Behind the Genes

Vivienne Parry, Louise Fish and Professor Matt Brown: Celebrating genomic breakthroughs - Insights from the Festival of Genomics

In January we saw experts from across the genomics ecosystem, including patients and those with an interest in genomics, gather at the Festival of Genomics - the UK's largest annual life sciences event.

In this episode, our host, Vivienne Parry, Head of Engagement at Genomics England, speaks to Louise Fish, CEO of Genetic Alliance UK, and Professor Matt Brown, Chief Scientific Officer at Genomics England, to discuss the event and emerging future trends in genomics. 

In this episode you'll also hear some exciting future advances in genomics research from some eminent speakers at the Festival:

• Harold Sneider, Professor of Genetic Epidemiology, University Medical Center Groningen sheds light on the "Identification of methylation markers for Type 2 diabetes up to 10 years before disease onset."
• Nagy Habib, Professor of Surgery, Imperial College London, delves into "The future of saRNA therapeutics and its potential for treatment". 
• Lennard Lee, National Clinical Advisor on innovation and cancer vaccines, presents his perspectives on "The Future of Cancer Vaccines," offering a glimpse into the promising advancements in this critical field.

"The scientific breakthroughs that are being made are absolutely incredible and they’re really exciting, but from the point of someone living with a genetic condition, what they want to see is those scientific breakthroughs making a real difference in the clinics...For some conditions, it’s about treatments, but it’s also about being able to get a diagnosis faster, to be able to understand what condition is impacting on you, how it might affect you over your lifetime and your wider family, and to be able to work with NHS services to understand and plan for the care and treatment that you’ll need throughout your lifetime."

 

You can download the transcript or read it below.

Vivienne Parry: Hello and welcome to the G Word.

The Festival of Genomics is the UK’s biggest genomics event, and it’s become an essential part of our year. It’s free for 90% of its delegates, it’s in person, and with more than 5,000 people expected, it’s now so big that it’s had to move to ExCel’s cavernous Dockland Halls. It’s the place to hear top science and to spot new trends, but actually for me the joy of the festival is the people you meet. Of course, it’s great to catch up with old friends, but it’s the new collaborations sparked by random encounters at the festival which I think are the lifeblood of the genomics ecosystem, and everyone with an interest in genomics is here, patients, clinicians from the NHS, researchers, industry, policymakers, and the G Word.

What we thought we’d do is bring you a flavour of this great event from the floor of the ExCel halls, and give you a quick soundbite from three of the speakers that we felt best exemplify the future of genomics. With me to discuss the event and future trends in genomics, Professor Matt Brown, Genomic England’s chief scientific officer, and Louise Fish, CEO of the Genetic Alliance UK, which as its name suggests, is an alliance of over 200 organisations reflecting the needs and concerns of those affected by genetic conditions. My name’s Vivienne Parry, I’m head of public engagement at Genomics England, and I’m delighted to be your host for today’s pod from the Festival of Genomics. Welcome to you both. So, let’s start with you, Matt. How important is the Festival of Genomics for genomics in the UK?

Matt Brown: Well, the Festival of Genomics has become a really key meeting for the genomics community in the UK, and I think increasingly in Europe as well. It’s a really large, high quality event that brings together commercial and academic and biotech companies in the one forum, and I think it’s a really exciting programme.

Vivienne Parry: And of course, Louise, it’s open to patients as well, which makes it an unusual event.

Louise Fish: Absolutely, and it’s brilliant to have patients and families here. So, people living with genetic conditions clearly need to be part of the debate when we’re talking about developing new services, and developing new treatments and diagnostics, so it’s absolutely fantastic to be able to come together in one room with people from the NHS and the broader sector.

Vivienne Parry: And it’s grown enormously, and I guess that reflects, as much as anything else, just how exciting genomics is. Matt, I’m going to pin you to the ground [laughter] and say, why is it so exciting in genomics at the moment?

Matt Brown: Look, the field’s really hitting its tracks. We’re seeing advances in technology, analytics, application in the clinical space, and of course booming commercial activity associated with that. But from a situation ten years ago, where we had research capability for using genomics to assist in diagnosis and cancer profiling, now we’re in a situation where we have multiple different approaches to assist with both of those things, transcriptomics, proteomics, spatial, single cell methods, optical mapping, a whole monopoly of different technologies that have developed out of the research world but are pretty close to being ready for clinical application. Of course, in analytics, the rise of AI and the potential that has for improving interpretation of genomes and improving personalised medicine prediction in cancers and in multivariant data, those are absolutely massive things. But aligned to that, there’s also, you know, the growing worldwide application of genomics in clinical spaces, of course led through the UK and the NHS Genomic Medical Service, which has really shown the way for the world about how this might make a difference.

Vivienne Parry: And Louise, that’s the really exciting thing is we’re now seeing not just talk about therapies, we are seeing the therapies for rare disease actually going into clinical trials and into services even.

Louise Fish: Yeah, absolutely, and that’s why people living with genetic conditions and their families want to see the change. The scientific breakthroughs that are being made are absolutely incredible and they’re really exciting, but from the point of someone living with a genetic condition, what they want to see is those scientific breakthroughs making a real difference in the clinics. And that’s sometimes about treatments, you know. For some conditions, it’s about treatments, but it’s also about being able to get a diagnosis faster, to be able to understand what condition is impacting on you, how it might affect you over your lifetime and your wider family, and to be able to work with NHS services to understand and plan for the care and treatment that you’ll need throughout your lifetime. So, treatment’s one part of it, but actually that ability to better understand what the future will hold for you, and to plan ahead for the care and support that you will need to live your life to the full is what really excites people living with genetic conditions and their families.

Vivienne Parry: Now, let’s hear the first of our three clips. The programme is absolutely vast, but these were three presentations that we just thought were terrific. Let’s hear the first one.

Nagy Habib: My name is Professor Nagy Habib. I’m a consultant surgeon at Hammersmith Hospital, Imperial College, London. We are going through a very exciting time, where we know what is the problem with the diseases, and so far we couldn’t do anything about it, but suddenly the door is opening and it all came with the RNA vaccine, because we had to go very fast to get a vaccine for covid, to protect the population, and that pushed the science to go very fast, and now we can apply it to other areas apart from covid, like cancer and rare genetic diseases. And these therapeutics are what you and I and everybody else have received during vaccination. There has been six billion injections around the world, so you can imagine that everybody had an RNA injection. And RNA is that molecule between our genome, the DNA, and the protein. For anything to happen in our body, it requires the protein, but there must be an RNA in between. In the past, it was all about DNA, but now it is RNA. Why can’t we get a vaccine against cancer?

And so now the field is growing very fast for a vaccine for cancer. Now, the way we think about it is that we can have an injection so that we don’t develop cancer of the prostate or cancer of the breast and so on, but in actual fact today what we can say is that if we take out a tumour with surgery, and we can take the RNA from the tumour and inject it in the patient, the early clinical trials tell us that this might work, and to stop the tumour coming back. It is very important to make sure that, once the tumour is out, it doesn’t come back. And I think there is hope that we can have RNA vaccines in cancer. Now, to treat cancer without surgery, still we have some way to go, but again, now we know that the problem with cancer is that some of our immune cells that are there to defend us from cancer, they change their mind and suddenly they collaborate with the enemy. So instead of helping us, they are destroying our immune system, and we are developing drugs that can stop that from happening to our immune systems.

Now, when you really think about what are the diseases that kill people, cancer is definitely very high up. The second one, not in a particular order, but cardiovascular system, we get heart attacks and we die from heart failure, or we get stroke and we die from stroke, and that’s because we eat too much. The food is very tasty [laughter]. So, now we have injections, and the injection can make us lose weight, and we lose weight very fast. The problem is again it’s very expensive. Who can afford £600 a week? And when you stop the injection, you put on weight again. So, now we are working again with RNA, and we have found a way where you inject only once every six months.

And then the final thing, which is really the dream of everybody, is to stop Alzheimer’s disease. So, Alzheimer’s disease, as we get old, there are toxic materials that are accumulating in our brain cells, and only this year we’ve got two drugs coming along that can help stopping Alzheimer’s disease at an early stage. Now, what we need to do is to bring that it works on all types, even the advance type of Alzheimer’s disease, and now there are [inaudible 0:09:26] where we can take it from the nose. So, you inhale it from the nose and it goes straight to the brain, because there is sort of a motorway that connects the roof of the nose with the base of the brain, which is very simple. It doesn’t even need an injection in the arm vein. So, it’s all very, very exciting.

Vivienne Parry: That is so fascinating. It’s real future casting. Matt, I mean, I say it’s future casting, but tell me a bit about the Rare Therapies Launchpad, because, you know, that picks up some of what Nagy has outlined.

Matt Brown: Yeah, so DNA and RNA therapeutics are absolutely booming, and that’s one of the big excitements is that we’re not only being able to diagnose people, but we’re coming up with new ways of actually providing treatments for patients with rare diseases and cancers through nucleic acid therapeutics. For rare diseases, the type of clinical trials that are involved are really quite different, and you can’t just basically translate what was used for common diseases into the rare disease space. It just doesn’t work, and that’s really held back the field a lot. So, to try and enable rare therapies to actually make that leap from a research setting into actual clinical practice, Genomics England, in partnership with the Medical Health Regulatory Authority and others, have set up a Rare Therapies Launchpad, to provide an end to end solution for people to be able to run clinical trials for rare and ultra rare diseases, particularly focusing on nucleic acid therapies, and linking that with both the regulatory authorities and health funding authorities so that we can get these ultimately into clinical practice. I think we need these sorts of initiatives so that we don’t continue to see rare therapies falling over because they’re being assessed and made to go through the hurdles that common therapies do nowadays.

Vivienne Parry: So Louise, we really are in the area of what people call N of 1 medicines.

Louise Fish: Yeah, absolutely. So, these are medicines that are made specifically for one person and will help that one person, and obviously that brings a whole heap of possibilities for people living with genetic conditions, but also a load of challenges that we understand for decision makers within the MHRA and NICE and the NHS. And so I think there are some real challenges that we’re really aware of from the decisions that are already being made by those decision making authorities about treatment. Obviously, putting it at the most basic level, you don’t have the same evidence base for treatment that’s just available for one person that you do from a clinical trial, where thousands of people will have taken part in a trial to understand how it affects a whole host of people.

So, we know that the decision making bodies are going to need to take a different approach to evidence, so are going to need to be willing to look at evidence that is just from a trial involving one person. They’re going to need to be able to extrapolate the benefits of that treatment across someone’s lifetime, and that can be challenging, and we’ve seen that before in rare disease medicines and the new treatments that have come along in recent years. So, there are definitely some challenges, and we’re really glad to see those challenges being acknowledged upfront by Genomics England, the MHRA and others, and being debated and discussed, and trying to find solution now rather than waiting for those treatments to come along later, and then trying to retrofit and decide how to manage them. So, it’s great to see this debate taking place early, and we’re really keen to make sure that the voices of people living with rare conditions and their families are part of that discussion.

Vivienne Parry: And the really cheering thing that we’re hearing from Professor Habib is that he thinks that the cost is going to be much less, because some of these things, you know, have million pound price tickets, so to have something that will be cheap is really going to be I think the gamechanger.  

Louise Fish: One of the challenges with that is understanding the lifetime costs of someone living with a genetic condition and all of the complexities that are involved, and not just the medical care that they need, but the social care and the wraparound care that they’ll need, the extra support from schools and colleges, the extra support from employers if they’re able to go in employment. So, I think we’re constantly trying to help the government and decision makers have a better understanding that those lifetime costs of living with a genetic condition are the things that should be taken into account when they’re making decisions about a new treatment that could be totally game changing for someone’s health and their future.

Vivienne Parry: Cheaper treatments on the way, Matt?

Matt Brown: So, I think we absolutely need to work on reducing the costs of these treatments, because at the moment the costs are so high that, were we to extrapolate that out to try and treat the thousands to tens of thousands of different rare diseases that there are out there, we couldn’t possibly afford it. I think it’s very promising that we will get cheaper treatments. This might come about through reducing the development costs, in particular reducing the clinical trial programmes, and the level of safety and efficacy evidence that you require before you can actually make these treatments available. I think that will make a massive difference, if we can simplify that.

And another thing is, by better collaboration between the different rare disease communities and genetic medical services around the world, to make sure that what might be an N equals 1 condition in the United Kingdom, when you consider it around the world, might actually be an N equals 100 people, and then basically the cost per patient drops substantially. To achieve that, we need much better coordination between the national genomic medical services.

Vivienne Parry: At the end there, you heard talk of using RNA therapies for obesity and Alzheimer’s, and we principally talk, particularly in Genomics England, not just about cancer and rare disease. But I wanted to present to you another presentation, which I just thought was extraordinary, which comes from the Netherlands, and it’s about picking up signs of diabetes using genomics ten years in advance. Just listen to this.

Harold Sneider: Hi, I’m Harold Sneider, I’m a genetic epidemiologist working at the University Medical Centre in Groningen in the Netherlands, and my focus is on cardiometabolic disease, and I have a great interest in hypertension, for example, obesity, but also type two diabetes. So, one of my major interests is to try and identify genes for common complex, mostly cardiometabolic diseases, so our approach is to do genome-wide association studies using genetics, but also epigenetics. And epigenetics can be screened for so-called methylation markers, and those methylation markers have an effect on expression of the genes, and we can look at this all over the genome. Then a very interesting question came up, whether these types of epigenetic signals or methylation markers could actually be used to predict disease in people that are still healthy.

So, the goal of this type of work always consists of two parts. First, it’s that we try to find out which genes are highlighted by these DNA methylation markers, because they are located at certain positions on the genome, so we know which genes are involved in those regions and we can learn more about the underlying biological mechanisms that play a role in the development of the disease. Because we found those signals up to ten years before the disease occurred, so that tells us something about changes that already happen at an early stage. It’s like an early detection mechanism. At the same time, a combination of these markers together lets you calculate what’s called a methylation score that can be used for the prediction of the disease, and the ultimate goal here is that even in healthy individuals, when you have those measurements, you can calculate such a score to improve the prediction and identify people with a higher probability to develop such a disease. I definitely think we can apply this general approach also to other – for example, cardiometabolic diseases, such as coronary artery disease or also hypertension.

Vivienne Parry: Harold Sneider there from Groningen. And extraordinary, the idea that you might be able to pick up not just diabetes perhaps ten years in advance, but also he was talking about potential for other lifestyle diseases, like cardiovascular disease, for instance. What are your thoughts about that, Matt?

Matt Brown: Look, I think it’s always been an aspiration of the clinical community to move treatments from treating patients with established disease to actually working in really early or preclinical spaces, where you’ve got a much better chance of preventing end organ damage, and secondly you’ve got a much better chance of actually inducing remissions or potentially actually curing diseases. And I think not just in diabetes, but also in a range of immune mediated diseases, there’s pretty good evidence now that you can, by intervening early, really make a massive difference to the natural history of diseases, and new methods are coming about to identify those patients, be it polygenic risk scores or other biomarkers, to enable us to sort of flip the approach of medicine from being reactive to pre-emptive.

Vivienne Parry: And rare conditions, as they do so often, Louise, are leading the way in understanding the issues, which will then spill out into a much wider area of the population.

Louise Fish: Yeah, absolutely, and rare conditions obviously is the space that we work in. So, Genetic Alliance UK, as you say, is an alliance of around 230 charities that support people largely with rare genetic conditions, and many of those charities are condition specific or look after groups of conditions, like metabolic rare diseases. So, that’s the kind of space that we come from, and obviously in our space, the excitement is around the work that we’re doing with Genomics England around the Generation Study, and trying to use that to understand whether it's possible to screen babies to understand whether they have a rare genetic condition, and if so to identify that condition and intervene early. And again, excitingly, that’s not just about treatment, it’s about whether there’s a way of helping that child and their family, if you can identify very early to help really improve their lifestyle choices. And one of the best examples we have is identifying children with brittle bone disease, where if you pick them up through screening, you’d be able to teach their parents to handle them safely, so they didn’t have breaks in their bones as babies, which is what we see now.

So from our perspective, it’s obviously different to the polygenic risk scoring, but again it’s that idea of using genomics as a way of identifying conditions very early, and intervening before signs and symptoms start, to try and improve the life chances of the person living with that condition, and help their wider family to help them, which is really exciting from our perspective.

Vivienne Parry: But the experience and knowledge that you’ve gained as rare disease organisations actually is enormously valuable to other people. I mean, rare has always been at the forefront. I mean, in cancer, for example, it was chronic myeloid leukaemia, which was a rare cancer, that kind of unlocked cancer targeted treatments for everybody else. And it always seems to me that rare is at the forefront. Although it’s often seen to be behind, it actually is the key to unlocking so many other things, and the experiences that you have all had are so valuable for much wider populations.

Louise Fish: Yeah, absolutely, and one of the reasons we run Genetic Alliance UK is so our member organisations can learn from one another, ‘cos there’s always one of the rare patient organisations which is surging ahead in a particular space, doing something really exciting, doing something really new, and we try and make sure that our members can learn from one another and don’t have to kind of reinvent that wheel. But I know that spills out into the wider cancer space and beyond, which is fantastic.

Vivienne Parry: And Louise, do you think there are particular conditions which, if I can put it like this, are on a roll at the moment, where genomics is really advancing fast for them?

