![Behind the Genes](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz.png)
We are Genomics England and our vision is to create a world where everyone benefits from genomic healthcare. Introducing our refreshed podcast identity: Behind the Genes, previously known as The G Word. Join us every fortnight, where we cover everything from the latest in cutting-edge research to real-life stories from those affected by rare conditions and cancer. With thoughtful conversations, we take you behind the science. You can also tune in to our Genomics 101 explainer series which breaks down complex terms in under 10 minutes.
Episodes
![Dr Rich Scott and Helen White: How can we work in partnership towards a new era of genomic medicine and research?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday Jul 17, 2024
Wednesday Jul 17, 2024
Genomics has changed considerably over the past 10 years, and we are now exploring how to integrate it into routine healthcare. In this episode, our guests reflect on this evolution and discuss how the key learnings from the past 10 years can shape the genomics ecosystem of the future. They highlight the importance of partnership across teams, organisations and participants, emphasising the importance of keeping participant and patient benefit at the heart of research, whilst also addressing the ethical and safe storage of patient data.
In this episode, our host, Helen White, who is the Participant Panel Vice-Chair for cancer at Genomics England, speaks with Dr Rich Scott, CEO of Genomics England.
"Our goal is to ensure that everyone can benefit from the advancements in genomics, but this requires collaboration across disciplines and a commitment to ethical practices in managing and sharing genomic data."
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/How_can_we_work_in_partnership_towards_a_new_era_of_genomic_medicine_and_research.docx
Helen: Welcome to Behind the Genes.
Rich: There’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care.
Helen: My name is Helen White and I am the Participant Panel Vice Chair for Cancer, at Genomics England. On today’s episode I’m joined by Dr Richard Scott, Chief Executive Officer for Genomics England. And today we’ll be discussing Richard’s recent appointment as CEO, lessons learnt from the last ten years in the evolution of genomics in healthcare, and how these learnings will be taken forward in the next ten years. And we’ll also visit the importance of keeping participant and patient benefit at the heart of research, as well as the ethical and safe storage of patient data. If you enjoy today’s episode we would love your support: please like, share and rate us on wherever you listen to your podcast.
Before we dive into the interview with Rich, I wanted to take a moment to share my story and tell you a little bit about myself. I have been a member of the Participant Panel at Genomics England since 2018. It was the year before that when I was diagnosed with endometrial, or womb cancer, and was offered the chance to join the 100,000 Genomes Project, which felt like something positive at what was otherwise quite a scary time. It turns out that I have something called Lynch syndrome, that’s a genetic condition that increases my chance of developing certain cancers, particularly womb and bowel cancer, which is actually a really useful thing to know as there are things I can do to reduce my chance of getting cancer; things like having regular colonoscopies and taking daily aspirin. I have now been on the participant panel for six years and one year ago I was appointed as Vice Chair for cancer. This is a new and developing role and I am excited to have so far helped recruit more people with lived experience of cancer to the panel and to be assisting Genomics England with connecting to organisations that advocate for people whose lives have been touched by cancer.
So that’s enough about me. I am delighted to be joined today by Richard Scott, and I am very much looking forward to our conversation. Welcome, Rich.
Thank you. So Rich, you’ve recently been appointed CEO of Genomics England. Can you tell me a bit about your background and what brought you to this role?
Rich: It’s a really good question and it’s one that doesn’t have a really very simple answer. I guess what it boils down to is I guess I’ve always had an interest, even as a child, for whatever reason, in genetics and genomics. I have also then always been drawn to things where I can have an impact and particularly the impact in healthcare and that’s what took me to being a medical student. And I guess it’s that combination of that particular interest in genetics and being able to see, even when I was at medical school I qualified in 2000 that this was an area of medicine that was going to be really important in the future. And then as I trained, as I did a PhD and as I saw the technology develop and change and then when I saw the UK government and the NHS investing in genomics in a really foresighted way, I found myself eight or nine years sitting at Great Ormond Street as a consultant in clinical genetics where I still practice, I still do one clinic a month there as a clinical genetics consultant seeing families with rare conditions.
But I could see when Genomics England was established that this was something, as I said, really foresightful where we could really collectively across the country make more of a difference together in terms of patient and healthcare outcomes. So I joined GEL eight or nine years ago initially in a subject matter expert role, and really found myself the more time it passed, understanding how working in my role at GEL and helping GEL be a really productive part of what is a busy genomics healthcare ecosystem in the UK, we can make a big difference, and that’s the thing that just wakes me up in the morning, is realising how much there is left to do, being proud of the stuff we’ve done, the difference we’ve made to participants in our programmes already, but realising that many of those still need our support to do better and the big distance left to go before we really deliver on I think the long-term promise of genomics, and I feel my mixture of skills and experience make me really excited to be in the middle of that.
Helen: Thank you. Yes, it sounds like you’ve brought many skills and experience, and interesting to hear that as a child you already had that interest in genetics and where that’s taken you. Can you tell me what being CEO Genomics England means for you? What are your aspirations for your first year in this position?
Rich: Well, I guess, as you can tell, I’m really excited to take on this role. As I said, as a doctor I’m always focused on the impact for patients and our participants and ultimately it’s the broader health of the nation. And the role I see Genomics England playing and being able to play in the future, sort of building on that, the leadership position the UK’s always had in genomics – you know if you look back to the discovery of the structure of DNA, the invention of sequencing technologies and also the clinical implementation coming from that government investment and the NHS investment, what excites me most about GEL is that we can be there, playing a critical role alongside others in that ecosystem, whether that’s in the NHS, whether it’s our participants and the patients who we’re aiming to support academia and industry, to create a whole that’s greater than the sum of the parts, and I genuinely feel that the UK remains uniquely placed to live out that potential that genomics has, engaging in the questions, not just you know, the scientific questions of: what could genomics test for? Or, how could this be implemented and is it cost-effective?
But also being able to have the nuanced conversation of what we all and our participants in the public and general, expect in terms of the care we receive or how our data is looked after, and getting that really balanced view on how we chart a path forwards where we can really see big differences being made in the future, and I think always being honest to ourselves about where we are today and that things don’t come in spotting some position a long time in the future that we want to navigate to, but also being really focused on the here and now and what is possible and what is evidenced, and what the next set of evidence or discussions or conversations in the public we need to have to help navigate ourselves there and that’s where at the moment our focus at Genomics England is both being very clear sighted on where Genomics could go, and also thinking very clearly about where we are today, and so very much at the moment for us it’s about focusing on the life service we offer to the NHS and we’re really proud to be part of a world-leading whole genome sequencing service, the first national health service in the world to be providing that in the context of cancer and rare disease, and so offering and providing our service that contributes to that.
Supporting researchers so that we can keep the flow of discoveries coming and also for example, making sure that our participants in existing programmes continue to get new answers as the science evolves. So, the last year more than 2,000 families had new findings fed back because of new knowledge that’s accumulating, keeping that flow going. And then we’ve got three big research initiatives going on at the moment where we’re really focusing on delivering around them. We’ve got a diverse data initiative where we’re really focused on making sure the research library, the National Genomic Research Library, our participants are representative of the UK population, so the discoveries that we’re supporting are relevant to everyone; our cancer initiative which is exploring the use of new sequencing technology in the context of cancer, and also looking at the use of image data and other modalities of data, alongside generic data to drive new discoveries.
And then the third initiative is our newborn genomes programme, where we’re asking a big question through a research study to generate evidence to ultimately answer the question: should every baby when they’re born be offered whole genome sequencing? Most pressingly to improve and broader the range of conditions that we can look for that are severe and treatable. So, this year we’re very much focused on delivering on those promises that we’ve made to our participants and our partners and through those programmes and very much with an eye to the future thinking about what we need to change in terms of the use of underpinning technology, so that we know that we’ve got the potential to scale, to think about the broader use of genomics in years to come as evidence evolves.
Helen: So Rich, there have been many advances in genomics in the last ten years. What do you think are the big lessons from those last ten years, and what do you think the next ten years will look like for the genomics ecosystem, what impact will this all have on healthcare as we know it?
Rich: So, genomics has changed extraordinarily in the last ten years thanks to shifts both in the technology, particularly the sequencing technology but also some of the computing technology that’s there to deal with the scale of data. Ten years ago we were talking about the 100,000 genomes project and beginning the project itself, but it was still very early in the use of whole genome sequencing, that’s gone from something where the big question around the 100,000 genomes project was: can this technology be used in routine care in cancer and for rare conditions, and if so, how do we do that?
And we’ve learnt both I think about that specific question and as I mentioned, we’re enormously proud to be part of enabling the NHS whole genome sequencing clinical service, so that has entered routine care. I think along the way the biggest lesson for me is actually one about this being about partnership and about working as a team across many different organisations and with our participants, and recognising that this isn’t just about one set of questions, or it’s not just about clinical or scientific questions, it’s about joining everything up together back to that point around, so a discussion about what people expect – this is about doing stuff together and learning often quite complex lessons about practicalities is one things, for example, one of the really big lessons we learnt around the use of whole genome sequencing in cancer are just practical lessons about handling of tissue samples and the need to make sure the right fridges are available on the right corridor of a hospital, with plugs available to plug them into, through to questions around, as I say, people’s expectations around how their data is stored, which it’s used for, which again there’s really strong precedent for, and as we explored, different uses of genomic technology, we shouldn’t just take those previous answers for granted, we need to make sure we validate and check with people what their expectations are.
So I think that’s the big one for me is sort of the number of different angles with which one explores questions and the fact that this is very much about doing it together. I think just one other piece which is so easy for us here to take for granted is that doing things at national scale with national scale investment from government, from other funders and from the NHS is absolutely critical and when you look across the world, we are in an extraordinarily privileged position here in this country because of that investment and because that investment recognises the need critically to join clinical care and research in a whole, where you recognise that you’re doing multiple things at once, but joining them up rather than them being two worlds, is really, really critical, and we’re really lucky to be able to do that at national scale.
So then thinking about what the next ten years might look like for the genomics ecosystem, I think lots of those things continue, so I think national scale and the need for ongoing investment to keep up our position at the forefront in terms of answering these big questions about the use of genomics in healthcare, and to where the evidence supports their implementation to roll them out and keep that link there between healthcare and research, and so making sure the systems talk to each other and I mean that in a digital sense as well as a human sense is absolutely critical.
And then, so in ten years’ time what are the areas of healthcare that will have been impacted, or could have been impacted by genomics, I’m really pleased that we’re doing a better job for families with rare conditions and people with cancer than we were ten years ago, I think there’s a long distance left to run even in those settings for us to do better and to continue to learn, so we expect our major focus to continue to be in those areas where we know they can have an impact and there’s more to do. We also then have the different areas where if the evidence pans out to support the use of genomics or if we can implement systems that can support it there can be a big sort of area of growth. For example, our newborn genomes programme is asking questions and developing evidence so that in the future policymakers can decide should that become part of routine care, and I think that’s something that could have become part of routine care in the next ten years if the evidence supports it and if that’s something that the public support.
If I were to pick one other area where there’s a real potential for growth in the coming handful of years it’s in something we refer to as pharmacogenomics. What that means is looking at your DNA code (genomics) to help make decisions about prescription of medicines and sometimes that’s about avoiding these medicines in people who are at a higher risk of having an adverse reaction, or it’s about tailoring the dose because of something about for example the way the person metabolises, chews up, the medicine and so can influence how much dose they need. That actually has an enormous potential; we all have variations in our DNA code that influence how we respond to or metabolise medicines. If you look across primary care, GPs and so forth, primary care physicians and in secondary care, hospital care, I think there’s good evidence that actually probably half of all appointments, interactions in those settings, if you were to have DNA data available that could influence how prescription choices are made; sometimes that’s about knowing that you’re doing the right thing, giving the normal prescription, but sometimes it's about modifying it, that’s an area where I think there’s a real potential for growth and that’s an area that the NHS also really recognise and we’re exploring ways in which we might look into that and think about how that might be implemented, because actually a lot of the questions there are about how you make sure the right data, the right information is available to clinical teams and patients at the time that prescriptions are being made.
There’s also real potential more broadly in thinking about more common disease settings, there’s lots of work going on from various research studies looking at the value of what people sometimes refer to as polygenic risk scores or integrated risk scores, where we use genomics as an element of estimating risk for common diseases like heart disease or cancer, that’s something where the evidence is being worked on and is developing, I think we’ll see a lot of evidence come out in the coming years and I think that will then influence how we implement genomics to help as part of that risk estimation process, which is routine now in GP practices where you go for an NHS health-check they do it with lots of complicated stuff, at the moment not genomics, and we’ll see how that plays out in the years to come.
So I think there’s enormous room for growth where genomics where at the moment it’s making an important difference to people with certain conditions that we can do better on. In the future I see it becoming very much more part of the routine day to day of healthcare. As we make that transition there’s lots to work through about the evidence, the order in which that’s done and the way in which we, for example, store data, and make people part of the choice about how their data is used and what I’m really excited about in Genomics England is the role we play in the middle of that, bringing our particular expertise around what we call bioinformatics, which is sort of managing genomic data at big scale, particularly national scale to support healthcare and research, generating evidence that can help inform policy, and also critically drawing things together into the conversation amongst different players in the ecosystem and participants in the public so that we can not just think about evidence in a sort of terribly scientific way but we think about it in the round.
Helen: That’s really interesting to hear you speak a lot about getting that evidence because that’s critical, but that takes a long time doesn’t it, so for example with the generation study, the newborn study it’s really important to measure the benefits of that if you’re testing young babies, newborn babies for diseases that if you pick up a condition that condition can be treated and something can be done about it early rather than poor parents going through this diagnostic odyssey, but also it’s that balance isn’t it with not leading to any harm, so if a number of parents come out of that thinking their baby might get a condition and it never happens there’s potential there isn’t there. But I think in terms of the public understanding of how long it takes to get evidence and everything else that needs to go on in the background I don’t think it’s always particularly clear that that’s a massive process that has to be gone through and there’s a lot of work going on behind the scenes – you can’t just do these things.
I think as patients/members of the public we’re eager to get on and for change to happen and things to be better but it’s a big, big process, but also good to hear that you talk about it being a collaborative approach, it’s not just Genomics England, it’s the NHS, it’s members of the public and patient voices, it’s other organisations working in partnership, it’s a big undertaking.
Rich: No, it is and I think that one of the words you used there was impatience, and I think that’s healthy and important to recognise, it can be easy, particularly for example as a doctor, sat in a clinic room to accept the status quo, and at the same time, one needs to recognise the complexity of the questions, the balance, the need to generate high-quality evidence to inform those opinions and I think combining both that sort of impatience and dissatisfaction with the status quo, and that mind-set about thinking really thoroughly and collaboratively about the right evidence that is needed to change policy.
Helen: Yes, really important that those patient voices are there from the beginning, from the planning of obtaining this evidence and that you’re measuring the things that matter most.
Rich: One of the areas where I think we’ve seen that play out, another area where I really see the potential for growth in the future is much more genomics-enabled treatments. We and you and the participant panel have helped us think about there’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer and thinking as we do that about how we structure the system to generate evidence and to respond to it and have a conversation about what the right balance of evidence for patients to make a choice about their own care, but also policymakers to make choices about funding, decisions and safety decisions, is really important and we’ve been supporting to a wider work in cancer in the UK called the Cancer Vaccine Launchpad, and likewise we’re part of something we call the Rare Therapies Launchpad, where in those two areas we’re exploring that, and that’s another area I think of real potential in the coming years, and also real nuance as we construct a way of navigating that together and making the most of the potential, but not just sort of rushing in and pretending we know all of the answers at the outset.
Helen: And those launchpads are of particular interest to participants in the wider patient population, there are a lot of people and children with rare, ultra-rare conditions who are desperate for treatments that just aren’t available right now, equally for cancer patients there’s a big need isn’t there for more effective treatments, fewer side effects, that target that person’s particular cancer, so it’s good news I think for the wider public.
It does seem that innovation and partnerships are crucial to Genomics England’s activities so how does Genomics England ensure that participant and wider patient benefit are at the heart of these activities?
Rich: I think one of the really important things is actually governance is sometimes a boring word, sounds like it, but I think thinking about how we’ve structured the organisation and placed you, as the participant panel, as part of our governance to make sure that when we’re thinking about for example access to data in the National Genomic Research Library, participants are sort of driving those decisions, it’s an independent committee that makes those decisions with representation from our panel. One of the things is thinking about the governance and making sure that you as our participant panel hold us to account for the decisions that we’re making, which I think is really critical.
I think then also as we’ve learnt a lot over the years, not always getting it right, about how we make sure that participants, or potential participants in the public are involved from the outset in the design of programmes because it always helps. I think certainly before I joined Genomics England I think I would have been unsure about the best ways of going about that and that brings with it sometimes a nervousness. I think the main advice I would say to people listening is to have confidence that just getting stuck in and have conversations is the way to do it. There are then also all sorts of expertise that we’ve really benefited from being to bear in terms of ways of doing that engagement work and that will come; the first thing is to have the confidence and the desire to put that at the centre of how you decide where your focus should be and how you design programmes.
Helen: I think Genomics England has been very successful with that by integrating that patient voice from the very early days and here we are what eight years on I think now, and yes, hopefully we’ll be there for some time to come yet, as long as Genomics England exists.
So Rich, with more and more health data being stored, how do we ensure that this sensitive personal data is stored and used safely and ethically across the genomics ecosystem. And actually while we’re on this question, can you just explain what genomics ecosystem means, because we use that term I think quite a lot, but I think it’s not necessarily understandable to the wider public?
Rich: What I mean when I talk about it is I mean the mixture of different people, whether that’s sometimes organisations, us, Genomics England, the NHS, the NIHR, National Institute for Health Research; industry partners whether they’re people who are from pharma companies or from biotech, academic researchers, participants in programmes – everyone who comes together to work on genomics in the UK and a bit like the word as it’s used in biology, it’s a sort of busy ecosystem with all sorts of people playing their own role and then working together, and so I think it’s a really important thing to recognise that we’re part of that and in fact it’s one of the things I love most about my role at Genomics England is thinking about all of the different partners that we need to work with and to those outside it I think it can also be a bit intimidating, because it’s hard to keep up with who on earth everyone is.
So then thinking about the question of how we make sure that data’s stored and looked after and used in the ways that people expect and safely and so forth, I think that’s absolutely at the heart of my role and our role. And I think one thing is actually always sort of starting at the: why are we doing this? What benefits are we seeking to bring to people? Is that what they expect? What have they signed up for if you like? But that’s in a research study or when they’ve decided to say yes to having a particular test, which is the same in any part of medicine. And if we use that to drive our decisions, that’s what’s so critical. And so that’s where thinking about programmes we run, and also the things that we think might be worth something that we should prioritise in the future is always first driven by the benefit that you might be bringing, weighing up the costs and the potential downsides and harm that might be caused by the use of genomic data in that way and that’s what should always drive things, and there isn’t a one-size-fits-all, you know, genomic data should be used and stored in this way and that’s one of the things that I think making sure that participants and the public are at the centre of the conversation is absolutely critical, it turns out that genomic data is very much like health data at large in many senses and it’s very precious for those reasons.
It is also special in a few ways. One of the ways that’s sort of peculiar if you like is that pretty much the DNA sequence, the genome, that you’re born with, is the same one that you hold throughout your life, that’s different from say if you do a blood count or something that varies for various reasons over your life and most things in medicine do change quite meaningfully over a much shorter time period. One of the things about the DNA code: A) it makes it more precious because it’s very much about you, your whole life; also it makes it more useful and reuseable in many ways, so one of the things that we think about a lot more in genomics is about the storage and reuse of data on an ongoing basis through the lifetime. And I do think that that model in certain settings and potentially more broadly as evidence accumulates, may well be the path that we take forward where you consider your genomic data part of your health record where it can be used and reused.
And what we need to do is explore why you would in the first case generate someone’s DNA sequence, and what sort of sequence, is it a whole genome or less than a whole genome? What would you use it for in the first place when you first generate it? And what other uses could there be to support the healthcare and have you involved them or the public more generally in decisions about how it’s used? Because we do, as I said, see the potential for genomics being just becoming part of the fabric if you like of healthcare, good healthcare, the best healthcare.
Linked to that is the point on research as well, like where people are happy for it, holding their genomic data and understanding how that impacts on longer term health outcomes, something we’ll continue to learn about for years and years. So I think the first point is about focusing on the why and whose data it is, one’s own genome belongs to you, it doesn’t belong to anyone else, what people are happy with and consent to and expect and then always holding that in mind as one makes the choices is critical. I’ve talked about how we think the governance and the involvement of the participant panel is really critical for that as well. And then it also comes down to doing in various ways, the job that people would expect in terms of, for example, that safety piece, using the very latest tooling to make sure that it’s held in a secure way, that it’s backed up so that it won’t be lost etc. and bringing sort of the right, very good minds around some of those more technical questions, but always with the expectations of the people whose genomes they are in mind and to say are we living up to their expectations, are we doing what they would expect?
