer vaccines?  [00:33:01] Florence: And what are your hopes for the future? I think we'll start with you, Victoria, if that's all right.   [00:33:08] Victoria: Yeah, absolutely. It's been a great conversation. Uh, there's so much to think about. I think when I think about what I'd like listeners to take away, I think it's that cancer vaccines, and particularly personalised cancer vaccines, really support and represent this paradigm shift that we're seeing towards a much more personalised, uh, treatment pathway.  [00:33:27] Victoria: You know, like we've described, generating a cancer vaccine that has come from the patient's tumour, so the, the, the vaccine is, is designed to recognise mutations that are specific to that patient. It is such an incredible thing to be sort of witnessing and to see how that's developing through into sort of really changing patient care, and that's, you know, we've spoken about this so much, but that's been due to such incredible collaboration across scientific disciplines, across the NHS, pathologists.  [00:33:58] Victoria: Everyone has come together to make all of this possible, and that's, that's an amazing thing to be a part of. In terms of my hopes for the future, well, I would like the Cancer Vaccine Launchpad to be open in every hospital across the UK to really sort of underpin that acceleration and to provide that opportunity for patients.  [00:34:17] Victoria: You know, I'd just like to give a, a final shout-out to everybody who has been part of the Cancer Vaccine Launchpad from its very start, who's enabled this to happen and, you know, it's just been fantastic to see how this has, you know, supported patient choice for trials. And I guess if there's one tiny other thing, perhaps we could see how this, you know, this, what we've put together could be applied to other disease areas as well.  [00:34:39] Victoria: But yeah, that, that would be my hope for the future, is it's open everywhere one day.   [00:34:43] Florence: And Ali, I'll come over to you next.   [00:34:45] Ali: I think what I'd say to any patient that was asked to go on a trial is, is just go for it.  [00:35:02] Ali: And you know, Victoria, Lennard, all the rest of the team, you know, you are not doing jobs. You're leaving a legacy in my view. That's such an important thing. So yeah, if you're offered a trial, get on it. And my hope for the future is that everybody can have kinder, gentler treatments. The radiologists and chemo nurses I came across were lovely, lovely people.  [00:35:31] Ali: But yes, I'd like to see them out of work and doing other things within the NHS because they don't need to do that work anymore. That, that's my dream.   [00:35:40] Florence: Mm. And Lennard, any, any final thoughts?   [00:35:44] Lennard: Thanks, Ali. I mean, your words gave me goosebumps about the amazing stuff that the whole community's doing for cancer vaccines, AI and genomic research.  [00:35:51] Lennard: It's so powerful. Um, okay. What's the final thing? I think it's hope. Look, the country's in a new place now. You've got brilliant scientists running clinical trials, like the Cancer Vaccine Launchpad, which is reaching out to every single hospital. You've got patients who are building up the NHS again to deliver future care, and scientists using AI and genomics to make cancer vaccines.  [00:36:11] Lennard: That is a good reason to be hopeful. When lots of things are going in other places of the world, great things are happening in the UK.   [00:36:20] Florence: This has been such a brilliant conversation.  [00:36:25] Florence: A huge, huge thank you to our guests today, Dr. Victoria Goss, Professor Lennard Lee, and Ali Richards, for joining me in our brilliant discussion about cancer vaccines.   [00:36:50] Victoria: Thank you so much for having me.  [00:36:55] Ali: Thank you, as always. I've learnt a lot.   [00:37:00] Lennard: Thank you very much, Florence, too, from me.   [00:37:10] Florence: If listeners have enjoyed this episode and you'd like to hear more, please subscribe to Behind the Genes on your favourite podcast app.  [00:37:16] Florence: I've been your host, Florence Cornish, and Behind the Genes is produced by Deanna Barac, Sharon Jones, Sophie McLachlan, and Patrick Wallace at Bespoken Media. Thank you for listening.   