Louise Fish: Oh goodness, that’s a really good question. There are lots of conditions where genomics is making a significant difference really quickly. For us, I think we go back to the Generation Study, and at the moment we only screen in this country for nine conditions, soon to be ten with the addition of a new condition, but the Generation Study’s looking at 200 conditions and whether it’s possible to screen for them. And for all of those 200 conditions, it’s a really exciting opportunity to see if we can learn more, both about the potential to understand and develop treatments early, but also just about the chance to understand the natural history of that condition so much earlier than we do at the moment. And I think that’s it, it’s that understanding of the natural history of the condition really early, and understanding how a family can be helped through all the aspects of the condition, which is giving people most excitement, I think, alongside the potential to develop treatments.

And I know we talk about treatments a lot, but at the moment only five percent of rare diseases have a condition specific treatment available, so we really try and balance, within Genetic Alliance UK, that hope for the small number of conditions that do have treatments, which is really exciting, or have treatments in development, and actually making sure that the scientific breakthroughs in genomics are something that all conditions can benefit from, whether there’s a treatment or not. The potential for early identification of people with a condition, understanding the natural history better, and wrapping a package of support and care around people that is not just about a drug itself, is really important to us and to all of our members.

Vivienne Parry: Matt, are you seeing any particular areas where there’s a really rapid success?

Matt Brown: Look, I think there have been some absolute standout successes in nucleic acid therapies in recent years. So, one is the treatment of familial hypercholesterolemia, with siRNAs for PCSK9, so the Inclisiran type approach, which has absolutely revolutionised management of that disease. In recent times, I’d highlight, for example, the treatment of sickle cell disease, an absolutely massive global problem, and now we’ve got a therapy which can really control sickling crisis and make a big difference to a disease which isn’t just a disease of developed countries, in fact it’s particularly a disease of Africa, of course. On a global level, that’s just going to have a huge effect.

But I think, yeah, I just would like to come back to that comment you made about things starting with rare diseases. So, in genomics, rare disease genomics has taught us a heck of a lot about what drives common diseases as well, and to my mind, gold dust for drug development companies is where you have genes that are associated with both rare and common forms of the same type of disease. And that tells you that basically you’re very likely, through your treatment, to be able to actually influence the disease, and that it will influence a large proportion of patients with the disease. So, I’m really enjoying seeing this division between rare diseases and common diseases broken down a little bit, and a lot more learning in therapies going from one to the other.

Vivienne Parry: Let’s move to a completely different area, one that’s very important to Genomics England and less important, Louise, at the Genetic Alliance UK, which is cancer. We’re going to hear from Lennard Lee about cancer vaccine.

Lennard Lee: I’m Dr Lennard Lee, I’m a medical oncologist, so I practice as an NHS doctor, treating cancer, and I’m an associate professor at the University of Oxford. We’ve come to a position whereby vaccines can be developed quicker than anyone thought. In the last few years, we’ve realised that the technology has moved on rapidly, MRNA technology, and you can make vaccines and update them really, really quickly. We’ve now come to a situation where vaccines can be made against cancer, and this is where genomics is really starting to supercharge this technology. If you can sequence a cancer then what we’re finding now is that the technology now exists for you to print off an MRNA vaccine for that patient, a truly personalised product. And it’s amazing because the genetic basis of the cancer, what the genomics sequencing shows then becomes a vaccine itself. The vaccine is designed based on that sequence, and that’s why genomics has really supercharged this field of vaccinations for cancer.

One of the possible things we just need to clarify and be aware of is that when people talk about cancer vaccines, they mean a number of things. Ultimately, what it involves is getting a new treatment for people with cancer, because it’s based on their genetic sequence, so it’s used to treat people with cancer. The future’s an exciting one, truly personalised medicine based on genomics. Genomics is going through so many different phases in the field of cancer. Firstly, we were starting to understand why cancer happened and what patients outcomes were. The second phase started to kick off where genomics would help patients select the right drugs at the right time for them, which is amazing. And now we’ve entered the final evolution of genomics, where it now becomes the actual drugs that we treat people with. And cancer vaccine is one of the first potential areas where genomics will start to form the basis of the treatments going ahead. In five years’ time, we’re going to know if it works or not, where an individual vaccine based on the genomic abnormality seen in that cancer is going to give better outcomes for patients than an off the shelf product.

We know that every cancer’s different, so genomics has showed us this, but all of a sudden that sequence could become that vaccine, which then primes that immune system, truly personalised therapy. And it is so exciting that we’re going to be talking about this in this festival, and it’s being driven as from the UK, which has got so much strength in terms of genomic capabilities as we’re developing vaccines.

Vivienne Parry: So Lennard Lee there, absolutely confident of the importance of cancer vaccines. Matt, what are your thoughts on that? 

Matt Brown: I think it’s a tremendously exciting field. The early data on cancer vaccines with melanoma, for example, showed that for a cancer which previously had been resistant to virtually all of our approaches, is actually quite responsive to novel cancer vaccine approaches. We are yet to see across what diversity of cancers this is actually going to work, so there’s clearly a huge clinical trial programme that’s going to be required to drive this, and the UK is playing a really central role through the Cancer Vaccines Launchpad that Lennard’s involved with running, in creating the evidence base about whether these are going to achieve the promise that they hold.

I also think that they’ve got a lot of possibility for inherited cancer types. For example, I think the programme’s looking at cancer vaccines for Lynch syndrome, to try and prevent colorectal cancer in that group of patients. So, I think they’ve got lots and lots of opportunities, and it’s nice to see something positive actually coming out of the pandemic like this, for what was a pretty bleak episode worldwide otherwise.

Vivienne Parry: They are a small part, I know, of your organisation, Louise, but in some ways, those people with inherited cancers in their families are seeing the benefits of genomics on both sides, both in that earlier diagnosis, picking up right from the very beginning, and of course in the promise of these new treatments.

Louise Fish: Yeah, absolutely, and you’re right, it’s a small part of our remit. We do have some organisations in our membership who specifically support people with rare inherited cancers, and we work very closely with an organisation called Cancer 52, who also represent organisations with rare cancers. I’ll just give them a quick shoutout in case anyone listening is not aware of them and their amazing work. But you’re right, I think there are a couple of things going on that are really exciting in the cancer space. It’s that ability to better understand why some people are likely to inherit cancers, how that pattern works within families, and to support those families and help them understand like the risk that they have, and to make informed decisions about their own treatment and care in the future. And also about whether they want to have children, and if they do want to have children, kind of how they want to approach that to try and reduce the risk of passing on that heritability. So, that’s a really important part for everybody. I think there’s also potential to develop new treatments, which is absolutely amazing and really exciting, and it is really exciting to hear about the potential for cancer vaccines.

The other area where I think people living with inherited cancers are interested to find out more is what impact it might have on better understanding which treatments will work for which people. And we know, for example, that there are some cancer treatments that only work for one in four people with that particular kind of cancer, but it’s been really hard to understand why that’s the case. And I think the potential for genomics to identify which people could benefit from a particular cancer treatment would have two huge benefits. A, cancer treatments, many of them are really horrible, you know. They’re horrible things to go through, and if you had a better confidence that a particular treatment was going to work for you because of your genetic makeup, that would make you a lot more confident about deciding to try that treatment, and taking on board the side effects of the treatment and how it’s going to impact on you.

That would also obviously massively impact on the cost effectiveness of that treatment. At the moment, we might give it to four people and only one of them would benefit, but you’re paying for the cost of giving it to all four people. If you could identify in advance which people were more likely to benefit then you’d give it to fewer people, they’d be more likely to benefit, and the cost would come down. So, I think that there is real potential in this field of genetics and genomics to help in all kinds of ways that people living with these conditions are really excited to see and explore.

Vivienne Parry: So Matt there, it’s not of course simply about identifying, you know, what the cancer is like and its genomic makeup, but actually it’s that wider field of pharmacogenomics, which is a big feature of the programme at the Festival of Genomics this year. And we’re very much involved in that, aren’t we?

Matt Brown: Yeah, we are. So, pharmacogenomics is one of those areas where genomics is about to make a big difference in clinical practice. What we’re hoping to get to is the point where we have people who are not yet treated with a medication actually already have the genetic profiling done, so that when they go to a general practitioner or a physician and be prescribed a medication, the data will already be there to say what the appropriate dose should be, and whether they’re at risk of getting adverse reactions to those medications, so we could avoid them or use alternate medications. So, that sort of pre-emptive pharmacogenomics is just over the horizon, and if we can achieve that, we’re going to significantly improve patient care and reduce the risk of adverse drug reactions, which are a major cause of morbidity and hospital admissions not just in the UK but worldwide.

Vivienne Parry: So Matt, perfect segue into our next question, which was, you’ve already identified one area which you think is going to be big in the next few years. You’re both absolutely in the centre of the genomics ecosystem. What do you think we’re going to be seeing at next year’s Festival of Genomics? What do you think is going to be the big thing that’s coming up on the inside rail?

Matt Brown: So look, I’d like to say what I think’s going to be in next year and what I think’s going to be in ten years. Next year, I think the big things are going to be advances in AI and genomic analytics. That’s really ramping up fast, and I think we’re going to see it in clinical implementation a lot more next year. I think the cancer therapy vaccines are going to be really big next year, as are nucleic acid therapies. Multiomics for rare disease diagnosis and cancer personalised medicine, I think is also ramping up very fast. In ten years’ time, the two areas that we’ve not discussed so far where I think genomics is going to make a big difference are going to be in infectious diseases and in pathology services. In infectious diseases, genomics I think has a fair chance of replacing to a large extent culture based practice, or serology based diagnosis of infectious diseases, which will be done by sequencing instead. And that will be a massive change to the practice there, because you’ll be able to rapidly work out, even if people have been treated with antibiotics already, what the infections are and what the likely treatment responses are going to be.

Louise Fish: So from my perspective, next year what I hope to see is people getting just as excited about the differences that some of the technology we hear about this year are actually making when they’re being applied in clinical practice. So I think from my perspective, it’s all about that move from being excited about the science to seeing people just as excited about the difference that science is actually making when it’s benefiting people living with rare conditions and their families through clinics across the UK and the NHS. Next year, I’d like to hear that excitement when people are talking about how it’s actually affecting real lives. In ten years’ time, I hope we’ll be talking about the massive difference that some of the amazing techniques we’ve heard about here this year have made to the lives of people living with genetic and rare conditions.

So, you know, in ten years’ time, I hope that some of the treatments and the opportunities and the tests we hear about today, we can see how they’ve affected the natural history of the condition across ten years of lives, and that we can really see that people are living their lives to the full as a result of the fantastic technological breakthroughs that we’re hearing about today.

Vivienne Parry: Fantastic. It’s been great to talk to you both, and it has been a fantastic festival.

Vivienne Parry: So, thank you to you again, and also thank you to Frontline Genomics, who organised the Festival of Genomics, because it really has been a wonderful, wonderful event. And if you’re interested in things genomic, you can subscribe to the G Word on your favourite podcast app, and if you’re new to our podcast, and we always welcome our new listeners, do check out our back catalogue. You’ll find it’s really extensive. There’s a wonderful set of genomic listening available to you, in which even spatial transcriptomics gets explained. I’ve been your host, Vivienne Parry. This podcast was edited by Mark Kendrick at Ventoux Digital, and produced by Naimah Callachand, and it's very good to have had you with us. Bye for now, and hope to see you at the Festival of Genomics next year.

Ana Lisa Tavares: Genomics 101 - What is a rare condition?

In this explainer episode, we’ve asked Ana Lisa Tavares, Clinical Lead for rare disease research at Genomics England, to explain what a rare condition is, 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: What is a rare condition?'

You can download the transcript or read it below.

Naimah: What is a rare condition? Today I’m joined by Ana Lisa Tavares, Clinical Lead for rare disease research at Genomics England, and she’s going to explain more.

Ana Lisa: There are thousands of rare conditions. I hesitate to say a number as we’re learning all the time, so this keeps changing. There are estimated to be perhaps around 10,000 different rare conditions, as an order of magnitude. Many rare conditions start in childhood, 75% or three quarters affect children. A little over 10% affect adults, only adults, and some, around 20% can start in children or adults.

Naimah: So, what makes a condition rare?

Ana Lisa: A rare condition can be defined as affecting less than one in 2,000 people in the general population. This is a definition that’s used in Europe. Different parts of the world use slightly different numbers and definitions, so for example, the number of people with a rare condition living in that country, there isn’t one single universal definition.

The important part I think is that this is a practical way to help shine a spotlight on rare conditions, which collectively affect a lot of people, and the particular challenges in making diagnoses and finding treatments for rare conditions. So together, it’s estimated 7% of people are affected by a rare disease in their lifetime, or one in 17, so that means that there are 3 and a half million people in the UK affected by a rare disease, and in the world, probably somewhere between 250 to 450 million people, so perhaps 350 million people, a really huge number.

When you look into these numbers, there are rare conditions that are much more common than others. So, 80% of people with a rare condition have one of the 150 most commonly occurring rare conditions. Cystic fibrosis would be an example that many people will have heard of, and if you look at those numbers from a different angle, 85% of rare conditions affect less than one in a million people, so are very rare, and it’s important to bring together these different voices to solve some of the common challenges.

Naimah: Can you explain to me how these differ from more common conditions?

Ana Lisa: The simplest answer is that they are defined by the frequency, so how often they happen in the general population, and one reason for grouping together thousands of rare conditions is to highlight some of the particular challenges. This includes delays in getting a correct diagnosis that can often take years, an increased chance of a misdiagnosis before getting to an accurate diagnosis, and treatment challenges, as 95% of rare conditions don’t have a specific treatment. This is a very good question, and I would like to note that it’s also an artificial distinction to some extent. So, human conditions have a range of underlying causes that can be broadly grouped together, including genetic and environmental, such as a viral infection.

However, it gets complicated, for example, a proportion of common conditions that may have many different causes will have a genetic component, so for example causing an early onset familial form of a condition, such as diabetes. And in fact, genetic causes may give or can give the clue or the key that’s necessary to develop a new drug therapy that can then help many people with the condition, so those that may have a rare genetic cause and those that have a more common cause, such as for high cholesterol.

So, one other way that rare and common conditions can differ, not just based on frequency, is the causes of those rare conditions and common conditions. I’ll start by saying that there are lots of rare conditions that aren’t genetic, and there are common conditions that do have a genetic basis, so none of these observations are absolute, but there’s a spectrum of different causes for rare and common conditions. So, I would say there are more rare conditions that are caused by a single genetic cause, and there are more common conditions that might be caused by many very small genetic effects acting together, and also many different environmental causes.

Naimah: So, are rare conditions always genetic?

Ana Lisa: The short answer is no. Many rare conditions do have a genetic cause, perhaps 70 to 80% of rare conditions, so if you had 10 people with different rare conditions together in a room, the chances are that 8 of them will have a genetic component to their rare condition. And when we talk about genetic causes, these can of course be very varied, from a single letter change in the DNA code to an extra chromosome with several hundred genes. Rare conditions include ones without any known genetic cause, so for example some rare infectious diseases and some rare cancers. And I think it’s important to say that there’s a lot that we collectively don’t know yet about rare conditions, so our understanding is incomplete and imperfect, and there’s still a huge amount to understand.

Naimah: And it would be good to understand what challenges patients with rare conditions might face.

Ana Lisa: There are many challenges in achieving an accurate diagnosis, getting well organised, coordinated care, and the fact that 95% of rare conditions don’t have a specific treatment. There’s a big impact on emotional wellbeing for those with rare conditions and their parents and carers. Genomic Alliance did a survey showing that 88% of those with a rare condition felt emotionally exhausted from having their rare condition, and there are big impacts on other aspects, such as education, employment, etc. 

Naimah: And what do you think the future looks like for the treatment of patients with rare conditions?

Ana Lisa: So, this is a huge question with many answers. I think key is coordinated care, and I’m personally really excited about the potential for new rare therapies to be made for particular types of genetic causes that perhaps one day could be modified to treat many different types of rare conditions. To me, this would be incredibly powerful and would be a dream to transform therapies for rare conditions.

Naimah: That was Ana Lisa Tavares explaining what a rare condition is. 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.

Dr Natalie Banner, Ismael Kherroubi García and Francisco Azuaje: Can Artificial Intelligence accelerate the impact of genomics?

On this episode, we delve into the promising advances that artificial intelligence (AI) brings to the world of genomics, exploring its potential to revolutionise patient care. Our guests discuss public perspectives on AI in genomics and address the ethical complexities that arise in this rapidly evolving field. Gain valuable insights into the future landscape of genomics and AI, as our experts discuss what to expect on the horizon. 

Our host Dr Natalie Banner, Director of Ethics at Genomics England, is joined by Ismael Kherroubi García, member of the Participant Panel and Ethics Advisory Committee at Genomics England, and Francisco Azuaje, Director of Bioinformatics at Genomics England. 

 

“So, AI is already driving the development of personalised medicine for both research and healthcare purposes. [...] In the context of healthcare, we are talking about AI tools that can support the prioritisation, the ranking of genomic variants. To allow clinicians to make more accurate and faster diagnosis.” 

 

You can download the transcript or read it below.

Natalie Banner: Hello, and welcome to the G Word. In the past few years, artificial intelligence, or AI as a shorthand, has taken centre stage in the headlines. Sometimes for really exciting, positive reasons about the potential to drive improvements for society, and sometimes because of its potential risks and harms.  These discussions and stories can sometimes seem like they're straight out of science fiction. There are a lot of questions, excitement, concerns about the societal impact of AI, so not just looking at individual patients, but that broader what does this mean for society?  