So, Helen, I wondered if I could ask you a couple of questions. The first one I wanted to ask is what you’re hopeful for in the coming years as a participant panel member?
Helen: Thank you. I’ve actually already posed these questions to some of the other panel members, so I’ll try and make sure I include their responses here as well as mine, but I think it’s important to hear from everybody, not just me, Rebecca Middleton and Emma Walters have recorded their responses as well. I think the four main things that panel members are hopeful for is the coming years, the first is equitable access to whole genome sequencing, basically everybody who needs whole genome sequencing should get access to it regardless of where they live, their income, ethnicity or disability, so that’s something that we’re hopeful will get better over the years.
We know this is essential to improving healthcare, to improving outcomes for patients and generally for sort of greater inclusivity and in genomic research, we want as well as Genomics England, the data is the National Genomics Research Library to be representative of the population as a whole, not just the people who 1) are offered, and 2) agree to have their data in the library. And also, obviously the more data that is held in that library, the more opportunity there is for research across those rare and ultra rare conditions and rare and less common cancers, where it’s all about numbers, you need numbers of sets of data in order to draw things together and make conclusions to look for patterns.
And the other thing which I guess comes more under the umbrella of the NHS is that the panel is quite keen, they want everybody who’s undergoing genomic testing to receive good support and after care, I think regardless of whether that testing is via the NHS or as part of a research study, sometimes it will be both, but that’s for the patients at the coal face that is obviously critically important.
The second, I think broad theme, coming from the panel members’ responses is that I think you’ve mentioned this already, is increased understanding of genomics amongst the general public is really important – there’s a need to demystify genomics and to generally improve public awareness of its benefits and to get those conversations going around its regulation and its ethical use, but to do that you need to get meaningful engagement from a wide range of people, you know, that’s not always straightforward, there are lots of challenges there, it’s all about prioritising inclusivity, accessibility, to make sure you get diverse views and perspectives on genomics and on genomics research.
The other thing that came out very strongly from the responses which we have talked quite a bit about already is about this individualised healthcare. I think we as a panel are very hopeful that there will be this shift towards treatment strategies that are tailored more to the individual and their specific health condition, rather than a one-size-fits-all approach, we want effective treatments that will minimise side effects but also through the use of pharmacogenomics, to make sure if there’s a risk of a severe, sometimes life-threatening side effect that that can be identified and that individual doesn’t have that treatment either at all or has a lower dose, so it’s not so toxic.
And let’s hear from Emma who talks about this.
Emma: My hope is that we move to a truly individualised healthcare system and I’m really excited to see how in particular pharmacogenomics changes the healthcare landscape. For a long time we’ve gone with a one-size-fits-all approach, and that’s easy to deliver on a large scale basis that the NHS works on, but we know fundamentally that’s not how patients work, so to be able to consider individualising medication and knowing which won’t work, interests and excites me.
Helen: So the panel is also very hopeful about the development of those innovative therapies, and you talked about the rare therapies launchpad and the cancer vaccine launchpad, because those offer real hope for treating previously untreatable conditions and generally improving accessibility to treatments. And we’re also hopeful that there will be a much better understanding of diagnosis of cancer, through things like the multi-model programme, because although there’s lots and lots of research going on with cancer there’s still a long way to go to have more effective treatments and to improve diagnosis of cancer.
And then just finally just in response to your question, patient and public involvement, this is what the participant panel is all about, we are a group of individuals whose lives have all been touched by either a rare condition or by cancer currently, either we’ve had that condition ourselves or it’s affected our loved one, and we do bring these diverse views and perspectives to Genomics England and I think we have a crucial role in influencing its decisions about what it does with participant data and who has access to that data. It’s critically important that Genomics England listens to what matters to the people whose data it holds and who do that, as Rebecca here explains.
Rebecca: Genomics is a fast-moving science and it has the impact to change lives and healthcare for future generations, but genomics is a science of people and therefore the only way you can truly understand the limitations and opportunities of it is to talk eye to eye to the very people it will impact, and not everyone will agree on everything. But how we understand genomics and its power to transform healthcare, our own and that of our children and the ones we love, can only progress at the pace of the people that it will benefit. It’s a simple equation but it’s not maths and indeed not science: we are all different and unique, our emotions, experience and history will be wrapped up in our viewpoints and thoughts, and that’s where the panel comes in, representing and advocating for the very many different voices of genomic healthcare, ensures Genomics England is stronger, healthcare design is more meaningful and research is more impactful.
I have no doubt that the panel of the future will continue to be heard and understood at Genomics England, and I hope it continues to grow to reflect more diverse voices and experiences and continues to be the people inside the science.
Helen: Finally, the panel is also hopeful for increased public and patient involvement in genomics research, this is integral for shaping research both academic and commercial, it helps with identifying research priorities, developing new treatments, basically getting that voice of the patient in there to tell researchers what’s the most important and what matters to them.
Rich: So another question Helen, how do the panel feel about the changing genomics landscape?
Helen: A good question and I think overall it’s a balance between excitement and hope on the one hand, and a bit of apprehension and caution on the other. So the panel is really excited about the advances going on in healthcare, we’re entering an age now where we’re promised a much more proactive, as opposed to reactive approach to healthcare. You were talking earlier Rich, about having your genome sequence, and this is something that you have for life, it’s like your passport, your fingerprint, so from infancy to old age you’ve got this data which is held somewhere which holds so much promise of predicting if you might develop a disease, whether you might react badly to a drug, so ultimately it offers great potential to improve outcomes for patients, their families and the NHS. Again, we spoke earlier about this holds so much promise for producing the diagnostic odyssey that so many parents go through when the children are born with a condition that doesn’t have a diagnosis, potential to diagnose things like cancer a lot earlier where it’s more treatable and to prevent disease as well, I know that’s something Genomics England isn’t specifically looking at, but through screening programmes, using things for example like circulating DNA which may be able to pick up that there are things going on and picking things up earlier means that those things can be dealt with earlier.
I mean thinking of my own personal example, I know I have Lynch Syndrome, I know that I am at risk of developing bowel cancer now, but that means I can do something about it. So I have my colonoscopies every two years, I take aspirin every day because that reduces my chance of getting bowel cancers and I’m much more symptom-aware, so having that knowledge up front is very helpful in being able to move forward and reduce my chance of getting an advanced cancer.
The panel is also very excited about the ongoing collaborations and the novel therapies that are being developed through the rare therapies launchpad, these offer a lot of hope for treating previously untreatable conditions, and improving accessibility to treatments, and obviously more targeted treatments for cancer, you know, we’d need more effective treatments for cancer but with reduced side effects, so that in a nutshell, those are the other positive sort of things that the panel feel excited about. Where they’re slightly more apprehensive or concerned, I mean they do acknowledge that there are challenges ahead and there are big concerns about the NHS’s ability to cope with increase in demand for genomic testing and particularly worries about education and training of healthcare professionals in genomics, how do they effectively communicate research findings or results to patients if they don’t have a broad understanding of genomics?
And then finally, let’s hear from Emma.
Emma: I think I’m excited but cautious. I think it’s really important to acknowledge that the research being undertaken is groundbreaking and the vast majority of clinicians have very little to know genomics education, and translating these findings into tangible benefits for participants is so very important, and something I think we’ve really got to make sure we don’t lose sight of.
Helen: We talked earlier about awareness among the public about genomics and we do feel that there’s a need to drive education forwards, you know but this is challenging, given the rapid pace of developments that we’ve spoken about, I think even for the panel members who I would say are relative experts in genomics now it’s hard to keep up to date, so how do we do that moving forwards? We’ve talked about security of data, we understand there are moves to link more genomic data sets both nationally and internationally and that clearly has significant benefits because that brings bigger numbers of patients data together, but opens up potential risks in terms of security, so how do we make sure that the security of that data is as good as it is currently when it’s held in one pot in Genomics England Research Library.
And just a couple of final concerns that were flagged by panel members, there is some apprehension regarding potential misuse with genomic data by insurance companies; we’re given a lot of reassurance about that but there are concerns that could potentially lead to the most vulnerable in society being unable to get affordable cover if they’re found to have genomic changes that mean they are at risk of conditions or have certain conditions and there are also concerns about the ethical implications of AI in diagnosis and clinical decision making, you know, AI is obviously a fantastic thing for looking at patterns amongst a big lot of data, but how accurate is it and where does the human come in, in terms of decision making?
So those are, I think, the broad concerns from the panel. I don’t know if you have any thoughts on those, Rich?
Rich: I think the big thing to say is I think having the participant panel there, you said in the middle of that, become collectively quite expert and you recognise that. Having the ability to have these complex nuance conversations and have people share that and speak directly to us about it I think is the biggest thing – lots of those points there made by the panel, I think both things that we have very much in our mind about things that one needs to balance and focus on, and there are also things that we already talk about which is reassuring I think as well, we talk about with the panel. I think one of the things for us as well is sort of being clear on some of the things where there are really clearly well-established red lines, for example, that point on insurance, but that is very clear and part of our role is making sure that that is there and people can feel comfortable in that context to understand that.
I think the main thing that I would say is thank you to you Helen, and to all of the panel and all of our participants because I said earlier, this is a team thing and you are all very much part of the team and we would not be able to do our jobs in any way, I wouldn’t even say effectively, I would say with the relevance, which is the thing that we drive for, the relevance to have impact for people’s lives whose data we hold and will hold in the future. And so thank you for being part of the team.
Helen: Thank you. And I think thank you to Genomics England for having the foresight to create the participant panel in the first instance, it was there from the get-go and I think a really great opportunity for all of us to be involved in this, to have our voices heard and listened to, so thank you.
We’ll wrap up there. Thank you for joining me today and thank you for discussing your appointment as CEO for Genomic England, and your view on what the genomics ecosystem might look like over the next ten years. If you would like to hear more like this, please subscribe to the Behind the Genes, on your favourite podcast app. Thank you for listening. I’ve been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
![James Duboff: Genomics 101 - How do pharmaceutical companies use genomic data for drug discovery?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday May 22, 2024
Wednesday May 22, 2024
In this explainer episode, we’ve asked James Duboff, Strategic Partnerships Director at Genomics England, to explain how genomic data can be used in drug discovery.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/How-do-pharmaceutical-companies-use-genomic-data-for-drug-discovery.docx
Naimah: How do pharmaceutical companies use genomic data for drug discovery? Today, I’m joined by James Duboff, a Strategic Partnerships Director here at Genomics England, to find out more.
So James, first of all, what is genomic data, and how does this relate to our genes?
James: Let’s start with a simple explanation of what we mean by genomic data and our genes. So, every cell in our body contains a complete copy of our genome. Now, genome is kind of a mini instruction manual that describes exactly how to make you. Now, those instructions are written in a language called DNA, which is over 99 percent identical in every single human on the planet, so you and I are actually genomically very, very similar. The differences, however, are called variants, and they’re what make us unique. Now, some of those variants can actually be very dangerous, and they can code for things like rare genetic diseases or even cancer. So, we need to read in detail exactly what’s going on in your DNA and in your genome to see where changes are and where those variants really are, and we do this by sequencing the genome. So, if you get a DNA sequence, that’s effectively an electronic readout of your genomic data, which is your genome in computational form.
Now, understanding that and working with that is still a relatively new field, so what we try and do is connect the genomic data, your genome, with health information, such as hospital records and what you’re presenting with in clinic, if you’re in a patient setting, and look at those together to give context to those variants in the genome. So, genomic research is actually where we look at how genes and physical outcomes could be linked. So thinking of, you know, biology and physiology term, what does a variant exactly do and how might it cause a disease.
Naimah: You mentioned both the genome and whole genome sequencing, and if our listeners aren’t too sure exactly what they are, they can listen to some of our other explainer episodes with Greg Elgar, who explains these concepts. So James, next could you tell me why are pharma and biotech companies interested in genomic data?
James: Ultimately, pharma and biotech companies are interested in genomic data because that really tells them what’s going on within the blueprint or that mini instruction manual of an individual. So, pharma and biotech have dedicated research teams that focus on genomic research, and they look through genetic databases across the world, such as Genomics England and others, to really understand the role of the genome in their target disease areas. By looking at those, that helps them develop new drugs and tools to specifically diagnose, treat and also even cure these diseases.
Naimah: So, how exactly do they do that? Can you explain it in some simple steps?
James: I think there are four key areas that they need to focus on. So, starting with the first, where, whereabouts on a genome should they focus? Now, the way that a pharma company would do this, or any researcher really, is by taking two populations of people. So, you’d take a population who have a known disease, and you’d compare that to people without. Now if you’re looking at the genomes of people with the disease and those without the disease, you can kind of play spot the difference between those two, and understand whereabouts on the genome variants appear for the disease population and not for the healthy or undiseased control group. Now, when you do that, you can kind of pinpoint exactly whereabouts you see variants only in that patient population. That helps you identify your target, and that’s known as target identification, which is essentially pinpointing that spot on the genome that’s linked only to the disease. Once you know that, you can use that as a potential target for a new drug.
So, once you’ve found that variant, the next step was, what does that variant do? Is it potentially overproducing something? Is it activating a promoter and therefore making more and more and more of a gene product that, you know, might be toxic inside a person if you have too much? Even too much of a good thing could be a bad thing. So, is that the case? Or does that variant cause an underproduction or something to just be not actually made by your body at all? So, if that variant kind of interferes with a piece of genetic code, it could stop that gene from producing anything, and therefore you might be effectively detrimented and deprived of that particular gene product. And both of those, an overproduction or an underproduction, could lead to a disease. So, to understand that in more detail, you might need to look at gene products as well.
The next step, once you know whereabouts in the genome you’re looking and what exactly a variant does, the next step really for a pharma company is how could you fix that. So, if you’re looking at too little of something – so, if a variant stops a gene from actually developing into a gene product then you might need a drug to boost or to compensate for that, so potentially a supplement or having some kind of drug that can get the body to make more of that product. If on the other hand your body is making too much of something in a way that could be toxic, you kind of want a drug to reduce those levels, so a drug that could potentially breakdown that gene product so that you don’t have too much of it, or stop it from working effectively, so that it doesn’t seem as if you have too much of it, or otherwise prevent it being made altogether.
Now, one example of this prevention is actually a gene silencing drug, or an ASO, as they’re effectively known, which can be used as a genetic mask. So, that sits on top of a gene and hides it, so the body can’t actually make that dangerous varied gene product. Now, if you’re going to make something like that, you need to be absolutely sure that masking that entire gene and stopping even a varied form of it isn’t dangerous, so that last step really is making sure that your drug is safe and wouldn’t cause any other issues. So, traditionally, that would have been done using animal models as kind of a surrogate organism, but now using genomic databases, you can use human genomics as kind of real world examples of applying say a genetic mask and hiding an entire gene or genetic section, and you can look through genetic databases to have a look for individuals who are alive and hopefully healthy in the population, who don’t express a certain gene. So, if you can find people who are healthy, who don’t have that gene or have variants that stop that gene from being produced, you kind of can be confident that you can make a drug to cover that and it would be considered safe.
Naimah: Okay, so that’s really interesting. So, what you’re saying is, by using human genomic data, we can test the impact and safety of gene targeting drugs directly in humans.
James: Yes, exactly. So, you can ask that question of would hiding that gene entirely cause any other health issues or any adverse effects really from a drug that hides it. And the really useful thing about that is that we’d know the impact of a gene targeting drug before you’d say start a clinical trial, so that really stacks the odds in your favour of the drug working safely, which is really powerful for a drug company that would otherwise invest a lot of money in a clinical trial that could be a risky endeavour for the company and also for participants. So, this is very useful for patients, and also fundamentally it’s a lot more useful for a company to be assessing safety using humans and human genomics directly as opposed to using a surrogate organism like a mouse, which many people would argue is not a good reflection of what would happen in humans.
Naimah: Can you tell me briefly if genomics can be applied to other stages of the drug delivery pipeline?
James: Yes, in fact genomics can be applied all along the drug discovery and development R&D pipeline. So, as an example, biomarker identification. A biomarker is a biological product or a chemical signal that’s associated with a disease, that you can find and monitor inside the
body. So, you can look at an increase in that biomarker or a decrease in that to monitor whether a drug is working as you’d expect. Is the drug increasing levels of something being produced, or is it decreasing that product being produced? And you can use that to understand whether it’s possible to potentially develop that treatment, would that treatment actually work. So, that’s really important in monitoring drug impact and also understanding clinical endpoints for a trial.
You can also look at biomarker identification to look for genes and variants that are associated with a disease that could help you understand who best to enrol in a clinical trial. So, clinical trial recruitment is another key area, where if you involve the genome in your enrolment criteria, you can essentially just recruit the most suitable people where you know the drug will work best, and also you’re sure that the drug would be most safe and effective at treating their condition. And then actually to go a step further on the clinical trial point, clinical genomic datasets are actually really useful, if you think about it, in the opportunity to recontact participants too where they’ve consented. So, what I mean by that is, a pharma company could directly find and recruit optimal patients with either a rare disease or a cancer where their drug would help most, based solely on their genome, and that’s a really, really exciting point, because that offers the opportunity for pharma to both develop a drug based on that genomic dataset, but also then deliver the drugs to treat those same exact people.
Naimah: So, how do pharmaceutical companies access this data?
James: Well, there are different datasets, and each different dataset has a different population within those, and each of them have their own consent models and governance rules on how that data can be used and who can access it, and how they access it. So, some of these datasets just hold genomic data, while others would have additional biochemical data and also health information potentially on participants. So, depending on the different types of data, there’ll be different access limitations and restrictions. So, some entities and some datasets can be simply downloaded, and that could be very useful for pharma and biotech companies, because that means that they could use them inhouse. Other datasets and groupings of genomic data and libraries of sorts would operate a TRE or an SDE model, so that stands for a trusted research environment or a secure data environment, and these are essentially – you could consider them as libraries, like a reading library, where you can come in and read the books but not take out those books, or genomes in this case.
Naimah: Can you tell me, what impact does the use of genomic data for drug discovery have on the public or patients?
James: Oh, there’s huge impact on drug discovery, and ultimately genomic research really helps drug companies make better treatments for patients and the public. So, we’ve already seen the benefits of genomics used in drug discovery, and I think we will do more and more as DNA sequencing is used more in clinic, and also that’s going to keep happening the more cost keeps dropping, which is making genomic medicine really and genomic healthcare increasingly feasible at scale. So, 20 years ago, it cost over £100 million and it took years to sequence a genome, but today you can sequence a genome within a few hours for under £1,000.
Naimah: What are the benefits of having your genomes sequenced in a healthcare setting?
James: Ultimately, genomics enable a faster and more accurate diagnosis. That enables early intervention, which can really maximise the treatment impact and improve outcomes. So, what I mean by early intervention, if you can give a drug before someone shows symptoms then you could prevent them ever getting the disease, so that’s moving towards preventative medicine, which is really exciting and absolutely enabled through genomics. So, genomics really help pharma companies make also better drugs and target the underlying disease directly rather than just addressing symptoms, so this helps them make more effective and safe treatments to really improve overall outcomes for patients.
Another thing to think about is that some drugs are already on the market but used for different reasons. Genomics can help pinpoint the root cause of that disease within a genomic setting, so that can highlight repurposing opportunities for existing drugs. Now, existing drugs are those that have already been proven safe in humans and approved for use, albeit potentially in a different setting. Now, if a drug could be shown by genomic research to be targeting the same root cause within the same biological pathway, they could very easily be repositioned and applied in an entirely new disease.
So, I guess to finish, through genomics, drug development can help us move towards precision healthcare, and by that I mean making targeted treatments for specific patients. That will be far more effective and have significantly fewer side effects. In the case of participants in clinical genomics sequencing programmes open to researchers, that also means matchmaking opportunities for companies to diagnose and treat unique patients. In the case of ultra rare conditions, that means they can create a treatment specifically for that patient and then work with their doctors to deliver the brand new drug just to them, to ultimately save lives.
Naimah: That was James Duboff explaining how pharmaceutical companies can use genomic data for drug discovery. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
![Professor Sir Jonathan Montgomery, Dr Latha Chandramouli and Dr Natalie Banner: Why do we need to consider ethics in genomic healthcare and research?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday May 15, 2024
Wednesday May 15, 2024
Ethical considerations are essential in genomic medicine and clinical practice. In this episode, our guests dive into the details of ethical principles, highlighting how they can be brought into practice in the clinic, whilst considering the experiences and feelings of patients and participants.