When people think of midwives, they often think about pregnancy and birth, but the reality of modern midwifery is far broader.  In this episode of Behind the Genes, our guests explore the many different roles midwives play across healthcare, from clinical care and safety improvement to research and genomics.  The conversation looks at how midwives are helping shape the future of maternity care through research, supporting families to make informed decisions about genomic testing, and contributing to studies like the Generation Study.  Our host, Sharon Jones is joined by:  Katie Handley - maternal and child health clinical lead for the Generation Study,  Fiona Smith - research midwife for the Generation Study at Rosie Hospital in Cambridgeshire  Jess Fletcher - safety and quality midwife at the Rosie Hospital and a participant on the Generation Study  You can find out more about the Generation Study via the study's official website.   “ The more brave we are as midwives, and the more that we're willing to be curious about what we can do to improve our care, the better we're going to be at our profession. All midwives want to do is to provide safe, effective care that is what is in the best interest of that woman. We are advocates for women and for their families.” You can download the transcript or read it below. [00:00:00] Sharon Jones: Welcome to Behind the Genes. How is genomics changing midwifery, and what role are midwives playing in shaping the future of genomic healthcare? Also, do midwives just deliver babies, or is their role much broader than many people realise? [00:00:16] My name is Sharon Jones, and in this podcast we cover everything from cutting-edge research to real life stories in genomic healthcare. [00:00:23] Joining me today are Katie Handley, Fiona Smith, and Jess Fletcher. Katie is Maternal and Child Health Clinical Lead for the Generation Study, Fiona is a research midwife for the Generation Study at Rosie Hospital in Cambridgeshire, and Jess is a safety and quality midwife at the Rosie Hospital, and a participant on the Generation Study. [00:00:42] Together, we'll be exploring how midwifery's evolving, where research fits into clinical practice, and what genomics mean for maternity care now and in the future. We kicked off this one by asking Katie what roles midwives play day to day. [00:00:56] Kate Handley: I think when people think of midwives, they think of helping a lady to have a baby. [00:01:01] We're there for the birth, we're there to catch the baby, but it is so, so much more than that. We're there from the moment a woman becomes pregnant or even before that. We can help with prenatal, uh, preconception care. We're there all the way through the pregnancy, for the birth, and then afterwards as well, we'll look after the lady, her family, until, until we hand the baby and, and her over to the health visitor or to whoever's next in her care pathway. [00:01:25] But that's just looking at clinical midwives for the... that are involved directly in that particular pregnancy. There's midwives doing all sorts of other roles. I think I'm a really good example of that. So I am a clinic- I was a clinical midwife. I am a registered midwife, but now I work as a clinical lead, so I'm using my midwifery background and my midwifery skills in a research environment, but to help people who don't know as much about midwifery to implement a research study, and how we can make a research study real in a clinical environment. [00:01:59] So that's one example, but there are so many other things, and we have midwives doing screening roles and lots and lots of midwives working in research as well. [00:02:08] Sharon Jones: That's interesting. I've got a couple of friends who are midwives, and I would never have known, like, the extent and scope of their role. [00:02:14] Kate Handley: Yeah, I think people might be surprised to hear that you can be a midwife but never actually even see a pregnant person. So we have midwives that are academics, for example, or midwives that are lecturing at universities, midwives that are working behind the scenes in risk and governance and looking after the safety aspect. [00:02:30] Sharon Jones: That's amazing. I would never have known that. So Fiona, how has your role as a midwife changed over the years? Because you've gone through quite a bit of a transition, haven't you? [00:02:39] Fiona Smith: I have. Before I even became a midwife, I was, I was nursing. That nursing pathway was not academic, as we now have to undertake academic training to become a midwife. [00:02:50] So we... the training was very different. It was very hospital-based, and this is what you do, this is what we do. You would do some observation. You'd have a go. You'd get signed off. That really was my nursing background, and then when I started to explore midwifery, and it was much more academic, and that I was going to do the university pathway, I doubted that that would be something that I could actually even contemplate. [00:03:15] Moving forward 20 years, here I am. I've had various roles: community midwife, running birth centres, and then more recently, the last six years, joining a university hospital which has a, a, a big emphasis on research and academic training, brought in lots of students, medical students, and others. I saw some research that was happening at the hospital and became quite curious, took the plunge, and the last two years I've been working as a research midwife, which was a real surprise to me to find that this is where I am, and to actually be working on a genomic study is an even bigger surprise. [00:03:57] If you'd asked me 20 years ago that this is where I'd be, I'd probably have laughed and said, "No, that's not something that I could even be contemplating." [00:04:07] Sharon Jones: That's fascinating. It's fascinating, the journey you've been on and how midwifery and nursing training has evolved more broadly. So Jess, how does that compare with your own journey in midwifery? [00:04:19] Jess Fletcher: Similarly, actually, like off the back of what Katie and Fiona are saying, you do kind of go into midwifery thinking that your career is going to very much look like providing labour care and catching babies, which is a wonderful part of the job. And that is very much my background, is that I have been, like, a labour and delivery midwife, usually on the birth centre or in the community doing home birth. [00:04:43] So, and never in my wildest dreams did I think that I would pivot and go into something specialist. I think you k- ... Well, in my case, certainly, I kind of fell into it, quite literally, uh, because I broke my ankle and then had- ... to work from home for quite some time. I was offered to be off sick, and I was working at a new trust, and I kind of wanted to, so to speak, keep my foot in the door. [00:05:05] And I said, "Oh, I, there must be something I can do from home." And they set me up to do some auditing, which quite frankly, a few years prior I would've ... Yeah, you couldn't have paid me all the money in the world to do auditing. And then, lo and behold, I found it so fascinating, not just the process, but kind of seeing how that then would kind of implement us in clinical practice. [00:05:28] And now I'm a safety and quality improvement midwife. My office is on a birth centre though, so it does mean that I still very much work clinically. So yeah, so a similar story. [00:05:38] We're such a highly skilled profession that we can apply it in so many different ways. And now of course, I'm on maternity leave with my third baby. [00:05:46] Sharon Jones: Congratulations. [00:05:47] Jess Fletcher: And so taking a little, a little break, but really lovely to talk about it all today actually. [00:05:52] Sharon Jones: Yeah. Thank you. Thank you for sharing that. [00:05:53] So as mentioned, alongside clinical care, midwives are, are playing this increasingly important role in research. [00:06:00] And though it's something that people might not necessarily realise and they might not associate with the profession, I'd love to explore what that actually means in practice and how midwives have become involved in this space. So Katie, where does research fit in with midwifery today, and how do midwives get involved in that space, and is that something that all midwives are engaged with? [00:06:21] Or is it a more specialist kind of pathway? [00:06:23] Kate Handley: It can be a specialist pathway, but I think what's really, really important to realise here is that every single midwife is involved in, in research, whether they realise it or not, or midwifery care, has got to be evidence-based. Everything we do is evidence-based, um, because that's what keeps midwifery care as safe as it possibly can be, and we can only get that evidence base from doing research. [00:06:46] So even if midwives aren't taking part in a research study themselves, if they're not, you know, getting consent from people to do research studies, the care that they are giving comes from research that has been done in some space. Even if that's not within the UK, it's research that has been done. So research is incredibly important. [00:07:03] That's how we evolve, um, our care, how we evolve our pathways, evolve our guidelines is through that, through that research. [00:07:11] Sharon Jones: So can you talk to the audience about what is a research midwife versus a clinical midwife? [00:07:16] Kate Handley: So a clinical midwife generally is somebody that will have hands-on care during the antenatal and intrapartum or, or postnatal period. [00:07:24] A research midwife, often that will be someone who still works on a ward, in a hospital, but is helping to put research into place. So that may be running a study and taking consent from women to take to be part of that study, and then doing whatever the study needs. Or it can be actually conducting their own research, it can be writing, it can be an academic form of, of midwifery as well. [00:07:49] It's really, really important, and it really depends on the hospital and on the trust how much that research is incorporated into the clinical care, and sometimes it can be quite separate. But both very, very important. And the Royal College of Midwives are really, really trying to work on making research part of general midwifery care. [00:08:09] It's something that undergraduates need to do now as part of their, their degree, which all midwives have to do a degree to become a midwife. They have to do research. They have to be involved in research. Midwives in their first year of being qualified should still be having a research role and looking at how research can broaden their clinical skills, and it's something that should be going on throughout their entire career [00:08:32] Sharon Jones: Yeah, that's great. [00:08:33] Fiona, what does a typical day look like in your kind of research-focused role? [00:08:38] Fiona Smith: Firstly, just to say, when I moved from a clinical role into the research role, I thought I was going to miss that kind of adrenaline rush that does come with being a clinical midwife. And so I thought, it-- this is so quiet, it's just a really very different pace. [00:08:54] But actually, there are deadlines and things like that. So yeah, on a daily basis, it is really... it's a really busy day. [00:09:02] So we can be answering our emails and inquiries about research. We're liaising with the clinical team, so I'm involved in a screening study, so we, we need to collect samples. So we go and collect samples, we register those samples. [00:09:19] We're then approaching our patients or ladies that come in to have scans, or they might be in the antenatal ward. We liaise with the community midwives who might have people that want to take part in the study, so we do a lot of communication with the women through that way. [00:09:38] And having the background as a midwife, having that holistic approach has really, really broadened, you know, and really helped support my role as a midwife. Having-- transferring those skills has been incredible. [00:09:53] Sharon Jones: So what kind of studies do midwives support? [00:10:03] Fiona Smith: So apart from the genomic studies, uh, because a, a lot of genetic-based studies are going on within our trust. Where they're looking at trying to understand why things happen and see if there's a genomic h- component that might be attributed to conditions. We've got observational studies where we use lots of questionnaires to ask patients about their experiences. We've got interventional studies, so that could be testing a new drug or an interventions, just testing something that might work and, and might build that into that evidence base to - [00:10:32] You know, to put into practice. I'm really surprised at the portfolio of, of studies that is available. So they could be, um, not just maternity-based, but the obviously obstetric-based and studies, and we do a lot of gynae studies as well, so we work alongside the gynecologists. [00:10:51] Sharon Jones: So Katie, genomics is becoming more visible in healthcare. How is that showing up in maternity care more broadly? [00:10:58] Kate Handley: So I think what's really important to note here is that genomics has always been really important in, um, maternity care. [00:11:04] It's just that midwives potentially didn't know that they were doing it. Um, so from the very moment that we book a pregnancy, so when, when a woman has her first appointment at, you know, 8-10 weeks, we're already using genomics to plan her, her care. So we're asking about family history. We're asking about a predisposition to, um, heart disease, for example, or heart conditions or diabetes, or things that we will then use to plan a, a pregnancy going forwards. [00:11:30] We're looking at, yeah, family history. Uh, we're doing screening, antenatal screening, which, uh, some of the tests there are genomic based. And then after the 20-week scan, for example, if we find some sorts of congenital abnormalities, we can use genomic testing then to find out what, what is potentially wrong with the baby and what we can do about it. [00:11:50] And then moving forward throughout that pregnancy, genomics is also really important in bereavement care. So if there's a history of multiple miscarriages, for example, or if a baby is stillborn, we can use genomic testing to find out any reasons for that and to hopefully improve, um, care for that woman going forwards as well. [00:12:08] The big thing that's going on at the moment for genomics in maternity and midwifery is, uh, newborn screening At the moment, our newborn screening is looking for, uh, nine or 10 different conditions, um, which are very rare, but do have some treatment if they are caught early. What we're doing with whole genome sequencing, where genomic testing is looking to see whether we can find a much larger range of conditions much earlier in the baby's life to see if we can improve outcomes for those babies. [00:12:38] And so that's a huge role of genetics. Yeah, absolutely. [00:12:41] Sharon Jones: So Fiona, how confident do midwives generally feel about discussing genomics with families, even though Katie's just said it's not sort of nothing new and it's always sort of been there, maybe badged differently. How do you feel that midwives feel about talking about it when they are talking to families? [00:12:59] Fiona Smith: They probably don't feel, you know, very confident speaking about it. And I definitely wouldn't have been able to speak confidently in a comm- as a community midwife, uh role. But what, what is great about the hospital is that we know that they're where to refer to. So we've got the fetal medicine midwives who are available at any point to talk us through what to say to women or to help us, and the screening team are really useful and are on hand to, again, help us navigate that and what to, you know, what to say to parents. [00:13:36] We've got a really good patient record system as well, so we should, we, you know, the notes are very accurate. We should be able to, uh, follow through from what the parents have been told already, what their journey looks like. So although we're not 100% confident, but I think the students coming through, they're going to have res- acquire a lot more knowledge. [00:13:59] And also our midwifery standards imply that genomics should be part of that everyday conversation that midwives are having. So although it isn't something that's familiar within our parlance. I think going forward, I think it definitely will become much more mainstay, if you like, just- [00:14:20] something that we will be naturally talking about because you know, let's face it, genomics is here. I want to say being part of the Generation Study team, because I'm quite visible and everybody seems to know me because I've, I've transitioned from one role to the other, you know, we are visible. I'm stopped quite a lot, and midwives are asking the questions and, "Well, why?" [00:14:43] You know, "Why is it important?" Just even to be able to talk about, you know, that we've, we're building up a database, data that's going to be used for future reference. Being able to have those conversations with, with the midwives now will really help that confidence. It's something that I didn't think I'd ever have a conversation with. [00:15:02] I don't have very deep conversations, but I know where there are people if I do need to get those answers. [00:15:09] Kate Handley: No, um, I think going with what, what Fiona says, I think it's really interesting that pregnancies generally now are becoming a lot more complex. Um, we're seeing a lot more high-risk pregnancies, and I think that we will find that, that women and their families, their knowledge of genomics is probably going to increase as well because we're going to see genomic testing more widely in, in healthcare, and that's going to have to then flow through into maternity and into midwifery knowledge because women are coming in with more of a baseline knowledge as well. [00:15:40] And when we're dealing with more complex pregnancies and more high-risk pregnancies, genomics is a huge part of that. We, you know- Mm ... because we're going to be looking at things like pharmacogenetics, where we can see what kind of treatments are going to be best for these women and how that can then impact on their pregnancies. [00:15:56] I think epigenetics is becoming more and more talked about and more interesting in maternity, you know, and it's really important that midwives are aware that we've been speaking for years about the impact of smoking, alcohol, all of the outside factors on a pregnancy. But when we actually consider that from a genetic point of view, and that these genetic changes could potentially then be feeding down through generations, it brings a whole new level to the, to that aspect of maternity that, that midwives do need to know about. [00:16:27] So I, I think Fiona's right. I think that there is a lack of confidence when you hear the word genomics, but as soon as you explain what genomics actually means, then that confidence can be boosted. And I think that as we go forwards, there's so much work being done in the training and education systems for universities, for midwives that are already practicing. [00:16:53] We're really trying to, to improve that confidence and competence. Within the Generation Study, that's something that we're working really, really hard on, is to make sure that we're giving all the really appropriate training to the midwives that are involved in it, and that's not just the research teams that are, uh, that are asking consent from the participants, but that's for the wider team as well to, to help the, the midwives who are taking samples, for example, understand why they need to take that particular blood sample, the importance of taking it at the time, and what that means for the family and how that can impact on, on the future. [00:17:26] Sharon Jones: So it's kind of a whole literacy raising across the piece, isn't it? Just to sort of go back to a couple of things you said there, for those who might not know who are listening, would you mind just explaining about, um, pharmacogenomics and epigenetics? Because I just wanted to make sure that we put it across for everyone who might not know those terms. [00:17:44] Katie Handley: So epigenetics, for example, that's looking at how environmental factors can influence gene expression. So how the impact of something on the outside can impact what's going on in the inside. And we do know now that, that environmental factors can change the way that your genes in your body work. So that can not only impact the individual, those gene changes can be passed down through to the next generations as well. [00:18:12] And we know that this can happen across the placenta, so what a mum does in her pregnancy can then change the gene expression of the baby as well. And then we've got pharmacogenetics, which is looking at how certain drugs and certain treatments can be individualised for personal care. So looking at a person's genome, looking at the way their individual genes all work together, and then seeing how specific drugs, specific treatments can be used for that individual rather than as a population level. [00:18:43] Sharon Jones: That's really helpful. Thank you. So Jess, did being a participant on the Generation study change how you approach conversations as a midwife? 