Ismael Kherroubi García: My somewhat hot take is that AI only accelerates societal impacts that genomics research and healthcare can have. So the impacts, of course, will be diverse and complex and quite widespread, especially given the quite nuance and sometimes difficult to understand areas of genomics and artificial intelligence.  But the key takeaway from what I want to say is that it only accelerates the impacts of genomics and healthcare. So if we take genomics research to promote human flourishing, ideally, artificial intelligence will also only help further human flourishing.  Conversely, applying artificial intelligence tools to genomics research can help perpetuate certain stereotypes and related harms.  

Natalie Banner: My name is Natalie Banner, and I'm the Director of Ethics at Genomics England. On today's episode I'm joined by Ismael Kherroubi García, member of the Participant Panel, and Ethics Advisory Committee at Genomics England. And Francisco Azuaje, Director of Bioinformatics at Genomics England. In today's episode we aim to cut through the hype and hyperbole and explore the real possibilities for AI within the domain of genomics and healthcare. We'll look at how AI tools and techniques have been used to date, and what the future holds, considering both the benefits and challenges faced in the genomics ecosystem. If you enjoy today's episode, we'd love your support. Please like, share, and rate us on wherever you listen to your podcasts.  

AI is in the news an awful lot, and not always for good reasons. There are many big and small tech companies that are exploring the use of AI in all walks of life, from finance to retail, to healthcare. And it's not always clear what AI means in these contexts, where it actually has the potential to really help people, drive improvements to healthcare and society, for example.  But there are some exciting stories, so recently, Genomics England undertook a collaboration with DeepMind on their AlphaMissense tool, and that sought to classify the effects of 71 million missense mutations in the human genome. So it could process data at a scale and a speed far faster than any human has ever been able to before. So there's an awful lot of exciting work going on in AI, but we should emphasise that although some of this technology is really cutting edge, a lot of the techniques that are being used and talked about in AI, have actually been around for quite a long time. So Francisco, if I could start with you, can you help us understand what artificial intelligence, AI really is in the context of genomics? And maybe explain to us the difference between AI and machine learning, and how they relate to one another? 

Francisco Azuaje: Sure, Natalie. AI involves the creation of computer systems capable of performing tasks that typically require human intelligence, such as understanding natural language, recognising patterns in big data sets, and making decisions. Now, machine learning is the most successful technology within the field of AI, but machine learning focuses on the use of algorithms that allow computers to learn from the data and make predictions about the data without the need for explicit programming for each task or application. 

Natalie Banner: Ismael, perhaps I can turn to you. What do you see as the primary motivations or reasons for incorporating AI into genomics research and, indeed, into healthcare? 

Ismael Kherroubi García: So I think it's already been mentioned and focusing on genomics research because challenges, the enormous amounts of data that are required to shift through and analyse and get insights from.  So one number that's worth just mentioning is that the human genome is made up of 3.2 billion base pairs, As with the Ts and the Gs with the Cs in our DNA. And one way to put that 3.2 billion, with a B, in terms we might understand, is to say that to list all of those letters we would have to be typing 60 words a minute, eight hours a day for about 50 years, that's how enormous just one human's genome is.  And I kept looking for other ways of depicting just how enormous this data set is, and it turns out if you uncoil those strands that we usually see depicted when talking about DNA, if we uncoil them for one person, we would have a string about 67 billion, again with a B, miles long for each person, that's roughly 150,000 round trips to the moon.  So, again, this is just one person, those numbers are enormous.  

It's also worth considering the role technology has had to play in enabling genomic research. So if we look back at maybe a very significant catalyst for genomics research, the human genome project which started in 1990, they took 13 years to sequence one human genome. Now, what we're talking about is estimating that by 2025 genomic-related data will be up to 40 exabytes of data. Now I didn't even know what an exabyte even was before this podcast, so I did look it up, that's about a billion gigabytes, I definitely don't know how to even begin to imagine what 40 exabytes even means.  Bringing it a bit closer to home, I try to figure out how many copies of Doctor Who we would need to make 40 exabytes of data, I found that Doctor Who is roughly 850 gigabytes, I found this on Reddit, very scientific. And the number is then 40 exabytes over 850 gigabytes, that's roughly 47 million copies of all the decades of Doctor Who media is what's necessary to reach the amount of data we expect from genomic research within a couple of years. So we need a technology capable of analysing the equivalent of 47 million copies of the entirety of Doctor Who, and currently, as you've both mentioned, AI provides the best way we have to do this. 

Natalie Banner: Wow! So we are talking absolutely vast amounts of data.  And I do love the analogies there, it's very helpful to actually sort of bring it home and make it real.  So we're talking vast amounts of data and currently it feels as thought AI may be the best way to try to analyse and explore that scale of data.  So given that's what we're talking about in genomics, in what ways is AI currently being applied in the field of healthcare and genomics?  Francisco, I'm wondering, can you give us any examples of how Genomics England is integrating AI models and tools into its research efforts? And I know particularly we have a programme of work exploring multimodal data, can you tell us a little bit about that?  

Francisco Azuaje: Absolutely. But first of all, just to give you an overview of the type of applications in research and healthcare, right now AI offers opportunities to develop tools that are needed to support interpretation of genomic variants, and the relationship between those variants and medical conditions, drug responses.  AI is also a powerful approach to supporting the detection of diseases and some subtypes of these conditions, and matching those conditions to treatments, using different types of data, in the clinic this is happening already in the clinic, and examples of data include medical images, clinical report, electronic health records. So AI is already driving the development of personalised medicine for both research and healthcare purposes.   

Now, at Genomics England we are investigating the use of AI to support a number of tasks with potential impact in both research and healthcare.  In the context of healthcare, we are talking about AI tools that can support the prioritisation, the ranking of genomic variants to allow clinicians to make more accurate and faster diagnosis. You mentioned the multimodal programme at Genomics England, as part of our mission to enabling research, we are developing tools and applications to help researchers extract information from different modalities of data or data types. In this context, AI plays a crucial role to deal not only with the size and the volumes of this data, but also to allow the meaningful extraction of useful information with clinical value based on the combination of different data sets. And that's a complex challenge, that only AI can approach. Here, we're talking about large, diverse, and complex data sets coming from different types of clinical imaging modalities. We are talking of course about genomic data, clinical reports, and in general any information that is included in the patient's medical health record. 

Natalie Banner: Thanks, Francisco. And can you talk a little more about the specific tools or projects you're working on at the moment in multimodal? 

Francisco Azuaje: Absolutely. So, in the case of multimodality, we are talking about applications that aim to improve the way we connect any of these data sources, including imaging and genomics, with clinical outcomes. For example, how to improve the way we predict not only a diagnostic type, but also how that information can be correlated with the potential response of a patient to a particular therapy. Or a prediction of the potential evolution of that patient within a particular subtype of condition or phenotype. To do this we rely on a type of a machine learning technique called deep learning, just very briefly, deep learning models are again a branch of AI, so within machine learning, these models are very powerful tools that apply deep neural networks. These networks consist of multiple layers of mathematical transformations that are applied to the data. And these transformations allow them the automatic discovery of complex patterns in this data, including all these modalities that I mentioned before. So this is a key approach that we need to extract useful features with diagnostic or prognostic value from these different modalities of clinical information. 

Natalie Banner: So there's obviously a really clear focus there on the benefits to patient, the patient outcomes, really trying to ensure that we can create personalised medicine as far as possible.  That every patient can have an outcome that's kind of very much about their own particular circumstances and condition.  So not just looking at individual patients, but broader, what does this mean for society? Ismael, I wonder if you can tell us a little bit, your thoughts on the questions about societal impacts with the increasing use of AI, particularly in genomics and healthcare more widely? 

Ismael Kherroubi García: Yeah. So my somewhat hot take is that AI only accelerates societal impacts that genomics research and healthcare can have.  So the impacts, of course, will be diverse and complex and quite widespread, especially given the quite nuanced and sometimes difficult to understand areas of genomics and artificial intelligence.  But the key takeaway from what I want to say is that, it only accelerates the impacts of genomics and healthcare.  So if we take genomics research to promote human flourishing, ideally artificial intelligence will also only help further human flourishing.  Conversely, applying artificial intelligence tools to genomics research can help perpetuate certain stereotypes and related harms. Genomics England has diverse data initiative and they show that Europeans represent 78% of people in genome-wide association studies.   

The challenge here is that, if we train artificial intelligence tools on complex interrelations of mainly the genomes of people with European ancestry, then we are over-sampling people with European ancestry, and the findings will have very limited effectiveness on different populations, both around the UK and diverse populations around the world and within the UK. So whilst artificial intelligence will have societal impacts as a general sort of technology that can be applied to many different fields, in the context of genomics and healthcare, I think that the societal impacts we should really be focusing on relate with genomics and healthcare in particular.   

Francisco Azuaje: I agree with Ismael, that the real value of AI is not only in the acceleration of technological progress, but in the impact at different levels of society. Including the way we improve health in an ethical way, and also in the way we support people to develop tools that have an impact in the way we operate as societies and the way we relate to each other. So I totally agree, it's more than just technological acceleration.   

Natalie Banner: Absolutely, okay. So we've talked about the potential societal impacts, and I mentioned at the outset that there's a lot of hype and a lot of interesting narratives about AI in the public domain.  Things can feel very utopian or dystopian as an awful lot of marketing, but understandably as well a lot of fear coming from the public perspective, especially if you think that most people's understandings of terms like AI have come from science fiction, for example. So, Ismael, what concerns are there from a public perspective? Particularly for, you know, when patients faced with the increasing use of AI and machine learning in genomics and healthcare, and the idea that their care or their treatment could be informed by these tools and technologies. What kind of challenges might arise for patients in the future as these technologies continue to advance? And what are the perceptions like from that public and patient perspective? 

Ismael Kherroubi García: I think you got it entirely right. The biggest concern relates with the public perception of AI and that perception in turn is significantly impacted by what we see in mainstream media, be it in the news media, social media in adverts, and so on. And unfortunately, as artificial intelligence is usually depicted as this extremely technical field, the conversation, the narrative is more often than not steered by big tech, so organisations and people with very clear agendas.  The example I want to make this case with is this open letter, I think it was in March this year, which was put together by a series of company CEOs, a few researchers as well, and it's ultimately been signed by over 30,000 people. And this open letter called for a six-month pause on what they called 'giant AI experiments'. So this was an open letter and direct response to the launch of ChatGPT, which is an AI-based chatbot launched by Open AI in November 2022.   

The open letter suggests that we might, in quotes, that 'we might be developing non-human minds that might eventually out-number and out-smart us. And we're risking loss of control of our civilisation'. These are extremely serious fears, and I would be really afraid if I believed them.  So the concern here is that the fears aren't really grounded in reality, but in common fiction or narratives about AI.  And very quick way to see that there's a lot of fiction around AI, if you go online, go to your favourite images browser, and look for 'artificial intelligence', you're going to find a lot of images of blue, floating brains, a few versions of the terminator, robot shaking hands with people.

There's one great image of a robot using a laptop – which always makes me laugh. These are not informative depictions of artificial intelligence, let alone genomics. And the risk is ultimately that, if the general public has easy access to unhelpful fictions about AI, then there's a great possibility that genomics research, which is going to remain intricately linked with AI advancements, will be perceived negatively, so genomics services fuelled by AI will not be trusted. And ultimately, given my stance, and I think the shared stance that AI is necessary for genomics, who's going to pay? Well, that will be the patient.  

Natalie Banner: So we have quite a battle on our hands, in terms of trying to create space for those informative discussions, as you call them, Ismael, about the realities of what AI can and will be doing in genomics.  Francisco, how are we addressing those kind of questions and concerns in our work at Genomics England?  What steps do you think we can take at Genomics England to talk more openly about the work that we're doing involving AI to try and create space for those informative discussions that aren't led by the hype or the fears of AI? 

Francisco Azuaje: I agree that we have to ensure that we are not distracted from many discussions that emphasise potentially fictional or existential risk of AI.  I think there are valid concerns about existential risks that don't represent the AI fictional view of Hollywood, but that really affect the way we operate our societies. For example, existential risk for democracies, if you have monopolies of this technology. If we have less accountability, in terms of governance. If we have electoral systems that do not work. So if that doesn't work it's going to be very hard to benefit from AI within healthcare, so that's something to be considered as well.  But I agree that sometimes the discussion is driven by this interest in very long-term potential scenarios. I think the key is to achieve a balance between longer-term and near-term priorities. And in the case of healthcare, there are many challenges and issues that we should be discussing and addressing by now, including challenges regarding the privacy and the respect of rights of our patients and individuals. Concerns about the biases embedded in the data used to build the systems, biases actually embedded in the practices for building the systems. So these are real risks, that in the case of healthcare and research need to be addressed now.   

In the case of Genomics England, we are doing a lot of work that is laying the groundwork for safer, ethical uses of AI. So this means, for example, that we will continue doing what we do, inspire and driven by the need to respect our patients' our participants' privacy and rights and voices, so that's essential.  In practice, this means that we work closely with our Participant Panel and different committees responsible and accountable for protecting these views and rights. From a machine learning point of view, there are technologies and tools that are quickly emerging that we are using to ensure that our systems are properly designed with ethical considerations in mind.  

For example, we ensure that our data sets are of good quality, and good quality means not only the information that we want to use for a particular application, but also means that we identify and quickly mitigate potential biases embedded in the data. It also means that if we share a tool, for example, within our Research Environment, these tools have been properly tested. Not only for reliability but also for potential risks associated with privacy, with biases, etc., before these tools are deployed to a production environment or shared with the wider community. So these are basic steps, but I think they are essential, starting with the protection of our data and also by applying best practice in the way we build and evaluate these models carefully before they are deployed to a wider use.   

Ismael Kherroubi García: And that, to me, makes perfect sense, and it's always encouraging to hear the practices around AI and Genomics England. There is one challenge that came to mind that you mentioned, the impact of democratic values, on potentially artificial intelligence informing social media, that informs electoral processes. And there's another very real, tangible issue with artificial intelligence, which is the environmental impact. So what's really interesting, the challenge here is that artificial intelligence tools have significant environmental impacts.  You have enormous data centres that need to be submerged in water, maintained, kept cool, and we're developing enormous algorithms, ChatGPT, and so on, that require these huge amounts of data I mentioned earlier on. So there is this really tricky balance between health and the natural environment, which I don't have the capacity to even begin to think about.   

So, I sit on the Participant Panel at Genomics England, and the conversation often goes around how Genomics England use our data, how our privacy is preserved. But at the intersection of artificial intelligence in Genomics England, I might have slightly different concerns that don't relate directly with privacy. I usually think about three – scalability, automation bias and explainability. So I mentioned before that there's a risk of promoting issues that genomics research already faces, that over-sampling of certain populations. So if we take what genomics can teach us based on mostly European ancestry data, we end up imposing assumptions on populations across the globe.  The role of AI here is in scaling the impact of those assumptions, taking bias algorithmic models, and applying them to diverse communities within and beyond the UK, risks not identifying certain conditions, missing patterns, potentially informing poor medical practices, if we take these bias data samples and ultimately algorithms. So the issue here about scalability is that artificial intelligence promotes the limitations of genomics research.   

The second issues I mentioned on automation bias is about individuals, people potentially valuing the output of computational systems because they're mathematical and therefore might seem objective. And the challenge here is very real, if we have a clinician who is diagnosing someone and the clinician says no, there's no clear evidence for there being cancer. Following all the metrics that this clinician has learnt over the years of their work, and they're faced with an AI tool that says that this agrees that says actually there is a case for there being cancer or whatever the other option is.  So the automation bias there, if it were to kick in, would be for the clinician to raise their hands, give up and say, "Well, the machine says that there is..." or "there isn't cancer, so we'll just go with what it says."  The other option of is for the clinician to actually challenge what the AI tool says.  And the crucial difference here is that the rationale of the clinician can be described, it can be outlined, explained. And that's the third issue, that's the issue of explainability.  

So modern AI tools tend to use an enormous data set and neural networks or other machine learning technologies where outputs are produced with little or no explanation. The clinician can explain why they decided on one diagnosis or another, the AI tool cannot. Ideally, this is the really tricky bit, hospitals, Genomics England and others, would have the government structures in place to handle these discrepancies in outputs from clinicians who can explain what they have to say, and AI tools which are mathematically very sophisticated, they sound pretty cool, it's a challenge.  

Natalie Banner: It absolutely is a challenge, and very helpful to talk through some of those broader ethical issues and questions. Because they are, they're questions to what I understand, you know, the law and regulation hasn't caught up yet with these very, very rapidly advancing tools and technologies. And actually, if we are working at the frontier of some of these, then these ethical questions are precisely the ones that we need to work how to navigate through.  Not necessarily because of a regulatory structure, but just through bringing different voices, different perspectives to the table, trying to anticipate consequences, and thinking through where some of those questions, for example, as you raised on explainability, what could we do? Where could we address some of those challenges? 

Francisco Azuaje: Yes. The issue of transparency is crucial, not only to ensure that we have useful tools, but to ensure that we improve privacy, that we respect the uses of these technologies. At the same time regardless of the techniques that we use to make systems more explainable or interpretable, the idea behind transparency also means, let's ensure that if we say that something works well, indeed, we are providing evidence that that something is working well. That means that we ensure that first of all we have reliable and robust systems, and that by doing that we are also bringing actual benefits to patients and society. So I think that's a more fundamental question than discussing which techniques can make this model or that model more explainable, or the actual practices for making something more transparent. So in general this transparency is there because we want to ensure that we deploy ethical, robust and fair systems.  And that this starts by enhancing the quality and transparency of the development of the tool, but also the evaluation of those tools before their deployment, and even after these systems have been deployed to a research environment or to a clinical setting.  