Our host, Dr Natalie Banner, Director of Ethics at Genomics England, speaks to Professor Sir Jonathan Montgomery and Dr Latha Chandramouli. Jonathan is the Chair of the Genomics England Ethics Advisory Committee, and a Professor of Health Care Law at University College London. Latha is a member of the Ethics Advisory Committee and the Participant Panel at Genomics England, and is a Consultant Community Paediatrician working with children with complex needs.
"You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things."
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Why-are-ethical-considerations-crucial-in-genomics-research-and-clinical-practice.docx
Natalie: Welcome to Behind the Genes.
Jonathan: The first difference is that the model we’ve traditionally had around clinical ethics, which sort of assumes all focus is around the patient individually, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions. Families differ enormously, some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approaches to genomic issues must respect everybody in that.
Natalie: My name is Natalie Banner and I’m the Director of Ethics here at Genomics England. On today’s episode, I’m joined by Chair of our Ethics Advisory Committee, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli, member of the Ethics Advisory Committee and the Participant Panel, who’s also a community paediatrician working with children with complex needs.
Today we’ll be discussing why ethical considerations are crucial in genomics research and clinical practice and what consent means in the context of genomics. If you enjoy today’s episode, we’d love your support. Please like, share and rate us wherever you listen to your podcasts.
At Genomics England, we have an Ethics Advisory Committee, which exists to promote a strong ethical foundation for all of our programmes, our processes, and our partnerships. This can mean things like acting as a critical friend, an external group of experts to consult. It can mean ensuring Genomics England is being reflective and responsive to emerging ethical questions, especially those that arise as we work with this really complex technology of genomics that sits right at the intersection of clinical care and advancing research. And it can also ensure that we are bringing participant voices to the fore in all of the work that we’re doing.
I’m really delighted today to welcome two of our esteemed members of the ethics advisory committee to the podcast. Professor Sir Jonathan Montgomery, our Chair, and Dr Latha Chandramouli, member of our Participant Panel. So, Jonathan, if I could start with you, could you tell us a little bit about your background and what you see as the role of the ethics advisory committee for us at Genomics England?
Jonathan: Thanks very much, Natalie. My background professionally is I’m an academic, I’m a professor at University College London, and I profess healthcare law the subject that I’ve sort of had technical skills in. But I’ve also spent many years involved in the governance of the National Health Service, so I currently chair the board of the Oxford University Hospital’s NHS Foundation Trust.
I’ve spent quite a lot of time on bodies trying to take sensible decisions on behalf of the public around difficult ethical issues. The most relevant one to Genomics England is I chaired the Human Genetics Commission for three years which was a really interesting group of people from many backgrounds. The commission itself primarily combined academics in ethics, law and in clinical areas, and there was a separate panel of citizens think grappling with things that are really important. Genomics England has a bit of that pattern, but it’s really important that the ethics advisory committee brings people together to do that.
You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things. My aim as Chair of the advisory committee is essentially to try and reassure myself that we’ve heard all the things that we need to hear and we’ve had a chance to discuss with each other as equals what it is that that leads us to think, and then to think about how to advise within Genomics England or other people on what we’ve learnt from those processes.
Natalie: Fantastic. Thank you, Jonathan. And as you mentioned, the necessity of multiple different perspectives, this brings me to Latha. You have lots of different hats that you bring to the Ethics Advisory Committee, could you tell us a little bit about those?
Latha: Thank you, Natalie, for that introduction. I’m Latha Chandramouli, I’m a Consultant Community Paediatrician and I’m based in Bristol employed by Siron Care & Health. I’m a parent of twins and from my personal journey, which is how I got involved, my twins are now 21 so doing alright, we had a very, very stormy difficult time when they were growing up with our daughter having epilepsy, which just seemed to happen quite out of the blue sometimes. It started to increase in frequency the year of GCSE, to the point that she would just fall anywhere with no warnings and hurt herself. This was difficult for me because as a clinician, I was also treating patients with epilepsy. I also was looking at the journeys of other people and was able to resonate with the anxiety as a parent. Worry about sudden death in epilepsy, for example, at night, these were the kind of difficult conversations I was having with parents, and I was now on the other side of the consultation table.
I was also doing neurology in those jobs in a unit where there was epilepsy surgery happening, so it was, in very simple terms, very close to home. It was quite hard to process, but equally my job I felt was I should not separate myself as a parent but also as a clinician because I had information, I had knowledge, and we had conversations with my daughter’s clinician.
We were then recruited into the 100,000 Genomes Project which had just started, so we were just a year after it had started. That was an interesting experience. We were in a tertiary centre with a lovely clinical geneticist team, we had the metabolic team, we had loads of teams involved in our daughter’s care. We could understand as a clinician, but there was also my husband, although a clinician, not into paediatrics and was in a different field. It was important that it was the whole family getting recruited into the journey. My daughter also was quite young, so obviously we have parenting responsibility, but we were very keen to make sure they knew exactly what they were getting into in terms of the long-term issues. Despite being informed, at times there were things that we went in with without understanding the full implications because life happens in that odyssey.
I think that was my biggest learning from those exercises when I began to question certain other things because I then had a breast cancer journey, but obviously I was not recruited as part of that process for the 100k. Those were kind of some of the questions coming in my head, how does the dynamic information sharing happen, and that’s how I got involved, found out a bit more about the participant panel, and that’s how I got involved from 2018 which has been an interesting experience.
Firstly, I think with Genomics England they are probably one of the groups of organisations having a big panel of people, genuinely interested in wanting to make a difference and represent thousands of participants who have got their data saved in the research library, recruited under the two broad arms of cancer and rare disease. We were under the rare disease arm, although I could resonate with the cancer arm because of my own experience.
At various times there were lots of opportunities to think about how data is accessed, are we getting more diverse access to data, all those different issues. At various points we have been involved in asking those questions. We all have different skillsets, you see, in our group. Some have got information governance hats; some have got data hats and PR hats. I’ve got a clinical hat and a clinical educator hat. I am a paediatrician, so I have recruited people for the same, for the DDD, for CGH etc, and I’ve always gone through the principles of consenting, confidentiality, the ethics. I also work in a field, Natalie, where there is a huge, as you are aware with the NHS resource issues, there’s huge gaps and waiting lists, so it’s trying to make sense of what is the best thing to do for that patient or that family at that point in life. Are we obsessed by a diagnostic label? Are we going down a needs-based approach? It’s having always those pragmatic decisions to be made. That’s one of my clinical hats.
I also am an educator so I’m very keen that young medical students, be it nursing students, everybody understands genomics and they’re signing up to it so that we can mainstream genomics. Those are some of my alternative hats which kind of kick in a bit.
Natalie: Fantastic, thank you, Latha. As you say, there are so many different perspectives there. You talk about kind of the role of the whole family as part of the journey. You talked about consent, confidentiality, data access issues, lots of questions of uncertainty. Perhaps, Jonathan, I can come to you first to talk a little bit about what is it about the ethical issues in genomics that may feel a little different. Are they unique or are they the same sorts of ethical issues that come across in other areas of clinical practice and research? Is there something particularly challenging in the area of genomics from an ethical perspective?
Jonathan: Thanks, Natalie. I think all interesting ethical issues are challenging, but they’re challenging in different ways. I’m always nervous about saying that it’s unique to genomics because there are overlaps with other areas. But I do think there are some distinctive features about the challenges in genomics and I suppose I would say they probably fall in three groups of things that we should think about. The first you’ve touched on which is that information about our genomics is important not just for the individual person where you generate that data but it’s important for their families as well. I think the first difference is that the model we’ve traditionally had around clinical ethics, which sort of assumes it all focuses around the patient individual, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions and families differ enormously. Some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approach is genomic issues must respect everybody in that, so I think that’s the first difference.
I think the second difference is that the type of uncertainty involved in genomics extends much further than many other areas. We’re talking about the impact on people’s whole lives and it’s not like a decision about a particular medication for a problem we have now or an operation. We’re having to help people think about the impact it has on their sense of identity, on things that are going to happen sometime in the future.
And then thirdly, I think the level of uncertainty is different in genomics from other areas of medicine, and the particular thing I think is different that we have to work out how to address is that we can’t really explain now all the things that are going to happen in the future, because we don’t know. But we do know that as we research the area, we’re going to find out more. So, what are our obligations to go back to people and say, “we worked with you before and you helped us out giving data into the studies. We couldn’t tell you anything then that would be useful to you, but actually we can now.”. Now, that’s different. That continuity sometimes talked about, you know, what are our obligations to recontact people after a study. You don’t usually have those in the ethical areas we’re familiar with; you’re usually able to deal with things in a much more focused way.
I think those differences, that it’s not just the individual, it’s the family, that it’s not just about a specific intervention but it’s about an impact on people’s lives and that we will need to think about what we had to do in the future as well as what we do immediately. They make it different in genomics. Some areas of healthcare have those as well, but I’m not aware of anywhere that has all of that in the same position.
Natalie: Latha, I’m wondering if that kind of resonates with your experience, particularly the navigating of uncertainty over time?
Latha: Yes. I would say that’s exactly what you’ve said, Jonathan. I think it’s the whole process of consenting with the view that you do not know much more beyond what you know about the situation here and now. Part of that is like any other situation, that’s why we have evolved from I would say penicillin to the SMA gene therapy. If we did not do this, we wouldn’t reach frontiers of medicine and kind of that’s how I explained to families when I’m recruiting and I’m also very clear that it’s not all about research but it’s combination of the tool and focusing on your, but it’s also helpful for research even if you do not get answers. I think it’s very important at that stage, Natalie, that we have to be clear we may not get many answers at the very outset and also when do we really look at data, do we have that kind of realistic pragmatic resources to be able to relook every time? Is there a method of dynamically having that information from our NHS spine if somebody of the trio has contracted a condition, would that be fed in.
Those are the kind of questions parents and families ask. I cannot honestly answer that, and I often say that is optimal plan. If things go to plan, that will be the area we’d be heading towards, but currently I can’t give you timelines. I think it’s important we are honest at the outset and manage expectations. That’s how you engage families and, in my case, it’s more these children and families, so engaging is crucial. As you mentioned, it’s also the question that gets asked is very simply in my mind, you know, sometimes there is that conflict because of my own personal recruitment to the 100k project, I have an interest in genomics and, therefore, I would be very keen to embark on that journey and I feel that is the way forward.
I also understand as a member of my clinical team, for example, where I know there’s a huge waiting list, how am I best using the taxpayers’ money that’s been entrusted to us. If I think the waiting list is so high, can I see two further patients in that time that I’m using to consent which is not going to add much more to that child’s journey, for example, with autism or ADHD. It’s trying to be careful where is the ethics in doing an investigation, and that’s like in any situation as a clinician. I think that’s not much different, but it is kind of similar, but it opens up a huge area of uncertainty. As you would with any investigations, if you just went and did scans on everybody, you might pick things up which you don’t need to do anything about. It’s being sensible and being honest.
Jonathan: And for me, Latha, that raises two areas which I think are really interesting about genomics. The first of those is the language we’ve tended to use about consent I don’t think captures all the ethical issues that we raise, because we’ve tended to think about consent of something that happens once and then gives people permission to do things. Whereas what you’ve described, and what we find ourselves often thinking about, is that we have to get a respectful relationship with people, so the consent is not to doing certain things, it’s to agree to part of what I think about as a common enterprise. So, patients and families are partners with the clinicians and the researchers, and it’s not that they sign a form and then the consent issue goes away, which is how lawyers tend to think about it, it’s that we’re starting something together and then we need to think about how do we keep the conversation going with mutual respect to make sure that everybody’s values are there.
I think the second thing you picked up is a sense of the need for a better explanation of how research and care interact with each other. Because the care we get now is built on the evidence that people have contributed to in the past, so we’re benefitting from our predecessors, and we want to contribute to our successors and our family getting better care in the future. I think one of the things about genomics is that the gap between those two things is really non-existent in genomics, whereas if you take a medicine, the research that’s been done to make sure that medicine is safe and effective will have been done on a group of people some time in the past that I’ll never meet, whereas in genomics I’m part of the production of that. I may get some benefit now, my friends or family may get some benefit, but there isn’t this sort of separation between the care and the research bit that we’re used to being able to think about. This is a much more mutual exercise and the stakes that we all have in it are therefore intertwined much more closely than they are in some areas of medicine.
Latha: I agree totally. In our case, for example, I went in in thinking we might get a targeted medication. I know there are certain levels of epilepsy medications anyway, so in principle it wouldn’t have mattered a lot. However, it was important to know what the outcome was going to be because we had various labels, potential mitochondrial disease, potentially some susceptibility disorder, so we were on a spectrum from something very minimal to the other end on neurodegenerative situation. We were left dangling and we thought it would be good to embark on this journey, at least there’ll be some outcome, some prognostic outcome, and more importantly we don’t have any answers, but we actually can be a hopeful story for someone else in that same position, and I think that’s how we’ve embarked on it. That’s kind of my personal experience.
But in just harking back to some of the ethical issues, it’s again very clear educating the clinicians, as you said, it’s that relationship; it’s not just a piece of paper, it’s that development of relationship with your families, some of whom have got very complex issues going on in their lives themselves. I work in a very, very deprived part of Bristol, which is the highest deprivation index, so they have got lots of intergenerational things going on, there is poverty, there is learning issues and crime, lots of things going on. You’ve got to time it right, what is important for this family here and now, and then work on it.
There’s also the other issue that we may not continue to remain their clinicians after recruiting. I think that’s so important to recognise because the results might come back but you kind of discharge them and it may take a few years by the time the results come. How do you then cross that bridge if some unexpected results come, which then means contacting various other extended family members. I think that’s the bit we all do because that’s part of the journey we’ve embarked on, but it’s also thinking is there someone else who’s probably better placed, like a GP or a primary care person who’s actually holding the entire family and not just one person, not just the adult who has been the index patient. It’s just trying to think the ethics of it because it’s all about engagement and being transparent with families.
Jonathan: I think you’ve put your finger on another element that’s really important about the ethics. In the same way as in relation to the position of the individual patient, and we need to see them in families, which doesn’t fit very easily with lots of the clinical ethics that we’ve been used to. It’s also the case that a lot of the traditional clinical ethics has focused on the individual responsibilities of clinicians, whereas what you’ve just described is that we have to work out what the system’s responsibilities are, because it may not be the same clinician who is enabling good ethical practice to be pursued. These are both ways in which our paradigm of ethics has to be expanded from other areas of medicine.
Latha: Yes, I agree. And the other bit I think we can probably reassure quite nicely is about the ethics about information governance and we as data custodians storing information, how do we give with great ethics and discussion the access to research and being mindful that it is again thinking along the same principles GMC kind of had about the good for the common good and using resources equitably, but again being sensible with equality issues that a single condition doesn’t get forgotten. It’s that right balance that whilst we are doing common good, we might have a condition which might have a treatable medication, but we have to focus on that as well as research. I think it’s interwoven, all these ethical questions.
Jonathan: I completely agree, Latha. That interwoven bit is something where we need to be able to think through, “what is the role of Genomics England to improving that?”. I think we’ve got issues around the good stewardship of information which can’t be left with an individual clinician, they can only do that effectively if the system supports them and their colleagues in doing that. But we’ve also got to be proactive, we’ve got to recognise the limitations of the system, so one of the really important initiatives from Genomics England is the Diverse Data initiative because we know that without aiming to solve the problem, we will get a skewed dataset and clinicians can’t properly look after people. That tells us that the ethics in this area has to do more than avoid things going wrong, it also has to work out what it means to do things right, and what systems we have to put in place to do that. I think that’s a particular example of a shift we need to do across our ethics around healthcare.
If speak to the sort of things that lawyers have got wrong around this in the past and some of our history, we focused a lot of our effort on stopping things going wrong. That has meant that we haven’t spent as much time as we need to on thinking about how to make things go right, because stopping things going wrong is almost always too late. What we have to do if we’re being proactive is work out how to set things up in a way that will make sure that the chances of it going wrong are quite small and the chances of doing good are much increased. I think that’s one of the key challenges that we have in Genomics England and as an Ethics Advisory Committee. The things we’ve inherited tell us quite a lot about things that have gone wrong, but actually what we’re trying to do is to get our heads around what could go right and how to make sure it does.
Latha: Also, you mentioned about Diverse Data, I think that’s another important thing as we noticed in COVID as well. There were lots of disparities in the social model and the inequalities that have resulted in death, but also potentially HLA or epigenetic issues which could have contributed. We do have the COVID-19 genomic datasets, but it’s again important to make sure that we don’t perceive certain ethnic minority populations. Just not accessing or considering them to be hard to reach, I would say for them Genomics England is hard to reach. It’s looking at it slightly differently and thinking, “how can we reach them? how do we maybe use community workers and maybe even clinicians?”, I think they’ve got the best trusting relationships with their clinicians and using them to recruit. As you say, even before things get more complicated, you recruit them earlier so that you’d go down the prevention route rather than the gone wrong route and then look for answers later.
Jonathan: Latha, I think you put your finger on something really challenging for a group like the Ethics Advisory Committee at Genomics England, which is that however hard we try to get a range of experiences and voices, that’s not a substitute for getting out and hearing from people in real world situations. I think one of the things I’ve learnt over the years from my national health service work is that you cannot expect people to come to you, you need to go to them. In COVID when we were trying to understand why some groups were more reluctant to take up vaccines than others, there was no point in doing that sitting in your own places, you had to listen to people’s concerns and understand why they were there. One of the things we’re going to have to be able to do as the Ethics Advisory Committee is work out when we need to hear more from people outside of the Genomics England system, and I’m a great believer that if it’s right that we need to go where people are, you have to try not to reinvent mechanisms to do that. You have to try and learn where are people already talking about it and go and listen to them there.
Latha: Absolutely, yeah. I think they listen because I do work as a paediatrician with a safeguarding hat, and I think the same principles resonate in child death work. For example, simple messages about cot deaths, you would think that if a professional tells the same message to a parent or a carer it’s better received if it’s another family, a younger person, another layperson giving the same message. It comes back to who’s more receptive. It could be a community worker.
As you mentioned about vaccination, during the vaccination initiative I decided early on that I’m probably not going to do a lot because I’m not an intensivist, how do I do my bit in the pandemic. I decided to become a vaccinator and I thought with my ethnic minority hat on, if I went out there to the mass centres and actually vaccinated there or in mosques or wherever else, without even saying a word I’m giving the message, aren’t I, that, look, I’m fearlessly coming and getting vaccinated and vaccinating others, so please come. I think that has helped to some extent, just trying to reach out. Other than saying these people are not reaching us, it’s got to be the other way around.
[Break for advertisements]
Natalie: I’m really enjoying this conversation. In part because I think it highlights just how valuable it is to sort of think about ethics a little bit differently. Historically, and certainly I think within the research community, ethics can just be associated with consent. Consent is the ethics issue and if you solve for consent, then you don’t have any other issues to think through. I think what this conversation is really highlighting is just how much broader the ethical considerations are. Beyond that, it’s still very important that consent can be that sort of anchor point for communication and engagement, but it’s not simply a one-off. And to be able to think through ethics not just in terms of risk or moving forward when things have gone wrong in the past, there is actually a really positive aspect to it which I think is critically important.
It’s great to hear your thoughts about that different approach to ethics that I think does embed it much more in community thinking, in questions of equity; it’s not just the individual. I want to follow-up by just asking where do you think the future lies in thinking about ethics both for Genomics England and the Ethics Advisory Committee, but in the space of genomic research and medicine more broadly, given that it sits in this kind of very interesting and quite complex space between research and care in the clinic.
Jonathan: I mentioned earlier in the conversation I think about this as a common enterprise that we have shared stakes in. Academic researchers have a stake in trying to build a better more robust evidence base, clinicians have a stake in being able to offer something to the people that they’re looking after. Families have stakes not just in their own immediate care, but they worry about their siblings, they worry about their children, their grandchildren. There are also of course industrial players, so people trying to build a business out of making better medicines in the future. There are government players trying to use public resources more effectively. I think what we have to try to create is a mutual process where we recognise that everybody has overlapping but slightly different values that they’re pursuing and trying to get out of it, and how can we make sure that we govern our work in a way that reflects all of those stakeholders and recognises the respect that’s due to them. I think this is more like a sort of membership of a common project. And the problem with consent is it risks us saying you can be a member of this club but only if you accept the terms and conditions that the committee has decided is there. That’s not going to be adequate going forward.
I think we need to make sure that everybody feels that they are respected, that they feel they can place their trust in the system that we’re designing. As an Ethics Advisory Committee, we have to ask ourselves what justifies us suggesting to people that this is trustworthy. We need to make sure we have good information governance that people are not going to expose themselves to breaches of privacy if they take part in this. But we also need to make sure that we don’t waste people’s efforts. If people are prepared to be part of the research project, we shouldn’t have rules coming down on the data usage that say that we’re going to reduce the value of that contribution by saying it can only be used for one project and can’t be used for others, because actually that would not respect properly people’s contribution to the process.