'Cause you're kind of like in both camps, which is a quite rare and interesting position to be in. [00:18:58] Jess Fletcher: Yeah, it's been a really amazing insight actually. Um, it definitely will, and I think this will kind of, uh, piggyback off of what, uh, Fiona was, and Katie was saying about how confident are midwives when, when they're counselling for studies. [00:19:10] So, you know, I'm, I'm particularly passionate about, and I mean mostly all midwives are, but I'm very passionate about making sure, ensuring that the people that we're providing care for are making truly fully informed decisions. Like very informed, you know, not, not just signposting, but making sure that they understand, you know, what does this mean for you? [00:19:31] Like what could these results mean for you and your family? Because I think the, I mean, this is a wonderful approach in some ways, but very often we'll be met with people under our care that go, "Yes, of course. Like sign me up for absolutely everything." Like the, the more we know, the better. Mm. And actually, I think it's- Then having that discussion about, well, actually, knowing things can be very complex because it then opens up a lot more questions for you and your family, and I'm not, not suggesting that ignorance is bliss, but actually, you know, really ensuring that they truly understand what this could mean for them and for their babies. [00:20:09] And the positives of that as well, what this could, you know, how this could really optimise your, your child's health throughout their life. And so for me, you know, I've always been very passionate about discussing studies with, with the people that I'm caring for. But it was really amazing actually being on the other side and applying that to me and my family and my baby. [00:20:32] What I talk about this, you know, every day, and actually Fiona's right, they're a very visible team, and it's, and it's amazing because, well, for Fiona, because often if she's on the birth centre and a bell goes, she's often having to get stuck in clinically in emergencies anyway. So you get a little touch of that every now and then, don't you, Fiona? [00:20:49] But it means that they are very accessible. I felt I had a really good understanding, but suddenly it felt very personal. And I can't quite remember how it went, whether Fiona approached me or I approached her, because we see each other so frequently at work. I think that when my pregnancy became, you know, common knowledge, correct me if I'm wrong, Fiona, it was more of a like, [00:21:11] "Oh, here we are again meeting in a corridor. Oh, yay, I can do the study," type of thing. [00:21:16] Fiona Smith: I think you came and sat in my office to do the consent. [00:21:19] Jess Fletcher: And that was a really interesting part for me because, of course, as a midwife, you know, you don't get to see behind the curtain, so to speak, as much as what I got to do as a participant. So I got to come and sit with Fiona in the office with the team. [00:21:33] It was wonderful from the perspective as a pregnant person, but also as a midwife, I've learnt quite a lot, and I think that, of course, I'm not at work, you know, currently, but when I return, um, certainly the way in which I signpost and, and the way that I talk about research and this, and the Generation Study in particular, all of that will still be there. [00:21:54] But I, I do wonder if there's going to be, there's a much deeper understanding on my side And yeah, I think undoubtedly that's probably going to, uh, I will adapt how I then, um, talk to people about the study because I've, you know, had more of an opportunity to delve into, you know, some of the great stories that have come out of it [00:22:15] and some of the real successes that have been shared from the team. I think there was very recently a case where a genetic condition was found, but it was found so early that actually his quality of life is now going to be, you know, really optimal. And I just found the whole story really fascinating. So I suppose it's opened a bit more of a door for me on a personal side and a professional side to read more, and I found it, you know, that much more intriguing, I suppose. [00:22:41] Sharon Jones: Yeah, I suppose it piques that curiosity and also just hearing those good news stories. Yeah, kind of showing how, you know, a family's life has been impacted in such a, sort of the early part instead of having that massive journey of finding out what possibly could be the challenges a child is facing and not knowing, having that result so much early on makes such a difference to, to a family. [00:23:03] Jess Fletcher: Absolutely. And, and also just I think as well, because I work in safety and quality, you know, the, a huge part of my role is looking at patient experience. It's been great to be on the other, I mean, yes, this is third time around, but this was the first time that I had a baby at this current trust that I'm working at. [00:23:18] So, you know, it was really great being on the other side of that and actually seeing how streamlined it was, how the communication between the research team and myself as the pregnant person, how efficient it was that I was receiving various things in the post and through the kind of patient portal that we use. [00:23:36] And then how swift the results were as well. [00:23:39] I mean, that, I'm sure that can vary between participants, but for me, you know, you're so caught up in the, in the newborn weeks that you can almost forget you were part of a study. And then I, and then I got the results through and I went, "Oh my gosh, of course. I mean, what a wonderful thing to participate in." [00:23:54] And the fact that we're still a part of it really until he's 16 years old and beyond, if he consents. So I just think, yeah, it's been a really great experience to participate, but it will undoubtedly change how I then talk about it moving forward because I've had this personal experience. [00:24:11] Sharon Jones: Yeah, yeah. Kind of hearing that seamless experience kind of builds on the trust that, you know, you have in the study and, and, you know, the sort of people behind it essentially, which is, is really important when you're kind of giving your genomic data essentially. [00:24:25] So it's, it's really good to hear that. Yeah. So looking to the future, it's clear that genomics is going to play a growing role in healthcare, so I'm really interested in what that means for midwifery. How might the role evolve, and what does that mean in terms of supporting midwives who need to feel confident in this space? [00:24:43] Kate Handley: I think that genomics is going to have a huge impact on maternity care, and I think it's going to be really great to see how we can really improve the personalised care that we give to individuals that come through the maternity system. We try really hard as midwives to treat every single woman that comes through our care as an individual, to personalise her care plan, and the more information that we've got about somebody, the more information they want to share, the better we can look after them and the better care plan we can actually put in place. [00:25:17] So by using any genomic data that we have, we can really improve that, that care. If whole genome sequencing does become part of newborn screening in the future, we can potentially find these babies every day that we think may have a rare condition, and we can do something to improve their quality of life. [00:25:37] Sharon Jones: Yeah. That's, that's incredible. If the study continues and, and rolls out into healthcare, that will be, um, such an impactful and, like, really game-changing Sort of effect for everyone. [00:25:49] Kate Handley: It will be really impactful and game-changing as long as we do it properly, and I think what Jessica was saying is really, really important about genomics can have huge implications for families and for people. [00:26:00] So it is so important that people understand what they're signing up for in any kind of genomic testing, not just in the Generation study. And because of that, the training that we give to midwives in the future, and I say we, I mean that as universities, as midwives teaching each other, as all education bodies, the information and the education that we give to midwives is so important because the only way that we can ensure that the individual signing up for any kind of genomic testing are giving informed consent is by making sure the people taking that consent are fully informed as well. [00:26:34] As us going forwards, if all midwives can just embrace genomics, everybody will help each other build to a position where we can provide really, really good care. [00:26:44] Jess Fletcher: From the perspective of, yes, a midwife, but also someone that's fairly freshly postnatal, you know, decision-making during a pregnancy is actually really complex. [00:26:53] There's a lot of grey areas, and I think that decision-making, that can be really tough if it's your first experience or if you're suddenly dealing with something in a pregnancy that is more complex than you anticipated, and there's no right or wrong answer, and you're having to make decisions with perhaps not quite all of the information. [00:27:14] I mean, Katie touched on the non-invasive prenatal testing when we are, yes, we're, we're screening in, in early pregnancy for a number of conditions, but the non-invasive prenatal testing, it's not 100%, but it, it gives us a lot more to work with. And I think everyone interprets risk differently, don't they? [00:27:34] So if you're given a one in something chance that your baby might have a condition, it's very, can be really difficult and, and a very emotional process to make decisions around that. What's my next move going to be? So if we have the ability with genomics to actually provide a lot more information and kind of broaden the decision-making process, then - [00:27:59] that can only, I think, be a positive thing, or give them the opportunity to then opt out of any further testing, which is equally as important. [00:28:08] Sharon Jones: Giving you as much agency to choose without pressure and just giving you as much knowledge that you need to make the best decision that you can in that, in that situation. [00:28:17] Jess Fletcher: Yeah, the situation that's right for, for you and for your family, which is going to look different for every family, isn't it? [00:28:23] Kate Handley: And midwives are in such a privileged position because of the amount of time that we potentially spend with a woman and to get to know that woman. We have got the ability to actually explain things in a way that, that woman may be able to understand as well, as long as we've got the knowledge. [00:28:40] So, you know, genomics can be really, really complex. Mm. And it can be really difficult for people to understand, even if we do have all that information. So by using the relationships that we can build with those women, I'm thinking particularly community midwives or people during the labour room that are building these really intense relationships really, really quickly. [00:28:58] We really need to be able to use that to our advantage when it comes to actually information given to, to patients as well, and to women and their families. [00:29:06] Jess Fletcher: We're in a really unique position in our profession because we're very highly skilled at having to explain something quickly and under pressure, and try and capture and provide all of the information possible. [00:29:18] But also we work as part of a multidisciplinary team, so we've got access to a lot of professionals that can provide input and help with educating the patient, but also educating us. So our knowledge is always growing, especially around kind of research and genomics in, in particular. Yes, it's becoming so much more a part of midwifery. [00:29:41] So I think, yeah, I, I feel really lucky that, you know, we're not just in a profession that, it, you know, we do this day to day and that's it. It just feels like that there's always a chance to learn and to grow as a professional, and then impart that on the people that we're caring for [00:29:57] Sharon Jones: So coming to my final question, if you could leave our listeners with one message about midwives and research, what would it be? [00:30:05] Fiona Smith: I'd say even though it does sound like it's a scary subject, I think we need to embrace it. The technology that's there, you know, we've got it. It's here to stay. Yeah, just don't be scared. Be curious and excited. [00:30:22] Jess Fletcher: Yeah, and I, I do think... I, I think midwives in general, I feel like when we qualify, we also qualify with a bit of an inferiority complex, you know? [00:30:30] That we worry about what we don't know, and actually, you're right, Fiona, we really mustn't be scared of this. We, we carry so much knowledge. Our profession is, as we've already spoken about, it's so... It's amazing how much we actually do as midwives and, and how broadly we practice, that actually it's absolutely okay if we're not confident in delivering this information, or we're not confident about, you know, where research is going. [00:30:55] The most important thing is, is, is accessing support so that we can make sure that we are, for ourselves and for the people that we're looking after, we have a- as deep of an understanding as we possibly can. [00:31:06] Sharon Jones: Definitely, and, and talking about sort of multi-skilling and, and being kind of pretty amazing, Jessica, I'm, I'm very impressed with our guest that has joined us on, on your shoulder [00:31:26] Jess Fletcher: The generation study baby! [00:31:28] Sharon Jones: A newborn baby. A Generation Study baby, that you've, uh, done this entire podcast with your baby. [00:31:32] Jess Fletcher: He's done amazingly well, hasn't he? [00:31:35] Sharon Jones: Yeah, he's done very well, and that really does, uh, sort of show the power of your, of your skills, not just a midwife, also as a mum, as we know. [00:31:43] Jess Fletcher: Always a juggle. [00:31:45] Sharon Jones: It certainly is. Katie, did you want to add any more about leaving our listeners with a, a message about midwives and, and research? [00:31:50] Kate Handley: Yeah. I, um... Fiona used the word curious, which I think is, is brilliant. I think if we can all be curious about research, we're already onto a winner. And Jessica said about being brave. The more brave we are as midwives, and the more that we're willing to be curious about what we can do to improve our care, the better we're going to be at our profession. All midwives want to do is to provide safe, effective care that is what is in the best interest of that woman. [00:32:07] We are advocates for women and for their families. We want what they want. But in order to do that, we have to embrace research, along with safeguarding and health and safety, I feel like it needs to be everyone's responsibility. You know, we all have this responsibility to improve care for, for the women that we're looking after, and research is at the heart of that. [00:32:30] And the more research that we can do, that we can be part of and that we can implement, the better that our profession will be and the safer that our women will be. [00:32:39] Sharon Jones: Thank you. Thank you to our guests, Katie, Fiona, and Jessica, and Jessica's newborn baby, for joining me today and sharing your insights into the evolving role of midwives. [00:32:50] It's been fascinating to hear how midwives are not only supporting families day-to-day, but also contributing to research and helping to bring genomic medicine into routine care. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. [00:33:06] I've been your host, Sharon Jones. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan, and Patrick Wallace at Bespoken Media.  