Ismael Kherroubi García: It sounds like there's a need for continuous monitoring, right. Throughout the life cycle of developing an AI tool, but also once implemented how we get feedback, so that the tool can be improved, but also future and other tools can be improved. 

Natalie Banner: Thank you so much. So we have had a real whistle stop tour through the world of AI and genomics.  We've highlighted some real potential advances in exciting areas. We've cautioned about some of the risks and questions about how to tackle some of the ethical complexities that are emerging. So just to wrap us up, Francisco, can I turn to you first, could you tell us what you see as being the biggest or the most significant impacts in the world of AI and genomics in the next, say, three to give years? 

Francisco Azuaje: In the next three to five years, we should expect significant advances in genomics, AI genomics, beyond the focus individual genes or markers or actually the idea of gene panels.  So we should expect that the full patient genomic analysis will become more common to provide a more comprehensive view of genetic influences on health, and also the combination of genomic data with other types of health information will offer deeper insights for supporting more accurate, faster medical decision-making.

The challenge lies in connecting this data to clinical decisions moving beyond diagnosis to actually recommend personalised treatment options.  Matching patients with relevant clinical trials based on their genomic and other types of clinical information will also become more effective, more efficient. However, concerns about reliability, safety of these applications remain, and I think that in the next few years we will see an acceleration in the development of tools and applications. But also an improvement in the way we evaluate these tools before they are deployed to a real-world environment.  So this will be crucial in the next few years, and despite all these challenges, there is reason to be very optimistic about the future of AI in genomics and medicine for the benefit of patients.   

Natalie Banner: Thank you, Francisco. And Ismael, a last word to you, what's your key takeaway for those developing AI tools for use in genomics? 

Ismael Kherroubi García: For me the biggest challenge is that there must be multidisciplinary approaches, so those developing these tools need to speak with one another and be exposed to patients. So, on the one hand, AI tools for medical applications must involve multidisciplinary collaborations, critically including the voices of clinicians, and that point was raised by Francisco. And the COVID-19 pandemic, to work with something... work for an example, already showed us the value of behavioural and other social sciences in understanding the impacts of public health policies. So genomics and general genomics research must consider multidisciplinarity in a similar way and bring different disciplines together.

On the other hand, genomics data remain intricately linked with individuals. Research participants and patients must be kept abreast of developments in the complex space that is this interaction of AI and genomics to avoid the trust issues mentioned earlier on. Ultimately, those developing AI tools for use in genomics must follow inclusive practices. 

Natalie Banner: We'll wrap up there. Thank you to our guests, Ismael Kherroubi García and Francisco Azuaje for joining me today as we discussed the role of AI in genomics and healthcare, and the importance of having open, informative conversations about both the promises and the challenges in this exciting space. If you'd like to her more like this, please subscribe to the G Word on your favourite podcast app. Thank you for listening, I've been your host, Natalie Banner. 

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

In this instalment, our guests engage in a compelling discussion centred around a recently published paper that supports the integration of whole genome sequencing into standard cancer care. 

Our guests shed light on the transformative potential of combining health data with whole genome data. Discover how this innovative approach empowers doctors to deliver more personalised and effective care. Our guests delve into the findings of a landmark national study, unravelling the significance of identifying inherited cancers for patients and their families. The episode explores not only the scientific advancements but also the real-world impact on individuals facing a cancer diagnosis. 

Our host Naimah Callachand is joined by Dr Nirupa Murugaesu, a Consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the Principal Clinician for Cancer Genomics and Clinical Studies at Genomics England.  And by Professor Sir Mark Caulfield, a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as Chief Scientist for Genomics England and was instrumental in the delivery of the 100,000 Genomes Project. 

 

"In cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients.  So this is a real opportunity to create precision cancer care." 

  

You can download the transcript or read it below.

Naimah: Welcome to the G Word.  What does it mean if we can test for inherited genes?   

Nirupa: It can influence how their cancer is treated.  So it means that there may be certain types of therapy that are available if they have a specific inherited cancer gene, number one.  It also can impact in terms of preventing further or other cancers related to those genes, and it may impact the type of surgery they have, and also the type of overall cancer treatment.  And then finally, if they have got an inherited cancer, then, as I mentioned before, it may impact in terms of testing and screening for their family members. 

Naimah: I'm your host Naimah: Callachand.  Today, I'm delighted to be joined by Dr Nirupa Murugaesu, who's a consultant in medical oncology at Guy's and St Thomas' NHS Foundation Trust, and the principal clinician for cancer genomics and clinical studies here at Genomics England.  And Professor Sir Mark Caufield, who's a Professor of Clinical Pharmacology at Queen Mary University of London, and who previously served as chief scientist for Genomics England and was instrumental in the delivery of the 100,000 genomes project.  Today, Mark and Nirupa are going to discuss key findings from a recent paper that's just been published in Nature.  If you enjoy today's podcast, we'd really love your support.  Please like, share and rate us on wherever you listen to your podcasts.  Now, let's get into the interview.  So first of all, Mark, I wondered if you could give me a bit of background on the 100,000 genomes project? 

Mark: So the 100,000 genomes project started in July 2013 following an announcement by the then prime minister, David Cameron, that the UK would be the first health system in the world to sequence 100,000 whole genomes, which is as much as you and I can read of the genetic code.  In the case of cancer, which we focused on here, in cancer we were sequencing sections of the tumour and comparing them to DNA inherited from your mum and dad, and that comparison allows us to work out what is driving the cancer, what may be affecting its potential for treatment and how we might choose treatments for patients.  So this is a real opportunity to create precision cancer care. 

Naimah: And Nirupa, can you tell me what the 100,000 genomes project meant for these patients with cancer?  

Nirupa: I think, firstly, we're very grateful for all of the participants in the programme, because what it's allowed us to do is to look at the data as a whole, and having all of that sequencing data alongside clinical information has been incredibly valuable, it has also developed the infrastructure for testing.  And really I think for patients with cancer, they participated in this programme as a research project, and unusually for a research project these results were returned back to treating clinicians to clinical teams, if there may have been a result that would impact or change their management.  But I think, importantly, what it enabled is the implementation of standardised cancer testing in the NHS, and really enabling that for a wider range of patients, not just those that participated in the project.  And because of patients participating, this then allowed all of the data to be stored in a single place, and this has been incredibly valuable for clinical academics and researchers.   

Naimah: And can I ask what specific types of cancer that were looked at in 100,000 genomes project?  

Nirupa: Again, the project was set up such that we allowed a number of different types of cancers to be sequenced and, therefore, very permissible, because we also wanted to ensure that some of the less common and rarer cancers were also sequenced and, as you would expect, more of the common cancers as well.  In addition, I think the opportunity to sequence paediatric cancers, as well as haematological malignancies, or blood cancers, was also key as part of the cancer programme.  Here, we focus on the solid cancers, but obviously there was a much wider range of cancers that were sequenced.   

Naimah: And next, can we move on to talk about the findings of the study? 

Nirupa: I think, firstly, by undertaking sort of a pan-cancer analysis, it really gave us an overview of the number of target and genes that were found to be actionable.  And what I mean by that is that they have a, well, clinically relevant, and we can see that in certain cancer types, such as in brain cancers, in colon cancers, lung cancers, there were within the genome sequence more than 50% of these cancers had something that was what we would call actionable.  So there was a mutation in a gene for which this would influence treatment.  And as we started to look more across the entire cohort of patients, you can really get an idea of the fact that the more that we sequence, and the more comprehensive the testing is, the number of different types of mutations that we were able to discover.    

Naimah: And when you mentioned that these findings were actionable, what does that mean? 

Nirupa: So what that means is that has an impact in how the patient will be managed and treated.  It may influence, firstly, the type of surgery they have, it may influence the type of cancer treatment that they receive.  And all of this, I suppose, comes back to the point that Mark mentioned, of precision oncology, so we more precisely treat patients based on their individual cancers.    

Naimah: And could you give me some examples of maybe some of these genes that were found in the study that were actionable? 

Nirupa: Yes, so the types of genes also matter, or the type of mutations.  So some of them were in known cancer genes, and if you have, for example, a mutation in lung cancer, in a gene called the EGFR gene, we know that there are cancer therapies that can be provided that target specifically this mutation.  So that's one example, and this is quite well characterised and understood in oncology care.  But what we were also able to do with whole genome sequencing, is identify different types of mutations that are harder to characterise routinely.  And these are often included things that we call pan-genomic markers, where we can see what the mutational landscape is of the cancer, the different patterns of mutations can be gleaned from this, and often this can then give you an idea of the underlying biology of the cancer.  But importantly, in certain types of cancers, such as high grade serious ovarian cancer, it highlights which patients may have a particular marker that means they may or may not benefit from a particular type of therapy.  So in this particular case, the class of therapy is called PARP inhibitors. 

Naimah: And how did the study compare to other similar stuff studies in the genomics area? 

Nirupa: That's a really good question, and I think we looked at this from other large sequencing endeavours, such as the ICGC, TCGA, so these are big studies where have been whole genomes sequencing.  Also within the Hartwig Institute in the Netherlands, they've also undertaken whole genome sequencing for cancer patients.  And what we were able to identify is that the patterns of mutations were as expected, we found, you know, a lot of similarities.  I think the difference, the main difference is not just identifying the type of mutations across the different cancers.  But the fact that we were then able to look at the longitudinal outcome, and correlate some of these genomic markers with outcomes related to both therapies, as well as survival impact of having certain mutations in terms of prognosis.   

Naimah: Mark, do you have something you'd like to add there as well? 

Mark: Yeah.  So one of the things that we did in the 100,000 genomes project, was to evaluate the best way of measuring the whole of your or my genetic code.  And we discovered that very early on that if you expose the tumour to a preservative, which is called formalin which keeps the tumour preserved, that actually you could get quite a number of misleading findings.  And so to address that, the distinctiveness from former programmes, such as Nirupa mentioned, like the Cancer Genome Atlas, is that all of the tumours that we studied in this paper were actually produced under fresh tissue conditions, and have not been exposed to a preservative.  And that means that what we have is a really accurate reflection of the variation within the tumours.  And the other thing about this particular resource is it's the biggest resource.  We were able to look at 13,000 people with solid tumours, but we also had blood cancers and other cancers which also feature of this paper.   

And a further remarkable thing about this is early on, Nirupa and the team and I decided that we would longitudinally life-course follow the patients and by accruing data from multiple sources in the health system.  So, every attendance at the hospital, what chemotherapy was had, we've been able in this paper to recapitulate signatures that clearly show that certain mutations are harmful.  And many of the findings that we've made are absolutely, if you look at the survival of patients particularly, you can see almost identical patterns to those in clinical trials.  What this means is that by the really rich data set which is now many billions of clinical data points on these patients, we can actually look for long-term signals of benefit and harm that perhaps would not be detected by a clinical trial that might last for six months or a year.  So this is a really valuable resource, and the really great thing is we can use what's called real-world data, which is where we take routine health data, and we can recapitulate the findings from tightly controlled clinical trials.  And I think that's quite an important finding.   

Naimah: That kind of brings me onto the next question, Mark, where I want to talk about the value and benefit of genomics sequencing for cancer patients.  I wondered if you could expand? 

Mark: Well, what we know from one of the genomics medicine centres which were regional hubs, is that they use the information that we return, that Nirupa outlined earlier in a report, for 25% of their patients.  Which means that they concluded having evaluated that as the clinical team locally, that there was something the patients could benefit from.  Now, what we think is this makes the case for certain cancers being part of the national genomics test directory whole genome sequencing, but it's still the case that the majority of testing for cancer is now very large focused panels that are focused on specific gene features.  But in some measure, this work is also able to reassure us that those gene features are the right ones to focus on, so this work has been very useful in that respect, even where the NHS today cannot make the financial or clinical case for using whole genomes in specific cancers.  So I think the programme's made a massive difference.   

The biggest thing it's done for patients, which Nirupa was very actively involved in, is it's allowed us to create a national genomics test directory.  So when we started this, cancer genomic testing was completely random and would vary from one postcode to another, one hospital to another.  And what Nirupa and the cancer team created is a national cancer genomic test directory, which now means that standard of care, that's the basis for reimbursement, and it's available across the landscape of 56 million people.  And given that one in two of us will have cancer, this is a massive advance.   

Naimah: Yeah, you've really highlighted the impact of having access to such a large database.  And I just wanted to ask as well, what are the challenges associated with implementing routine whole genome sequencing into clinical care? 

Nirupa: I think as with all of these things when implementing something new within a healthcare system, it requires a level of education, upskilling and also, as Mark has touched on, how we handle the tumour tissue, so that it's handled in a genomic-friendly way to enable the best results if you like, because we want to ensure that their DNA is not damaged so that we can get accurate read-outs on the results.  So there are challenges and there is also cost implications in weighing up the pros and cons.  And I think what we were able to show, and by undertaking this sort of pan-cancer analysis, is where there are those cancer type where there is a real need for whole genome sequencing, or where it can be justified, because there are a number of different types of mutations both within the tumour.  And also from a blood sample that is also taken, so this is your constitutional DNA, so this is if there is a risk of an inherited cancer.  So we are able to pull together all of this information, and obviously that's important, not just for the patient, and their management, but also for family members.  So I think really what this shows is that where you have to identify many of these different types of mutations, whole genome sequencing enables that through a single test.  

Naimah: Mark, would you like to add something else there? 

Mark: One thing I think which Nirupa's very much part of, is the distinctiveness of the Genomics England approach has been to involve the NHS at every stage.  Now, what that means is we estimate that at the peak of the 100,000 genomes project, 5,000 frontline NHS staff touched the project at some point in their working week.  What that does mean is that Nirupa and the cancer team could realign the cancer tissue handling pathways.  But it also meant that we were able to upskill the frontline workforce, such that at the end of the programme, when we produced a genomic test directory, they were really up for it because they did not want all the hard work they'd put in to stop.  And so what we've done is produce the national test directory within five years of starting, that wasn't a deliverable for the project, but it was nonetheless obvious to all of us working in it, including NHS England, that there needed to be service transformation, and we've managed to effect it.   

Now, if you look at other settings where perhaps Nirupa and I might have a research team, we might do it some distance from the health system, it would be in the health system, but not with the health system, then it takes between nine and 16 years to get these things into clinical practice.  And that was achieved here in five years.  So there is a lesson from this, the cancer programme particularly, because the cancer programme testing was very limited when we started, but you can take an entire workforce on a journey and leave them with the legacy of an entirely transformed system for patients.  And thankfully because we got, Nirupa and I, the NHS to agree to reimburse for the testing directory being used, we have eliminated a lot of randomness that was in the system previously.  So it's quite an important advance in that respect, and it really does show in the beautiful work that Nirupa was describing exactly how you can use this information to change an entire system.  And the NHS is not the easiest system to change in the world. 

Naimah: Nirupa, you mentioned the findings show that there was potentially inherited genes.  Can you tell me what does that really mean for patients, if we're able to diagnose these inherited genes sooner in life? 

Nirupa: It can influence how their cancer is treated, so it means that there may be certain types of therapy that are available if they have a specific inherited cancer gene, number one.  It also, can impact in terms of preventing further or other cancers related to those genes, and it may impact the type of surgery they have, and also the type of overall cancer treatment.  And then, finally, if they have got an inherited cancer, then, as I mentioned before, it may impact in terms of testing and screening for their family members.  And that's really key as well, because this means that their cancer can be diagnosed, if they do develop a cancer, because they're being monitored, because it's much more targeted, their approach in terms of screening for a particular type of cancer, they can potentially have their cancer treated much earlier.  Or even better, before it becomes what we call an invasive cancer but at the pre-cancerous stage.  So this has huge implications, and what we're finding actually with more and more testing – and this is not just... our study was consistent with other studies that have been published – is that when you undertake more routine testing, then you are able to identify this.  It is not common amongst the population, but in those patients where it is relevant, it really can impact their care. 

Naimah: Mark, do you have something to add there? 

Mark: Well, I think Nirupa's just highlighted a really important point.  So to bring that into a little bit more ways of which people listening to this can relate to it, we have a family where there was a women who had no family history of breast cancer, she developed breast cancer, and in the tumour we found that she had a BRCA 2 mutation.  We also found that she'd probably acquired that or inherited it, we don't know.  That for her meant that she could enter the Olympia trial, which was running at the time, which Nirupa alluded to earlier, was a study of PARP inhibitors.  But without that genetic makeup she'd never have got into that trial, and she probably wouldn't have been tested for BRCA at that time in the NHS because she had no family history, I think that's probably right, Nirupa.   

And then there was a family-wide consequence for that, because she had a brother and son, and she also had a daughter, and the daughter was under 30 at the time and underwent BRCA testing and was BRCA 2 positive.  But she has the opportunity now to enter intensive breast screening from the age of 30, and that's what's happened.  And her brother, and this is the lady who had the breast cancer, her brother and her son may be at risk of prostate cancer, so they can consider testing.  So Nirupa makes a really important point, that when people have inherited a previous disposition to cancer, that can have a family-wide impact.  And one test in one family member can open the doors to opportunity for others to understand their risk and to be screened more actively and intensively, hopefully with meaning that if they do develop cancer it will be detected very early, or maybe we can just prevent it altogether.    

Naimah: Thanks, Mark, a really good example of the impact that this testing has had.  I just wanted to touch back on your point, Mark, that you'd made about real-world data.  And I wondered actually, Nirupa, if you could kind of explain to me why it's important to link real-world data to the genomic data? 