We need to ask ourselves not just about the protective element of trustworthiness but that element that says we will make sure that you get as much as we can design of the things that you think are important from this project. They won’t be identical for each group, and they won’t be identical within each group. Different family members of participants will have different balances, but they all have to believe that this is a good club to be part of and that they have been part of agreeing ways of working that they think will produce a better future that they want to be part of and that they want to be proud of saying we have helped create this future.
Latha: I kind of agree with all that you’ve said. I think it’s most important not to forget because I’m also a participant, like my trio sample is there in the pipeline, and I know my data is sitting there. I also have trust that there is good information governance, the data is secure, so it’s reinforcing that, but it’s also being very honest that it’s obviously the data is there, but we can’t forget the person or the persons at the centre of it, so it’s not just alphabets or sequences of alphabets, but it is that whole person, and that person represents a group of individuals, family members, different generations, and they have embarked on it. Even if they know they may not get hope they might provide hope for others. It’s being therefore respectful.
I think that is the first thing I think is the principle of it and if you respect. If you think it could be the same principle that we use in clinical practice, the friends and family test, because I’ve been on both sides of the consultation table, I think I’ve become a better doctor because I’ve been an anxious mum, and my anxieties were dismissed as being an anxious mum and I don’t care. As far as my child is concerned, my anxiety was valid and so I would do everything to reach an outcome as to what’s best for that person. It’s made me a better doctor because I can see it from both the perspectives. Most of us are human beings, apart from AI technology looking at the dataset, so we all have conditions ourselves, we’ve got doctors with health conditions, we’ve got clinicians, academics, technicians, nurses everybody who’s got a friend or a family member or themselves having a health condition. I think its fundamental principle is that friends and family test. How would I like my data stored? How would I like my data analysed? Could it do this, could it give me some information on how I would get cured or treated or be managed? How would it affect my insurance, or will it find out data about who’s the father of this child, for example? It’s being honest and being honest about the uncertainties as well.
When I’m recruiting, I’m very clear that these are what I know that I can tell you about the risks. But then there may be other risks that I do not know about. If you’re honest about it and acknowledge what is the limit of the knowledge of science at this point in time, because you said there are so many stakeholders, there are researchers and academics who’ve got interest in some areas, it could have developed because of a family member having that problem, but whatever it is that is a great interest because that intelligent mind is thinking ahead and we need to encourage that. It could be for writing up papers, it doesn’t matter. Whatever be the reason, if it’s for the common good, that’s fine. It’s also thinking how are we keeping our families in the loop, so you have newborns, you’ve got young people sometimes with significant disabilities so they are relying on a parent or a carer to consent for them, but some are not so disabled but they have needs, they’ve got rare conditions, but they can make their consenting issues known when they turn 16, for example. It’s the changing policies and they can withdraw at some point in life or there may be a member of the family who doesn’t want to be part of that journey anymore. It’s allowing that to happen.
Jonathan: I think that’s a really interesting example you’ve just touched on, Latha, where I may diverge a bit in terms of what I think is the key issue. The right to withdraw I think is a really interesting challenge for us going forward, because we developed the right to withdraw in the ethics of research studies that had physical interventions. It’s really clear that someone who is being put to discomfort and is having things done to her body, if she wants to stop that, we can’t justify continuing on the basis of it being a research project. But I’m less clear whether that applies to withdrawing data from data pools. I think there are a few dimensions to that which I hope as an Ethics Advisory Committee we’ll have a chance to think through a bit more. One is the mutual obligations that we owe to each other. I’m not in these particular studies but I do try and take part in research studies when I’m eligible and invited to because I think research is important. When I take part in things and when our participants have taken part, they’re doing something in which they rely on other people participating because the aggregation of the data is what makes it power.
One of the things we have to be honest about is what are our mutual expectations of each other, so I think we absolutely have to hold on to the fact that people should be able to withdraw from further interventions, but I’m not convinced that you should have the right to say the data I’ve previously contributed that other people have relied on can suddenly be sucked out and taken out of it, because I think it’s reasonable for us to say if this is a sort of part of an enterprise. While you’re part of it, you’ve made some commitments as well as, and that’s part of the mutuality of the respect. I think I personally would want to argue you can withdraw from new things, but provided that your privacy is not intruded on, so we’re talking about data health anonymously, you shouldn’t be able to say don’t process it anymore.
Latha: No, no, no. What I meant was from my perspective I would like to be constantly involved and get information through trickling. I don’t know what my daughter feels years down the line, she might say I’m happy for my data to be used for research, but I don’t want to know anymore. There are two aspects of that, and I think if we are clear with that and say continue with my data being used for research, but I don’t want to get anymore letters. I think those are the kind of questions I face when I tell them families that these are the uncertainties, you can have your blood stored, you may not be approached again for a resampling unless you have some other issues, but are we happy with this? I think that’s what I understand, and I try and recruit with that intention.
Jonathan: And that makes lots of sense to me. As you say, you probably can’t speak for your daughters now, and you certainly can’t speak for them when they become parents for themselves and those things, but we do need to create an ethical framework which recognises that people will change their mind on things and people will vary about what they want to do. But because we have mutual obligations, what that means and the control we can give, we have to be open and honest about what choices we can give people without undermining the enterprise and what choices we say, “you don’t have to do this, but if you want to be part of it, there are some common mutual obligations that are intrinsic”, and that’s true of researchers, it’s true of clinicians, it’s true of anyone who works in Genomics England or the NHS.
But I don’t think we’ve been very good at explaining to people that there’s an element of this which is a package. A bit like when I bank, I allow the bank to track my transactions and to call me if they see something that looks out of the ordinary as a part of the protections from me. I can’t opt out of that bit. I can opt out of them sending me letters and just say do it by email or whatever and I have some choices, but there’s an infrastructure of the system which is helping it to function well and do the things it’s able to do. I don’t think we’ve been very good at explaining that to people, because we’ve tended to say, “as long as you’ve signed the consent form at the beginning of the process, it doesn’t really matter what happens after that, you’ve been told.”. That’s not enough I think for good ethics.
Latha: And I think that comes back to the other issue about training those who are consenting. I speak from personal experience within my own teams I can see somebody might say, “I don’t do whole genomic sequencing consenting; I don’t have the time for it.”. I might even have my organisational lead saying when we had a letter come through to say now we’re no longer doing this, we’re going to be doing this test for everybody, there’s a whole gasp because it’s at least two hours’ worth of time and how are we going to generate that time with the best of intentions. I think that’s where I think the vision and the pragmatic, you know, the grounding, those two should somehow link with each other. The vision of Genomics England with working with NHS England and with the future, Health Education England arm that is not amalgamated with NHS England, is trying to see how do we train our future clinicians who will hopefully consider it as part of their embedded working thinking and analysis, but also, how do we change the here and the now?
The more senior conservative thinking people, who are worried about how do they have to generate time to manage, we’re probably already a bit burnt out or burning out, how do they generate time? If you then discover new conditions whether there is already bottleneck in various pathways, how are we ethically managing the new diagnosis and how will they fit in in the waiting list criteria of those people on the journey who are symptomatic. I find that bottleneck when I have conversations with colleagues is the anxiety, how is that going to be addressed.
Jonathan: Latha, you’ve sort of taken us around in a circle. We started off thinking what was special about genomics, and we’ve reflected on ‘we have to solve the problems of the health service’. I think that there’s some wisdom in that, because we are learning how to do things that are not unique to genomics, but there’s an opportunity in genomics to do it better and an opportunity for us to help other areas of the health service do better, too. I think we’ve come around in full circle in a sense.
Natalie: Which feels like a lovely way to wrap up our conversation. I feel like we’ve gone into some of the deep ethical principles but also really shown how they can be brought into the practice, into the clinic and brought to bear the thinking and the feelings, the hopes the anxieties of participants. There’s a very, very important range of different voices so a very rich discussion.
I’d just like to thank you both very much for joining us on the podcast. Thank you to our guests, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli for joining me today as we discussed ethics in genomics research and practice. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
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Wednesday May 08, 2024
Professor Matt Brown: Genomics 101 - What is personalised medicine?
Wednesday May 08, 2024
Wednesday May 08, 2024
In this explainer episode, we’ve asked Professor Matt Brown, Chief Scientific Officer at Genomics England, to explain what personalised medicine is and how it could change the way we treat genetic conditions and cancer.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/What-is-personalised-medicine.docx
Naimah: What is personalised medicine? I’m joined by Matt Brown, chief scientific officer for Genomics England, to find out more. So, first of all, Matt, can you tell me, what is personalised medicine?
Matt: So, personalised medicine is about giving the right dose of a medicine and the right medicine to the right person. So, it’s exactly the opposite of one size fits all. It’s what doctors have been trying to do ever since we had effective medicines, that is generally looking at the patient, what disease have they got, what factors are there about the patient that can help judge what dose they should give and for how long, of which medicine.
Naimah: So, people often refer to this as precision medicine. Is this the same thing?
Matt: Generally, the two terms are used interchangeably. I think precision medicine is more specifically about the dose perhaps, but effectively they both mean the right medicine at the right dose for the right person.
Naimah: And how can we predict what treatment will suit each individual patient best?
Matt: Well, to some extent, of course, this depends on the disease the patient actually has. We also know from a patient’s history how they’ve reacted to similar medications in the past. So for example, some patients have lots of problems with anti-inflammatories, other patients don’t, so if you give an anti-inflammatory to somebody who’s had problems with them before, you’re likely to cause the same problems all over again. So nowadays, we have much, much better ways, other than trial and error, to predict what treatment will suit a patient best, and in particular, development of genetic markers to look at how their condition is going to respond best, and how the patient is going to tolerate the medicine you give them, and what dose you should be giving them.
Naimah: How could personalised medicine change the way we treat genetic conditions and cancer?
Matt: So, I’ll talk about cancer first up. In the past, we used to treat cancers based on the organ from which the cancer actually arose, and the more we’ve learnt about what the genetic mutations are that cause cancers, the more cancer treatments are being decided based on the genetic mutation which is driving the cancer, and this has proven to be more effective than just looking at the organ from which the cancer arose. It turns out then that some medications which were only being used for specific cancers, are actually useful across multiple cancers that are driven by the same genetic mutations.
In lots of other common diseases though, we now know a lot about genetic variants which predispose people to adverse drug reactions, and so we can use genetic tests to predict who’s going to get those adverse drug reactions and avoid them. And similarly, we also know about genetic determinants of how people metabolise and, in many cases, activate medications, and that helps us a lot learning about what dose to give people.
Naimah: And how far away are we from seeing this routinely in clinical care?
Matt: We are seeing it in routine clinical care in some pretty narrow settings. So, there are genetic tests available for enzymes which are involved in activation of particular chemotherapy 5 agents. So, DPYD testing, for example, is widely used to predict people’s likely response to a class of chemotherapy agent called fluoropyrimidines, or 5-Fluorouracil is a common one, and the genetic test basically picks out a group of people, a small number of people who are likely to have severe adverse drug reactions to that class of medication, and that’s been a really big success.
We also use it for picking some other severe adverse drug reactions to medications like gout medications, HIV medications and so on, but generally it’s pretty narrow. What we want to get to the point is where we have people tested in advance of them needing medications, so that when they go to the doctor to be seen about a particular condition, the doctor already has the genetic test available to them, so the doctor can say if the medication is safe and what dose to use. This is what we call pre-emptive testing.
Naimah: That was Matt Brown explaining what is personalised medicine. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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Wednesday May 01, 2024
Will Navaie: Genomics 101 - What is 'ethics'?
Wednesday May 01, 2024
Wednesday May 01, 2024
In this explainer episode, we’ve asked Will Navaie, Head of Ethics Operations at Genomics England, to explain what ethics is and why it's important, in the context of genomics.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
Want to find out more? Check out the blog 'Genomics 101: What is ethics?'.
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/What-is-ethics.docx
Naimah: What is ethics? Today I’m joined by Will Navaie, who’s Head of Ethics Operations at Genomics England, to find out more.
Will: Ethics is part of philosophy, and it’s part of philosophy that talks through a set of moral principles that govern our behaviour and our conduct. So, it might be thinking about whether something is good or bad. It might be thinking about whether something is good or better, or whether something is bad and worse. So, it’s about values and how we demonstrate those values kind of in a moral framework. So, I like to think of ethics as, just because you can do something, it doesn’t mean that you should do something. So, the law dictates to us what we can do, but ethics then talks about actually you need to look at the context around a law and to see whether something is reasonable, and so ethics to me is the should. So, should we do something? Just because we can do something, it doesn’t mean that we necessarily should do that thing.
So, in medical ethics, we have four pillars or four areas that we concentrate on. One is justice, and that’s making sure that something is fair and equitable and inclusive. And equity being the key here, so equity recognises that individuals have different circumstances, and equity allocates opportunities based on the needs of the individual. So, it’s not about giving everybody the same, but it’s recognising that to get an equal outcome for something, that some people will require more of something because of their set of circumstances. We also have autonomy, and autonomy in medical ethics is a bit of a focus sometimes, and what that is, is giving choices and respecting people’s decisions around that choice. Consent, we talk about a lot in medical ethics, but it is not the be all and end all. It’s really important, but actually it’s one principle among many that kind of make up ethics.
Another one of those four is beneficence, and that’s talking about everything we do must create benefit for people, and that benefit might be at an individual level, it might be at a societal level, so there’s lots of different ways of realising benefit. And the other, which is the flipside of that, is non-maleficence, and that’s making sure that everything we do doesn’t cause any harm to people.
Naimah: Okay, and then so if we’re thinking about ethics in the context of genomics, what does that mean?
Will: So, those four principles that we just talked about are applied to genomics as much as anything else, so there’s no exceptionalism to those, so we live by those four pillars, if you like. But what does make things complicated in genomics is that genomic data is not just about you. It’s not just about an individual. It’s about your family, it’s about your future family, and what that means is that we need to take those four pillars, those four areas, and look at them through a lens of a group rather than an individual. Where it becomes more complicated is the kind of interface between the law and ethics, and the way that the laws are written in this country and in healthcare are very much around individual rights, and that becomes really tricky when the decision making of an individual can affect other people in their family. And so, what we try to do is to think about how we can influence behaviour that we want to see. So, the law says an individual has to give their consent for a thing to happen. What we do is we take a step back and we say, “okay, but because there’s other people involved, we need to respect that.”
And so, we’re constantly thinking about how can we influence the behaviour that we want to see. So, we might say, “when you are thinking about whether you want to take part in medical research, or genomic medical research, you might want to speak to your family about this. You might want to speak to your children about this, because it does have implications on them.” And so again we’re using the sort of vehicle of consent to try and nudge those behaviours that we want to see. So again, it’s this kind of ethics complementing the law. So, the law’s not really working – it’s working to protect an individual, but it’s not necessarily respecting everybody, and so we just try to kind of affect those behaviours as much as we can.
Naimah: Okay, and then what’s the best way to demonstrate ethics?
Will: I think that’s a really interesting question, and I think it’s really important because ethics being part of philosophy means that very clever people have lots of opinions, and write lots of things, and there’s lots of words around ethics, but actually the really important thing is demonstrating that. So, in order to kind of build trust in something, you need to be able to demonstrate your trustworthiness, and i think the best way to do that is really through public engagement. If you don’t understand what people expect of you, it is not your role to tell people what to expect. It’s your role to listen and see what people expect of you, and once you understand what people expect of you, you then know how to act, how to behave in line with what people want from you, rather than telling people what to expect. So, in medical ethics, we talk about – or in healthcare in general, we talk about doing things with people, not to people, and i think the best way to demonstrate that is to listen. It’s to engage. It’s to act upon what the public are telling you, and sometimes those aren’t the things that you want to hear. But that’s how we make improvements. That’s how we build trust.
I think a really good example of this from Genomics England is the newborns programme. In ethics, we talk about the needs of science should never outweigh the needs of society, and scientists have said, “we think genomics can help with newborn screening and diagnosis of rare diseases.” So, what we’ve done is said, “okay, science has said this, we think that we can make improvements, but actually we now need to go and see what society thinks about this. Is it acceptable? If it is acceptable, what are people’s thresholds for what we can do? And so the whole programme and the generation study has all been driven by user involvement, public involvement, and we have learnt so much, and we’ve adapted our approach so much to that. And i think that it’s a really good way of us demonstrating that we have listened and that we have acted upon what we’ve heard. I’m really proud of the way that ethics has been actually genuinely embedded in the decision making around that.
Naimah: That was Will Navaie, explaining what we mean by ethics. I’ve been your host, Naimah Callachand, and if you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
![Marie Nugent: Genomics 101 - Why is diversity important in genomics research?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday Apr 17, 2024
Marie Nugent: Genomics 101 - Why is diversity important in genomics research?
Wednesday Apr 17, 2024
Wednesday Apr 17, 2024
In this explainer episode, we’ve asked Marie Nugent, Community Manager for the Diverse Data Initiative at Genomics England, to explain what diversity is and why it's important, in the context of genomics.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/006-Why-is-diversity-important-in-genomics-research.docx
Naimah: Why is diversity important in genomics? Today, I’m joined by Marie Nugent, who’s an engagement manager for the Diverse Data Initiative at Genomics England, and she’s going to explain more. So first of all, Marie, let’s start at the beginning. What is diversity?
Marie: I think it’s sort of a fiendishly seeming simple question, isn’t it, what is diversity, and I think you’ll get just as broad a range of answers as the people you might ask that question to. But for me, you know, it’s really got to be about how we do things. So to me, diversity is about recognising that there’s maybe a limited way in which certain things work, or the way in which we might go about doing certain things, and it’s also limited in terms of who’s involved in that and who might benefit from that. So, in the broadest sense, I think diversity means recognising the limitations of maybe what you currently do, and really looking for how can we open that up a lot more to provide the space and opportunity for a broader range of people and voices and experiences to really be brought into that and shape it.
Naimah: And can you tell me a bit more about what diversity means in the context of genomics?
Marie: I find this absolutely fascinating in the context of genomics, because genomics is really about how do we understand, you know, how our DNA, as an entire piece of information, is building us and shaping us as people, and having an impact on our lives, and, you know, for us predominantly our health. And the way in which we currently think about grouping people in genomics is unfortunately still very, very heavily influenced by social understandings of how people group together, not necessarily anything that’s really about your genetic ancestry, for example, which is very different. So at the moment, you know, it’s an interesting thing to play with and think about because in genomics it’s absolutely crucial that we understand the broadest sense of human diversity in terms of genetics and genomics, and only by doing that can we start to really fully understand what it means to be distinct, and therefore how small changes in DNA can have a massive impact on people’s health.
So, diversity in the context of genomics has to actually completely change the very fundamental ways in which we currently understand how people group together, so it’s really getting at the heart of that academic thinking about the topic. But it’s more than that, of course, as well, because as I’ve sort of already mentioned about what diversity means more broadly, it’s got to be about how we do things and who’s involved in that, and who benefits from it. So, in the context of genomics, it’s playing at the ideas of how we even understand how people relate to each other and how they’re different from each other, as well as how we do things. It’s a really complex but fascinating topic, to be honest, to be able to look at and study in some way.
Naimah: How does the inclusion of diverse populations contribute to improving genomic research?
Marie: Yeah, so following on from what I’ve just said, we fundamentally need to include everyone, you know. In order for us to really understand what genetic ancestry means and what difference looks like across different groups, and how that impacts health, we have to be able to capture, as best as we possibly can, you know, what true genetic diversity looks like in people. So, including as many people as possible who are different from what we currently understand is absolutely crucial. It’s the only way in which we can progress this area. And as I say, that’s in terms of how we think about it maybe academically and what we can do in terms of research, and what we understand, but it’s got to also be about the practice and how we do things. So, there’s involving people and having good representation of people in, say, data, but we have to think about how we’re involving people in how we do things and how we understand things, and how we make decisions about these things too.
Naimah: So, for these large groups of people, what are the challenges and barriers for including everyone?
Marie: So, I think there are a lot of challenges and barriers that hinder the inclusion of a broader range of groups of people in studies. I suppose the main one that I’m going to focus on is it’s actually the way in which we do research. It’s actually our culture, if you like, of work in this area. That’s one of the biggest barriers, and that’s because, you know, research is a very fast paced, very competitive environment and area of work to be in. Quite often, you know, things need to be done at pace, and things need results, and things need to be published and all that sort of thing, and I think there is sometimes this perception of not having enough time to slow down a little bit, think a bit more carefully and outside the box about how we might approach a piece of work, for example.
So for me, I think the biggest barriers actually exist within the existing organisations and people who do this work currently. We’re quite sort of blinkered, I think, still in terms of how we can even approach this work. And finding ways of approaching doing research in a way that’s kind of outside the traditional sort of ways of thinking is for me personally, in my experience of working in this area, one of the biggest challenges still.