In this episode, we explore how individualised medicines are evolving from “n=1” treatments (a treatment effective for a single individual) into approaches that could transform care for many people living with rare conditions.  Advances in genomic medicine are making it possible to design highly targeted treatments based on an individual's genetic information. While these therapies may begin as bespoke solutions for a single patient, they can often be adapted, refined or reused to benefit others with similar conditions.  While the research is evolving, the systems needed to deliver these treatments at scale are still catching up. From regulation to access, our guests discuss what needs to change to turn this potential into reality.  Our host Sharon Jones, is joined by:  Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England  Mel Dixon, Participant Panel member and CEO and Founder of Cure DHDDS  If you enjoyed today's conversation, please like and share wherever you listen to your podcasts.  “However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.” You can download the transcript or read it below. Sharon: What if treatments once designed for just one person could now help many others? Thanks to advances in genomic medicine, regulations are changing and research is expanding. This opens up more options for treatments for rare conditions. But what does this mean and how close is real change? I'm Sharon Jones, and this is Behind the Genes. We look at how genomics is changing healthcare, covering everything from cutting-edge research to real-life stories. Individualised medicines are a fast-moving area, but there's still a big gap between scientific progress and what's actually happening to patients. You could call it the gap between hype and hope. Ana Lisa: However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment. Sharon: Coming up, we'll hear from Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, and Consultant in Clinical Genetics at Cambridge University Hospital, as well as Mel Dixon, member of the Participant Panel at Genomics England and CEO and founder of Cure DHDDS. Mel opens this chat by explaining why developments in individualised healthcare really matter to her. Mel: This issue is really personal to me. I have three children, two of whom are affected with an ultra-rare DHDDS gene variant, for which there is currently no treatment. Their condition causes symptoms such as, well, it varies between mild to severe learning difficulties, seizures, tremors, and movement and coordination difficulties. But the, the most worrying thing for us was that this condition is actually also progressive. So over time it becomes more of a Parkinsonism and some patients experience dementia-like symptoms and psychosis. So for us to get a treatment that targets the genetic cause of, of their condition is, like, the most important thing in, in our lives. If we could intervene now, they could potentially, at the stage they're at, you know, live an independent life with, with some supports. But if the disease is left to progress, it would be a very different outcome for them. Sharon: I mean, that sounds so difficult and I can't even imagine how life is for you and your family. And I can see what is driving you to find anything to extend the life of your children and to give them that opportunity to, to have a better quality of life. And then Lisa. Ana Lisa: It's a huge burden for families to carry. And I think at the moment there's an additional layer of burden, which shouldn't fall on families, to feel like they need to forge a pathway for their child to have a chance of a treatment. That's, that's a lot to bear. Mel: I think as well, families feel they almost have to become mini scientists in their children's specific condition overnight, because you go to these appointments with the consultants and nobody's heard of the condition and they don't know, they just don't really know what to do with you. So they're asking you, you know, so tell me about this, this gene change. What, what does it do? What does it mean? So you have to become the mini professor in your child's condition to be able to advocate for them. We've had to really learn on our feet so that we're able to advocate and push for research into DHDDS, because without us doing it, nobody else was going to be. Sharon: Yeah. So that's, you know, that's partly what we're here and what this podcast is for, it's here to support families to, to understand this stuff. And Ana Lisa, can you just break it down to us, what is individualised medicines? Ana Lisa: An individualised medicine that's made for one individual person. In reality, sometimes there are other individuals that can also benefit from the same medicines, and sometimes actually, although the medicine is made for one specific person, it might be made using a strategy that other patients could also benefit from, either directly, exactly the same, even, or through tweaking them so that they could work for a different patient. In the context that they're most often referred to at the moment, they're therapies that are being made based on the genetic information about somebody. Sharon: Thank you. I mean, that sounds amazing. And now coming to you, Mel, what does receiving a diagnosis mean for a family? And how do you navigate the space between finally having answers and the reality that the treatment may not yet exist? Mel: So for us, I think, we went down the, the diagnostic route in the hope that we would be able to find a treatment for our children, or there would already be a treatment in place. But unfortunately when we got their diagnosis, we were told that their, their condition was ultra rare, neurodegenerative and also newly discovered. So there was, there was no treatment pathway and actually minimal research happening into it at the time. So it was frustrating, upsetting, um, and it felt like quite a hopeless situation at the start, but actually this was just over three years ago. And through a lot of proactiveness on our part in fundraising, we've been able to better understand the condition and we now have treatments in the pipeline. So in that three-year window, from there being nothing, we now have treatments both in terms of potential drug repurposing candidates and also, um, an individualised therapy called an ASO is also in development for them. So it was hard, but it's given huge benefit to us. Otherwise, we'd just be going, remaining going from specialist to specialist without having any answers or understanding why their symptoms were progressing. Sharon: I mean, that sounds really, really tough and you know, coming back to you, Ana Lisa, could you talk us through how genomics is changing the way we can treat rare conditions? You know, what types of individualised medicines now exist and how do they even work? Ana Lisa: Maybe I'll start with how some of these medicines are working. So with, without going into details, but the sort of principle that these medicines might be able to, to do something called gene editing. So our, our DNA, uh, the instruction manual is made up of genes and it's now can be possible scientifically to change even a single DNA letter code in somebody to try and ameliorate the symptoms of their rare condition. You know that's phenomenal scientific progress to be able to do that. I think a lot of people have heard about gene therapy, where one is trying to get into the body a gene or part of a gene that might be able to sort of replace the function of a gene that isn't working as it should. There are various other strategies. So our DNA is actually used to send messages to our body, if you like, to, to decode these instructions. And so there are medicines that target the next step in this process, the RNA, which are the ASO therapies that Mel was referring to earlier. And really what those are doing are either trying to correct for a protein in our body that isn't working as it should, or to try and get rid of one that shouldn't be there. And so they can act in different ways. And that's actually quite powerful, because you can, theoretically, use these strategies to correct for different genetic rare conditions. So I think going to the sort of first part of your question, maybe if I can phrase it as "directly at source". If you can go upstream and target in a very direct way the cause of a rare condition, then actually you might be able to apply those same principles to many different types of rare condition. We know that there are, you know, 8,000 as a very ballpark number of rare conditions, and it might be that these strategies could be used I don't want to say for all rare conditions, but for many rare conditions where we find the genetic cause, these strategies could collectively be a very powerful way to treat them. And traditionally we've had to understand all the underlying biology, find a druggable target, find a drug that could target that, that's safe, effective, et cetera. And that's a lot of work. And that's still very, very valuable. If we were going to do this for these thousands of conditions, it would probably take us hundreds to thousands of years, collectively. And these strategies provide a lot of hope for being able to do this in a, in a more efficient way, where we can actually use the information used to treat one rare condition and apply those learnings to another rare condition. Sharon : I mean, that's really helpful to understand. So if the science is there, why aren't more patients benefiting from it yet? You know, what's standing in the way from your perspective? Ana Lisa: That's a really good question, and it's complex because the, our whole ecosystem is made up of, of many parts that go from finding a potential strategy that could help a rare condition to a patient benefiting from that. And I think one thing that maybe we haven't touched on yet is the fact that rare conditions can be really rare and affect a really small number of people individually, even though we know collectively they affect so many. You know, in the past it's been easier, if you're taking a condition that's common, that affects thousands of people, it's easier to see and to be sure whether your new medicine is actually working as you think it does and should, and having the benefits that you think. The, the sort of regulators have really clear guidance. We have lots of knowledge about how to assess treatments and have a randomised clinical trial, for example. How the reimbursement process may work in a public healthcare system. And when you, when you, when you sort of set down into the really rare, this is difficult for each stage of the journey. The transformation that's needed is a whole, system-wide transformation to be able to regulate in a scalable, equitable way, these therapies that could actually be an N of one treatment for one individual, that actually maybe one day another individual may also benefit, and sometimes even a group of individuals. It's not just the, the regulator, it's also how do you make it viable. So again, you have to make it scalable, equitable. And even to implement in the NHS down to this very "N equals one" level, and demonstrate that patients could benefit from these treatments, might require sort of fancier ways of assessing these treatments, whether it's statistics, other methodology and I think it's really the system-wide nature that makes this tricky, but is also a fantastic opportunity for, for collaboration, because that, that sort of end goal and benefits could be so, so great. Sharon: Yeah, absolutely. And I mean, Mel, for your side of things, it must sound, you know, quite frustrating where the people in the rare community to not see the support being made more readily available? Mel: Yeah, it is particularly difficult for patients and their families. I think in our case, when you're dealing with a neurodegenerative condition, time is of the essence. So when you know that the science is available or it's ready, but you don't have the systems in place to implement them to the patients so that they can access these much-needed therapies, it's worrying and frustrating. And also I see our children are affected with, with, you know, one of these N of few conditions that there's, you know, there's only 59 confirmed cases of DHDDS worldwide, and we've seen how the system firsthand doesn't fit ultra-rare patients. We can't, when we were looking at drug repurposing, we can't do a traditional clinical trial because we don't have the patient numbers and we don't have the funding. So a placebo-controlled trial just wouldn't be possible for us when there's only, I think, seven confirmed patients in the UK and, um, four that we're actually in, in, in touch with. So it does feel, I think, as Ana Lisa was saying, that we really need a system rethink, um, and refit so that it does start to accommodate these ultra-rare conditions, especially now as there's therapies which are showing huge benefit to patients. Sharon: And so with like all of these challenges, where are you seeing things shift and what does meaningful progress really look like for you? Mel: At the end of last year, the MHRA announced that they were rewriting the regulatory framework for rare conditions, and that fills us with lots of hope for the future. They're recognising that the traditional systems don't work for particularly ultra-rare conditions, and now that we do have these therapies in the pipeline, we, we want to get the patients to be able to access them. And we're also seeing innovation in how evidence is generated and measured. We witnessed this firsthand with our son as he was undergoing baseline tests for his ASO therapy. You know, the use of digital biomarkers, of real-world evidence, how they're increasingly being used for these N of one or N of few populations. And how the individual receiving the treatment becomes their own comparator. So you're not relying on these big natural history studies of the disease or placebo controls. It's you're looking specifically at that individual, getting a really strong baseline and then looking, once they're dosed with the medication, is that improving or stabilising symptoms? So I think this shift in focus is really meaningful for the ultra-rare community and also for them to be part of the decision-making process of what, what benefits do they want from a drug? Like what is meaningful to them? I think there's much more talk about the patients and how the, what will benefit them most. It's not necessarily what the scientists would think or research would think would most benefit, but what, what would make a meaningful difference to the patient? Sharon: I mean, that's good to know because it's kind of putting the person at the centre of, you know, this is what it's all about, isn't it? It's not just the science. We're trying to treat people and it's putting people, people first. Ana Lisa: Just to build on that, it's exactly that, that awareness that is, is growing, I think, that there are so many people affected by a rare condition and, and however rare your condition is, someone has a right to have hope and that the system should be able to cater for many rare conditions, you know, whether they're an ultra-rare or an actually almost common rare condition, everybody should have a hope that we should be able to find a treatment. And it's not a hopeless situation that it's, you know, never going to happen or be too difficult. It's quite powerful, hope. If you can solve for the truly individualised medicine, then you at the same time may also be helping everyone in-between a really common condition and a really rare condition, because right now the system works for common conditions. And if you can take it right down to the sort of radical of, example of an individualised medicine made for one person, then you are also forcing the system to a change for everybody else. And I think that's one of the great benefits of thinking about it as a joined-up system. Sharon: So how do you each navigate between hype versus hope when it comes to rare therapies? Mel? Mel: I like to focus on hope, because when we got our diagnosis, we felt really hopeless and that's a really dark place for a family to be. But as we learnt more about their condition and the rare condition landscape and genomics, we actually learned of all these new therapies that were in the pipeline. We were hearing about, you know, recently, conditions like Huntington's Disease that you never, never previously had any disease-modifying treatment, how they're now being able to be treated with gene therapy with really positive effects. Similarly for other neurodegenerative conditions that have been treated with ASOs, how they're seeing not just disease stabilisation, but improvements. So I know it's, it's still, like, relatively early days with these technologies and therapies, but I think it, it allows families to have hope, which is, which is really, really important, because that statistic, you know, of the, of 95% of rare conditions not having a treatment, it's, it's a really brutal one, uh, to be told at the outset or to learn at the outset. So, you know, if, if these therapies can, can make a huge dent in that, that would be life-changing. It would make a profound difference to many, many families, and I think there's a lot of reason to have hope, taking all of that into consideration. Sharon: And then Lisa? Ana Lisa: I think to work in this area, one needs to be full of hope and optimism because there are so many, um, challenges to overcome as a community. Uh, but I think that means that people are also incredibly collaborative, because they know that we need to work together for this to succeed. And no one, you know, one individual, one organisation can do it on their own. It truly has to be a crosscutting, collaborative endeavour. The fact that we, in the UK, have resources like the National Healthcare System,Genomics England in partnership with the NHS runs a National Genomic Research Library. And so the fact that you could look at, at tens of thousands of, of genomes for many, many individuals with rare conditions. That gives me hope because it means that if a treatment is made for another person, it could be in a different country in the world, and if we could find another patient, it doesn't matter what specialty they're under, where they are, we should be able to find them and connect with their clinical team if, you know, if they've consented for the National Genomic Research Library. And so to me, that feels, that whilst there's, there is a lot of hype in the sense that some of the really well-publicised cases, really had a lot of people working on them and a lot of resources to make it happen. But that gives hope to everybody else that follows that actually it is doable and if we can make better systems, and having these national resources that we do, the fact that, there are a lot of guidelines being written at the moment, both international and national. And again, they show that the sort of scaffolding is starting to be in place to apply these in an equitable scalable way. It might not be that you're so much looking for a specific rare condition as for a particular type of genetic variant that could be targeted in the same strategic way, and that therefore you could look across many different rare conditions. So again, all these sort of pieces of the puzzle are, are filling me with, with, with hope. Sharon: You touched upon, um, inequity there. Now, you know, is there a risk of inequity given what we've talked about in terms of those challenges? Ana Lisa: I think we, we always have to have the lens of equity in everything we, we do. And that, and that really does apply to healthcare and, and in fact, probably the whole rare disease community are, are, are not well served in terms of therapies at the moment. There are so few, um, therapeutic options and so I think there's a massive inequity in that this, our systems are not geared, uh, towards rare conditions. I suppose, you know, different countries have different healthcare systems and some of the sort of first personalised therapies may require a lot of money behind them to, to happen, but they will be pioneers in leading the way for how this can be done. And I think in the UK we have a lot of the infrastructure and the, a sort of a strong, that's very equitable, I think. And so we could do this in a, in a much more open and equitable way. Sharon: Mel? Mel: Cost is always, unfortunately, and it, when it's your family that's affected you, you know, you hate the thought that things are coming down to cost and, and money. But I, I think as Ana Lisa said, if, if the system absorbs the initial cost. You know, it seems that those longer-term costs could come down significantly. We already see with our very small DHDDS community that an ASO, which is an allele specific that was made personally for one, for one child, can actually also benefit my son, even though they have a different variant. So if the cost of the ASO is 1.2 million per person, but if you suddenly find actually one other person can share that, that's almost halving the, the cost. And then if then you're finding out that actually, oh no, 3, 4, 5, 10 people can all have that same ASO, suddenly it becomes much more cost-effective and more sustainable. So I think, as we have to think about cost, I think that also allows us to have more hope that these therapies can, the cost of these therapies that are obviously hugely expensive at the moment, can be brought down in the longer term. Ana Lisa: There are a lot of things that people want to do in the NHS. People can be working under quite hard circumstances, so to talk about making a therapy for one individual can be difficult and people can sometimes, I think, think that it's a pie-in-the-sky conversation. However, I think that, you know, all the clinicians I know who work with families with rare conditions, what they'd most like to be able to do is to be able to offer a therapy. And so I think a lot of people see this as a, as a big opportunity, despite these initial hurdles. One thing I often think about is my grandfather, when he was alive, every phone conversation, he would start with, "How many lives have you saved today?" And so I think that's the, that's our challenge. Sharon: Wow. That's, that's really powerful. Mel: Just echoing really what Ana Lisa was saying, I feel the, um, inequity lies in rare conditions as a, as a whole, from the point of diagnosis to the lack of pathway, um, to, to the lack of system in place for them. You wouldn't have a patient with a life-changing cancer diagnosis receive that information in a telephone call, and that is the stark reality for many rare disease patients. That's how they receive the, that's how they often receive the news. That was certainly our, our experience. And, and from that point, there was then no pathway. It's just this horrendous feeling of isolation. And I think now that there are these treatments in place and therapies in, in place, it's about time we change that because often the rare, the rare condition community, and certainly those with ultra-rare conditions as well, they're probably like some of the most underserved members of the community in that it's their parents and their families that have to advocate. Otherwise, without that, they, they often wouldn't stand a chance of understanding the disease, let alone finding a treatment. So I think the whole system needs to have a reset, to think about these rare condition patients and, put them at the heart as they do for more common conditions. Ana Lisa : I completely agree. And you mentioned cancer, and there are actually quite a few parallels. So there might be really common cancers that affect a lot of people that are being, uh, subsetted down into different groups depending on the genetics that are related to that particular cancer and therefore what treatments might be most effective. And so I think there's, there's a lot we can each learn from each other between the rare disease and cancer communities. Perhaps as in rare disease we scale up to apply the same strategies to many different rare conditions and patients. Even if they're being tweaked for their particular genetic variant and cancer, sometimes one is subsetting down to treat specifically that, exactly that cancer subtype. So there's a lot we can learn and I completely agree that the, the rare disease community deserves the same chance at at treatments, and the hope that that comes with. Sharon: Thank you. It feels like there needs to be some kind of seismic system change along with this piece around collaboration and how, you know, the science is there, but it's how do we bring it to families who are facing these difficulties with it, you know, their children and, and rare conditions. We'll wrap it up there. Thank you to our guests, Ana Lisa Tavares and Mel Dixon, for joining me as we discussed the evolving landscape of individualised medicines. And thank you for listening. If you'd like to hear more like this, please subscribe on your favorite podcast app. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan and Patrick Wallace at Bespoken Media.  