Nirupa: Yeah.  So I think the work we've done here really does emphasise this, because when we refer to real-world data, we're talking about different types of healthcare data across the population.  And we had the opportunity to link the genomic data to a number of key data sets that are curated by the cancer registry, the national cancer registry database.  And this includes things like all of the population base systemic anti-cancer therapy, so we know that for each of the participants the type of cancer therapy they receive, and also, as Mark has mentioned previously, the hospital episode.  So when patients needed to be... we can see their data in terms of admissions, investigations, and so on.  And these are really valuable data points, because you get an indication of when patients may have had to then have further testing, or if there is a risk of recurrence and importantly survival data, because a lot of this has been, in terms of a lot of the cancer genes have been well characterised and tested.   

But what we were able to do here at a pan-cancer level on a large cohort of patients over a period of time, is to look at if you had a particular mutation, what is the impact of that in terms of outcome for a particular cancer type, and even more broadly, on a pan-cancer level?  And actually, as this type of data accumulates, I think the real value, and if you've got a larger number, you know, what is the value for patients who've participated in this programme going forwards, is that as that data accumulates and the numbers go up, we are able to then ask more detailed questions.  What is the impact of a particular type of mutation, or a particular type of variant within a gene?  And, importantly, what happens when you get a different sequence or a combination of genes?  And how does that impact?  And this, I feel, is the way that we are going to move more towards precision oncology, because we are beginning to understand the cancer in more detail, how it is going to behave, and then try and tailor therapies accordingly.  

Naimah: And Nirupa, I wondered if you could tell me as well if the findings from this study have benefited directly those patients that were involved in the 100,000 genome project? 

Nirupa: It has benefited some of the patients because, as Mark has mentioned, there are findings that we weren't expecting in terms of potentially inherited cancers and, therefore, this has had implications.  The way that the project was set up from the outset, is that we were obtaining tumour samples from patients who had not received any previous cancer therapy.  And what this meant is that this was predominantly in patients, so they were treatment naïve with early stage disease that were having surgery to treat their cancers.  And as such, what we know is that fortunately most of those patients did not require further therapy, because their cancers were treated successfully with surgery.  But what it did tell us, and what it's really highlighted, is the number of important genes that were identified.  And so whilst it may not have impacted patients directly, it's enabled us to study the biology of the different types of cancers, how they behave, along with the longitudinal clinical data.   

But what it is doing now, is through the national test directory through the genomic medicine service, is enabling testing for patients that unfortunately now have more advanced cancers, but where these genomic findings are more likely to impact directly in terms of therapy.  So, for instance, as we've mentioned, the ability to have whole genome sequencing for patients with high grade serious ovarian cancers, means that this will impact the type of treatment they have.  And this also was the tumour type where we found the highest number of patients with BRCA mutations, so we have a potential inherited risk of a cancer as well.  So now what we have learnt and the infrastructure that we have developed has enabled this to have a real impact, not just for patients in the project now, but wider within the NHS. 

Naimah: Mark, would you like to add something else there? 

Mark: I think Nirupa's encapsulated it very well.  There were a range of benefits, so I mentioned earlier that in one centre 25% we have evidence got a benefit for their treatment for their cancer in some way shape or form.  So an example to what there might be is that some people got a medicine they wouldn't have received from routine care, and that might have been licensed for the treatment of that tumour, but it wouldn't have been the first line treatment choice.  Some people got medicines that they wouldn't have got because we don't normally associate using that medicine with that cancer, but they had a signature that showed that they were very likely to benefit.  Quite high numbers got an opportunity to get into a clinical trial, which is really important because if you look, over 50% of global oncology trials now have some kind of biomarker or diagnostic, or something like this alongside, what better than to have a comprehensive inventory of the variants and the cancer, and to be able over time to use that library to understand better the treatment course of that patient.  And that's what I think a whole genome adds, rather than the single, look at a single part of the genetic makeup.  

And then finally, some had lots of mutations, really high rates of mutations, and maybe they should receive specific advance therapies, like immunotherapies.  Or alternatively, they had a feature in their genetic makeup which it looks like they inherited, as Nirupa absolutely correctly said earlier, these people need to be followed-up and they need more intensive screening, because this is how you detect cancer at an earlier stage.  And the final way people benefited is we could detect genetic changes in  their DNA that meant that if they were exposed to certain medicines, they were likely to suffer harm. And there's a particular, two medicines, 5-fluorouracil capecitabine, where possibly about 5% of people will need either a reduced dose or a completely different medicine, because it will be very harmful.  And so this is about getting the right medicine to the right patient first time, and getting the right outcome for that patient downstream.   

And I think, you know, Nirupa's encapsulated it perfectly, there's a whole range of benefits that the patients can accrue from this.  And I think we should probably, Nirupa, say that people were quite cynical when we started, about what it would be that you would get over and above, for example, the cancer genome map that's at the international cancer genome consortium.  And, you know, I'd had leading cancer scientists in Britain say, "Oh well, we've discovered it all, there's nothing to find here."  And I think what this paper shows is that's not entirely true.   

Nirupa: I would agree with that Mark, but I would also probably add that it highlights the value of having a large data set alongside that clinical information.  And what we were also able to do,  is whilst we very much talked about what were the gene targets that had a direct impact or genomic markers that impact care now, for which there is an approved therapy.  What we've also been able to do through this analysis, is actually highlight the number of mutations that have been identified for which there is a licence therapy in another cancer type, but not in that particular cancer type.  And what that means, is that specially now, as we have more and more biomarker-driven therapies, I mean, if we look at that compared to when the project started and now, that has increased dramatically.  And what that means is then there are sort of licensed medications that actually can be used in non-licensed indications via a clinical trial, via these very, you know, these basket studies which are across cancer types and are actually based on different types of molecular markers.  And really, we're able to show this at a pan-cancer level across the 13,000 tumours through the results from whole genome sequencing. 

Naimah: You've both kind of touched on this throughout and, you know, we've talked about the development of personalised medicine.  And where do you see the future of cancer treatment in the next five years?  Maybe, Nirupa, we can go to you first? 

Nirupa: That's a very good question.  I think and what I hope is that with more comprehensive and equitable and standardised testing for patients, especially within the NHS, that this will enable more personalised and targeted therapy alongside, you know, systemic chemotherapy.  And as well as that, better selection of patients that are likely to benefit from the newer immunotherapies.  And also where sequencing is very exciting, is that once we begin to understand more about the individual tumours, you know, going forwards there are a number of cancer vaccine trials, and the aim of those are to have specific vaccines that are going to target an individual's tumour.  So I think in the next five years, this is I think a very exciting space, I hope so, because we need to keep doing more in the space for our patients to try and improve therapy and precision oncology for them. 

Naimah: And Mark, do you have anything to add to that point? 

Mark: I think Nirupa's right, that there are new therapy extractions coming on, vaccination's one way.  But I think that what will become clear is whether we can use any molecular mechanisms for early detection of cancer.  The battleground here is that we all too often detect cancer late, when it's already outside of the organ it originated in and may be spread in other parts of the body.  It's very hard to effect a cure, almost impossible in that setting.  But what if we could detect cancer earlier?  And then what if we could place a whole genome or detailed molecular characterisation alongside that?  And then, as Nirupa suggested, give someone a vaccine tailored to their tumour that would eliminate it.  The real problem is all too often we detect cancer late, so maybe some of these new molecular diagnostics, such as cell-free tumour DNA will usher in an era of early detection.   

And one of the things, and particularly before we did this project but also up until the beginning of the last decade, there were very few good biomarkers of cancer that were usable in the health system.  So we have for the first time opened the vista of having early detection, if we combine early detection with detailed molecular characterisation, possibly a whole genome, possibly another test, then I think we really can usher in the era of precision medicine.  And so I think Nirupa's absolutely right, there will be new treatments, there always will be, but what we have to do is to get detection at an earlier stage. 

Naimah: We'll wrap up there.  Thank you to our guests, Dr Nirupa Murugaesu and Professor Sir Mark Caulfield for joining me today.  If you'd like to hear more about this, please subscribe to the G Word on your favourite podcast app.  Thank you for listening. 

 

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

As we approach the conclusion of 2023, we reflect on a year that not only signifies our 10-year anniversary but also marks another chapter of our podcast. Throughout the year, guests have joined us fortnightly to share their research, stories, and aspirations for the future of genomic healthcare. 

In this special end-of-year episode, Naimah Callachand sits down with Dr Rich Scott, Interim Chief Executive Officer at Genomics England, to look back on the last decade of Genomics England. Tune in as we revisit memorable moments from the 2023 podcast episodes through key quotes, reflecting on the transformative journey of Genomics England. Join us for this insightful recap and a glimpse into the exciting future ahead! 

Below are the links to the podcasts mentioned in this episode, in order of appearance: 

• Adam Rutherford, Laurence Hurst, Cristina Fonseca and Vivienne Parry: Public views on genetics - what have we learnt? 
• Dr Jack Bartram: Can genomics improve our understanding of childhood cancers? 
• Helen Webb, Lizzie Mordey, Kirsty Russell and Prabs Arumugam: How can advances in genome sequencing support patients through their sarcoma journey?
• Vivienne Parry and David Bick: Which conditions will we look for initially in the Generation Study?  
• Dr Nicola Byrne: What are the challenges of data governance in the digital age? 
• Chris Wigley: The journey to the Human Genome Project and beyond with Dr Francis Collins

 

“We’re also looking to the future where, as I say, we’re proud of the impact that there already has been, and the NHS Genomic Medicine Service is the first national healthcare system to offer whole genome sequencing and that is extraordinary. Thinking about how we can broaden our impact is a really important part of that, and that’s thinking about how we can be supportive of genomic technologies broader than just whole genome.” 

 

You can download the transcript or read it below.

Naimah: Welcome to the G Word.

Rich: We’re in an extraordinary time. The power to analyse genomic data has changed enormously. These are big changes in terms of the, sort of, analytics that AI could bring and the potential to work not just within the UK but with other countries and other big initiatives to make sure that we’re answering the questions as best we can.

Naimah: I’m your host Naimah Callachand and today we’ll be hearing from Rich Scott, Interim CEO for Genomics England. He’ll be sharing insights with us from the last year, and we’ll be revisiting key moments from earlier podcasts in the year featuring some of the voices that have shaped our discussions. If you enjoyed today’s episode we would love your support, please like, share and rate us on wherever you listen to your podcasts. Now let’s get into the interview.

So, this year we celebrated our ten-year anniversary and as 2023 comes to a close we want to reflect on our achievements not just in the last year but over the last ten. So, Rich first of all can you talk us through where we started in 2013 and where we are now?

Rich: It’s amazing really to think about how much things have changed in terms of genomics in clinic and in hospitals and then for us as Genomics England over the last ten years. So, actually thinking back ten years ago was only ten years after the Human Genome Project was completed, and when one thinks about what one could do in clinic and those questions you could answer using genomics in clinic. We could see what was coming, we could see these new technologies, next generation sequence in coming, but it was much more dependent on very targeted testing.

And now with, you know, our founding project, the 100,000 Genomes Project that Genomics England was founded to deliver in partnership with the NHS we asked the first big question if you like which was how can whole genome sequencing play a role in routine clinical care. And that’s now played out where evidence from the project, what we’ve learnt, the infrastructure we’ve built, and also evidence from around the world that through the NHS Genomics Medicine Service has now put that into practice and we’re working in partnership to help them deliver it.

So, it has gone from an idea where we could see this new technology, this potential, to a position where now patients in the NHS with cancer or with rare conditions have whole genome sequencing as a routine part of their clinical care where that’s in that national genomic test directory that NHS England have set up.

Naimah: Earlier in the year we heard from Dr Adam Rutherford, geneticist, author and broadcaster who commented on how the public perception of genetics and science has evolved over the last few decades.

“I’ve been doing this a long time and I think that when it comes down to it, genetics which is a relatively young science and really in a sophisticated way, you know, a mere few decades old, but what is it at its absolute core, it’s thinking about families, it’s thinking about inheritance and it’s thinking about sex. And these have been the major preoccupations of humans for thousands of years, and it’s only really in the last century, really only in the last 30 years or so, that we’ve had a sophisticated understanding of how these things work, if indeed we have had at all.”

Naimah: Let’s get back to Rich.

Rich, I’ve already touched briefly on it, but can we dive a bit deeper into the 100,000 Genomes Project and can you tell me a bit more about how it started.

Rich: Yes, so the 100,000 Genomes Project as I said was there to ask what role can whole genome sequencing play in understanding medical conditions, you know, is it ready for clinical prime time. And also how can we link routine clinical care to research so that we’re not just asking questions with today’s knowledge, but we can continue to build that knowledge for the future.

So, the 100,000 Genomes Project was driven by that idea that people realising, the government realising and the NHS forming a partnership with us Genomics England to explore that question in real depth. And it’s not just about the clinical aspects and the scientific questions, it has also been working with participants and the public to understand how we could do that.

And through the 100,000 Genomes Project we worked particularly with patients with cancer and rare conditions to see how we could help make diagnosis and improve care. And also with their consent make their data available in our secure, trusted research environment so that researchers could continue to look for answers that we couldn’t answer today, and we continue to do that work for those participants now.

Naimah: Next we’re going to hear from an interview with Dr Jack Bartram, a Consultant Paediatric Haematologist at Great Ormond Street Hospital for Children. He spoke about the significance and impact of integrating genomics into routine clinical care in diagnosing cancer in children.

“If I look back and if I reflect on the last three years, you know, we could probably accurately say at least a quarter of patients it has given us additional information which is either aided in diagnosis or like I had said help risk stratify a patient or potentially reveal a target for a therapy that we didn’t know of before. And what this has led to and what we’ve seen over the last three years or so is that we have actually changed management of patients based on this.

So, definitely we’ve got examples where we scan clarify the diagnosis, we’ve changed the risk category, or we’ve identified for example that an unexpected cancer predisposition in a family which has then led onto screening for the family which can then give the family the knowledge to try and do things to either modify the risk of cancer in the family or at least screen for it so they can detect things early to prevent things presenting too late.”

Naimah: Okay, now let’s talk a little bit about some of the initiatives at Genomics England. Can we talk about how they’ve progressed and what they might look like in the future.

Rich: Yeah, so we really are on a journey both as an organisation but with all of those partners that we work with across the UK system. And one of the great things I think about genomics and genomics in the UK is that the ecosystem that we’re in and the strong partnerships that we can form to ask these really big questions. So, if you like when we formed as an organisation we had the questions that we’re asking around diagnostic use of whole genome sequencing in the 100,000 Genomes Project.

And if you like in our second chapter as we’ve moved on to support the NHS in delivery of life clinical care we also have been thinking about the other big questions that we need to address. And those have played out and we’ve been really fortunate to gain the funding and to work in partnership with the NHS and others on these big questions. So, firstly our newborn genomes programme, secondly our diverse data programme and then our cancer 2.0 initiative.

And each of them have big questions behind them so that we’re saying, you know, where could genomics better support healthcare and move forward and improve care for everyone. Our vision at Genomics England is a world where everyone can benefit from genomic healthcare and each of them is pushing those boundaries, asking those questions in different ways.

For the newborns programme the big question is should every newborn baby be offered whole genome sequencing driven particularly by that potential to identify more treatable severe genetic conditions at birth, and if so how should we do that. Again, developing evidence in and around really broadly across the clinical and scientific aspects, but also engaging and understanding public attitudes how we might do that. And really understanding how that might impact on the healthcare system, how it might be delivered in clinical care.

For the diverse data initiative we recognise the challenges historically that there have been because of the inequity in terms of the communities who have been engaged with and included in genomic research. And the diverse data initiative aims to both understand where we are today but also to make sure for example the national genomic research library is at least representative of the UK population so that we can work towards again that word that’s in our vision, everyone, a world where everyone can benefit from genomic healthcare.

And in the cancer 2.0 initiative we’ve been exploring two really promising areas in terms of cancer genomics. Firstly, exploring different sequencing technologies and in this case partnering with the NHS to work on the Oxford Nanopore technology which we think is really promising in terms of use in diagnostics to speed up and better diagnose and treat cancers.

And also looking in our multimodal element of our cancer 2.0 initiative at bringing in a broader range of data alongside the genomic and clinical data that participants in our programme consent to us holding in our trusted research environments. And bringing in image data, images of their tumours on the histopathology slides that are looked at traditionally down a microscope but scanning those at very high resolution and with uniformity between participants working with NPIC to do that.

And also bringing in imaging, so radiology type imaging, of tumours so that that data is there to drive new discovery. And working in partnership with academics and with industry for example insitro to understand how we can both bring that data together usefully, put the right tools next to it and then allow that discovery so that our participants know that we’re looking not just on what we know today but to improve things for the future.

Naimah: Rich mentioned some of our initiatives here at Genomics England. And now we’re going to hear from some G Word guests on how these programmes can make a difference for those with a genetic diagnosis. We spoke to Lizzy Mordey, a clinical trials co-ordinator, whose husband Steve sadly passed away last year after receiving a sarcoma diagnosis. Lizzy commented on the pivotal role whole genome sequencing can play in receiving a quicker diagnosis on the identification of suitable treatments for patients with sarcoma.