Naimah: And finally Marie, how can we address these challenges?
Marie: I think it’s not easy for sure, because this isn’t a new thing that people have been trying to do, you know. There’s a big body of work, you know, in the context of the UK that’s been going on for a number of years, that’s been about sort of trying to open up and challenge, you know, existing research culture and things like that. But I think it has to be about our approach. So, for example, we have the power at Genomics England to think about how we approach the new initiatives, the new pieces of work that we would like to initiate. We talk about trust a lot in this space, but for me, it has to link back to how do we therefore change the way in which we do things so that it opens up a little bit more, people can see for themselves that we’re trustworthy and they can trust in this, rather than just saying, “Obviously, you can trust us because we’re doing research,” or, “We’re doing something that’s going to be brought into the NHS.” Unfortunately, that just doesn’t quite cut it for a lot of people for various fairly understandable reasons.
And I think, you know, we can make decisions about how we go about doing that work, and I think it’s about your priorities and things like that. So for me, the most effective way of actually addressing some of these existing challenges and barriers is to almost be brave enough to do it differently, and take that sort of perceived risk of maybe not doing things as expected and slowing it down, and allowing that extra time and space for people to come in and shape it, and not actually feel like we have to know everything and we have to make all the decisions. Sometimes I think it’s about, we hold the space, we have the resources and we have the access to the expertise, but how can we create the space where actually other people shape it and we just simply facilitate it. That’s the kind of thing I’d like to see organisations like ours and other research institutions and things like that start moving towards as facilitators of shaping work that will bring some sort of public benefit.
Naimah: That was Marie Nugent explaining diversity in genomics. I’ve been your host, Naimah Callachand, and if you want to hear more Explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
![Ellen Thomas: Genomics 101 - What is genetic or genomic testing?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday Apr 03, 2024
Ellen Thomas: Genomics 101 - What is genetic or genomic testing?
Wednesday Apr 03, 2024
Wednesday Apr 03, 2024
In this explainer episode, we’ve asked Ellen Thomas, Interim Chief Medical Officer at Genomics England, to explain what genetic and genomic tests are, why someone might do a test, and how they are performed, in less than 10 minutes.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/005-What-is-genetic-or-genomic-testing.docx
Naimah: What is genetic or genomic testing? Today, I’m joined by Ellen Thomas, interim chief medical officer for Genomics England, who’s going to explain more. So, first of all Ellen, what is a genetic test?
Ellen: Well, genetic tests examine a person’s genes to see if they have any changes in their DNA which might explain their symptoms. We all have DNA in most of the cells of our bodies, we inherit it from our parents and pass it on to our children. DNA provides the blueprint for our genes, and the proteins which build and run our bodies. Nearly all of our DNA is exactly the same across all of us, but around 5 million out of our 3 billion DNA letters are different, and each of these we call a genetic variant. The pattern of genetic variants that we all carry helps to make us who we are, and genetic testing is designed to examine some of these variants to help inform our healthcare.
Naimah: So, why are they sometimes called genetic tests and sometimes called genomic tests?
Ellen: Well, the words genetic and genomic are often used in exactly the same way, but broadly, genetic tests are usually used to look at just one or a small number of a patient’s genes, while a genomic test will look at hundreds or even thousands of genes at the same time. In general, it’s fine to use either.
Naimah: If you want to hear more about the difference between genetics and genomics, you can find another explainer episode with Rich Scott on our website, which goes into more detail.
Okay, so coming back to you, Ellen, what are the reasons we might do a genomic test?
Ellen: Some rare health conditions are caused by DNA variants in our genes, conditions such as cystic fibrosis, Huntington’s disease or sickle cell disease. In these 3 conditions, there is usually just one gene that is responsible, the same gene for all patients. That means that you can often find the DNA variant which has caused a patient’s symptoms by doing a test which looks just at that gene, or even sometimes just at a part of the gene. But for other genetic conditions, a variant could be found in any of dozens or even hundreds of genes, which could cause the same condition or a group of conditions, and examples of that include familial forms of epilepsy or developmental disorders in children.
For these conditions, to find an answer you often need to do a broader genomic test, looking at many genes at the same time, and also sometimes in between the genes. Finding the variant in a patient’s DNA which has caused the condition is useful, because it helps understand how the condition is passing down in the family, and whether it could affect anyone else in the family in the future. It is also increasingly used to work out which treatment an individual patient might respond to best.
Genomic tests are also used to help diagnose and treat cancer. A tumour develops and spreads because new variants in the DNA build up inside the tumour, which are not present in the patient’s healthy cells. By testing the DNA of the tumour, you can sometimes understand more about why it happened and what treatment might be most effective.
Naimah: So, can you tell me a bit about what sort of questions you can and can’t address with genomic testing, and how has this changed over time?
Ellen: Well, at the most basic level, if a condition is not caused by DNA variants, then a genomic test will not provide any useful information. So, doctors use genomic tests when they suspect that a patient might have an explanation of their symptoms in their genes, but we don’t always find an answer. Sometimes patients with a genomic cause and those with a different cause may have very similar symptoms.
We do constantly learn more about the ways in which genetic variants cause disease through research. Patients may have a gene variant causing their condition, but it’s so rare that it hasn’t yet been discovered, or so complex that it can’t be seen in the test analysis, so the test won’t identify the cause. Sometimes new understanding through research can then find the answer, which can be many years after the patient first developed symptoms.
Naimah: And how are these tests performed? For example, are they a blood sample?
Ellen: Yes, for most rare conditions, the tests use a blood sample. In cancers, a sample of the tumour needs to be tested after it’s removed by surgery or biopsy. The blood or the tumour is then processed to extract the DNA, and then there’s a range of different tests which can be used to read the DNA sequence. Expert scientists in the NHS then review variants in the DNA to make sense of the results and provide information to clinicians and patients about what it means for their diagnosis or treatment.
Naimah: And why are there lots of different genomic tests which can be used in healthcare?
Ellen: There are different types of genetic variants, and there are tests available that are specialised for these different types of genetic variant. Some tests look at a single gene, some tests look at many genes, often known as a panel of genes. Some also compare genomic information from a patient and their parents to understand which DNA variants are likely to be important. The tests will be selected to match what is understood about the patient’s symptoms and their likely cause, and to provide the best chance of finding information which will be useful for their care.
Naimah: That was Ellen Thomas explaining genetic and genomic testing. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
![Shaun Pye, Sarah Crawford, Sarah Wynn and Naimah Callachand: Shining a light on rare conditions](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday Mar 27, 2024
Wednesday Mar 27, 2024
Joey was diagnosed with DYRK1A syndrome at the age of 13, through the 100,000 Genomes Project. DYRK1A syndrome is a rare chromosomal disorder, caused by changes in the DYRK1A gene which causes a degree of developmental delay or learning difficulty.
In today's episode, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, speaks to Joey's parents, Shaun Pye and Sarah Crawford, and Sarah Wynn, CEO of Unique, as they discuss Joey's story and how her diagnosis enabled them to connect with other parents of children with similar conditions through the charity Unique. Shaun and Sarah also discuss their role in writing the BBC television comedy drama series 'There She Goes' and how this has helped to shine a light on the rare condition community.
Unique provides support, information and networking to families affected by rare chromosome and gene disorders. For more information and support please visit the website.
You can read more about Joey's story on our website.
"Although we’re a group supporting families and patients, actually a big part of what we’re doing is around translating those complicated genetics terms, and trying to explain them to families, so they can understand the testing they’ve been offered, the results of testing, and really what the benefits and limitations of testing are...just knowing why it’s happened, being able to connect with others, being able to meet others, but actually often it doesn’t necessarily change treatment."
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Shining-a-light-on-rare-conditions.docx
Naimah: Welcome to the G Word.
[Music]
Sarah Crawford: But I would also say it’s okay to grieve the child that you didn’t have that you thought you were going to have. I just think that’s so important. And I think for me, the most difficult thing in the early couple of years was feeling like I couldn’t do that because nobody appreciated that I’d actually lost anything.
[Music]
Naimah: My name is Naimah Callachand and I’m head of product engagement and growth at Genomics England. On today’s episode, I’m joined by Shaun Pye and Sarah Crawford, who are parents of Joey, who was diagnosed with DYRK1A syndrome at the age of 13, and Sarah Wynn, CEO of Unique, a charity which provides support, information and networking to families affected by rare chromosome and gene disorders. Today, Shaun and Sarah are going to share Joey’s story, and discuss how their role in writing the BBC comedy drama There She Goes has helped to raise awareness of people with rare conditions in mainstream culture. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts.
So first of all, Shaun and Sarah, I wonder if you could tell us a bit about Joey and what she’s like.
Shaun Pye: Yes. So, the medical stuff is that she’s got DYRK1A syndrome, which was diagnosed a few years ago, which means that she’s extremely learning disabled, nonverbal.
Sarah Crawford: Yeah, autistic traits.
Shaun Pye: Eating disorder, very challenging behaviour. She can be quite violent. She can be quite unpredictable. Doubly incontinent, let’s throw that in. She’s 17 but she obviously has a sort of childlike persona, I would say, you know. She sort of likes things that toddlers like, like toys and that sort of thing. But that’s the medical thing. What’s she like, she’s a vast mixture of different things. She can be infuriating, she can be obsessive, but she can be adorable. Occasionally, she can be very loving, especially to her mum.
Sarah Crawford: She’s very strong willed, you know. Once she knows she wants something, it’s impossible to shift her, isn’t it? So, she’s got a lot of self-determination [laughter].
Shaun Pye: So, her obsession at the minute, or it’s fading slightly, which is quite funny, is that she’s become obsessed by – there’s a toy called a Whoozit that she loves, but she became obsessed by the idea of – she was typing buggy baby Whoozit into her iPad, so that’s how she communicates. She’s got quite good literacy skills.
Sarah Crawford: Yeah.
Shaun Pye: And we figured out eventually that what she wanted was she wanted her mum to take her to the park to find a buggy with a baby in it that also had a Whoozit in it that she could steal, and when Sarah explained to her at some length that it was not yours, she would say, “It’s not yours,” that drove her insane with excitement, at the idea that she could steal another child’s toy. So, it’s a good example of her because it’s funny, and, you know, it is funny, and she’s so cheeky about it and she flaps her hands, she’s very hand flappy, and she sort of giggles and she gets really excited, but, you know, the 2,000 time she asked to do that, and we have to walk to Mortlake Green near our house, and to the point where – again, it’s funny when it happens, but you get to the green and she doesn’t even look for the buggies anymore. So, that’s an example.
But she’s a lot of different things, you know, and I suppose the thing that is dawning on us at the minute is that she’s 17, she’s going to be 18 very soon, and, you know, the list of presents that she gets on her birthday is always the same, ‘cos she’s autistic. So, at Christmas, she always gets the same presents. But the idea that, for her 18th birthday, we’re going to have to buy her children’s toys and – you know –
Sarah Crawford: Toddlers’ toys.
Shaun Pye: Toddlers’ toys and everything, it’s sort of hitting home, but that’s something – a bridge we’re going to cross on July 27th [laughter].
Naimah: Yeah, I can imagine that’s quite a difficult bridge to cross, but it sounds like, you know, Joey’s got lots of personality and you have lots of, you know, lovely times with her as well. I wanted to go back a bit before the diagnosis. So, you mentioned Joey’s been diagnosed with DYRK1A syndrome, but can you tell me what it was like before you both – and a bit about your journey, and when you suspected maybe something might be wrong and what you did first of all.
Sarah Crawford: I mean, there were hints that things might be wrong before she was born. The measurements were such that they thought there might be intrauterine growth restriction, because basically my belly wasn’t as big as it should be for dates, and that was obviously the working hypothesis. And they actually did a scan, an ultrasound quite late on in the pregnancy, which I picked up when I looked at the report was showing a small head measurement. And I remember querying it with the consultant, who said it was probably measurement artefact and nothing to worry about. But after she was born, she wouldn’t latch on, you know. We had to switch to bottle feeding straight away. She was small, and the head measurement actually was small. You know, you could see on the very early one, they must have taken it kind of three times to try and get it bigger, probably angling the tape measure, and it had been crossed out and rewritten. That was the pattern. So, her head simply did not grow in those early days in the way that you would expect.
So, I was wildly anxious about this right from the get-go, and very adamant very early on that I thought that, you know, she was learning disabled. And to be fair, you know, the GP took that seriously. You know, at the six-week check-up, things weren’t quite how they should be. We got in the system very early on, saw a paediatrician really quite early. So, I was, you know, fairly convinced very early. I mean, I’m a clinical psychologist, I’ve got training in learning disability, a bit more clued into these sorts of things I guess than the general public on the whole, and I think the bigger challenge for us wasn’t so much the attitude of, you know, the healthcare system. It was more trying to debate this with family, who were very much of the, “There’s nothing wrong with her,” kind of mantra.
Shaun Pye: She wasn’t our first child, so we had experience – and all children are different, but because we had that comparison – all children are different. Obviously, there’s not a set thing. But we had a benchmark in our own minds and hearts sort of, to know that she was missing things that he’d hit, and something wasn’t right. And the parental thing – basically, we’re talking about grandparents – it was sort of – there were two approaches that they took, one of which was to tell us nothing was wrong, because they couldn’t bear the idea that me and Sarah were in pain or unhappy. It was just out of pure love. It’s just a natural human reaction to say, “I’m sure everything’s going to be alright.” They were just trying to be supportive because that’s, you know, what they thought they should say.
And then the other approach from other members of the family was again from just a supportive, loving aspect, but it was a sort of, “They just need a bit of tough love, pull your socks up. Lots of children are different and you just need to learn ways of dealing with it.” And the way I describe it nowadays is that they’d mistaken Joey for someone on the far end of a spectrum of abilities or behaviours, whereas she wasn’t really on that spectrum at all. She was on a different spectrum [laughter]. She wasn’t a difficult child. She wasn’t a naughty child, was she?
Sarah Crawford: No, no, she was a child whose brain hadn’t developed.
Shaun Pye: She was a very, very different child. So, all of that has gone on over the years. And genetics wise, we had early genetics testing. Kingston Hospital took quite a lot of interest early on, and then they sort of didn’t take any interest [laughter].
Sarah Crawford: No, it’s more that they ran out of technology, so they couldn’t pinpoint the diagnosis with the technology they had. I mean, the geneticist was excellent, wasn’t he? We really loved him.
Shaun Pye: Yeah, Sarah’s going to like this, ‘cos I’m about to say I love geneticists ‘cos they’re – on the spectrum of doctors, I love them, ‘cos one of the guys we saw just looked at it like a puzzle and he was sort of excited to solve it, and he really wanted to work out – and in a way, you could have walked away from that thinking, “We wanted the bedside manner and we wanted the, “Oh, that’s terrible,”” whereas he really was just a sort of – he was terribly excited about the whole thing, and he wanted to solve a Sudoku, basically, yeah. But me and Sarah walked away from that just thrilled, ‘cos we’re the same [laughter]. There’s not a Sudoku or a crossword that we don’t love finishing. So, we walked away thinking, “These are exactly the people we want involved.”
And so when I say they gave up, that’s not fair. They just ran out of – you know, they can’t spend increasing amounts of NHS money. So, they tried – you know, different genes were mentioned.
Sarah Crawford: Yeah, they tested for a whole load. I mean, his attitude was right from the get-go, you know, based on the history, everything else that had been ruled out, dysmorphic features, those kinds of things – I don’t know if that’s the terminology they would use now – but that this was going to be a chromosomal disorder, and that they would do the tests that were available, but that it was possible that those wouldn’t pinpoint in, but that the technology was changing all the time, and that if they didn’t find it now, they would in the future. And that was how it played out.
Shaun Pye: There was one meeting that I did get a little bit – having said that, I got slightly – but you didn’t – about one of the geneticists, who sat there and said, “We’ll do this test and this test, and if they come back with any interesting things then we can get really excited.” And he used the word excited, and I was sort of a bit, “I’m not that excited by all of this.” But actually I calmed down quite quickly, and in hindsight I really wanted someone to get excited by the idea of working out – but then a long time went past. I wouldn’t say that we lost interest in finding out what her genetic condition was, we didn’t. It’s just it’s something that became less and less – it wasn’t like a holy grail for us. But then the opportunity came along with 100,000 Genomes, and we signed up immediately, and then they did that and it was a few years before that went through the system.
And then out of the blue really, we were asked to go and see a geneticist, and we had no idea that this is what it was. I honestly thought it was just a routine sort of, “We’ve got a few more theories,” or something, and she just said, “We’ve found out what it is.” And that moment is – well, we tried to describe it in the TV programme, but it’s quite hard to describe what goes through your mind when, after 13 and a half years, somebody suddenly says, “Oh, by the way, that thing that happened with your daughter, we’ve worked out what it is.”
[Music]
Naimah: I wonder if you could talk a bit about what the diagnosis meant for you both.
Shaun Pye: It was sort of different for both of us, wasn’t it? I was a bit more excited, Sarah was a bit more…
Sarah Crawford: My attitude early on was that, while the label would be nice to have, it wouldn’t make any material difference to anything to do – I mean, it was never going to be precise enough that it would give a map out of what we’d expect for her as an individual, and it wasn’t going to change the fact that there was a severe learning disability. It wasn’t going to change the challenges that we would have over things like schooling, therapies, you know, what the future holds for her. It is useful to have it, but it doesn’t really change the day to day.
Shaun Pye: But what it did change, and this is where Unique is so brilliant and important, is that it puts you in touch with people who have children with a similar condition. That’s the main takeaway from getting the diagnosis. ‘Cos Unique is great, and obviously in a broad sense it’s great, but to actually meet people and be in touch with people whose children have DRYK1A – so, I’ve met quite a lot of them now and I’ve met quite a few of the children. There was a meetup last year, and you just walk in and you just go, “Oh my god, oh my god” [laughter]. Literally girls running around, just the same as Joey, just the same, and the different ages as well. So, there were some in their twenties and there were some just starting out on their – who’d only, you know, very young, been diagnosed. But just to see your life just in front of you [laughter] is very useful. So, that’s the basic takeaway, I would say, from the diagnosis.
Naimah: Yeah. It must have been really nice to be connected with those other parents and to kind of share experiences as well.
Shaun Pye: It was, it was. And this applies to most – well, every family from Unique that I’ve ever encountered actually. Nearly all of the DYRK1A – ‘cos it’s spread around the world as well, so, you know, there’s slight cultural differences, but just to see that they are all of a very similar mindset is comforting, ‘cos it sort of makes you think, “Actually, we haven’t been doing this wrong.” It’s a sense of humour thing. It’s an attitude to the world. It’s the way they see their children. It’s the way they see the outside world. I’m not saying we’re all uniform, of course we’re not, but you can see it. When you talk to them, you can just see that they have the same sensibilities as you about the whole thing, and it’s sort of quite reassuring really that, you know, we’re not outliers.
Naimah: I just wanted to go back to, you know, when you were talking about the bit before the diagnosis, and I wanted to come to you, Sarah, to ask, you know, Shaun and Sarah both described their journey with a lot of uncertainty, but I wondered, could you tell me a bit more about the role Unique plays in this part of the journey for parents?
Sarah Wynn: Yes. Well, actually I think Shaun’s done such a good job of summing up why Unique exists already, thank you, Shaun. But I think really what we’re aiming to do is to try to alleviate that sense of helplessness and being overwhelmed, and isolation that often families feel when they have a child that’s got additional needs. I think our experience with our Unique community is very similar to that that Shaun and Sarah have described. So, many parents know that there is something – that their child isn’t developing as they would expect. And we hear lots and lots of stories of families going to healthcare professionals and actually not being taken seriously, or like Shaun and Sarah were saying, you know, everybody saying, “No, they’re just a bit delayed, it will all be fine.” And so I think that’s a common experience of many families, that the parents inherently understand and know their child better than everyone else, and it’s very common that families have to wait quite a long time to get to that point where they get to a diagnosis.
And often I think the uncertainty continues after you get that diagnosis, because as Shaun and Sarah said, you get a diagnosis of a rare condition and actually there just isn’t that much information available. So at Unique, we try to help in various ways. One is by connecting families with other families, and that might be other families who’ve got the same condition, but it might also be families who are just going through the same experiences as you are, so you’ve got someone to share your journey with. And the other thing we try to do is to help families understand the kinds of genetic testing they’ve been offered, and a bit about the results of genetic testing. Because of course genetics is something that lots of people haven’t thought about since school, and actually quite often hoped they never had to think about again.