Kyle and Owen are joined by Patrick Wallace from Goalie Gurus. The discussion covers the unique mentality and challenges of lacrosse goalies, including their psychological pressures and the evolution of goalie training techniques. Patrick shares his expertise on recruiting goalies, evaluating their performance, and the importance of mental health and leadership training. The conversation also touches on the changing landscape of goaltending, the effectiveness of the 10-man ride, and the importance of athletic and quick decision-making abilities for goalies.   Visit www.goaliegurus.com   Topics 00:47 Introducing the Goalie Coach 01:25 The Mentality of a Successful Goalie 02:58 Recruiting and Training Goalies 04:57 Evolving Goalie Techniques 08:03 Challenges and Psychology in Coaching 13:42 Youth Coaching and Goalkeeping IQ 22:43 Advanced Strategies and Sub Games 25:25 The Role of LSM in Lacrosse 26:14 Specialty Positions and Their Impact 27:02 Evaluating Goalie Performance 28:20 The Importance of Game Data 28:58 Club vs. College Rules 30:07 The Evolution of Midfielders 31:58 The 10-Man Ride Strategy 34:29 Coaching Techniques for Goalies 45:01 Memorable Saves and Goalie Stories 49:15 Conclusion and Goalie Gurus Information

Patrick Wallace, assistant coach of the Iona Gaels, joins Tobin Anderson's staff in year one at Iona. He gives a behind-the-scenes look at the process of continuing the winning tradition there with the Gaels.This episode is sponsored by the Dr. Dish Basketball Shooting Machine. Mention "Quick Timeout" and receive $300 off on the Dr. Dish Rebel, All-Star, and CT models.Hudl continues to make advancements to their suite of performance analysis solutions. Tools you know like Sportscode are enhanced by their industry-leading tech like Hudl Focus - an AI-powered smart camera that's built to integrate into Sportscode right out of the box. It captures and uploads video automatically from any gym. Head over to Hudl.com/AQuickTimeout to get a peek at all they're bringing to the hardwood, for every level of the game.Thanks to our sponsors at 323 Sports. If you're in the market for a team dealer, the guys at 323 Sports will not disappoint. Low prices, high quality, and GREAT customer service. They'll "Do It Right" for you and your sports program!

Adam Cox is joined by Patrick Wallace, Co-Founder of Curam, to discuss a new survey commissioned by Curam, which has revealed that nearly three-quarters (73%) of UK adults are worried about not having access to publicly funded care as they get older. They discuss the biggest issues being faced by the sector today and explains how service platforms could help. https://www.curamcare.com/

Coach Wallace joins the show at the 37:25 mark to discuss this new team, some X's and O's and the trio touch on some memories as well.

Todd Furniss talks with Patrick Wallace of Beyond Risk, a firm created to become the largest, most comprehensive, alternative risk-insurance company to aid middle-market clients manage their agency's risk. Beyond Risk combines years of best-in-class experience in Property & Casualty management, Employee Benefits, and Captive Management, Beyond Risk offers a comprehensive portfolio of end-to-end alternative risk solutions. To learn more please visit https://www.beyondrisk.com/https://www.TFIP.group/------------------------------------00:00 | Introducing Patrick Wallace of Beyond Risk01:29 | What does Beyond Risk do02:38 | What are alternative risk strategies06:58 | How does sharing the risk lower costs08:49 | How do costs at Beyond Risk compare to competitors11:28 | Where do CEOs get their insurance from20:25 | How do you break the mold of preconceived ideas21:17 | Do your connections create inertia23:51 | What perspectives do you contend with when talking to HR reps28:54 | What is the biggest challenge you face31:55 | Do you have a community for captives33:38 | Do you have a pool of information for new members35:00 | How can we do better to lower costs for all------------------------------------Todd Furniss is the author of the new book The 60% Solution: Rethinking Healthcare #Book https://bit.ly/36h3E4L#CivilDiscourse | #Fb bit.ly/3JwkaMv#CivilDiscourse | #Rumble bit.ly/3wnUsWU#CivilDiscourse | #YT bit.ly/3wmPdqz#Furniss | #LinkedIn bit.ly/3tBFjQd#Furniss | #Twitter bit.ly/36ASqaV#TFIP | #Instagram bit.ly/36ASDLf#TFIP | #TikTok bit.ly/3IrN7bh

With the first pre-season game set to begin this week, the Jets were hit with their first piece of adversity so far this season with OT Mekhi Becton suffering a knee injury, costing him the season. Lorenzo, Sean, and guest Patrick Wallace discuss the impact this has on the outlook on the Jets season and where the team goes from here. Also, the crew shares their expectations for Friday's pre-season opener and the overall feelings on training camp reports as we are in the midst of week three.

Adam Cox is joined by Patrick Wallace, co-founder of Curam, to discuss the current social care crisis and how it is impacting both the carers and those receiving care. He explains the changes that need to be made to overcome this, in addition to providing advice to both carers disheartened by the industry and those who have struggled to receive care. www.curamcare.com

Jake, Sean, and Lorenzo are joined by Patrick Wallace to run back the mock offseason episode of 2022 that the four men did a year ago. free agent predictions and a full mock draft, the crew makes their predictions for a big next few weeks for the New York Jets.

In our first episode we feature Mr. Patrick Wallace from the Georgia Department of Education. 

Leo Scullion (born 10 April 1958) is a professional snooker referee from Glasgow, Scotland, who has been officiating on the main tour since 1999. His first senior match was in the 1999 Challenge Tour, and he officiated his first televised match in the 2001 Regal Scottish Masters, a tie between Stephen Lee and Patrick Wallace. Scullion started to become a Snooker personality in the 2000s and eventually officiated his first final in 2011, at the China Open. He then took charge of another two finals the following year, at the World Open and the UK Championship respectively.[2] He officiated his first World Championship final in 2019.

Coach Patrick Wallace shares his journey from growing up in the "Hoop State" to being a coach at Loyola Chicago. He grew up in the Charlotte area, then spent a year of post-grad at Brewster Academy. Patrick committed to be a preferred walk-on at NC State and eventually transferred to Charleston Southern and played there on a full scholarship. After a successful playing career he became a Graduate Assistant at Northwestern under Chris Collins and remained there for two years while completing his master's degree in sports administration. Porter Moser hired him to be the Video Coordinator at Loyola Chicago and he completed his second season on staff at the MVC powerhouse. We talk all things from being in the NCAA Tournament "Bubble", Julia Louis-Dreyfus, and of course - SISTER JEAN!

Longtime Pre-K paraprofessional Mr. Patrick drops by and discusses his high school experience, what he loves about being a paraprofessional as opposed to a teacher, and being a father of twin 2-year-old girls. Then Mr. Gordon reveals this week's Beard Power Rankings.

Jake, Sean, Lorenzo and guest Patrick Wallace give their way too early offseason predictions. Roster cuts, free agency signings, and a full Jets 7 round mock draft. The guys are fired up and are ready to debate how Joe Douglas should build this roster. Like what you've heard? Follow the show on Twitter (@JetsWayPodcast) and feel free to subscribe/rate! We truly appreciate all of the support.

Hank Gossett, Patrick Wallace, Matthew Porter and Aaron Treadway join host Nate Adams to discuss 2000's LITTLE NICKY which just turned 20 in November. - NSFW contains explicit language. SUBSCRIBE WHEREVER YOU GET PODCASTS!

This was a recorded conversation with Jeanelle and Patrick along with a couple of other good people discussing what racial justice, end times, and race look like all together. Yeah, good stuff!

Presented by Patrick Wallace, DO, a resident at University of Nevada, Las Vegas and member of the AAEM/RSA Education Committee, and Jorge Antonio Fernandez, MD, Assistant Professor of Clinical Emergency Medicine at Los Angeles County + USC Medical Center. Intro music by Akashic Records, Key to Success - Discover the Possibility from the album Corporate Presentation - Key to Success, powered by JAMENDO.

Presented by Patrick Wallace, DO, a resident at University of Nevada, Las Vegas and member of the AAEM/RSA Education Committee, and Jorge Antonio Fernandez, MD, Assistant Professor of Clinical Emergency Medicine at Los Angeles County + USC Medical Center. Intro music by Akashic Records, Key to Success - Discover the Possibility from the album Corporate Presentation - Key to Success, powered by JAMENDO.