“Personally, I would hope for quicker diagnosis, and I know that’s super hard to do and I think as we’ve discussed before on this call it’s such a rare thing and it, kind of, often doesn’t fit the standard clinical pathway and that’s one of the reasons why it’s so frustrating. So, anything that we can do on that front that I think would be hugely valuable to anyone experiencing a journey like what me and Steve went through, and yes advances like genome sequencing are really amazing in supporting that. Yes, as I mentioned as well any information about types of treatment, you know, the diagnosis is important but then the other aspect of getting a diagnosis and a specific diagnosis is understanding what’s most likely to help.”

Naimah: Next we’re going to hear from David Bick who is a principal clinician for the Newborn Genomes Programme at Genomics England. He spoke about the generation study which is being delivered in partnership with the NHS.

“I’m doing this because I imagine a day when all over the world we will find and treat children before they get ill. This is one of the most wonderful programmes to be involved with because I can see that future. I want there to be a healthcare system. I really want to help children stay healthy and really live their best lives, that’s what’s so exciting for me.”

Naimah: Now let’s get back to the interview with Rich. You mentioned all of the partnerships there and also one important one is with the NHS. As you know the NHS also celebrated its 75^th anniversary year as well as our tenth anniversary. And I wondered if you could tell me a bit more about that relationship with Genomics England and the NHS and how we’re working together. 

Rich: Our relationship with the NHS is absolutely critical. So, as we’re thinking about what we can do to enable better genomic healthcare we’re so fortunate in this country to have a national healthcare system. And for us and for our work at Genomics England it’s absolutely critical to work hand in hand with NHS England both in supporting their live clinical services so we enable their national whole genome sequencing service through the Genomic Medicine Service and also as we work through all of our patient facing research.

So, as we did for the 100,000 Genomes Project, as we are for our Newborn Genomes Programme and so forth co-designing these programmes so that the evidence that we’re able to generate is relevant in the UK for our healthcare system but also that national scale is just so extraordinarily powerful. And I think we’re really lucky for many reasons, the UK genomics ecosystem, it’s richness, the investment that has come from government and from the NHS in genomics and the recognition of its importance and from funders, and then that ability to ask questions at national scale.

And when you look internationally I think that’s the piece that people are often most jealous of in terms of the power of the questions that we can ask together with the NHS so that we can do exactly what we want to do which is transform care so that it’s better in the future.

Naimah: Rich highlighted the importance of our relationship with the NHS in transforming patient care. Louise Fish, CEO of Genetic Alliance UK commented on the importance of joined up care following diagnosis to support them throughout their lives.

“So, there is a lot more we need to do to work with the NHS to make sure that the care from the health service is joined up and co-ordinated for people. And then beyond that how does the co-ordination reach out to education, to housing, to benefits, to social care. The bit that almost should be simplest is if the NHS has someone who understands your child’s condition. But it should be possible for their school to be in touch and to find out how that condition is going to affect them and what support the school might need to put in place through an education health and care plan, but those links out to the other services aren’t there either.

So, for us there is a lot of work to do that’s not just around the diagnosis but it’s about ensuring that lifelong care and support is delivered in a co-ordinated way. And as more people are getting genetic diagnosis through this amazing, kind of, clinical advances how do we make sure there is also investment into the clinical services that are going to support people throughout their lives.”

Naimah: One of the key factors in supporting Genomics England to deliver this important work and all of our initiatives is the participants and the trust that they have in us. I wondered if you could share a bit more on this, so how Genomics England works with their participant panel.

Rich: Yes, so I think one of the things I’m proudest about at Genomics England and it was established about the time I was arriving at the organisation is the participant panel who are a group of our participants who represent a broader participant across the national genomic research library. And they’re a part of our governance, which governance sounds like a boring word, our relationship with the participant panel and their role in our governance is absolutely critical. They are the people whose data we are the custodians of, and we have a responsibility to them to live up to their expectations and also to make sure that they’re driving the decisions that we’re making.

An example is how we setup the access to data for researchers. So, I mentioned that the way the national genomic research library works and a model that we developed through engagement with the public and with the input of our participants is that people can visit the de-identified data in our trusted research environment, but they can’t take it away. They come and look at the data, they carry out their research which is on approved projects that is exploring healthcare questions. Those researchers have to go through an access process overseen by an independent access review committee that has our participants on it. So, they are making the decisions about the sort of research that they are comfortable with and that they want to be done on their data, and I think that’s really critical.

It has also been a real pleasure to work with our participants as we design future programmes either on for example finding further answers or looking for better treatments for people who are already in the national genomic research library, already a part of our participants or to help us design future programmes, for example our Newborn Genomes Programme. Our participants as well as engagement with potential future participants and the public more broadly has been absolutely critical in guiding us on how we do that.

It’s a team sport what we’re doing in many different ways. That’s with our broader ecosystem, it’s with our participants, and that means this isn’t about some people going away and sort of thinking up what sounds like the right programme and using all of their knowledge and expertise and producing something which is set in stone. This is about dialogue and engagement and using that to understand the right way of us approaching the questions we are and responding to what we hear. And our participant panel are absolutely critical in that.

Naimah: And maybe it would be good now to discuss a bit about the new challenges that we’re currently facing such as AI and issues with data sharing and data protection. Can you comment a bit on that.

Rich: Yeah, so genomics is a fast moving area. We’re really proud of the impact that we’ve had already, but we also recognise that at the moment we can only use genomics in a particular number of clinical situations. And even within those we can only help a certain proportion of patients. And what our participants say to us is that we need to be restless if you like and not accept where we are today. I think it’s quite easy to merely celebrate progress but it’s really important to also then ask where we need to be going next. I’m always guided by our participants thinking about what the new technologies are and what the different ways of approaching these scientific questions is critical.

We’re in an extraordinary time, genomic technology has changed enormously. The power to analyse genomic data has changed enormously. These are big changes in terms of the sorts of analytics that AI could bring and the potential to work not just within the UK but with other countries and other big initiatives to make sure that we’re answering the questions as best we can. That brings with it as with all of these areas questions about how you best do things and how you balance the importance of privacy, data privacy, with the benefits of being able to look across larger number of research participants to find answers that you just wouldn’t otherwise.

Likewise with AI there is the potential for us to both speed up current processes but also ask broader questions that we can’t yet using some of these technologies. Doing that in conversation with our participants and the public to understand how to best balance the different benefits and also clarify where there are, sort of, very clear expectations that we shouldn’t exceed is really important.

And I think that’s one of the things that puts us in such a strong position is that confidence that our participants are guiding us and often, and speaking as a doctor myself, it’s interesting the medical community is often quite paternalistic, quite cautious and quite narrow in what they might think their participants would want. What we like to do is be driven by what our participants want and expect, and I think that has been really important for us in our history up to now as an organisation and increasingly in the future.

Naimah: Yeah, and I think you’ve really highlighted how Genomics England were trying to keep the participants at the heart of everything that we do. Dr Nicola Byrne, the National Data Guardian for health and adult social care in England spoke about challenges with sharing health data and the importance of transparency and accountability in how data is used to support better outcomes from health and care services.

“So, it’s absolutely important that people feel that they can share that information and then feel confident that any information they do share is going to be used in ways that are safe, appropriate and ethical. Whether that’s for their own care or thinking about the benefit of other people in future through research, innovation and planning.”

Naimah: Well, let’s get back to the interview for some final reflections with Rich.

So, we’ve been looking back at our achievements over the last ten years, and I’ll be keen for us to look at what’s next. So, we’ve touched on it, but let’s take some time to reflect on the research that has taken place across the global genomic landscape for example and, you know, what we’ve done here at Genomics England.

Rich: The world has changed a lot in ten years. We’ve learnt a lot ourselves as an organisation and the researchers that work with our participants data and the national genomic research library have done extraordinary work. So, to give you a flavour of the sorts of things that I guess have changed in terms of what we can enable them doing in terms of research and research work. When participants data enters the research library they’re consenting to their genomic data sitting there alongside deidentified clinical data from their longitudinal health records.

As I said through our multimodal cancer initiative we’re also now able to bring in image data for our cancer participants. And increasingly, and this is something that Matt Brown, our chief scientist, was talking a lot about at our research summit in September, was bringing in additional modalities of data alongside that.

So, for example, in our rare disease participants bringing in proteomic, transcriptomic and long read data alongside the current sets of data. It means that that resource becomes even more powerful and able to answer a broader set of questions and able to ask questions across a broader set of data in terms of what might be useful for improving the understanding of medical conditions and improving clinical care.

So, for example, there has been amazing work over the last few years on cancer and the mutational signatures that are there in tumours. For example, Serena Nik-Zainal’s group understanding the patterns of mutation that are there in tumours driven by the underlying biology, not just because it helps us understand how things have happened, but also because it helps us understand about prognosis and how to treat conditions.

We’ve got really exciting early insights from the work on the image data, that multimodal data, working as I said with academia and also looking at the work that insitro are doing. Recognising patterns between you can see down the microscope of a tumour and the genomics. To understand some of those processes that we’ve just not been in a position to explore before.

And I think one of the really powerful pieces of work that is ongoing and will continue to is the ability for researchers and teams within Genomics England to continue to look for answers as our knowledge improves. So, some of the research work that we’re doing is discovering some new fields if you like of understanding. We also know that each year literally hundreds of new genes linked to rare conditions are identified.

So, enabling research that allows us to go back and look in our existing participants data to see if that new knowledge, that new knowledge about gene to condition links or better understanding of genomic variation means that we can keep looking for and finding things relevant to people who at the moment are research studies, 100,000 Genomes Project, or the Genomic Medicine Service initial testing with today’s knowledge or the knowledge of today or whenever their test was couldn’t identify because of the limitations of knowledge.

Now we can go back and identify through by sharing likely insights of clinical importance with NHS laboratories. We can then pass those findings back to participants and that has been the case in more than 2,000 of our 100,000 Genomes participants already and it’s enormously powerful. I think as we think about the direction of travel in the future, I think thinking about how we make sure that the breadth of questions that can be addressed for our participants in the national genomic research library is even broader, is really important. And that’s, as I say, something that’s particularly bringing in other types of data alongside has been a really important part of.

We’re also looking to the future where as I say we’re proud of the impact that there already has been, and the NHS Genomic Medicine Service is the first national healthcare system to offer whole genome sequencing and that is extraordinary. Thinking about how we can broaden our impact is a really important part of that, and that’s thinking about how we can be supportive of genomic technologies broader than just whole genome. So, for example,  panel and exome data and thinking about some of those other modalities of data like transcriptomes is really important as well for us. And that’s something that we’re exploring at the moment how we best do that, how we might do that.

Also thinking about the range of settings that genomics is currently playing a role and we can see a future in five to ten years’ time where rather than genomics being something where it plays a role in a small proportion of healthcare encounters where it could be impactful, over a much larger proportion, perhaps even up to a half of all healthcare encounters through, for example, pharmacogenomics potentially. And our Newborn Genome Programme is developing evidence that will help us understand whether that whole genome sequencing should be offered to all newborns. Potentially in research studies like Our Future Health are asking questions around the value of integrated or polygenic risk scores.

Through those sorts of elements we can see genomics playing a role much more broadly both in terms of the number, proportion of clinical settings where it’s relevant, much more towards it being a routine part of healthcare, but also across the lifetime at different stages and thinking about the value of genomic data if you like through the life course as something that can be looked at repeatedly increasingly without requiring specialist knowledge from the clinical teams so that it can have the impact it can. And thinking about how we might play a role in developing that evidence but also supporting the infrastructure through our expert knowledge in the management of coherent national genomic data sets.

And also having that dialogue in public about how genomic data might be used and working out how we generate evidence that can drive policy change. I think there is enormous potential in the future and we in the UK I think remain uniquely placed to explore those sorts of questions.

Naimah: So, we’ll wrap up there and that brings us to the end of our podcast for 2023. Thanks to Rich Scott for sharing his reflections on the last ten years of Genomics England and his aspirations for the future. Moving into the new year we’ll leave you with a powerful quote from our podcast with Dr Francis Collins who is renowned for his landmark discoveries and leadership in the Human Genome Project. 

“My dream Chris is that we come up with in the next decade a scalable approach to every genetic disease where you know the mutation.”

You can find all of the podcast episodes mentioned in this podcast plus many more on our website www.genomicsengland.co.uk or on your favourite podcast app. We look forward to bringing you some new episodes with more exciting guests in the New Year but do get in touch if you have any topics you would like us to cover. I’ve been your host Naimah Callachand, and this episode was edited by Mark Kendrick at Ventoux Digital. Thank you for listening.

 

Dr Helen Hanson, Kelly Kohut, Rochelle Gold and Amanda Pichini: How are genetic tests transforming cancer prevention?

On today's episode, our guests will be discussing the CanGene-CanVar programme. Funded by Cancer Research UK, the 5-year programme aims to create an interface between NHS clinical care and research that will expand genetic testing access for those with inherited cancers.

Our host Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Dr Helen Hanson, Consultant in cancer genetics at the Peninsular Regional Genetic Service, Kelly Kohut, Lead Genetic Counsellor at the South West Thames Centre for Genomics, and Rochelle Gold, Patient Representative on the CanGene-Canvar research programme and co-founder of BRCA Journey.

 

"There is also the possibility of finding out genetic information that’s familial or inherited, which could mean that the information is not only important for the person who is being treated for cancer at the current time but also as a next step informing relatives that they might have a higher chance of getting cancers in the future due to a genetic variant..."

 

You can download the transcript or read it below.

Amanda: Hello and welcome to The G Word.  My name is Amanda Pichini and I’m the Clinical Lead for Genetic Counselling at Genomics England.  We know that cancer is a very common disease.  About one in two people will develop cancer at some point in their lifetime.  Cancer is a disease of the genome involving many changes to a person’s genome over time as well as other factors.  Only a small proportion of all cancers are inherited, but this can have a significant impact for those families who have a much higher risk of cancer and options to reduce their risk.   

Today I’m delighted to be joined by Dr Helen Hanson, Consultant Clinical Geneticist; Kelly Kohut, Consultant Genetic Counsellor; and Rochelle Gold, Patient Representative and co-founder of BRCA Journey.  We’ll be discussing the CanGene-CanVar programme which aims to link NHS clinical care and research to expand access to genetic testing and care for people with inherited cancers.  Welcome, Rochelle, Helen and Kelly to The G Word.  Thank you for joining me today.  Let’s start with some introductions.  Rochelle, over to you? 

Rochelle: Hi, everyone.  I’m Rochelle and I’m one of the Patient Reps on the CanGene-CanVar research programme.  I also co-founded an organisation called BRCA Journey that helps to raise awareness of the BRCA genetic mutation amongst both clinicians and the community, and also supports people who might be at risk of the mutation or who are thinking about testing, all the way through to maybe having preventative treatment or preventative surgery.  We support those with that decisions.  We’re not genetic counsellors but we do basically talk to people about our experience and knowledge that we have of what it’s like as a patient to be someone living with the mutation.   

Amanda: Thank you.  Could you briefly tell us what BRCA is and how you came to be a patient? 

Rochelle: BRCA is a genetic mutation that puts people at greater risk of breast and ovarian cancer.  My mum had the mutation, in fact she had two of the mutations which is apparently quite rare.  She passed away from breast cancer and just before she passed away I found out that I had the genetic mutation as well.  I personally have had preventative surgery and reconstruction to prevent myself from getting breast and ovarian cancer.  I got involved in being a patient rep so that I can advocate for people who may have the mutation, but also make sure that as many people as possible can be tested and be aware that they have the mutation and have that power to have the knowledge to be able to do something about it should they so wish. 

Amanda: Thank you so much for sharing that with us.  Kelly, over to you? 

Kelly: Hello, everyone.  I’m Kelly Kohut, I’m the Lead Consultant Genetic Counsellor at the South West Thames Centre for Genomics, which is based at St George’s Hospital in London.  For many years I’ve been working in clinical practice in genetic counselling, seeing patients and their families regarding personal or family history of cancer, offering genetic testing where that’s available, and then giving the results and helping to refer people on for surveillance programmes and to discuss risk reducing options, and also help a lot with communication within families, sharing the information from the genetic test results.   

For the past few years, I’ve also been doing my own research as part of the CanGene-CanVar programme, funded by the charity Cancer Research UK.  This has involved partnering directly with patients and other expert stakeholders to co-design a patient website to support decision-making around the genetic chances of getting cancer in families.    

Amanda: Thank you.  And Helen? 

Helen: Hi, everyone.  I’m Helen Hanson, I’m a Consultant in Cancer Genetics.  I’m based at the Peninsular Regional Genetic Service which is in Exeter.  In my clinical practice I see patients who either have a cancer diagnosis to consider whether they may have an inherited susceptibility or people who maybe have a family history of cancer to try and determine if they are at risk due to their family history.  Like Kelly and Rochelle I’ve also been involved in the CanGene-CanVar programme for the last four years.  I’ve been involved in work package three of the programme which is developing clinical guidelines with the patients who have an inherited predisposition to cancer.  I was also fortunate enough to be given some funding to carry on with this work beyond the programme in the new NIHR Exeter Biomedical Research Centre.   

Also, I’m currently chair of the UK Cancer Genetics Group, who has an aim of improving the management of patients who have an inherited predisposition to cancer.  It’s been really great to work on all these different things and try and bring things together to try and improve care for patients who do have rare inherited genetic conditions predisposing to cancer.  

Amanda: Fantastic.  Thanks, everyone.  Kelly, I wondered if you could start us off by just explaining a little bit more about how genetics and genomics is relevant to cancer.  Especially inherited cancers, why is this an important thing to talk about? 