Although we’re a group supporting families and patients, actually a big part of what we’re doing is around translating those complicated genetics terms, and trying to explain them to families, so they can understand the testing they’ve been offered, the results of testing, and really what the benefits and limitations of testing are. Sarah said, often you get a result and a diagnosis from genetic testing, but that doesn’t give you a magic treatment that’s going to cure your child. It’s really important, for all the reasons Shaun and Sarah have already said, just knowing why it’s happened, being able to connect with others, being able to meet others, but actually often it doesn’t necessarily change treatment.
Shaun Pye: I guess one thing I would say, just ‘cos it was important to us, and it’s de novo in our case, but that’s comforting to know. We always suspected it was and we were always told it was, but to have that confirmed means – I mean, we’re not going to have anymore children, but it’s more to do with our son and whether there’s something inherent that could be passed on.
Sarah Wynn: Yeah, it gives you information that you can use for either your own family planning or other family members.
Naimah: You mentioned that Joey received her diagnosis via the 100,000 Genomes Project. How did that come about?
Sarah Crawford: I think it was offered, as in the 100,000 Genomes Project was the only way that that was potentially available at the time, that this was effectively a project that was going on to try to answer those unanswerable questions with the technology they had at the time. I mean, it was years between us enrolling in it and getting the answer.
Shaun Pye: It’s so important to me in hindsight the diagnosis, just for all the reasons that we’ve been discussing, but without doing down the role of genetics, there was a period of Joey’s life when we thought we’d run out of road with the testing, and it wasn’t something that really I was obsessed with or occupied my mind massively. It wasn’t like me and Sarah were saying, “We must get back to Kingston Hospital. We must get back to the geneticists. We must write to the NHS. We must insist that they do this.” We’d sort of resigned ourselves to the fact that they’d done all that they could and they hadn’t found it, and that’s what it was going to be. Having said that, when 100,000 came along, we obviously jumped at the chance. We had no misgivings about it whatsoever, ‘cos I think we’d resigned ourselves to the fact that we might never know.
Sarah Crawford: I think I thought that at some point we would, because the technology, the methodology that they’re using obviously was changing all the time, but it didn’t preoccupy me because I didn’t think it would make a massive amount of difference. It probably made a bit more difference than I thought it would, for the reasons that Shaun and Sarah have said, about, you know, particularly the sort of connecting with others, you know, just realising how useful it is to be able to hear about the similarities and differences that other families experience.
Shaun Pye: I think a key point for us, and I’m sure this is true for the vast majority of Unique families, that we never thought that there was a cure. We never ever, ever, ever, ever, ever thought there was. And nobody in our family did. It’s not like anyone was saying, “Oh, with this treatment or that treatment…” Once you know that it’s DYRK1A, there’s obviously things that you can tailor towards her in terms of therapy, you know, there are things that you can do, but we were never under the illusion that if we found out what it was, she could go on and some sort of drug would suddenly make it better.
Sarah Crawford: Yeah, we’re not queuing up for experimental stem cell treatment [laughter] in weird and wonderful parts of the world, you know. What’s happened has happened. Her brain didn’t develop properly in utero and beyond. There is no changing that.
Naimah: But I guess with diagnosis, and like you said, if you can get some relief from some of those other symptoms that are caused by it, then, you know, that’s some sort of relief for Joey and a bit of help.
Shaun Pye: Yeah, there are absolutely concrete things that you can learn that will – Joey will never be better, but talking to the other families – eating disorder, that’s one of them. Constipation, that’s another thing. But hearing their experiences, hearing the roads they’ve gone down, finding out that there’s, you know, a unit somewhere in the country that specialises in this, that or the other, these are concrete things. It’s not just about emotional support. It’s absolutely about practical support. But there’s no magic wand, but there are things that, you know, we’ve learnt that can help.
Naimah: And then Sarah, to come to you then, do you find that families find it difficult to seek out help from Unique once they’ve received a diagnosis, or are they likely to come quite quickly to you? What’s your experience?
Sarah Wynn: It’s a really good question, and of course we don’t know the ones that never find their way to us. But what we try to do at Unique is to be sort of warm and friendly and welcoming, so that it’s not too daunting. ‘Cos I think all of these things are an extra thing for parents who are already busy and dealing with lots of medical appointments and therapies, so we try to make it as easy as possible to join us. Many, many families do join us at that point of diagnosis, because that’s when they’re looking for more information. Actually, you can get in touch with Unique and if you decided you didn’t want to join us, that’s also fine. So, we have a helpline that you can call. And for some people, joining a support group just isn’t their cup of tea, and that’s really fine. Other people find us a little bit later on, you know, perhaps when their child starts school or, you know, there’s sorts of crunch points where people are looking for extra information or support that they tend to find their way to us.
But one of the things we try really hard to do is to get the word out that organisations like ours exist, so that we can be contacted if people want to. And lots of our families come, like Shaun and Sarah, after the geneticist has told them that we’re there. So, that’s a really important thing for us is that everybody knows we’re there. You can join us and involve yourself as much or as little as you want. So, as we’ve already talked about, one of the things we do is put families in touch with each other, but not all families want that. So, you know, you can join and remain no contact, and stay quietly under the radar if you’d like to. But those people often want their child to be sort of counted in the system, you know. When you say how x number of people have DYRK1A, they want their child to be in that number even if they don’t want to go to the meetups, or they’re not quite ready to do that. And of course people change. So, some people join us and think, “We’re just going to quietly sit here for a bit,” and then change their mind a bit further down the line.
I think, although There She Goes, and what Sarah and Shaun have said about their journey is really similar to many people’s journeys, of course everyone is a bit different, and so people want different things at different times. And what we try to do at Unique is to be those things for whenever families need us.
Naimah: Yeah, that must be really reassuring for families, knowing that they can come to you whenever they feel ready to more than anything.
Shaun Pye: Just to jump in quickly as a sort of user of Unique, from the sort of different perspective from Sarah, that is literally how the service presents. That’s not an ideal that they aspire to. That’s what it’s like. So, I can confirm that – I mean, people think different things, and within our DYRK1A group, for example, you know, there’s a broad range of people who think various things, but the one thing about it and Unique is it’s very well self-policed, so people know how to behave. You won’t be subjected to ill informed sort of medical nonsense. It’s very well self-policed, but it’s also very, very occasionally – I’m speaking for the DYRK1A group – the example they gave me was around covid and vaccinations, and, you know, people have very strong views about it, and these forums aren’t the places to be having that sort of discussion.
Sarah Wynn: I think that’s exactly it. One of the ways families can connect with each other is via an online forum, and generally we take quite a light touch in moderating it, because the forum is for the families, and we want them to feel ownership and that it’s their safe space. But yeah, ever so occasionally, it needs just a tiny little bit of input. But yeah, I think Shaun’s right, everybody’s there for the same reason, and that’s to kind of share experiences, sometimes vent about the world, ask questions, and actually celebrate things that other people might not see as such a celebration. You know, lots of our families, their children might be late to walk, and it’s a place where you can celebrate all of those sorts of things as well.
[Music]
Naimah: So, next I want to move on to talk about 'There She Goes'. So, you mentioned it briefly there, Sarah. So, this is the BBC Two comedy drama, for which Shaun and Sarah were both writers on, and it really draws upon your real-life experiences of caring for Joey. And although the series is posed as a gentle comedy, it also displays really frank and honest emotions experienced by Emily and Simon, who are the parents of Rosie in the programme. Let’s listen to the poignant clip from the series by Jessica Hynes, who plays the mother, Emily.
Emily: You know, when you’re younger and daydream about what family you might have – so, I was the girl who thought Claire always got away with murder. Or when we found out Ben was going to be a boy, if it would be like you and Soph, you know, dorky older brother, biffy outdoor sister who everyone liked, you know. But in none of my dreams was there a girl who… Yeah, who was like Rosie. Yeah… No one ever dreams of a child like Rosie… You know, and I… I love Rosie, but why do I have to be defined by her? You know, for a long time, I felt cheated by her, because she wasn’t the girl that I dreamt about, you know. She’d taken her place. And then as she got older and I accepted her more, you know, what if it wasn’t that she’d taken her place, what if she just pushed in the queue and then if we started again, then if I had, you know, a normal girl, and then I wouldn’t have to… I wouldn’t have to resent Rosie anymore because I’d have the family that I’d always wanted, and I’d have – I’d have Rosie as well, yeah. [Sobbing] Just after all these years, haven’t I earnt that?
[Music]
Naimah: Off the back of that, I wondered if you could both tell me a bit more about what it meant for you being able to write for the programme and, you know, what it’s meant in the aftermath as well.
Shaun Pye: So, it came about - I basically am a TV writer and Sarah’s a psychologist, but it came about primarily because I was trying to think of something to write about and we realised that Joey’s just an incredible character. Those sort of children aren’t featured on mainstream television really at all, I would say. And so we thought it would be an interesting thing to do. But from that sort of slightly selfish motive, I wrote an episode, and Sarah read it and said, “You’re not doing that, it’s not honest enough” [laughter]. So, Sarah came on board as a writer with me and we cowrote it. The whole thing’s cowritten. And it’s the most important piece of work I’ve ever done, I ever will do, and it became far more than just a TV programme.
The first series went out and we had a screening, and Unique came to the screening, along with some of the other charities, and we were so terrified of what the response would be. And the fact that the response was what it was, which was overwhelmingly, “It’s like looking at our own lives on television,” it was recognition. It was nothing to do with whether the stupid jokes were funny or anything [laughter]. It was purely whether – if anyone had turned round and said, “This has got nothing to do with what it’s like bringing up our child,” or our brother or sister or whatever, that would have been quite bad for us, but it wasn’t, and that’s been the overwhelming response since. It’s, “Thank you for putting our life on television, ‘cos it’s not normally on television.”
So, it became that, and so the second series was even more about that, and then the special that we did was almost totally aimed at, we need to tell these stories because there are so many people in this country who this story isn’t being told for them. And it so happened that Joey hit puberty and had some very, very, very problematic behaviours, sort of self-harming behaviours, it happened quite close to her being diagnosed, so we thought this story is just written for us. Joey’s written it for us. So, we just sort of wrote down what happened. That was sort of what it was. And then obviously the response to that was very good. So yeah, and we wanted to feature Unique ‘cos that was such an important part of what we’d been through.
So yeah, it went from me wanting to further my career to that having nothing to do with it, and me wanting to [laughter] tell the story of children with rare chromosomal disorders and learning disability, and that’s what it became.
Naimah: I’m sure it must have been almost quite cathartic, I imagine, in a way, to share your story that way, and also, you know, give you a real sense of accomplishment to be able to kind of share your story on that platform. Like you said, like it’s never been done before in such a way, and to get that kind of response from other families, it must have really just helped you both in your journey as well, I can imagine.
Shaun Pye: For me, because it’s what I do for a living, it still retained a certain sense of my job. And, you know, emotionally, obviously, entirely committed to it. All the bits that make you sort of cry, or all the bits that are like, oh my god, Sarah wrote – I wrote all the stupid bits that David Tennant says [laughter]. So, I think it was more cathartic for you. You really had to dig deep into some quite unpleasant memories [laughter].
Sarah Crawford: Yeah, it wasn’t always the most comfortable process, you know. We’d sort of agree – I mean, particularly in the earlier process, we’d sort of have a little think about what we wanted to talk about, and then I’d go off and like kind of delve deep into memory, and just type a stream of consciousness, and I’d be sitting there sobbing [laughter], you know, with tears rolling down my face, you know, just reliving these really awful experiences. But yeah, I think the end process ended up being cathartic, and a lot of that was stuff that I would never have imagined sharing with anybody [laughter], let alone, you know, this huge audience of people, which – yeah, strange how things evolve.
Shaun Pye: Yeah, I think possibly if we hadn’t done this then we might have just tried to not think about these things and not bring them back, and I think we probably wouldn’t have spoken to each other – we may have, I don’t know. I don’t know what would have happened. But I don’t think these things would have come out into the open. And very interestingly, another side aspect of it in the catharsis way is the effect the programme had on the wider family. There were certain members of the family who were really shaken by that programme, really shaken, because they had a set view. Even as Joey got older, they had a set view of the history and what had happened, and they were really shaken by the idea that their – out of love again, there’s nothing bad here, but they were really shaken by the idea that their actions had a detrimental effect on us when Joey was born.
You know, there were people saying, “Well, I didn’t say that there was nothing wrong with her,” and, “I didn’t say this or that,” but actually when you see it presented in the programme then there was a lot of re-evaluation that went on, in a good way, in a positive way and it’s all good.
Sarah Crawford: I think there’s something about seeing it, you know, and especially given, you know, we were so fortunate with the cast because they’re so good at portraying it. And I think there’s a power in seeing things played out rather than just hearing about them in the abstract.
Naimah: Yeah, definitely. I definitely had moments of crying and laughing, and a range of emotions while I was watching it, so yeah, definitely very powerful. And I guess it’s really great for other families going through similar circumstances, for their families to see what’s happening and, you know, there’s a lot that can be learned from the programme as well. So, you know, it’s, yeah, really a powerful piece that you put together.
Sarah Wynn: I would really like to echo that. I think Shaun and Sarah have said before that they didn’t do it to represent everybody’s experience, but actually that is exactly what it has provided. I would say that huge numbers of people are really grateful that that portrayal is there, so that they can be seen and heard and understood so brilliantly. But it has provided other families with the opportunity to show it to their friends and family, so that they understand their life as well. And so I think it’s had a hugely positive reaction from our Unique community. And I think it’s not always an easy watch, I think lots of families would say it’s challenging to see it up close in front of you, but I think it’s really cathartic and has been just incredibly powerful at showing these sorts of stories, which, as you said, just don’t get shown very often.
And I think particularly when we think that rare conditions, although they’re individually rare, if you put all of the rare chromosome conditions together, they’re not actually that rare, so these are stories that are going on up and down the country and all over the world.
Shaun Pye: Just to follow up on something Sarah said earlier on about, you can take as much or little as you like from Unique, it’s the same with the show. I’ve had lots of people get in touch with me or talk to me in person and say, “I’m really sorry, I tried to watch ‘There She Goes’ and I can’t watch it,” and I have to say, “Don’t apologise, you have nothing to apologise for. You take what you need from it. If you can’t watch it then don’t watch it. If you can watch it then do. There is literally no right or wrong way of doing this. There really isn’t.” But having said that, the nicest comment – well, one of the nicest comments I’ve seen was on the DYRK1A forum. It was someone who casually referred to it as “our show,” as in the DYRK1A community, it belongs to them, and that – yeah, a little tear, a little tear went down my face [laughter].
Naimah: Yeah, that must have been a lovely thing for you to read. That’s really nice.
Sarah Wynn: Also from the Unique and general people who have rare conditions community, it’s been so fantastic for raising awareness about genetic testing and rare conditions in general, and, you know, there just isn’t – because these stories don’t get talked about or shown about very often, it’s been really great from that point of view as well.
Naimah: And hopefully this will be the catalyst for similar programmes and, you know, more things in the mainstream media as well. And you did touch on it briefly there, Sarah, about, you know, what the programme’s meant for Unique, you know, and the Unique community being very supportive, but have more people reached out to Unique since the programme?
Sarah Wynn: I think the main takeaway is that being heard, “Our family’s being heard and represented,” which I think is really important. But yes, we’ve got lots and lots of new families that have come to us through watching There She Goes. And it was really fortuitous that when the special aired last spring/summer, it was the evening before our awareness day, which I think was a complete coincidence but actually turned out to be really great timing. So, we got lots and lots of new families get in touch with us, many of whom then went on to join us. But actually what it also did was get lots of members who’d been members for a long time but perhaps had been a bit quiet, or hadn’t been in touch, so it sort of also reinvigorated that engagement from other members who we might not have heard about for ages, and who might have got older children and had been in touch at the point when they were diagnosed, and then hadn’t been.
So, it has just been such a brilliant, brilliant experience to have Unique as part of it. And I think that’s really important. At Unique, we have members from 120 different countries, and the reason is that when you have these rare conditions, you’re really unlikely to find someone in the same town as you, possibly not even the same country with some rare conditions, and so the idea that you can connect with people all over the world I think is really important, particularly in rare conditions.
Naimah: Yeah, that’s great, and hopefully, you know, it just continues to increase support with Unique and, you know, families know they can still come to you as a resource and as that continues. So, I just wanted to kind of wrap up here and come to the final question. So, you know, your story highlights a lot of challenges, a lot of difficulties, a lot of ups and downs, but I just wondered, Shaun and Sarah, if you had any advice for other parents going through similar circumstances.
Shaun Pye: Yeah, I think one of the things is what I just said, which is I would tell people there’s no right or wrong way of doing this. I would say, from my experience, don’t be hard on yourself, and you’re going to think that you wish it never happened to you and that’s fine. That is absolutely fine. That’s normal. We’ve all thought that. It doesn’t make you a bad parent. It makes you a normal human being. I would say to get in touch with Unique. I shied away a little bit from help and charities, ‘cos I think it was a sort of pride. I think I had a preconception that it would be glass half full, put on a happy smile, best foot forward, blitz spirit sort of. We have encountered it a little bit over the years, not very much, but we’ve encountered a little bit of, you know, “As long as you love them, that’s the most important thing,” and, you know, which is fine and that is an okay perspective to have, but there are times when it’s just not what you want to hear. I want to be allowed to feel the feelings that I’m having without feeling guilty.
So, I would encourage people to seek support from Unique or from wherever. But, you know, generally, the thing I’ve learnt about people is that the vast, vast majority of people are nice and kind and understanding about this. Not everyone, but most people are good people and, you know, people should remember that, I think.
Sarah Crawford: Yeah. I mean, the first thing I was going to say in terms of advice to other people was something Shaun said already, which is the don’t be harsh on yourself, because, you know, you’re allowed to find it difficult. But I would also say it’s okay to grieve the child that you didn’t have that you thought you were going to have. I just think that’s so important. And I think for me, the most difficult thing in the early couple of years was feeling like I couldn’t do that because nobody appreciated that I’d actually lost anything. The world seems to use the word difference a lot at the minute, you know, “These children are different, they’re differently abled,” but actually it is disability [laughter], and it is more difficult, you know.
There are rewards, there are positives, but, you know, she’s 17 and a half now, our daughter. When our son was 17 and a half, you know, the challenges were different, but they were also nowhere near as big [laughter], and I don’t think that should get lost. Because I think parents need to feel it’s okay to get the help they need and to push for the help they need, and not feel like they’ve just got to kind of put on a brave face and, you know, as Shaun was saying, the attitude sometimes of, “Well, you’ve just got to get on with it.” Because while you do, actually, you know, you do need help to do that. It is difficult.
Shaun Pye: The only other thing I’d say is, just ‘cos Sarah just mentioned it and it gets forgotten, is the siblings thing. The families with Unique will have all manner of different configurations. I can only speak from our own experience, but Joey has an elder brother, Frank, who is, well, in my opinion, the best human being in the world [laughter], and I’m sure in his mother’s opinion as well, but my experience, never forget about the toll it takes on siblings. ‘Cos Frank is a very, very loving brother. Only last night, Joey was typing, “Frank book.” ‘Cos he’s gone to university, she likes looking at pictures of him in the photo albums. She likes looking at pictures of old toys mainly.
Sarah Crawford: Yeah, yeah, she likes looking at her as a baby and the toys they had.
Shaun Pye: Yeah, but it’s not really advice, it’s just, you know, there’s a danger that Joey could have taken over our entire family life, and especially Sarah made sure that didn’t happen and that, you know, we were a unit and he was – but, you know, it is possible that it can swallow up your entire life.
[Music]
Naimah: Okay, so we’ll wrap the interview up there. Thank you so much to our guests, Shaun Pye, Sarah Crawford and Sarah Wynn for joining us today as we discussed Shaun and Sarah’s journey to Joey’s diagnosis, and how charities like Unique can support families of those living with rare conditions. If you’d like to hear more like this, please subscribe to the G Word on your favourite podcast app. Thank you for listening. I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.
![Clare Kennedy: Genomics 101 - What is the difference between DNA and RNA?](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Wednesday Mar 20, 2024
Clare Kennedy: Genomics 101 - What is the difference between DNA and RNA?
Wednesday Mar 20, 2024
Wednesday Mar 20, 2024
In this explainer episode, we’ve asked Clare Kennedy, Clinical Bioinformatician at Genomics England, to explain what the difference is between DNA and RNA, in less than 10 minutes.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.
Want to find out more? Check out the blog 'Genomics 101: RNA vs DNA, what's the difference?'
You can read the transcript below or download it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/004-What-is-the-difference-between-DNA-and-RNA.docx
Naimah: What is the difference between DNA and RNA? Today, I’m joined by Clare Kennedy, who’s a Clinical Bioinformatician here at Genomics England, who’s going to tell us more.
So first of all, Clare, what is DNA?