I had a very interesting conversation Shelby Grossman - political scientist at Stanford University. We talked about her research on informal trade in Lagos, and what we can learn generally about how institutions form from her findings. You can read this essay for a general background and explanation on what Shelby and I discussed on this episode.Download and other listening options are here - and you can kindly give us a rating here.TranscriptTL: Today, I am on with Shelby Grossman. Shelby is a research scholar at Stanford Internet Observatory and she is a political scientist. Welcome, Shelby. SG: Thanks so much, Tobi, for having me. TL: One question I would like to start with is that institutions that promote prosperity and positive economic activities like trade, like property rights, how do they develop in countries that do not yet have them? SG: Yeah, that's a great question and a lot of political scientists try to figure this out and you know, no one knows for sure. So there are many political scientists who think that there is a correlation between democracy and rule of law and contract enforcement. But I think what is interesting to me is how even within the same country, in different places, you can have different levels of rule of law and different types of property, of contract enforcement. TL: What are the patterns and the correlations that you noticed that really stand out from your research over the years? SG: In terms of property rights protection?TL: Yes.And so what I've observed, I think the main pattern is that good private governance, good private contract enforcement, is more likely when the state is actually threatening the group - SGSG: I think the thing that I have observed is, you know, a lot of people tend to think that when the state does not provide property rights protection, that private groups will emerge to provide this service. So private groups will emerge to provide impartial contract enforcements and those types of services. And the pattern that I've observed is that that doesn't always happen. So sometimes you have private groups that emerge that actually extort from their own group members. And so what I've observed, I think the main pattern is that good private governance, good private contract enforcement, is more likely when the state is actually threatening the group. So when the state threatens to intervene in a private group, that's when the group organises to provide these services. And in the absence of threats from the government, private group leaders actually extort from their own members. TL: I think that's one bit I found most fascinating from your field study in Lagos. I mean, usually, the intuition is that without government intervention, people would handle their business, enforce property rights within their groups. But, which I found counter-intuitive in a way, you're saying that the threat of government intervention actually promotes institutions that protect the interest of group members. What are the channels for such emergence?SG: So there are a couple of channels. To make it more concrete, my research focuses on markets associations in Lagos, so these are like when traders organise themselves or when traders are all in like a certain area and then they elect one of their own traders to be the head of the Market Association. And so to make this really concrete, there is one Market Association that I find super fascinating. It's called Oke-Arin in Lagos Island, it's predominantly a wine market. And this is a Market Association that, at least, at the time that I was studying them, they were kind of a paragon of good governance. So the market leader did all sorts of things to promote trade in the market. If a supplier sold one of his traders bad wine, like substandard wine or falsely labelled wine, he would organise a market-wide boycott of the supplier. And by doing things like that you just make it less likely that suppliers are going to cheat anyone in the market because they're afraid that they too will be boycotted. So what explains this? What is the reason for why this market is so well-governed and what I found from talking to the market leader and lots of traders is that this market is really threatened by NAFDAC, the National Food and Drug Administration, is that right? TL: Yes. SG: So NAFDAC has lots of authority to intervene in Oke-Arin and if they catch a trader selling falsely branded wine or substandard wine, they can arrest the trader. And so it's in the face of that state threat that the market leader does super aggressive policing of his own traders. So if he catches a trader selling falsely branded wine, he will lock up the shop, he will confiscate the goods. And he told me, literally...he said that 'the reason I do this is because I want to keep NAFDAC out of my market.' And you know when NAFDAC comes, it's not just NAFDAC. They come with the mobile police who are, kind of, a frightening sight sometimes, I'm sure you've seen them, they have those like big guns and the trucks and they scare away customers and so the market leader thinks it's in the best interest of the market to try to keep these people out of his market. And he does this by really regulating the quality of the goods that the traders are selling. So to step back and abstract from that, I think one channel is that when you face threats from the state, you want to keep them out of your business and so the way to do that is to not give them any excuse to intervene. And to not give them an excuse to intervene, you need to be kind of keeping your house in order, essentially.TL: Yeah. And maybe I'm trying to project too much into this one study. I'm just wondering, the findings...does it scale into other areas of the society? Like the relationship between citizens and police?SG: Interesting, tell me more about what you're thinking there? TL: Oh yeah, so what I'm thinking is, for example, there's been a movement, largely on Twitter, about the anti-robbery squad in the police called SARS. They're abusive, Amnesty just did a report recently about police brutality, which is pretty damning. They're abusive. There is no rule of law. Citizens basically have no rights when it comes to their relationship with the police. So I'm looking at this study as... if you have citizens' groups like the market associations, can they extract compromises that further entrenches the rule of law and the value for obeying the law and respecting rights in that arrangement the way we do with market associations?SG: Yeah, that's really fascinating. I think you definitely do see market associations negotiating with [the] police, negotiating with government officials. So the main way you see this...and let me know if this is not answering your question... the main way you see this is with the local government. So local government fees are set at the market level. So you can have two trade us in the same local government, but they will pay different fees depending on what market they’re at. And typically what happens is the market association negotiates with the local governments over fee collection and you can argue that this is kind of a way of encouraging rule of law, at least for, like, the well run market associations. Because sometimes market associations negotiate with the local government in a way that only benefits the market leader; essentially, the market leader and the local government are like colluding against the traders. But when it works well, what's happening is the market association is making local government taxation more predictable for the traders, more fair and I think that in itself is a form of strengthening the rule of law, because traders don't want to have unpredictable visits from my the local government where each time they come, a new fee is charged because that really makes it hard for traders to make plans for their business when they don't know what their level of taxation will be. So I think in that way - and many other scholars of argued this as well, I'm not the first person to say this - by having organised societal groups negotiate with different government entities, it can be a way of creating rule of law. The downside is that they're only creating these agreements for themselves, so it's not clear it's going to affect anyone other than the market association that's doing the negotiation. But I would argue that that's better than nothing and that is maybe the first step to a more like generalised rule of law. TL: I think you just went where I was going with that question that how does what is generally viewed as the ideal institutional form, how does it emerge from such group arrangements? And what I mean is constitutional individualism. That is, you, as a citizen, have a rights and your rights are protected and secured under the law?SG: Yeah, so there are different theories, one big theory is that war can actually make this more likely. For example, in Europe when, you know, various territories were about to be invaded, the way that they were able to defend themselves was by taxing people. Because taxes would help them pay for people who could fight off these attackers. But people aren't just going to agree to be taxed just, like, easily. They're going to want to hold onto their own money, and so the way that leaders were able to get people to pay taxes was by offering them various rights. And this is, you know, one theory for the emergence of democratic forms of government and rule of law. So it's kind of counter-intuitive that interstate war can actually make the emergence of democracy more likely. And so one of the things that's really interesting about Africa is since independence, there isn't really that much interstate conflict in Africa. Of course, there's a fair amount of intrastate, like civil war, but there isn't really that much interstate conflict. And some people argue that this has actually kind of stymied the emergence of [the] rule of law in some sense. Certainly, no one is advocating that there should be interstate war, but it's kind of a counter-intuitive silver lining of that kind of conflict. TL: What role does government capability play in this? So thinking about NAFDAC from the example you talked about, NAFDAC had this era where they took the job of regulating and policing fake and substandard products seriously. So now, the leadership changes and so is zeal or the mission for that regulatory drive. So, if the incentive or the ability or the capability weakens for government or any particular institution, does it change the incentive for the market association? SG: Yeah. Absolutely. I think, for example, I definitely don't want to say things are perfect in the US, things are not perfect in the US. We have many issues related to the rule of law, but in general in the US, you don't see like business associations operating at the same level as you do in Nigeria. And I think that's in part because rule of law is stronger in the US. And So what I mean by that is like when you can feel pretty comfortable relying on [the] courts to enforce contracts, you don't actually need these private associations to do that for you. And so what's interesting about dive of the Lagos markets is that many of the traders are themselves informal, by which I mean either that they are not registered with the Corporate Affairs Commission or some of their transactions are Informal. So some of their transactions are undocumented, and when that's the case you obviously can't rely on the courts for contract enforcement because nothing about the transaction was formal, and so that causes you to need these private associations. I think in general, as the rule of law increases, the role of the private associations decreases. That being said, that's not always the case, so there are many types of products that are sold in the US for which people cannot rely on the courts for contract enforcement. So a famous example of this that Barak Richman has done a lot of really fascinating work on is the diamond trade. It's actually really hard for courts to enforce diamond contracts for many reasons, it's also just really easy to steal diamonds and get away with it because they're so tiny. And so as a result of this, there's actually a really big role for private associations in the diamond industry in the US. In the US it's predominantly Orthodox Jews who trade diamonds and have all this really fascinating associations that Richmond has written about. But to answer your question, I think, yes, in general as a rule of law increases, the role of these associations is less critical.TL: I'm also wondering about the role of the civil society in all this. We can also view them as some form of association or groups who are trying to organize citizens like themselves and advocate for various rights or stop various form of abuses. Do they have the same incentive as traders who basically have a lot of skin in the game? They have a lot to lose if those institutions are actually predatory. Or are the incentives different?SG: Yeah, so actually one of my colleagues Hakeem Bishi is starting to work on this by looking at residents associations like neighbourhood associations in Lagos and I'll be interested to see what he finds. But my hunch is that these traders actually aren't that unique, that I think this would apply to other types of civil society groups. So you can easily imagine a head of a residents' association being predatory and collecting funds that they say will be used for private security, but maybe underpaying the security guards or saying that they'll hire ten security guards when in fact they only hire five. So I think it's simple to imagine that there will be similar incentives for other types of associations, but of course, also, it could be different, so I'm excited to see what my colleague Hakeem figures out.TL: Again, I see your study...and I'm sorry if I'm projecting too much onto this. Please stop me if you think I'm overreaching. So again, I'm just curious that in Africa we're not in the original state anymore, so, we just have intermediate states. We can't have wars anymore. A lot of the channels by which these institutions emerge are way, way into the past. And of course, globalization has allowed for all kinds of interventions. So how do you approach things like political reforms? Like you want to reform the judiciary, you want to reform the police, is it more effective with an approach like this bottom-up market association types or top-down? Which offers a country the most feasible path to credible political evolution?SG: Yeah, I mean, this is a really tough question. Like, if people knew the answer to this, then it would be pretty easy to just, you know, have judicial reform everywhere in the world. And so I think no one really knows the answer to this question. I think there are some theories that elite competition can lead to some of these reforms. There are other theories that, as you mentioned, like grassroots movements are more effective? I definitely don't know the answer to this. I think my one opinion is that I don't think international aid is really the way to go. You know, I've just seen too many examples of international organizations coming in and, like, thinking that it's just an education problem that if only people knew that this policy is better for rule of law, then they would implement it. And thinking that if you just tell people to do that, it will happen. And of course, that's not the issue. There are so many reasons that things are the way they are. Various people benefit from [the] current structures of power. So yeah, I don't really know the answer.So one other thing I would say is, I think there's really space for looking at subnational variation and I have a colleague Jonathan [...] who does this. Like Nigeria is such a cool country because it's a federal system and there's huge variation in rule of law at a state level. Jigawa, Kaduna, Lagos, of course, they have their problems but I think in general people think they're relatively well government compared to some of the other states when it comes to rule of law. And so trying to figure out what's going on there, what explains that variation and some people have theories and say, 'oh, it's just because Tinubu exists.' A very like individualist account, like Tinubu has a long time horizon and for various reasons, maybe like earlier...this is an argument made by D.N. Degremont, that... when the APC did not control the Federal Government, Tinubu aspired to control the Federal Government and thought that by improving some of these things in South-Western Nigeria, that that could increase the strength of the APC vis a vis the Federal Government. So there are those types of theories as well, but I think there is a lot more room for people to do more research on this kind of subnational variation. But I'd be curious to know what your thoughts are on this question. TL: Yeah, I think there is some... in my opinion, again, I should state that I don't have any clear evidence, but I think there's some credibility to that explanation. I mean, one area where Tinubu really did punch above his weight, so to speak, was in the area of revenue. When there was a power struggle between Lagos and the Federal Government over local government creation, and Obasanjo did not release federal allocation to Lagos, Tinubu did a lot of things and increased Lagos' revenue and the state was able to punch above its weight in public infrastructure projects and some of that legacy still abounds. Again, there are political benefits because he was also able to finance electoral competition for the party in federal controlled states, so I think that explanation has some merits, in my opinion. SG: Yeah, and it'd be interesting to see if the explanation holds outside of Nigeria. So like if in other federal countries where you have a similar political dynamic where there is a politician who is not currently in the ruling party but aspires to be in as a long time horizon... I don't know maybe these conditions are pretty narrow, but it'll just be interesting to see if you'll see similar dynamics playing out when those conditions hold in other federal countries. TL: What explanatory power would you grant to the so-called resource curse in all of this? SG: Yeah, I mean, I think the resource curse is really compelling. But as you just noted, I think it holds a lot of explanatory power for why the Federal