Kelly: The availability of genetic testing has been increasing steadily over the years.  Currently from pretty much anyone who’s been diagnosed with cancer there should be some awareness around the possible benefit of knowing the genetics behind the development of that cancer and whether any genetic or genomic testing might help to choose more personalised treatments or surgical options for that cancer that’s been diagnosed.  There is also the possibility of finding out genetic information that’s familial or inherited, which could mean that the information is not only important for the person who is being treated for cancer at the current time but also as a next step informing relatives that they might have a higher chance of getting cancers in the future due to a genetic variant and that they could ask their GP for referral to genetics to be offered genetic testing and to find out about their chances of getting cancer and the choices for how to manage that.   

Amanda: Thank you.  There are clearly some important things that someone would do differently when they know they have an inherited cancer.  Helen, how can we make sure that clinicians and patients and families know what do to in these situations? 

Helen: Following on from Kelly explaining the amount of genetic testing we can offer has really increased over the last five to ten years and we’re not in a position to offer many more patients genetic testing, it’s important that we also consider what to do with that information when we discover somebody does have a pathogenic variant or a mutation in a cancer predisposition gene.  There are over 100 different cancer predisposition genes described and actually having a variant in one these genes is rare.  It’s difficult and like other conditions in medicine due to their rarity to really understand how best to manage these patients.  But what’s very important is that we try to understand how best we can help patients manage their cancer risk based on the lifetime risk of cancer and the particular cancers that they can develop and ensure that patients across the country are all being given the same advice, the same information about their cancer risks.   

Through the CanGene-CanVar programme we’ve had a whole work package which is devoted to clinical guideline development where we’ve looked at a number of these genes and looked at the evidence that is available in terms of cancer risks, the utility of surveillance or early detection of cancers in that condition, and also whether risk-reducing surgery could be offered.  Really try to bring together groups of experts to discuss the evidence because for some genes it really is quite limited due to the rarity of the condition.  The overarching aim is really to develop guidance that is relevant and can be offered in our current clinical practice and is consistent to all patients who have a variant in one of these genes. 

Amanda: You mentioned that many of these inherited cancer conditions are very rare. Is there a need to look internationally or collaborate internationally?  How do you pull some of these things together when there’s so little information?   

Helen: We definitely have found it really helpful to have international collaborations.  Some of these conditions there may be very few patients in the UK who have this condition, so each individual clinician who works in cancer genetics may have only seen one or two patients with the condition than themselves and, therefore, collaborating with international colleagues has been very helpful and we have recently published some guidance for a condition BAP1 tumour predisposition syndrome which increases an individual’s lifetime risk of developing mesothelioma, which is a type of lung cancer, renal cancer and melanomas of the skin and eye.  This is a rare condition, but we worked with European colleagues to develop a set of guidelines advising what surveillance the patient should have, so looking to melanomas, looking for early detection of kidney cancers, so having that international collaboration has been really very helpful because in the UK there are so few cases per centre of individuals who have that condition.    

Amanda: That sounds really helpful.  Rochelle, we know that shared decision-making is so important in healthcare.  How can we make sure that the voices of patients are reflected within these guidelines that were developing and that it’s clear to them what needs to happen for their healthcare?    

Rochelle: I think it’s really important that patients are involved in the development of the guidelines, first of all, and actually within those guidelines there is stuff that talks about that, being about shared decision-making.  A lot of these guidelines are in a language that are quite a clinical language that is not necessarily accessible to patients themselves.  It’s really important that they’re part of the creation of them but also that there are things out there that enable people to understand what are these guidelines about, what do these guidelines actually mean in practice.  When you find out that you have a particular genetic mutation, of course, the first place you probably go is Google.  You find a hell of a lot of information and you find all sorts from different countries and different people and different organisations.  You’re like which is the thing I need to look at, which is the thing that actually tells me what’s going on, which is the thing that really helps me to understand what this actually means for me and what should happen to me?  What is the pathway for me, etc.   

I think we also need to recognise that people have different levels of health literacy as well.  I am someone who can probably navigate my way around a very complex system, which is the NHS, maybe better than other people.  But there are plenty of people out there who this is new people, this is a completely new thing that’s happened to them, a completely new thing to understand.  If you’re not used to being part of health systems and navigating your way around it, it can be quite scary.  What does mutation mean?  What does it mean for me?  What does it mean to my future?  What does it mean for my family?  All this information.  There needs to be something somewhere that talks about this, some sort of lay way and helps people to understand what this means for them and helps them to engage with it.  To some extent, that’s where my organisation was born from, that thing about having somebody who can just talk about it in normal words, in normal terms and normal views of what these guidelines actually do mean.  The fact is they are just guidelines, they don’t tell you this is what you do.  You’re this person, you’re in this circumstance, you do this, it doesn’t.  There’s some ambiguity there that needs to be navigated by the patient and they need support in order to do that. 

Amanda: That’s a great point.  Having previously worked as a genetic counsellor, also seeing patients with inherited cancer conditions, it really strikes you how individual each person’s journey and decisions are.  They’re thinking about all kinds of factors in their life or in their family’s life.  Navigating through that and understanding do I have surgery or do I have screening and how do I make decisions about this is based on my previous experiences and so many other factors.  Having access to different sources of support to help people navigate through that feels incredibly important.   

We’ve been talking a bit about inherited cancers in general, but you’re all here because you’re involved in the CanGene-CanVar programme.  Kelly, could you tell us a bit more about what that is and what he programme is aiming to achieve? 

Kelly: The CanGene-CanVar programme is a five year grant funded by Cancer Research UK.  It involves six different work packages, so lots of experts all around the UK have been allowed to have some dedicated time to work on specific areas where there hasn’t been enough resource put in in the past which has resulted in a real gap between the research and the current findings and actually using that information to benefit patients by bridging the gap and putting those research findings into clinical care.   

My programme is in work package four which is co-designing patient resources which are decision support interventions.  Basically, it’s a website and it can be printed as a booklet and it’s interactive and it’s up to date and it’s personalised to help convey the complicated information about genetic cancer conditions in a way that’s meaningful and patients can understand, and it helps them with their personalised shared decision-making.  The CanGene-CanVar programme is underpinned by the patient reference panel and they’ve been involved, including Rochelle and others, from the conception of the idea of the programme and all the way through with various different activities helping to look at documents as they’re developed, before their finalised, and giving input in focus groups and one-on-one and email conversations.  They’re called upon frequently to share their lived experience and say what’s important to them when they make decisions and that’s really helped to drive the direction of the research and inform the results before they’re published.    

Amanda: That sounds like a really helpful approach to developing something in a way that’s really working very closely with patients and participants.  Rochelle, it sounded like you were involved in that.  Can you tell us a bit about what that was like from your perspective? 

Rochelle: It’s really rewarding, it’s really motivating to be actually one of the patient reps in relation to this.  I don’t want to make my colleagues from the team blush, but it’s just such an inclusive environment where as a patient is really welcomed, really heard, it’s very much a partnership and that’s been really, really important and it makes you feel valued as a patient and actually the importance of the lived experience the patient view has really been prominent in this.  I would say that’s why it’s helped develop such a useful tool, the fact as a patient people are really valuing and taking into account our lived experience, our views, our understanding.  It’s been quite fun in some of the sessions.  There have been some good debates between us and some of the clinicians and it’s been really good and really useful.  I think some of the people who maybe haven’t encountered a patient panel before and engaged with patient’s lived experience have probably learn a lot from it because we are pretty empowered to use our voice in this.  It’s been a really great experience.  

Amanda: I’d love to dig into those debates a bit more.  Kelly, were there things that you changed in the decision aid as a result of some of those discussions or as a result of that input that maybe surprised you?  

Kelly: We have made changes based directly on what we’ve learned from the patients presenting their lived experiences.  They’ve been very open and honest with us.  Like Rochelle, I felt so privileged to be part of this real partnership with the patients.  As a genetic counsellor who had many years of experience in clinical practice before moving into this research role, I’ve been really surprised but also gratified by how much I’ve been able to learn from the patients in a different way because I am sort of taking a step back, I’m there as a researcher and not directly as a clinician looking after someone one-on-one in clinic and just thinking about their specific needs at that time.  But because I’m hearing from people from all different situations, different parts of the UK and other countries and maybe it’s 10/20 years since they had their genetic diagnosis are actually getting a bigger picture of their care needs that we might not have heard about as the clinicians on the ground because they might not be coming back to tell us.  If we haven’t opened the door to that conversation about their personal situation or who’s influencing them or what’s important to them when they make decisions, we just might not have learned about the thing they’re grappling with and they’ve gone off and maybe Googled, they’ve found a patient support group or something else to support them.   

In my research and in my interviews and the focus groups, all of the activities I’ve been learning about the gaps in care, what might be needed to address that.  The decision aid has not been yet ruled into clinical practice but we’re very keen to get it out there and everyone wants it and wants to use it.  We want to make sure that we’ve developed it in a robust patient-centred way as much as we can for us before we put it out.  It will always be updated and go through refinements, but hopefully in the New Year we will be able to let people start using it in the real world situation. 

Amanda: That’s great, I’m sure you’re looking forward to that. 

Helen: I was just going to add to that in terms of the guideline development we’ve had a number of consensus meetings where we’ve made decisions about guidelines, for example, genes that can be predisposed to ovarian cancer and we’ve included patients from the patient reference panel and from other patient groups in those consensus meetings.  Again, as Kelly said, that’s been so helpful because it’s really brought something to those discussions and it is a different perspective than when we see patients in clinic because often we’re seeing them at the point of genetic testing or maybe for their results, but actually that doesn’t give us that overview of the whole patient journey and the whole patient experience.  I think that has been really one of the benefits of this programme and Kelly has been really pioneering the co-design of patient information leaflets, decision aids with patients.  Rather than clinicians designing things for patients that we think that they will understand, it’s actually working with patients from the start to get things right the first time.  It’s been a really great part of this programme. 

Amanda: Rochelle, did you want to add something further here?  

Rochelle: Yes.  I think one of the sessions that we had as a patient and clinician and researcher session that really stood out for me was when we started looking at how do people make decisions. We had academics and researchers who’ve looked at how do people make decisions, talk about the knowledge base and the research base that we have about it.  As a larger group of patients we got together to discuss about how have we made decisions.  It was really interesting because I don’t think I’ve ever reflected on how I made the decision and what came from that in terms of what I did about having my mutation.  Hearing about how other people did as well, that session really does stick in my mind and actually I learnt a lot as a person about decision-making theory but also about myself and reflecting on how I make decisions.  So as a patient involved in this, it’s not always about what I bring to this but actually as a patient rep you get a lot from it, too.  I’ve learnt a lot from the colleagues that I’ve worked with. 

Amanda: That’s fantastic.  It’s really great to hear the careful thought that’s gone into this, a real excellent example that hopefully others can look to.  I think, Kelly, hasn’t your work won an award recently as well? 

Kelly: We as a whole team won an award from the academic health science network and the NHS Confederation, it’s called the Innovate Awards 2023.  This was for excellence in patient and public involvement in transformation and innovation.  Yes, it was a chance to showcase the really positive experience that we’ve had.  I think on all sides we’ve learnt a lot from each other and just to hope to inspire other researchers and clinicians to take this co-design approach with patients because we all benefit from it so much.  We think that the resources, the guidelines, everything that we develop will be better from the start if we work together throughout the project.   

We’re really hoping to encourage others to consider from the beginning of their idea about a research programme or clinical development to bring the patients in right at the start, because they can really help to guide where things go next and then throughout.  Even through to publications being on, committees, being co-chairs, presenting together at conferences, that can all help to really share the experience and the benefits that we get from the partnership. 

Amanda: That’s great, congratulations.  Coming back now to some of the aims of CanGene-CanVar and trying to bridge that gap, as you said, between research and clinical care, I guess that means there are some needs that still aren’t being met that are falling through that gap at the moment.  Helen, from your perspective what are some of those unmet needs that we currently have or areas that are still needing improvement?   

Helen: I think there’s still lots that we have to learn, particularly about individual risks for patients.  We might have patients who all have a pathogenic variant in a certain gene but their risks might be slightly different due to factors that can modify their risk.  Trying to understand some of those risks better so that we can really have much better informed discussions with patients about their lifetime cancer risks I think would be really helpful.  Work package one of the programme is really focussing on that and looking at some of the information we have through national registries and trying to understand risks for specific genes better, which will help our discussions with patients, and then we still need to understand, which is more outside the programme, more how surveillance, so early cancer detection through screenings such as mammograms or ultrasounds for different cancers can help detect cancers early. There’s still lots of information that we need to learn.   

I think Kelly’s decision aid which has been focussed on Lynch Syndrome, I think that can be translated across lots of other genetic conditions, because for each gene there is a different set of decisions.  For some of the genes that we developed clinical guidelines for we might be recommending slightly different management or for some of the genes we’ve recommended maybe a minimum and an extended level of surveillance, particularly for a gene called DICER1 where we’ve offered different options in childhood.  Decision aids would potentially help in some of those other genes building on the work that’s already been developed as part of the programme.  Although the programme is coming to an end in the next year, I think there’s still lots of work to be done in this area.  

Amanda: It really sounds like you’ve all been collectively improving how much this work is worthwhile, so that’s great to hear.  Rochelle, how about for you, are there areas that you would see as unmet needs or areas where we or research can improve to help patients and families with inherited cancers. 

Rochelle: Similar to some of the stuff that Helen was saying, knowing more about what happens when people have different types of treatment, different types of surveillance and monitoring and stuff like that, I think there are things that are evolving all the time.  I think in the end when you think about gaps, there’s nothing that’s going to be written down on paper that says if you have this, do this.  In the end, every single patient is an individual with individual circumstances.  I think until we actually know that if you do this, this happens and this happens, this is going to be your chances of survival if you go through this route.  Even then when you’ve got the chance of survival, that’s literally just a probability, it’s not a binary this will happen or that will happen.  There’s always going to be a need for discussion, there’s always going to be a need for these brilliant genetic counsellors that we have to talk us through some of those complex decisions that we have to make.  I think, yes, we’ll get more information, we’ll get more evidence, we’ll get more understanding of treatments that work best for different people, and we’ll get it out there and we absolutely do need to do that.   

Even when you have all the information you need, even if you made a solid decision, I mean, when I found out I had the mutation immediately I was like, right, that’s it, I’ll have preventative surgery after what happened to my mum.  It was an absolute no-brainer for me.  For other people it might not have been if they were at a different life stage.  I’d had my kids, I didn’t need my ovaries, I didn’t need my womb, it was pretty clear cut.  Even then when I was thinking about the different treatment and when to have that surgery, I got most of my information from bumping into somebody in the ladies’ toilets who has been through it before.  I think there’s always going to be a need in terms of being able to have those conversations to take in all the information you do that and make some sort of informed decision.  What came out of that decision-making workshop and all the other things that we did about probabilities, it’s all just a model.  It’s a model of what might happen.  The thing is, all of these models, they’re all wrong, they just help you maybe make a discussion or a decision that might be right.  You just never know.  I still don’t know if the decisions I made were the right decisions either.  There needs to be that space for people to consider their options, you’re never going to get the definitive answer.   

Amanda: An important message there.  We talk a lot about using digital tools to be able to do things better at scale, better ways to give information, but I think what you’re saying is we can’t replace certain elements of human connection, we can’t underestimate the value of that.  You made a really good point earlier as well about how so many of these decisions have uncertainty and it can be really difficult to navigate the complexities of a health system.  Perhaps even more challenging if you have struggles with health literacy or if you are an underserved group in some way or another.    

Kelly, I think you mentioned that some of your research has also touched on developing information for underserved groups.  Can you tell us a bit more about that? 

Kelly: We recognised that there are many underserved groups that are not represented in research, in literature, and applied for additional funding to do some specific targeted projects in the community.  There were a couple of examples I can mention.  One was inspired by colleagues at the Royal Marsden who made some videos about prostate screening and the had black men and their family members talking about this in a relaxed barber’s shop setting.  Through reaching out into the community I was connected with Lee Townsend from Macmillan who’s been making these barbershop videos around London for the last seven years.  He’s focussed on a number of topics like mental health, vaccination and cancer.  We connected and it was really about making that connection in the community, him as a trusted leader, and having formed partnerships with some of the barbers who opened up their barbershops for filming these sessions and went way beyond that.   

One of them has actually trained as a counsellor himself because he said men are coming for a haircut and actually they have a bald head, they don’t need the haircut, they’re coming actually for the chat.  Because it’s benefitting their mental health and they felt able to open up about topics that they wouldn’t talk about even at home with their family members or with their friends, such as symptoms of cancer, going for cancer screening or presenting for treatment if they were symptomatic.  It’s really powerful.  We’ve actually filmed six videos with black and minority ethnicity patients, talking about their cancer experience and they’ve really both helped others by setting an example that it’s okay to talk about these things.  Also, through the process an added benefit was helping themselves, so it was peer support.  When they came to the barbershop to film their stories, they didn’t need to stay for the whole time but they did stay for the three hours.  They said afterwards how helpful it was just to hear others in a similar situation sharing their stories.  One of them told me he’s got up on stage and shared his cancer journey and he’s been going to these patient groups and talking when he didn’t feel able to do that in the past.  It’s been a great project and we’re going to be adding the videos to the CanGene-CanVar patient decision aid website soon. 