Clare: So, DNA stands for deoxyribonucleic acid, and although this is quite a mouthful, DNA is essentially an instruction manual for our body on how to function, and a copy of this manual is stored within almost every cell of the body in a structure called the nucleus. So, our DNA essentially comprises all of the genetic information we inherit from our parents, and this information is contained within two long strands of code, and we inherit one strand of code from our mother and one from our father, and both strands combine and they form a twisted ladder like structure that we call the DNA double helix. So, each strand is made up of small units called nucleotides, and these nucleotides, they differ based on their chemical composition. They can either contain a molecule of adenine, guanine, cytosine or thiamine, and this is why we often see our DNA sequence represented by the letters A, G, C or T. And in total, our entire DNA sequence consists of three billion of these nucleotides.
So, as this DNA instruction manual is quite long, it needs to be broken up into smaller sections that the body can read, and that’s where genes come in. So, a gene is a segment of the DNA and it contains a particular set of instructions, normally on how to make a protein. So, proteins are essential for life and they’re involved in almost every process within our body, and that is why we have around 20,000 protein coding genes in our DNA.
Naimah: So then can you tell me, what is RNA and how does this differ from DNA?
Clare: So, like DNA, RNA, which stands for ribonucleic acid, is an incredibly important molecule that encodes genetic information, and it’s found in all cells of the body. So, RNA consists of only a single strand of nucleotide units, and just like DNA, RNA can be represented by four letters that reflect the chemical composition of each nucleotide. These four letters do differ slightly though, because RNA contains uracil instead of thiamine, so you can distinguish a DNA sequence from an RNA sequence by the presence of the letter U and the absence of the letter T. So, while we think of the DNA as the instruction manual for the body that contains all of our genetic code, RNA is the reader of this instruction manual, and it helps the cell to carry out these instructions, so the proteins can be made.
Naimah: So, can you tell me a bit more about this protein production, and how are DNA and RNA involved?
Clare: So, protein production all starts in the nucleus with the DNA. So, if we want to make protein, we must first read the portion of the DNA or the gene that contains the instructions to make this protein. So, because DNA is so long, it’s really tightly packed into our nucleus, and the
region we’re interested in might not be accessible, so we first need to open this region out. So, molecules and enzymes help us open this region of the DNA, and once the gene is accessible, they start to read it, and they start to transcribe the instructions that are encoded within the gene into a type of RNA called messenger RNA. So, as the name suggests, messenger RNA is the communicator of the instructions contained within our DNA, and this process is called transcription.
So, the messenger RNA then leaves the nucleus and enters the main body of our cell, which is called the cytoplasm, and messenger RNA is transported to the ribosome. Now, the ribosome is a piece of machinery which will build the protein, and it’ll use the instructions that are encoded by the messenger RNA. But we need materials to build the protein, and that’s where a type of RNA called transfer RNA comes in. So, transfer RNA is instructed to hunt down the building blocks or the amino acids that we need to build the protein, and it brings these back to the ribosome. And then we have a third type of RNA that gets involved called ribosomal RNA. So, ribosomal RNA helps the ribosome assemble these amino acids into proteins in a process known as translation.
So, it really is a group effort between the messenger RNA, the transfer RNA and the ribosomal RNA. And once the protein has been assembled, it might go through some more processing steps, and it’s eventually exported by the cell to where it’s needed.
Naimah: Okay, so apart from their roles, are there other key differences between DNA and RNA?
Clare: So, as we touched on earlier, the main difference between DNA and RNA is in their structure. So, we have, DNA is in a double stranded helical structure, whereas RNA is single stranded. And because of DNA having this double standard helical structure, it’s actually much more stable than RNA, which is more susceptible to degradation by enzymes and other molecules. As DNA contains our genetic code, it’s much longer than RNA, and you can only find DNA in the nucleus of the cell as it’s much too large to leave the nucleus, whereas you can see RNA in the nucleus and in the cytoplasm. RNA and DNA also differ in the type of code or the lettering they use, so they both use the A, G and C letters in their code, while DNA’s is the T lettering and RNA’s is the U lettering, and this is due to the differences in the chemical compositions of the nucleotides that make up DNA and RNA.
And the nucleotides in DNA also contain different types of sugars from the nucleotides used in RNAs. So, in DNAs, you would have a deoxyribose sugar, whereas an RNA uses a ribose sugar. That’s where we get the deoxyribonucleic acid and the ribonucleic acid.
Naimah: So Clare, we’ve talked about the difference between DNA and RNA, but why are these important in clinical care?
Clare: So, we can use DNA and RNA to diagnose illness and to also develop therapies against these illnesses.
Naimah: Can you give me some examples of where DNA and RNA are used for diagnosing conditions?
Clare: Absolutely, so an excellent example is in the diagnosis of cancer. So, the majority of cancers are caused by mistakes in the genetic information encoded within our DNA, and result in the production of malformed proteins. So, we can normally look at the DNA and we can identify certain genetic mutations that cause the cancer. So, examples are breast cancer, ovarian cancers, lung cancers, essentially all types of cancers that you can think of will have genetic mutations associated with them. But then there are cases where no problem with the DNA can be identified, but then when we look at the RNA, we do see a problem. So, a particular example was recently shown in breast and ovarian cancer, where a gene that encodes for a protein called BRCA1 was not shown to have any genetic mutations, however when we looked at the RNA produced from that gene, we could see there are problems with that RNA and essentially identify a genetic cause for that cancer.
Naimah: Could you also give me any examples of where RNA or DNA are being used in therapies?
Clare: So, absolutely. So, most of us will have heard of RNA vaccines in recent times, such as those that were generated against COVID-19. And essentially how these vaccines work is they deliver small messenger RNA from the virus into the body. The body can then make a protein from this messenger RNA, and the immune system recognises this as an invader and destroys it. So, this low level of viral exposure essentially trains your immune system to respond in the event of an infection, and really the success of the MRNA vaccines against covid has really paved the way for the use of MRNA vaccines against cancer. So, it’s believed that we can stimulate an immune response that would destroy a cancer cell using MRNA vaccines, and there are now some studies that are looking at developing messenger RNA vaccines against cervical cancer in particular.
So, DNA therapies can actually target genetic mutations and correct them to prevent illness, and one such example is a gene editing treatment that has been developed for the treatment of blood disorders, such as sickle cell anaemia.
Naimah: That was Clare Kennedy explaining the difference between DNA and RNA. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
![Lisa Beaton, Dr Celine Lewis, Jana Gurasashvili and Louise Fish: Hope for those with "no primary findings"](https://pbcdn1.podbean.com/imglogo/image-logo/10639619/CopyofBehindtheGenestemplates_g5qetz_300x300.png)
Thursday Mar 14, 2024
Thursday Mar 14, 2024
There are a range of outcomes from a genomic test. The results might provide a diagnosis, there may be a variant of uncertain significance, where a genetic variant is likely the cause of the condition, or there might be no particular gene found that is linked to the phenotype or clinical condition - also known as a "no primary finding" result. In this episode, our guests explore the impact of a "no primary finding" result on families, discussing the common experiences and expectations of parents and patients who undergo that genetic testing, and the role that hope plays in the experiences of children with rare and undiagnosed conditions.
Today's host, Lisa Beaton, member of the Participant Panel at Genomics England is joined by Dr Celine Lewis, Principal Research Fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a Genetic Counsellor, and Louise Fish, CEO of Genetic Alliance.
"I think it’s also really important to add that hope isn’t necessarily lost when you don’t get a diagnostic result. And in a sense, what can be really helpful is for genetic counsellors to reframe that hope...sort of giving it a different context."
- For more information on the SWAN UK project which supports families with children that have been through genetic testing but have not found a result following that genetic testing, visit the website.
- Read more about the study by Jana Gurasashvili and Dr Celine Lewis: The disequilibrium of hope: a grounded theory analysis of parents' experiences of receiving a "no primary finding" result from genome sequencing.
You can read the transcript below or down it here: https://files.genomicsengland.co.uk/documents/Podcast-transcripts/Hope-for-those-with-no-primary-findings.docx
Lisa: Hello, welcome to the G Word.
Lisa: I think in the back of my mind, subconsciously, I had hoped that when we eventually got a diagnosis, it would – I don’t know, bells and whistles, balloons going off, fireworks, etc. And then the experience of a letter thumping on the doormat, and I recognised the postmark quite quickly, and it was at that moment I suddenly thought, “Oh gosh, I haven’t buried all these feelings of hope.” Because I opened that letter with quite trembly hands, and then this diagnosis or lack of diagnosis, you know, nothing had been found, and it was a bit… I don’t know if it’s been described as like a nail in the coffin experience, because I really hadn’t realised I was still clinging to this hope all that time, and then again it was, you know, another, “No, nothing’s there.
Lisa: My name is Lisa Beaton and I’m a member of the participant panel at Genomics England. On today’s episode, I’m joined by Dr Celine Lewis, the principal research fellow in Genomics at UCL, Great Ormond Street Institute of Child Health, Jana Gurasashvili, a genetic counsellor, and Louise Fish, the CEO of Genetic Alliance. Today we’ll be discussing the impact on parents with children with rare conditions, who received a no primary findings result after diagnostic whole genome sequencing. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts.
Can I ask all of us here present to introduce themselves, please?
Celine: Hi everyone, I’m Celine, I’m a behavioural scientist in genomics at UCL Institute of Child Health, and I currently hold an NAHR advanced fellowship to look at the implementation of WGS, or whole genome sequencing, in the NHS.
Jana: I’m Jana Gurasashvili and I’m a genetic counsellor at Northwest Thames Regional Genetic Service, and prior to that I was at Great Ormond Street, involved with consenting families to the 100,000 Genomes Project, and I also have an ongoing interest in the lived experience of patients and parents of genetic counselling and rare disease.
Louise: Hi, I’m Louise Fish, I’m the chief executive of Genetic Alliance UK, and we are an alliance of around 230 charities and support groups that work with patients and families who have particular rare conditions. We also run a really longstanding project called SWAN UK, and SWAN stands for syndromes without a name. And the SWAN UK project supports families with children that have been through genetic testing but have not found a result following that genetic testing. So, it’s clear they have a genetic condition, but science hasn’t quite advanced far enough yet to tell us what that means and what that will mean for their child, and what that will mean for their family over the coming years.
Lisa: And I personally can attest to the wonderful support that SWAN UK can offer because, as the parent of a still undiagnosed child, I have been involved myself with SWAN UK since my daughter was around the age of three to four years old. It’s brilliant being a part of my big SWAN UK family. We first realised that there were some – I suppose something wrong with our daughter when she was around two weeks of age, but it wasn’t something I could specifically put my finger on. I couldn’t at that point have taken her to a doctor and said, “I don’t know what’s wrong but there’s something wrong.” I just knew in my heart of hearts, probably because I have three elder children, that there were issues, and things weren’t developing as they should. She cried a lot, she screamed a lot, she never seemed to be comfortable in any position when you held her, when she was asleep, when she was upright. It didn’t seem to matter what you did, she was just a rigid, stuck child, for want of a better word. And all my mum senses were screaming, but it completely sounded ridiculous to take her to a doctor saying, “She feels wrong.”
And I think that’s quite a SWAN UK experience, from chatting to other families with similar situations. The parents just know that there’s something not right, but it can be very isolating not to be able to identify kind of where that starts and what it is. In our case, it wasn’t until our daughter was nine weeks old that things became much more obvious, that there were developmental concerns physically and medically, and at that point we went from my sort of mutterings that there was something wrong but I wasn’t sure what it was, to a sudden hospital admission with quite a shocking turn of events. From something that had started out quite normally, as a routine visit to the baby clinic, to suddenly being seen by a troop of different paediatricians, and doctors coming in and out constantly, asking different questions, and sending us off all over the building for different tests and x-rays and imaging. And being given a partial diagnosis that our daughter had a condition called arthrogryposis, but it was clear that there was much more going on than that, and we would need referring to many more different fields. And that day really our diagnostic odyssey, for want of a better word, began.
So actually, in terms of that diagnostic odyssey, many parents of children with rare undiagnosed conditions experience this, and when we agree to have genetic testing, we feel that we are going to get these answers straight away, and that every appointment that you go along to is going to be the one that brings you the answers. But certainly in our experience kind of 15 years on, that’s not been the story at all. Celine, can I ask you to explain what the words no primary findings actually mean when a parent receives that regarding their child?
Celine: So, there’s a range of different possible outcomes from a genomic test. So, the results might provide a diagnosis to that patient and family, or other situations, there might be a variant of uncertain significance, so we don’t necessarily know if the gene that we found, a genetic variant is the likely cause of the condition, or we might find no particular gene at all that we think is linked to the child’s phenotype or clinical condition. So, that’s what we mean really when we’re sort of saying no primary finding.
Lisa: Louise, would you be kind enough to explain what you think the impact of no primary findings means to families like my own, parents who don’t have a genetic likelihood cause, just a gene thrown up to diagnose their child?
Louise: Yeah, I think it’s a huge challenge for families, and you’ll obviously know that from your own experience. People go to have genetic testing hoping it will give them some answers, first and foremost, just to kind of understand, you know, what condition their child has and what the likely impact that’s going to be on their child and on the child’s life, and on the family’s wider life. And I think one of the things that we really ask genetic counsellors and geneticists to do is help people understand before the genetic testing takes place that there may be nothing found from it, so that that kind of expectation is built in. Because people hope that they will get a diagnosis that will give them answers about what the impact of the condition will be on their lives. In a best-case scenario, access to a particular treatment that might be a huge help for their child, but at the very least, access to a range of services and support for their child. So, that kind of diagnosis is often seen by families as the key to unlocking a range of services and support that will help them and their families at what is the beginning of a lifelong journey.
And I think when families get no diagnosis, there’s a real concern on behalf of families, a, that they don’t understand how their child’s going to be affected by the condition. What we’re really careful to say to families is, “Just ‘cos you don’t have a diagnosis with a name, your child is still the same person they were before. They still have exactly the same bundle of needs as they had before, and you will still need to work with the NHS and with wider services to make sure that they can access speech and language therapy, and physiotherapy, and all of the services that they are going to need and you are going to need to help them live their lives to the full.” But I think that moment of not getting a diagnosis is when people feel I think real – the uncertainty continues, and uncertainty, we know, is a really hard thing to live with, and the lack of clarity about which services you’ll be able to access. So, I think psychologically it’s a massive impact on the family not to have the answers that they were looking for, or the key to the services that they were hoping would be there.
Lisa: Thank you, Louise, yeah, I would definitely agree with that. We had a no primary findings result in I think it was 2019. It was a really bittersweet moment because my daughter’s list of various different conditions kind of – by this point, named parts of difficulties for her spans over sort of two pages of A4, and yet on the letter back from the genomics service, it just says that, you know, nothing causative has been found. And so part of you is left wondering, well, how can there be all these different conditions or difficulties, and yet there’s still nothing there? And I know personally, I had comments when she was much younger, every time a test came back, where people would say things like, “Oh well, that’s great news,” and to some extent it was great news that something hadn’t been found, but also if that hadn’t been found, what was still out there? And that fear of kind of the unknown was extremely difficult.
And also paradoxically, there was a sense of some very well meaning people saying things like, “Oh well, if they haven’t found anything then there can’t be too much wrong.” But yeah, I have a child who is tube fed and on multiple different medications, and cared for basically for 24 hours a day, so that doesn’t really fit in with the picture of there not being very much wrong from a personal perspective. And I think it can make you as a parent/carer feel perhaps there’s a tendency to downplay that there is an issue and that perhaps, you know, you’re making it up, for want of a better word, and that sense of isolation around that can certainly be problematic. Celine, if I can come to you, that diagnostic odyssey, what are the common experiences and expectations of parents and patients who undergo that genetic testing from your perspective?
Celine: Well, I think sort of parents go into genetics testing for a whole range of reasons really, and Louise has already alluded to many of these. Ones that I’ve come across in my own work include wanting to know why their child has a particular health problem, so that that child can access the most suitable treatments or therapies, or even access clinical trials. Even relief from guilt for many parents, a validation that the parents hadn’t done anything wrong during their pregnancy to cause the child’s condition, and that’s hugely important really, to try and get that relief from guilt. Also to know whether future children might be affected by the same condition, and then more social reasons really, for example, making contact with other parents through support groups, or access to social and educational support.
And I think there’s also a drive from many parents to feel that they’re doing everything absolutely possible for their child. I mean, particularly with something like the 100,000 Genomes Project, it was really a sort of first of its kind project, where patients were on a significant scale able to access this new whole genome sequencing technology. So, many of the parents taking part in that project felt like pioneers, and there was really a lot of expectations around whole genome sequencing in delivering a diagnosis for those parents who’d previously not been able to get hold of one.
Lisa: Yes, I strongly can resonate with a number of the points you made there, particularly the feelings of guilt. I must have asked myself a thousand times whether, you know, something I did do, something I didn’t do, something I thought of, something I hadn’t thought of [laughter], all those questions that swirl around, particularly in the small hours of the night when you feel particularly alone. And yes, I can completely relate to that. And also although SWAN UK is primarily for children and parent/carers whose children don’t have a diagnosis, actually a number of the parent/carers on there will have children with diagnoses that are so very rare that absolutely, you know, very, very little is known. They might be the only parent – the diagnosis, for want of a better word, they may have received may just be a series of kind of numbers and genetic dot-dashes, forgive my layman’s terms there, but it may not actually help them any further along in terms of feeling that they know anything further or the direction of, you know, where that will lead their children, and that can feel very, very isolating, I’m sure, probably just as much for those of us who don’t have that diagnosis.
Louise: Yeah, just to add to that, I think that’s absolutely right, Lisa, and I just want to give a shoutout – at SWAN UK, we tend to support families who don’t have a diagnosis at all, or, as you say, a small number of families who do but have been part of the SWAN UK family for so long that we’re very happy to keep them because of the support they’re finding from other parents. We work really closely with another of our members, Unique, who are a charity that support parents in exactly the situation you’ve talked about, where people have finally got a diagnosis and it’s that kind of relief of having a name, but it’s a super long name, and you find out you’re one of only three families in the world with that diagnosis. And so although there’s a real I think comfort for people, perhaps if you have a five year old and you’re meeting a family who have a 13 year old and a family of a 19 year old, then you start to see a little bit about how your child might develop, but there’s not enough kids affected that you can be really certain about that.
So, it gives you a little bit more information, but not the kind of wealth of information you were hoping for about how your child’s going to be impacted by a particular condition, and what the future might hold for you and for them. So, SWAN UK and Unique very much work alongside each other to kind of support families on whichever part of that journey they’re on, because there’s still a huge amount of uncertainty for families with those super rare conditions, as you say.
Lisa: Definitely, and I’m sure you’ll be familiar, Louise, yourself if you get time to go on the online communities and seeing the question that pops up quite regularly when somebody has received a diagnosis of, “Can we still remain part of the SWAN UK family?” And they very much use that word, family, because I think they do feel that, although all our children are different, there are children with physical, medical, cognitive, a combination of all the above syndromes, conditions, etc, they feel that kind of embrace of all being in a collective club of rare and unique and undiagnosed, and that’s very comforting to the members.
Louise: Absolutely, yeah, I think that sense of belonging and being able to reach out to other families that you’ve been on that journey with for many, many years. You know, many of our families join when their children are like one or two, and they’re still with us when, you know, their children are 26, 27 [laughter], and that sense of having that community and that family and that belonging is really, really important to people, I agree. It makes a big difference psychologically to be part of a community you can reach out to and ask the questions that perhaps you can’t ask to other people.
Lisa: Celine, can I ask you how many patients for the 100,000 Genome Project have had a no primary findings diagnosis back?
Celine: Well, back in 2021, there was a paper published in the New England Journal of Medicine, which reported that, in the initial pilot for the 100K, a diagnosis was found for around 25 percent of rare disease participants, and other studies looking at the diagnostic yield of whole genome sequencing have put the number anywhere between 25 percent to 55 percent, depending on the clinical indication. And we know that even already from the 100,000 Genomes Project, this pioneering project has led to more than 6,000 diagnoses being identified, and that number will obviously continue to go up as they explore the data and gather new insights. However, that still obviously leaves a significant number that won’t get a result from whole genome sequencing, as many as half of those rare disease patients, and that was really the basis of the study that Jana and I worked on.
So, we felt that there had been so much research really looking at the experience of parents who do receive a genetic diagnosis, and that a lot of attention rightfully does focus on the amazing successes of the 100,000 Genomes Project and genomic medicine more broadly, but actually that there is a considerable number of patients and parents and families who don’t get a result, and we felt that it was important that we also focus on those parents and patients, and try and understand their experiences.