Government of Nigeria is the way it is, but at the same time, it's so fascinating that Lagos was getting these oil checks as well and still felt the need to increase its own tax base for some of the reasons you were just saying, like, Obasanjo not recognizing all the local governments and withholding funds for that reason. So, I think the oil curse is not deterministic, that even in a country that has a lot of oil revenue as a percent of total national revenue, there are still ways to overcome that which we see in Kaduna, in Lagos, in Jigawa. TL: And I want to go back to elite competition, something you mentioned earlier. It's a bit of a chicken and egg problem, as some of my colleagues have put it. Some have argued that before we can have some of these reforms take hold in Nigeria, there has to be a new middle class that would emerge, with [a] new ethos that can drive the discourse and push back and ask pertinent questions of the government and maybe even run for office and change the system from [the] inside. But, the flip side is that without policies that promote growth, you cannot have the enrichment that allows for the emergence of a middle class. So how do I, for example, resolve that dilemma? You're the expert. SG: Well, I don't know if I'm the expert on that question, but yeah, I think the thing that's really fascinating about West Africa, but this is probably true more generally, is how expensive it is to run for office. So one of my friends, Amanda Pingston, has done research on this in Benin Republic, and she shows that it's so expensive to run for local office, to be an MP in Benin. That basically because... you know, Benin is very different from Nigeria in that it doesn't have this big of a private sector economy, and so as a result, really the only people who can afford to mount this campaigns are people who already had positions in government because that's the way that you can make money in Benin.And so as a result, the people who are running to be MPs are people who have already had positions in government, and it really prevents the emergence of a new ruling class of people who were shopkeepers and built up a little business. In Benin, the public sector employment is just such a high share of employment that that can't happen. So obviously, to some extent, that's different in Nigeria, but to some extent, it's not. So you can imagine that there are many states in Nigeria, maybe in the northwest, the northeast, where, really, the only people who could afford to run for office are people already connected to the government in one way or another. I think Lagos is a little different because there are so many other ways to make money beyond being connected to the government. So I think that's part of the problem, but it's all chicken or the egg, what has to happen first for the nature of the ruling class to change? But I definitely think money is a big part of it.TL: One other thing I want to get your reaction to is corruption. We can agree that corruption is bad, especially in relation to [the] public treasury and its influence in robbing people of the provision of public goods, which is [the] government's job. But one thing I've encountered recently from political scientists, Ang Yuen Yuen (I hope I'm getting her name correctly), using China as an example, is that low corruption, especially at the local level, can actually be harnessed for positive institutional building and building the state. She gave examples of how Chinese officials will leverage personal relationships that we would standardly label as corrupt constitutionally to provide roads, build schools, build bridges, allocate land. What's your reaction to that view? Is there a positive niche for corruption? SG: Yeah, so I have kind of complicated views about corruption and in general, I don't really use the word in my research just because I feel like people define corruption differently. So one of the things that I found so fascinating in talking to traders in Lagos is they don't mean the same thing I mean by corruption. So, for example, it is very common in Lagos for local government officials, when they collect fees from traders, to pocket some portion of them and then the other portion goes into the official local government bank account. So I would consider that corruption - that's the use of public funds for private gain. Traders, on the other hand, do not consider that corruption. What traders consider corruption is if all of the sudden the local government raises fees exorbitantly, or if the local government has been collecting 500, 500, 500 and then one time they say, ah, today, we are collecting 1500, that's what traders consider corruption. And traders don't necessarily care about what proportion of their fees are just going straight to the chairman versus into the official bank account.So, most people would say 'oh, that's bad,' that these local government chairmen and the lower level bureaucrats are pocketing these funds. On the other hand, they're probably on underpaid. So maybe this is a way of topping up their salary, not in a way that's going to let them buy a Mercedes, but just in a way that's going to give them a decent salary. So I don't really feel like it's my place to say this is bad corruption versus this is good corruption. But I think there are a lot of political scientists who actually think that focusing on corruption as a way to get to better rule of law is kind of misguided, and that actually you want to align incentive between politicians and advocates for the rule of law and maybe by getting angry about the 20 percent of the contracts they took as kickbacks is not really the most productive way to go. TL: The control of violence, how important is it in the emergence of institutions? I know Douglas North, Patrick Wallace and co. have done some work in this area but what are your views?SG: Yeah, so I don't have any great thoughts on this because I've never really studied violent areas. I guess Lagos used to be more violent than it is today, but, yeah, I think it's complicated. I'm really only familiar with these big picture arguments about the history of Europe and wars and state-making. But I think in general, violence is certainly bad for trade, in the short term at least, it just makes the lives of traders unpredictable and you really want predictability when you're a trader because it allows you to plan and make long term decisions. TL: So I have a bit of pet theory and I want you to tell me where I'm wrong. Now, the way I think about this... it's not mutually exclusive, but I see some form of tension, especially in a country like Nigeria, between rights and social order. And I think that sometimes our push for rights, especially with institutions that do not have the capacity to establish or govern that order may be a bit asking too much. So in a way, I think that for institutions to emerge and develop and mature, the state has to establish its monopoly of violence, so to speak. And in that process, citizens may have to tolerate, of course, not to a great extent, but the question is where do you draw the line? So citizens may have to tolerate some form of abuse of their rights. What do you think of that? SG: Can you tell me more specifically, like, what rights you're thinking of? TL: Okay, let me give you an example. There's a common practice here which, again, some aid agencies and nongovernmental organizations have documented quite a lot, which is arrests and imprisonment of innocent people. There's this policing form where, to establish order in a particular neighbourhood, the police just go and do these raids. You know, there are no investigations, they just pack a lot of all these young men and lock them up. And in some cases, again, I should specify...in some cases, some of them are truly guilty, but in other cases, they pack a lot of innocent people and then lock them up. Sadly, some, for years. But I've also kind of noticed that the problem with policing in relation to that problem is that the police, as an institution itself, does not have any capacity to actually investigate crime, so they just have this one-cap fits all approach. But as citizens, the way we demand for our rights to be respected is that, 'uh, well, no. There is no excuse for arresting the innocent, the police should be able to investigate the details and know who is guilty and who is not and what happened behind the scenes,' and...you know, we have this list of demands. And sometimes I feel we are demanding something that our institutions cannot deliver at the moment. SG: Yeah, that's really fascinating. I don't know. There might be something to that. At the same time, I would be a little afraid that when you arrest an innocent person and keep them in prison for several years you're going to be creating someone who when they're released is not going to be promoting societal order and is probably going to be really angry at the government and probably isn't going to be the most productive member of society after that. And also probably, you know, his entire extended family is just going to be really angry at the state as well. So I don't think that is super productive but at the same time, I hear what you're saying. Should we arrest no one because the police don't have the capacity to do true investigations? That doesn't seem like the right answer either.So, yeah, I don't really know what's best with that. And probably there is some middle ground where, I don't know, maybe you could have like community groups that partner with the police? Obviously, this could be problematic in various ways but I think there are some models of community policing where the community maybe has better information on what actually went down than the police do. But I totally hear what you're describing and I think people will comment and are like (citizens who are like), 'you shouldn't arrest anyone if you don't have a capacity to perfectly investigate the case,' I think that seems misguided as well.TL: Yeah. I agree with you. Tell us about what you're working on currently. I know you're working on disinformation, what threats does misinformation pose to developing countries like Nigeria?SG: Yeah, so, I've recently shifted a bit to focus on disinformation campaigns and in particular foreign, online, disinformation campaigns. You know, for example, I helped to uncover at the end of last year a Russian disinformation campaign that was targeting a bunch of African countries, not Nigeria, but Libya, Madagascar, Mozambique, DRC. And what was really interesting about the campaign was this was a campaign that was linked to a Russian oligarch named Yevgeny Prigozhin, so this is the same guy who coordinated the social media information campaigns that targeted the US in 2016. And what's really interesting about these campaigns was that he'd created all these Facebook pages that were working to bolster the ruling party in these countries or other political actors that he supported. But he actually wasn't pushing fake news or misinformation, he was just posting like hyper-partisan contents. Contents that said things like: 'wouldn't this guy make a great president again? You should vote for him.' So that's not necessarily untrue. It's not even falsifiable, it's just like a sentiment. But this operation was trying to create the impression that there was a whole lot of grassroots support for these very individuals, and I think that's really dangerous especially given that so many people get their news and information from social media these days. If you think that there is so much grassroots support for someone, that can possibly change the way that you think about things.So that's like some of what I'm doing, and then more recently I've started investigating belief in misinformation in Nigeria. So there have been a lot, a lot, a lot of untrue things about the coronavirus that has spread around the world. For example, there are conspiracy theories about the role of 5G, about Bill Gates trying to kill people, and so I've been looking into belief in those types of misinformation, which also can be dangerous. Because if you believe 5G causes coronavirus, then maybe you're not going to wash your hands because you don't believe that that's the way in which the disease spreads. TL: And what responsibility do you think that the big Tech companies who owned some of the platforms where a lot of this disinformation campaigns happen, what responsibility do you think they should have in relation to this problem? I know there's a lot of accountability in the developed countries, but it's almost absent in public discuss over here. SG: Yeah, I think the platforms should have primary responsibility in dealing with this stuff, in part because they have more information than you or I do. They have information like IP addresses, and so they are better placed to figure out that certain posts are not coming from within Nigeria, even though they are pretending to be coming from within Nigeria, and, you know, just give it their automated methods. I think they are in a better place to put warning labels on 5G misinformation, that type of thing. And I think to some extent they're actually doing a ton. I think they're increasingly taking content moderation seriously. They found much of the Russian network targeting Africa, so to some extent, they are actually doing quite a bit of investigation into disinformation campaigns targeting countries outside the US.But at the same time, for sure, their work is US-centric and the policies that they have in place are not implemented equally across countries. I think that is problematic. And I think there should be pressure placed on the platforms to hire more people who can help them implement content moderation policies carefully across countries because it's really hard for an American to know what hate speech in Myanmar looks like. You really need someone who is from Myanmar to do that. I mean, the challenge then is that it's actually really hard to hire the right people to do this kind of content moderation work. This is a point that my boss has made a few times. If you want someone to do content moderation in Myanmar, first of all, Facebook often doesn't want to hire people who are in Myanmar. For safety reasons, they want the content moderators to be outside of the country. But then you have to find someone who's not based in Myanmar and who is kind of impartial. So not connected to the ruling party or anything like that, and that can be really tricky. I think they can be doing better but there also are real hurdles to defining the scope of some of these policies across different cultures. TL: Tell me how does a country like the US find itself in, if we were to believe the media... in a place where there's been some form of institutional decline? There are different investigations about presidential abuse of power or corruption, and even the government's response to the coronavirus. You're a political scientist, so tell me, how does a hyper-developed country like the US find itself in such a position? SG: Yeah, so it's a tough question. I think you know the big picture of what happened is we elected a populist president and populist presidents globally are generally not good for democracy. So Trump is in my mind not that exceptional. He, in many ways, acts similarly to people like Chavez and populists elsewhere. And I think there are a number of ways in which populists can lead to democratic decline. Trump is always bashing the mainstream media and that's a common, common, common strategy of populists. And when you reduce trust in mainstream media, then the only person you trust is the president and so Trump can say anything he wants and people will believe him because there're not going to believe what the New York Times or the Washington Post or the Wall Street Journal says. So I think that's part of what explains the situation that we're in right now is that a huge portion of society just doesn't believe mainstream media anymore, and so they're willing to go along with or not try to counter various actions that Trump takes. I do think a lot of people who voted for Trump, they're not dumb. I think they do often see what he's doing and they're angry about it. But I think in general like that's what's going on. We elected a populist and he is acting in the same way that populists always do and more times than not, having a populist leads to democratic erosion. My hope is that America is strong enough to surmount this. Many other countries that have had populist presidents have been a kind of weaker democracies, like they haven't been democracies for that long and I think the fact that America has been a democracy for so long means that maybe trump won't do a ton of permanent damage, but I think it's hard to say. TL: I hope it gets sorted out as well. SG: Thanks. TL: I'm going to ask you one last question which is a bit of a tradition for the show and our listeners. What's the one big idea you're most excited about right now and that you would like to see spread everywhere?SG: I think I'm going to do two big ideas. TL: SureSG: Related to my two, kind of, fields of research. So I think in terms of the disinformation stuff, the big idea is that most disinformation is no longer untrue. So most disinformation is people spreading hyper-partisan content, but trying to deceive people about their identity. So I think so often when people think about disinformation they think about fake news, but increasingly the sophisticated actors are not pushing fake news, they're pushing unfalsifiable hyper-partisan content, and I think people need to be more aware of that. I think the second big idea that I want people to think about more is that, as I mentioned before, not all private governance is good. That often times when the rule of law is weak and private groups emerge, the leaders of those groups are predatory and extort from their own group members. And I think a lot of times when people think about private associations and civil society, they're just thinking about the upside but oftentimes civil society groups can be predatory. So I think that will be the second big idea. TL: Thank you very much, Shelby. Shelby Grossman it's been wonderful talking to you. SG: This is fantastic, so fascinating. Thanks so much, Tobi. This is a public episode. Get access to private episodes at www.ideasuntrapped.com/subscribe