Lisa: Yes, you can feel, if your child, for example, is under multiple different care specialists, that it can be quite hard, when you’ve just got this list of different names of things that are wrong, that you feel very much still out on the limb and forgotten about. But it’s clear that, from your work, you’re identifying that and pointing that back to the specialists, the consultants, to remind them that these parents and these children are still finding their ways through. Can I ask you, Jana, the study that was conducted, what would you say the main things from that study told us? Can you describe some of the emotions experienced by the parents, and what challenges that they have faced along that receiving the no primary findings diagnosis?
Jana: Yes. So, many participants really felt very strong disappointment and sadness on receiving that no result, and for many, it kind of reflected the feelings they had had when they first realised they had a child and there was no diagnosis for their condition. And as Celine said, this was such a new technology that people had invested a lot of hope in, and so many felt that it had been their last chance of finding a reason for their child’s condition, and that they’d come to the end of the road with that no primary finding result. And, well, one person described it as another door shut. And people talked about the actual toll taken, the emotional and physical toll, and one person described feeling low for several weeks following the result. And some talked about the timing of the result. Somebody got it as a letter just before Christmas, and so their whole family holiday that they’d prepared was marred by getting that news just before Christmas.
And it often seemed to leave parents feeling isolated and unable to contribute to normal parental roles, such as going to parent groups, etc, because they felt that other mothers particularly - as it’s mothers we were speaking to, other mothers, their experience of motherhood was so incredibly different to their own, and they felt a lack of support. And one parent actually talked about wanting to lock everyone in the house just to escape the feeling of judgement and pity from outside the front door. And some parents talked about finding it hard when other people would post on support groups that they had got results from the 100,000 Genomes Project, which was very difficult. And some talked about hope as finding it hard to keep hopeful but needing to keep hopeful. So, they talked of hanging onto a little bit of hope, as though that was quite an intense thing, which I think, Celine, you’ll agree, that made us able to kind of identify that hope was really part of a coping mechanism for this whole process of going through this diagnostic odyssey.
Celine: Yeah, people sort of talked about not wanting to let go of hope and the importance of hope, and that without hope, there was no sense of wanting to continue this journey of trying to find a diagnosis, and that it was still very important to people. And I think that parents did understand that, even though a no primary findings result now, that doesn’t necessarily mean that they won’t get a diagnosis at some point in the future. So, there’s obviously the opportunity to do future reanalysis of the genome, particularly as we understand more about the function of different genes, and as new genes are added to many of the panels that we’re using in whole genome sequencing. So, I don’t think not finding a result means that there is no hope in these circumstances, but for many parents, they did talk about hope being too painful, and not wanting to be let down again, and really preferred to focus on the here and the now rather than necessarily focus on the future.
Lisa: Yes, I can only speak from my own experience here, but I think I primed myself to actually forget about going on the 100,000 genomes sequencing because, having undergone genetic testing for certain conditions that they were quite convinced my daughter had from around the age of four months through to around the age of three years, I’d gone to so many appointments and thought, “Oh, this’ll be the time that I turn up and somebody will tell me this is what is the diagnosis.” And when I then joined the 100,000 Genomes Project in 2015 with my husband and my daughter, the genetic experience, the discussions that we had at the time were very helpful in that it was made quite clear to me that potentially we wouldn’t get a finding, and actually that any information that did come forward was perhaps unlikely to be hugely beneficial to our family at that point. So, I was quite clear what potential finding would mean to us.
But I think in the back of my mind, subconsciously, I had hoped that, when we eventually got a diagnosis, it would – I don’t know, bells, whistles, balloons going up, fireworks, etc. And then the experience of a letter thumping on the doormat, and I recognised the postmark quite quickly, and it was at that moment I suddenly thought, “Oh gosh, I haven’t buried all these feelings of hope.” Because I opened that letter with quite trembly hands, and then this diagnosis or lack of diagnosis, you know, nothing had been found, and it was a bit… I don’t know if it’s been described as like a nail in the coffin experience, because I really hadn’t realised I was still clinging to this hope all that time, and then again it was, you know, another, “No, nothing’s there.”
And I think because of the work I’ve undertaken with SWAN UK as a volunteer, and being quite involved in wanting to sort of educate myself and learn more, I did understand that, even though we had no primary findings, it didn’t mean that the study, everything was closed to us. It didn’t mean, you know, that things won’t still be looked for. But equally, at the same time, it just meant that we had nothing yet to pin anything on at that point. And I think it’s quite hard to pick yourself up and dust yourself off again, to be like, “Okay, we’re still here, we’re still circling that drain,” as it were.
I think actually that takes us on quite nicely really, about what role hope has in the experiences of a child with rare and undiagnosed conditions. And again if I can just say that there’s hope and there’s realism, and somewhere along the way, if you’ve been on the journey for quite a long period of time like ourselves, you have to try and find a way of living with that hope and realism all at the same time. So, we’re still hopeful that one day we might get some answers, but we’re realistic that day to day we need to focus on the difficulties or the experiences that my daughter has, so that we can manage to give her the skills to live her life to the very best of her abilities. Certainly, that’s our experience. And also I think if I’d let myself dwell forever on not having a diagnosis or a pathway specifically for that, it would have been quite difficult to carry on, pick ourselves up every day. What would you think about the role of hope there, Louise? What would you say your experience is from chatting to fellow parent/carers?
Louise: Yeah, I think you’ve described it really eloquently and better than I’ll be able to do, but when we talk to people, the phrase I always have in my head is kind of hope for tomorrow and help for today are the two things that people are looking for. So, making sure that that hope for tomorrow’s still there both in terms of, you know, the NHS being really clear that it will provide support for individuals without a diagnosis, and there may be opportunities for reanalysis in the future as science makes future progress. And, you know, there is progress being made so fast at the moment in genomics and that’s really welcome. So, making sure that people who’ve already had whole genome sequencing but not found anything continue to have access to that potential reanalysis I think is really important.
As you’ve rightly said, Lisa, as well, thinking through in terms of hope for tomorrow, the opportunity to take part in clinical trials and to make that as easy as possible where treatments are being delivered, to have the opportunities to take part in trials for non-condition specific treatments, whether that’s for epilepsy, which affects people across a whole range of conditions, or sleeplessness, which affects people across a whole range of genetic conditions. You know, there are both trials that only people who have a particular condition can take part in, and trials that are open more broadly, so making sure those opportunities are available as well, so that people have that kind of hope for the future.
But alongside that, I think it’s really important for the NHS to be clear with people about what help for today will continue to be available, and so we are working really hard with the NHS to emphasise the fact that when no diagnosis is possible, the NHS still needs to be clear to people about how they will be supported, whether that’s through the genetics team or a particular discipline, perhaps the one that is the closest fit for their child’s biggest need, whatever that may be, that they can still access more joined up care. So, you know, who is the person in the NHS, if you don’t have a diagnosis, who’s going to help you secure referrals to speech and language therapy, to physiotherapy, to learning disability nurses, and to the package of care that your child may need.
Who is the clinician, if you don’t have a clear diagnosis, who’s going to be the person with the authority and the confidence to lead the multidisciplinary team, maybe up to 30 healthcare professionals who are going to support your child. You know, who is going to be the lead clinician that’s going to pull that multidisciplinary team together and make sure that your child’s not being prescribed stuff that’s contraindicated, or that’s going to help one element of their condition but make another element worse. So, we are really trying to work with the NHS to make sure they’re thinking through, where will that support be for the family in terms of their healthcare.
And alongside that, you know, many wider services like schools or social care or employers welcome the chance to talk to a geneticist or a genetic counsellor or nurse to understand what adjustments they might need to make for someone who clearly has a genetic condition but doesn’t have a clear diagnosis. And so we’re trying to kind of make sure the NHS is both focused on the kind of science side and making sure that the hope for future findings is there, but also the help side, and making sure that the right package of care is still available for families who clearly have a genetic condition.
Lisa: Actually Louise, yeah, you’ve really summed it up excellently there, and whilst I am hugely grateful to the NHS and the various services, I can say, hand on my heart, my daughter has a huge number of professionals involved, both from the health side of things and social care side of things, and actually the person that kind of holds all that together is myself. And because we’re under multiple different teams, every time a new medication, for example, is prescribed, I need to go back to our lead team, which in this case happens to be neuromuscular, and check that, for example, if gastroenterology have prescribed a medication, that it’s not contraindicated from a neuromuscular side of things and so forth.
It’s all a bit like having sort of interlocking parts of a jigsaw, but perhaps no picture to follow [laughter], and that can be quite an isolating experience. And certainly, having chatted to fellow parent/carers, I know that’s their experience as well. And I imagine, Celine and Jana, you found sort of similar experiences when conducting the research.
Celine: Yeah, so my PhD actually was focusing on the sort of journey for parents as they go through the diagnostic process, and one of the things that came out really strongly from that body of work was how the parents were really carving their own care pathway, how they had to sort of push and fight to access services, but at the same time were the gatekeepers for their child’s health. Having to make sure all the various teams and clinicians were kept up to date with all the different tests that they had and all the results. And, you know, at times, this could be really frustrating for a lot of parents, ‘cos they had to keep repeating their story over and over again, particularly ‘cos they didn’t have a diagnosis. So, these parents really were having a very different parental experience to many of their friends and family, because their experience of being a parent to a child with an undiagnosed condition was really sort of as being a patient advocate, and as having to push and fight to access services.
Lisa: Yeah, it’s quite a unique experience. You are the specialist for your own child in that sense, I think would be the way I’d describe it. And I suppose over the years, I’ve got so used to sort of trotting out different medical explanations in terms that you can almost sound like you know what you’re doing [laughter]. And a few times when I’ve been at medical appointments, and perhaps we’ve met a new specialist or consultant, they’ve said, “Oh, what’s your field? What’s your area of expertise?” And actually you just think, “No, I’m just a specialist in my own child” [laughter]. But that’s quite an empowering feeling actually, so I guess that plays back into the feelings around hope and expectation, even with having an undiagnosed child.
Lisa: When I was recruited to the 100,000 Genome Programme, we didn’t actually as a family receive genetic counselling specifically, and I know that this is something that is incredibly important to many families, and how that can support you sort of going forward. We were quite lucky in our experience in that we knew that our daughter was definitely going to be our last child, so we didn’t have the thoughts and insecurities around potentially what it might mean for any future children that we had. But certainly as my daughter has got older and she’s asking her own questions, and our older children are at a stage in life where they’re looking at potentially having families in the future, I know that those things have come up, and we’re just still exploring what that will mean in the bigger picture. But can you tell us, Jana, really what can genetic counsellors do to help parents feel less isolated and better to cope with the uncertainty surrounding their child’s condition?
Jana: Yes, well, I’m sorry to hear you didn’t have any genetic counselling prior to going on the 100,000 Genomes Project, because that consent conversation right at the beginning, before the whole genome sequencing, is really important. It’s important to know what the range of outcomes may be, so that it may be that you might get a result, you might get a variant of uncertain significance, or you might get no result. And parents in our study did suggest that their sense of isolation when they got a no primary finding result would have been alleviated if they’d known how many were not getting results. So I think in the longer run, it’s 40 percent perhaps received a result, so that’s 60 percent that didn’t receive a result, so those parents were not alone, but they felt very alone. And some suggested if they’d just had a leaflet really explaining that, and explaining that they’d still contributed to research and that that had been, you know, a good outcome in a sense, then they would have felt better about it.
So, a lot of work can be done before the testing really, to explore how you might feel on that range of results, and then that way sort of prepare parents for how they’re going to feel, and perhaps that helps them to have things in place, to know that it might be a vulnerable time with that letter, although that was particular for the 100,000 Genomes Project, to get the result in a letter in that way, and as you described, after such a long time, that you’d been able to forget that you’d been on the project. But to actually be a little bit prepared that it make take its toll on you might actually help with preparing oneself. It also might be helpful to include ways of promoting ways to enhance health and wellbeing for parents in terms of practical support, such as those things that you’re already attempting to access, like the respite services, school support, support groups, and thinking about psychological wellbeing and ways of managing stress, psychological support for parents, and possibly spirituality based resources as well.
And focusing maybe on what is known about the child’s condition even without a diagnosis, so what’s likely to be beneficial, and support parents in actively coping, such as what research they might be able to access, and continued medical support. And also actually having a named person within the genetics service, so they have someone to go to for any follow-up that has a name, and so they don’t feel isolated from the genetic service. And signposting to those external resources, such as SWAN UK, can be very important as well, of course.
Celine: I think it’s also really important to add that hope isn’t necessarily lost when you don’t get a diagnostic result. And in a sense, what can be really helpful is for genetic counsellors to reframe that hope, if you like. So, one thing that we talk about in our paper is that it might be useful for health professionals to ask a question such as, “In light of the new information that we now have from the whole genome sequencing result, what are you hoping for now?” So in a way, it’s sort of reframing that hope, sort of giving it a different context.
Lisa: Definitely, and I think one of the things as well is that, because potentially for when parents were first recruited to a study such as the 100,000 Genome specifically in this case, that it might be quite a length of time between that initial recruitment and when the actual result comes out. And of course, in that time, with the advances in genetics, it’s sort of somewhat of a Pandora’s box really, isn’t it, in that we’re almost kind of finding the information out quicker than we actually know how to process it and what it potentially means. So actually if there’s a genetic counsellor available to speak to those parents, or for those parents to be signposted to somebody who can say, “Well look, since you were recruited, actually this is happening, that’s happening,” or, “These research projects are happening,” personally, I can say that is going to be really helpful and handy, and would have been really useful. I just know that for myself anyway and my family, that if there was a leaflet or something that had given me a way of knowing how I could contact somebody in the future, that would be really helpful.
What ways do genetic counsellors use in maintaining a delicate balance between not creating false hope but also providing meaningful support to parents? What would you say around that, Jana?
Jana: I think as we’ve already touched on, it’s that managing expectations from the outset when the test is offered. So, not generating too much hype or excitement, but setting those expectations, giving that information about the diagnostic yield. Also, informing parents that what people do experience has been described as a rollercoaster of emotions. It’s normal. You might also want to explore people, not only what they’re hoping for, but also the outcomes that they might be fearing, and giving them a chance to voice those, because they can be very powerful things as well. A diagnosis might not be what you want to hear, so there can be a lot of ambivalence around wanting a diagnosis when it might actually be a life limiting condition, that you didn’t really want that certainty.
And also helping parents to explore how not receiving a result might feel, so that they’ve actually rehearsed it a little bit, and where they might go to when they need a bit of extra support. So, they already know, “I go and talk to my friends, that’s where I get my support from,” so that they’re kind of ready for it, and that might help them with that sense of isolation, but also validating these feelings. So, it’s okay, it’s okay to have that dip, it’s okay to feel, that it’s something that many people experience. And creating a safe space for people to feel that, so if they want to talk to a professional or a friend, that those feelings are validated.
And in that way, kind of with that pre-counselling really, helping parents to develop their own set of resources, so they’ve got those to draw on. And as you’ve mentioned, Lisa, it’s like having your own resources also helps generate that feeling of empowerment and control. And as Celine has said, it’s really facilitating parents through that passage of reframing what you’re hoping for, reframing what the future looks like, if you had one picture of a future. You need to become comfortable with the future you’re now looking at.
Lisa: Thank you, Jana. Louise, if I can ask you really, we’ve already touched on the role that SWAN UK can play for parents dealing with undiagnosed rare conditions, but perhaps if you could home in on that and explain in more detail the main focus of SWAN UK, and what that can do for parent/carers.
Louise: So, what SWAN UK primarily does is bring together parents who are in a similar situation. So, we have a team of amazing parent representatives, who Lisa is one, who help us shape the support that SWAN UK can provide, and really make sure that it’s based on a really strong understanding of what it’s like to be a parent of a child with an undiagnosed genetic condition, and an understanding of that kind of expertise that parents who have been on that journey themselves will bring. So, we have a series of Facebook groups. Some of them are for different regions, so people come into contact with other parents in their area who are going through similar circumstances. Some of them are more around age. So, you know, we have Facebook groups for parents who are waiting for a diagnosis or have got a new diagnosis, and then we have a group called SWAN Graduates, which is for children who are older and over 18, so their parents can come together and share their experiences.
So, it’s really to help parents be able to talk to one another, to share their experiences, to support one another, and often to ask for advice. They’re often kind of practical questions about, you know, “My child needs this kind of wheelchair, has anybody been able to source that from somewhere?” “My child’s having real difficulties eating at the moment, can anyone give some advice on this particular challenge?” “This thing someone else has faced, how did you approach it? Where did you reach out for support?” So, that peer to peer advice and support is really at the heart of SWAN UK.
And then what we try and provide around that is access sometimes to information events, where there’s particular issues that are affecting a lot of SWAN families. So, we hope over the coming year to have a series of information events targeted at families with children who don’t have a diagnosis, and some of it is just trying to have social events and bring people together again. We’ve had, for example, an active dads group in Wales, who’ve been bowling and wanted to go axe throwing, and really they just want to come together with other dads who are in the same situation, and being able to talk to one another and provide emotional support to one another.
So, that’s kind of the nub of SWAN UK and what we do, and then alongside that, that kind of fits in with Genetic Alliance’s wider goal, which is much more around campaigning for improved services. So for example, the Genetic Alliance UK team has worked really closely with commissioners in Wales, who actually commissioned the first SWAN clinic, which is in Cardiff. That was a two year pilot, to see what support could be provided both to help SWAN families get a diagnosis, but far beyond that, to make sure that the care for families who don’t have a diagnosis is better joined up. And that we feel has been a real success. Again, there hasn’t been a really high diagnostic yield, there have been very few new diagnoses, but the support provided to the families who are in contact with that clinic, in terms of helping them access better joined up care both from the NHS and from services more widely, has been brilliant. And we’re currently working with NHS England in the UK, who are exploring an opportunity to commission two SWAN clinics in England.
So, that trying to kind of improve services, and then the third aspect of that is just working generally with the new genomic medicine service alliances as they emerge across England, to try and make sure they are thinking through what support they will need to continue providing to families who’ve gone for whole genome sequencing in future, not through a research project like 100,000 Genomes, but just through routine clinical practice and routine clinical diagnostics, what support will they need to provide for families who go through that process and don’t get an answer. And that won’t change the support they will need from the NHS. It will just mean that perhaps that clinic needs to play a more active role in helping them access those services. So, all of that kind of campaigning to have better services for family who have an undiagnosed genetic condition continues as well.
Lisa: So, I think one of the things really just to finish off today, is of course looking at the future. Considering advancements in technology, would you say that future reanalysis of the 100,000 Genome Project is going to yield additional insights? Celine, can I ask you to comment on that?
Celine: Yes, absolutely. As we understand more about the role and function of different genes, and as new genes are added to the panels, we will definitely be able to provide a diagnosis for more parents and more families. But I think we don’t yet necessarily know exactly what that reanalysis will look like, and it’s not really clear yet how this will work in practice.
Lisa: And Louise, would you have anything else to add to that at all really?
Louise: No, I think it is just that hope for the future and kind of help for today. I think the NHS needs to be equally clear about, you know, there’s some amazing investment by the UK government in genomic research, and that’s brilliant and we want that to continue, but equally we want the investment to be taking place into routine clinical services and diagnostic services, so that we can talk to people both about the hope of potentially getting a diagnosis in future, but making sure that the help continues to be available for as long as they don’t have a diagnosis, and that help for families who don’t have a diagnosis is going to be just as important. And what we try to ask for is both real clarity around what the NHS can provide, and really clear signposting to organisations like SWAN for families that continue to not have a diagnosis. And again, just to give an equal shout out to Unique, who are able to support families who have an ultrarare diagnosis, where perhaps they’re the only person in the country with that particular diagnosis, or one of a handful of families around the world. Signposting to that peer to peer support will continue to be a really important part of the process as well, so that families can help one another, learn from one another, and just give each other support that they are kind of sharing that same journey and walking alongside one another on that journey as it continues.
Lisa: And bringing this podcast to a close, can I just ask you really, any final thoughts, anything that you would sum up from your experience of researching the no primary findings and where we now are today?
Celine: I think the main thing for me is just to sort of make it clear to parents that a diagnosis isn’t necessarily a magic wand, even though it is obviously very important to a lot of parents. But that even without a diagnosis, we still have the opportunity to manage patients’ symptoms, and often a diagnosis doesn’t make a substantial difference, because parents are sometimes left with a lot of uncertainties and a lot of unanswered questions. So I think, and as Louise and Jana have said before, it’s really sort of on focusing what we do know, and thinking about what we can offer and what support we can provide to parents and families even without a diagnosis.
Lisa: Thank you very much to our guests today, Jana Gurasashvili, Celine Lewis and Louise Fish, for joining me as we discussed the impact of a no primary findings result. If you’d like to hear more like this then please subscribe to the G Word on your favourite podcast app. Thank you for listening. I’ve been your host, Lisa Beaton. This podcast was edited by Mark Kendrick at Ventoux Digital, and produced by Naimah Callachand.