Presented by Patrick Wallace, DO, a resident at University of Nevada, Las Vegas and member of the AAEM/RSA Education Committee, and Robert P. Lam, MD FAAEM, Clinical Assistant Professor at the University of Colorado and AAEM Wellness Committee Chair. Intro music by Akashic Records, Key to Success - Discover the Possibility from the album Corporate Presentation - Key to Success, powered by JAMENDO.

Program Specialist for World Languages and Global Workforce Initiatives with the Georgia Department of Education, Patrick Wallace is in studio for today's episode of Atlanta Real Estate Forum Radio. Joined by co­-hosts Carol Morgan and Todd Schnick, Wallace discusses the broad scope of his job, why knowledge of other languages is especially important in the current climate and more in today's Around Atlanta segment of Radio. Wallace oversees the 216 school districts in the state of Georgia in the area of world languages. This includes more than 550,000 students learning a language across the state. Wallace serves and supports the administration, as well as the students with day-to-day activities such as curriculum questions, articulation questions, hiring and finding talents across Georgia. Wallace is also involved in several programs, including the Georgia Seal of Biliteracy. The Georgia Seal of Biliteracy is an insignia students have the opportunity to receive upon graduation that recognizes them for high proficiency in a second language. Another program Wallace is involved with is the International Skills Diplomacy program. This organization is a unique program that started in 2015. It consists of international businesses recognizing leaders in the school system who have a global or international focus on their education. A third program Wallace dedicates his time to is the Dual Language Immersion Initiative. This program seeks to teach students in two different languages throughout the day. The goal is to have students immersed in two separate languages every day in school. Apart from the many programs Wallace is involved in supporting and overseeing, he also spends his time meeting with other international agencies and departments to work with and grow the international community in Georgia. This includes outreach to non-English-speaking families to complete tasks such as interpreting, translating and clarifying objectives. “These are all the things that go into my wheelhouse,” said Wallace. “It's quite a large area, but it has never been boring. The job has always been exciting with plenty to do. There is a tremendous amount of progress happening in global education in Georgia.” Wallace believes that the understanding of several different languages and cultures is especially important during current times. With the incredible amount of uncertainty and fear surrounding the global COVID-19 (coronavirus) pandemic, several countries are experiencing similar repercussions and consequences of the virus. The knowledge of other languages and the ability to interact with different cultures experiencing a similar way of life due to outside influences is increasingly important. “We also need to have that cooperation within the context of our society to be able to work with people from different backgrounds,” said Wallace. “I constantly hear from business professionals again and again how collaboration and communication are increasingly important.” These ideals are fostered in the world language classroom where Wallace and his organization are working to improve knowledge, skills and interaction between nations. In addition to the advantages on a global scale, learning a second language can also be beneficial for a number of other reasons. Cognitive and academic advancement is a huge value to students who learn a second language, as well as higher empathy and understanding levels. To learn more about Patrick Wallace or the World Languages and Global Workforce Initiatives, visit the link here. You can also listen to the full interview above. Never miss an episode of Atlanta Real Estate Forum Radio! Subscribe to the podcast here. You can also get a recap of any past episodes on our Radio page. Georgia Residential Mortgage Licensee, License #22564. NMLS ID #6606. Subject to borrower and property qualifications. Not all applicants will qualify. New American Funding and the World Languages and Global Workforc...

Program Specialist for World Languages and Global Workforce Initiatives with the Georgia Department of Education, Patrick Wallace is in studio for today’s episode of Atlanta Real Estate Forum Radio. Joined by co­-hosts Carol Morgan and Todd Schnick, Wallace discusses the broad scope of his job, why knowledge of other languages is especially important in the […] The post World Languages and Global Workforce Initiatives on Radio appeared first on Atlanta Real Estate Forum.

Zu Gast im Muttersprache Podcast ist Patrick Wallace Program Specialist for World Languages & Global Work Initiativespwallace@doe.k12.ga.usFacebook: Georgia Department of Education World Languages​Instagram: gadoeworldlanguagesTwitter: gadoeworldlanguages​Georgia Seal of Biliteracy - https://www.gadoe.org/Curriculum-Instruction-and-Assessment/Curriculum-and-Instruction/Pages/Georgia%27s-Seal-of-Biliteracy.aspxGeorgia International Skills Diploma Seal - https://www.gadoe.org/Curriculum-Instruction-and-Assessment/Curriculum-and-Instruction/Pages/International-Skills-Diploma-Seal.aspxGeorgia Dual Language Immersion Initiative - https://www.gadoe.org/Curriculum-Instruction-and-Assessment/Curriculum-and-Instruction/Pages/Dual-Immersion-Language-Programs-in-Georgia.aspxDLI Dashboard - https://ksugis.maps.arcgis.com/apps/MapSeries/index.html?appid=cc276aae229e4148891a07783074f677March GaDOE World Language Update - https://www.gadoe.org/Curriculum-Instruction-and-Assessment/Curriculum-and-Instruction/2019%20%202020%20HLS/GaDOE%20World%20Language%20Update%20March%202020.pdfDiese Podcast Episode wurde gesponsored von www.mygermany.comHost Monique Menesi www.meetus.us German/American Executive Search & Recruiting, Global Leadership & Career Coaching monique@meetus.us 

The boys are back and dive into Tom Brady going to the Buccaneers, NFL Free Agency being underway, the Coronavirus ruining everything, and more. Also, Taylor interviews two senior college baseball players from SUNY Purchase, Patrick Wallace & CJ Owens. They talk about how their senior season was cancelled due to the Coronavirus and how they have been coping with it. Finally, at the end of the show Taylor and Liam dive into the 1996 World Series. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/end-of-the-bench/support

Welcome to Chapter 3 of An AE's Story! This week, we are joined by Patrick Wallace, an association executive with over 40 years of experience in the real estate industry. This is.. an AE Story. 

Today's show highlighted the Atlanta Jewish Film Festival, the upcoming Savannah Book Festival and the importance of foreign language education for Georgia students. GPB reporter Stephen Fowler stopped by "On Second Thought" to discuss the State of the Union and former Georgia gubernatorial candidate Stacey Abrams' Democratic response. We also heard from Patrick Wallace , program specialist for world languages and global workforce initiatives at the Georgia Department of Education, and Jacques Marcotte with the French-American Chamber of Commerce in Atlanta. They discussed Georgia students' readiness for the global workforce through language learning.

In this episode, Patrick Wallace, OMS-IV, and Ilene Bezjian, DBA discuss professionalism and etiquette that every emergency medicine medical student should know while preparing to interview. Mr. Wallace is a Medical Student at Rocky Vista University College of Osteopathic Medicine and a member of the RSA Education Committee. Dr. Bezjian is a senior strategy consultant and former Dean of the School of Business and Management at Azusa Pacific University.

Presented by Patrick Wallace, OMS-IV, Medical Student at Rocky Vista University College of Osteopathic Medicine and a member of the RSA Education Committee, and Ilene Bezjian DBA, senior strategy consultant and former Dean of the School of Business and Management at Azusa Pacific University. Intro music by Akashic Records, Key to Success - Discover the Possibility from the album Corporate Presentation - Key to Success, powered by JAMENDO.

In this episode, Patrick Wallace and Sameed Shaikh, DO discuss the approach to working up an acutely Psychotic patient. Mr. Wallace is a medical student at Rocky Vista University and '17-‘18 RSA Education Committee member. Dr. Shaikh is an emergency physician at UCHealth Memorial Hospital in Colorado Springs.

Presented by Patrick Wallace, medical student at Rocky Vista University and 17-18 RSA Education Committee member, and Sameed Shaikh, DO, emergency physician at UCHealth Memorial Hospital in Colorado Springs. Intro music by Akashic Records, Key to Success - Discover the Possibility from the album Corporate Presentation - Key to Success, powered by JAMENDO.

Joel Ramos speaks with Patrick Wallace, ‎Vice President of Business Development at eSight, about the eSight 3, which brings a revolutionary technology to those who can no longer see. eSight 3 is a versatile, wearable, hands-free solution that provides sight without the need for any surgery. It is a game-changing breakthrough that uses advanced technology, built upon many years of research and development, to replicate sight for an individual who is legally blind or living with low vision.

Joel Ramos speaks with Patrick Wallace, ‎Vice President of Business Development at eSight, about the eSight 3, which brings a revolutionary technology to those who can no longer see. eSight 3 is a versatile, wearable, hands-free solution that provides sight without the need for any surgery. It is a game-changing breakthrough that uses advanced technology, built upon many years of research and development, to replicate sight for an individual who is legally blind or living with low vision.

Welcome back to The Fantasy Six Pack hour with your hosts Joe Bond and Patrick Wallace.  In this episode we will be talking about the tragedy that was the Jamaal Charles injury and how to move on if you were an unlucky owner of him. We then discuss Andy Dalton, not doing Andy Dalton things and other oddities of the NFL this season that just seem to becoming the norm. Last we get you prepped for Week 6 by going over the top waiver wire adds, injuries and reviewing the best/worst game and our sleeper/bust picks of the week. Feel free to call in at anytime to ask for our advice or join the conversation.

Tonight we are back with another episode of the Home Run The Jewels Fantasy Baseball Podcast with me, your host Travis Pastore, and brought to you by the "So-Called Fantasy Experts". We have staff writer Patrick Wallace as our guest to talk the art of midseason trades, some of his buy low candidates and maybe play a game of buy or sell.  I'd like Patrick's opinion on the top prospect influx we have seen and maybe he'll let me vent about how every league needs an innings cap. All that and more tonight on the Home Run The Jewels Podcast!

Lauren joins me this week to discuss the losses of Trevor Lacey, Kyle Washington and Patrick Wallace from the State basketball team, the calling up of Carlos Rodon to the majors...and we dispense a little advice as well.

Patrick Wallace and I discuss his dynasty rankings and other strategies on how to build a dynasty that rivals the 1990s Yankess. We discuss how to judge prospect hype prospects and what to do with closers on tonights podcast!