Another thing that we’ve done in the diet and lifestyle section of the website where it talks about things that people might do to lower their chances of getting cancer have partnered with Professor Ranjit Manchanda who had some colleagues in India and made some infographics that specifically depict patients of a South Asian heritage and the types of foods that they might be choosing to give examples of how they might for example try to get more fibre in their diet to lower the chances of getting bowel cancer or trying to eat more fruits and vegetables or drink less alcohol.  It shows images of Indian patients.  What people have told me in my research, my interviews, focus groups, is they tend to go and try to search for something that means something to them, so they’re looking for someone like me.  One of the patients I filmed she said that she had breast cancer as a young black woman and she was only middle-aged women on the websites.  She thought why is this, do black women not get breast cancer or young women like me?  For her to share her story was very brave but also has the potential to help a lot of other people in the community.  

Amanda: That’s really powerful, so understanding those nuances in different cultures or communities or groups is just so crucial to really being able to also develop information or messages or provide care that’s going to really reach those people where they are, I guess. 

This has been a really fantastic conversation.  If we could end with a final question, it would be great to hear from your perspective just one thing that you’d like to see in the next five to ten years when it comes to care for inherited cancer susceptibility conditions.  Helen, let’s start with you? 

Helen: I think that in developing the guidelines one of the things that we’ve had to struggle or grapple with is a lack of evidence and the lack of the data that’s available for some of these conditions.  I’m really hoping that over the next five to ten years that we will see much more data on cancer risks and outcomes of surveillance progress for people who have an inherited predisposition.  Then we can utilise that information to be able to share with patients to enable them to make best decisions about their care.  There’s a number of initiatives that are currently underway thinking about how we might better collect data on patients with inherited cancer predisposition in the UK, through registries, so I am really hoping that we manage to get some useful data that we can then use in our discussions with patients going forward. 

Amanda: Thank you.  Kelly? 

Kelly: I think that over the next five to ten years as awareness and availability of genetic testing continues to increase, we know that there will be more and more families identified who have a higher genetic risk of getting certain cancers.  We can’t replace that personalised counselling that takes place, face-to-face or sometimes telephone and video appointments with a healthcare profession.  So there are more resources needed for the NHS to deliver this.  To compliment that, the patient website decision aid that we have co-designed is one way to help.  What patients tell us they would like, access to a central trusted source of information that’s up to date.  Importantly in genetics it’s very fastmoving, there’s a lot of research, guidelines are changing, and it’s very crucial to have information that’s correct and relevant for people, and also meaningful.  We can only do that by partnering together with patients and co-designing things rather than designing them and asking them afterwards if they’re useful.  It’s a partnership all the way through that we all benefit from.   

As I said earlier, it’s not a one-size-fits-all, decision-making is so personal and shared decision-making is recommended but we don’t always have enough time in clinic to really address all of the issues that the patient might not have even thought about themselves.  Having something like a patient-facing resource website booklet that they can look at in their own time, prepare for their questions that they really want to focus on in clinic, it might help give them the confidence to bring something up that they might not have otherwise.  It’s about a number of different ways of helping to support people.  We’ve identified that there are gaps in care that we could try to help address if we have more resource in future.  Those are my aspirations.  Thank you, Amanda.  

Amanda: Thank you.  And Rochelle, to you? 

Rochelle: I think for me I would like to have as many people as possible to understand or know about their genetic mutation status.  We know people don’t even know about the fact that they may have a genetic mutation that may make them more susceptible to cancers, and we know that even then if you do can you get access to testing to know whether you’ve got it or not.  That is the most important thing.  My mum, if she’d known that some of this was related, if she’d had that awareness that breast and ovarian cancer in your family was related to potential genetic risk, maybe she would have pushed harder to get testing and maybe she wouldn’t have been tested when it’s too late.  In the end, all this knowledge and empowering people with knowledge, whether that be about empowering people with the knowledge that they may have a genetic mutation, there’s a possibility of the genetic mutation, that these things are related and empowering people through the knowledge of knowing their genetic mutation status, all that is something that saves lives.  From my view, it undoubtedly probably has saved my life and so my hope for the future is that we can empower more people like me and we can save more lives.  

Amanda: Thank you for our guests today Dr Helen Hansen, Rochelle Gold and Kelly Kohut.  If you enjoyed today’s episode, we’d love your support.  Please subscribe to The G Word on your favourite podcast app and like, share and rate us wherever you listen.  I’ve been your host, Amanda Pichini.  This podcast was edited by Mark Kendrick at Ventoux Digital and produced by Naimah Callachand.  Thanks for listening.   

 

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

This year as we celebrated our 10-year annivesary, the NHS celebrated a significant milestone of 75 years. In this episode we reflect on our journey over the last 10 years, including the impact of embedding genomic testing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today.

Host Rebecca Middleton, Vice Chair of The Participant Panel at Genomics England is joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England in this special episode of the G Word.

 

"To date, we’ve had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they’ve been given or make treatments available. That is a real positive benefit from that pipeline to individual patients."

 

Listen to the other episodes in our 10-year series:

• Shelley Simmonds, member of the Participant Panel at Genomics England, speaks to Louise Fish, CEO of Genetic Alliance UK, and Amanda Pichini, clinical lead for genetic counselling for Genomics England as they reflect on how the patient journey has changed over the last 10 years for those living with rare conditions.
• Dave McCormick, member of the Participant Panel at Genomics England is joined by Jenny Taylor, a valued member of our research community, and Professor Matt Brown, our Chief Scientific Officer, discussed the last decade of genomic research at Genomics England.

 

Transcript

You can read the transcript below or download it here: Transforming-the-NHS-with-genomic-testing.docx

 

Rebecca: Hello and welcome to the G Word. My name is Rebecca Middleton and I’m the Vice Chair of The Participant Panel at Genomics England. On today’s episode, I’m joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England. Today we’ll be reflecting on the last ten years of genomics, including the impact of embedding whole genome sequencing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. If you’ve enjoyed today’s episode, we would love your support. Please like, share and rate us on wherever you listen to your podcasts.

Thank you, Sue and Rich, for joining me today as we look back at how genomics has developed in the NHS over the past decade and impacted tens of thousands of lives. It all started with the creation of Genomics England and it’s first groundbreaking initiative, the 100,000 Genomes Project, which sequenced around 85,000 NHS patients affected by rare conditions or cancers and led to groundbreaking insights and discoveries for so many families. I’m one of those rare condition patients and my genome sits in the National Genomics Research Library besides thousands of others. Along with the project, I’ve been on a journey over the past ten years and I’m still hopeful that through time and further scientific discovery, my family and many others will get the answers they need for the future.

Today is a chance to reflect back over the progress of the past ten years and to look forward about what’s next for genomics, for genomic science, the genomic service, and for the patients and families it impacts. Sue, welcome. If we can come to you first, and it’s a very big ask coming up, but can you briefly sum up your critical role in genomics over the past ten years and talk us through how you’ve shaped the service in the NHS to date?

Sue: My role in genomics in the NHS has actually been much longer than ten years, because particularly genetic services have been part of the NHS journey since it was formed in 1948. As Chief Scientific Officer for England, part of my responsibility since I was first in that post in the Department of Health at that time and now subsequently in NHS England, but still with a crosscutting health and social care role, genetics and genomic services actually sit under the remit of the Chief Scientific Officer for England. Shortly after the 100,000 Genomes Project was announced and that the NHS would be a major contributor to the 10,000 Genomes Project, I was asked to lead the NHS contribution to the 100,000 Genomes Project. My role has been both of leading the NHS contribution to the 100,000 Genomes Project, and then as Senior Responsible Officer for Genomics in the NHS in introducing the NHS Genomic Medicine Service to the NHS and its subsequent role in delivery and in supporting research and other initiatives.

Rebecca: Rich, over to you. Ten years ago I believe your role was very different and you were in clinic, so how has it changed over the past decade as genomics has embedded itself into the NHS?

Rich: That’s right. As you say, I’m a doctor by background and ten years ago I was consultant in clinical genetics at Great Ormond Street, where I still practice, I still do one clinic a month, but my role is primarily sat there meeting families with a child normally with some symptoms or some problems which people thought might be those of a rare condition and thinking about how we did that testing. At that time I was beginning to think about how we use in Great Ormond Street some of the newer technologies that were coming along. Using, for example, gene panels to help diagnose children who had epilepsy of early onset. Eight years ago, I joined Genomics England, where I could see the work of Genomics England and the partnership with NHS to deliver the 100,000 Genomes Project was something where at national scale we could do something, which at that stage I was just thinking about within one hospital setting. That’s really changed things for me in clinic, but also my role in that has changed. I joined Genomics England originally as the clinical lead for rare disease, so bringing that specialist clinical expertise to give advice on how we establish the rare disease component of the 100,000 Genomes Project.

More recently, in my role as Chief Medical Officer, I’m actually now as interim CEO thinking about how we’ve made that transition from the learning that we’ve gained through the 100,000 Genomes Project to working in partnership with the NHS and Sue and team to play our role in supporting their NHS Genomic Medicine Service. The next phase, if you like, or questions for us to make sure that we are still thinking in a forward looking way about how genomics can do what we believe it can do to be really there in the mainstream for everyone in terms of healthcare.

Rebecca: And it really has been quite a journey over these past ten years, moving from a research project with 100,000 Genomes Project to a live clinical service and all the challenges that that must bring. Sue, what are you most proud of, what are those challenges that you’ve had to overcome and how do you see genomics medicine service moving forwards so it can help even more families?

Sue: I think in answering your question, first of all, the Genomic Medicine Service is much broader than the whole genome sequence service that is delivered in partnership with Genomics England, and I’ll come back to that. In terms of what I’m most proud of, I think when we started the 100,000 Genomes Project there was a view that we shouldn’t involve the whole of the NHS in recruitment and in feedback to participants. I pushed really hard to have the whole of the NHS involved, recognising that if we were going to enter into a transformative project particularly for the use of cutting edge technologies by whole genome sequencing and the analytics that went alongside that, if we only started with a small number of centres we wouldn’t get the transformation that was required within a whole health system.

I’m really proud of the NHS contribution because the number of patients that were recruited over the period of time where we didn’t start active recruitment until 2013 and then we completed early in 2019, to deliver this from routine care in the NHS in terms of recruitment and then for feedback I think is something that is unsurpassed by many other research projects, let alone research initiatives in genomics across the world. So while this is a world leading project, it’s also I think a world leading contribution from the NHS from its routine care position.

I was also proud myself to be a participant in the 100,000 Genomes Project within the cancer arm of the project and being able to speak at different public events around the benefits of sharing data through the National Genomics Research Library, in that it’s a benefit that is much broader than you as an individual and has the potential to impact on thousands of people.

The other thing I’m most proud of is introducing the NHS Genomic Medicine Service because we still remain in the NHS world leading. Of course, a key part of that is that we have whole genome sequencing now available within routine care, within the NHS for patients with rare and inherited disease and cancer. Obviously not for all of those patients, but for the group of patients that fit within those broad-brush clinical groupings where there is the most need, but also the ability to deliver a diagnosis compared to what we could do from standard of care testing.

I think it’s those two halves for me with myself being a participant and being part of the NGRL right in the middle. Because, of course, from the NHS Genomic Medicine Service, which is what many other countries are grappling with, as soon as you introduce a whole genome sequencing service within a health system, how do you also continue to support research and continue to populate a research database that can be accessible, access is approved and in a safe data environment, how can you continue to support that?

Rebecca: Over to you now, Rich, on what you’re most proud of for yourself, but also for Genomics England and being the custodian of people’s data, that people have given their data through the 100,000 Genomes Project and they continue to give their data through the GMS. If you could pick up also on the research side, so the role that Genomics England has played in the development of the Genomics Medicine Service and the genomics within the NHS, but also in the wider ecosystem as well in terms of driving discovery and driving answers for the many families and for many patients out there who are still looking for those answers.

Rich: I think really there is one word that I come back to quite a lot which is the word together, where the journey that we’ve been on as Genomics England, me playing my role at Genomics England, but all of those involved across the ecosystem, that key partnership that we have with the NHS and with our participants, but also broader than that into the other people involved in delivering a live clinical service now that we support the whole genome element of. Also, collaborators in research, whether that’s in academia or industry, this is a team sport. What I’m proud of most is the impact that we’ve had together and recognising that when this journey started there was a real vision about the potential that genomics could bring in the coming years because of the changes that came. For example, the next generation sequencing technology, but also the changes in ability to hold and analyse data at scale. I think rightly no one would have pretended to know what the journey was.

I think the thing I’m most proud of is that we have navigated that together. In a way, we’ve continued to learn and we’ve learnt from the challenges that we have encountered, whether it’s through delivering the 100,000 Genomes Project or our work since, because there always will be challenges. The reason that we’re so proud of the impact that there has been is because we recognise it’s hard to do. I think that point particularly of linking healthcare and research is absolutely key. That’s something that we’re working with Sue and the teams across the NHS are absolutely committed to and recognising that this is an ongoing learning area. That means learning how we do every element of it, but it also means that marrying clinical care and research is absolutely critical to getting the best outcomes for the system as a whole and for participants/patients individually.

We’ve learnt how to set up a system that works in that way. We’ve worked through the consent models that patients in the NHS receiving routine care are comfortable with. The models of presenting data de-identified for researchers to use for purposes that those participants are comfortable within, as we call it, a trusted research environment, is a model that comes with challenges in terms of the data access for researchers but is one that is really broadly accepted and we can get to work at scale. I think it’s that ongoing learning and that we’ve now I think shaped an approach to genomics across clinical care and research which no one would say is perfect, but we definitely understand that we’ve learnt about a model that we can keep iterating on and, crucially, we’ll keep learning for participants present and future.

So that, as you say, Rebecca, one example of that situation is where families have had a test, whether that’s through 100,000 Genomes Project or more recently through the NHS Genomic Medicine Service, if today’s knowledge can’t find the answer in terms of a rare condition diagnosis, we know that one really important element of that research offer is that researchers will continue to look for answers. If something is found that is relevant, that can be fed back to the clinical laboratories to look at. If there is something that is clinically actionable, that can be reported.

Rebecca: Thank you, Rich. I suppose, Sue, we’ve had a decade of navigation, a decade of learning and a decade of adapting to really take us from the 100,000 Genomes Project to the NHS Genomics Medicine Service. There have been challenges along the way, no less we’ve had COVID to deal with, a global pandemic. What other challenges have you had to overcome to embed a workable world class service within the NHS, how have you navigated that with your partners such as Genomics England?

Sue: What’s been really important is actually understanding the challenges. I see the challenges more in the sense of the transformation that we need to drive rather than them actually being challenges. Some of the transformation that was driven through the 100,000 Genomes Project we’ve actually baked into the Genomic Medicine Service. For example, during the 100,000 Genomes Project we understood the importance of clinical leadership; particularly if genomics was going to be embedded across the NHS for patient benefit, then it would involve more clinical specialties than clinical genetics. Through the 100,000 Genomes Project, we really drove leadership and engagement across multiple clinical specialties.

We also drove this whole model that Rich talked about earlier about data sharing for broader benefit, and that benefit has then transferred over into the Genomic Medicine Service. We also recognise that if we were going to hold genome sequence a number of the processes, technical processes that happen within now our genomic laboratory hubs, needed to be standardised with quality and also external quality assurance at the core. That’s right from taking a sample from a patient, extracting DNA, the sequencing methodology, whatever that is, whether it’s whole genome sequencing of the type of testing within the NHS, so large gene panels, whole exome sequencing, or even smaller gene panels and other types of testing, that had to be consolidated and standardised. When results are returned we needed a standardised approach to results and interpretation. Across all of those areas if we’re trying to drive a national approach as we were in the 100,000 Genomes Project and we’re now in the Genomic Medicine Service is having an external quality assurance process that can look externally at each of those components that has been an important learning from the 100,000 Genomes Project into the Genomic Medicine Service.

A key other element of transformation, and I hope you’ll agree with this, Rebecca, was the involvement of members of the public and also participants. So right through the 100,000 Genomes Projects from Genomics England establishing The Participant Panel, through to the involvement of patients and public throughout the national programme for the 100,000 Genomes Project in NHS England, through to the genomic medicine centres that we created at that time, all of that has now been reproduced in the Genomic Medicine Service. So, patient and public involvement is a key part of the delivery mechanism.

Finally, we’ve had to change and continually adapt and develop the underpinning data and digital infrastructure in the NHS. Initially in the 100,000 Genomes Project we standardised the data that was collected for rare disease. We introduced the use of terms called human phenotype ontology system that enabled individual patients and their presenting characteristics to be classified; that’s continued on into the Genomic Medicine Service. But still more work to do in the 100,000 Genomes Project, we have to get multiple informatic systems to talk to one another. As we moved into the Genomic Medicine Service, we’ve both with Genomics England had to develop the analytical pipeline. We’ve had to develop a system that’s enabled whole genome sequencing, for example, to be ordered and then to be returned after sequencing and the semi-automatic analytical pipeline in Genomics England to generate a report that could then be looked at and interpreted in the genomic laboratory hubs and returned to patients.

What’s been a key part of that has also been the establishment of genomic multidisciplinary team meetings that came out of the 100,000 Genomes Project, but now is embedded into the Genomic Medicine Service. Of course, the difference between the 100,000 Genomes Project contribution and now in the genomic medicine service is to ensure there’s equity of access across the country in terms of the testing that is provided. A key part of the way in which the testing is offered is that introduction of the National Genomic Test Directory that sets out the standardised offer that will be funded by NHS England. That’s across where an inherited disease or cancers, as well as common diseases and some other pharmacogenomic applications.

The challenge always is standardisation, equity of access, and the infrastructure and leadership that makes this happen, together with developing a workforce that is genomically enabled so that it can spread out beyond that clinical genetics specialty into those multiple specialties to make sure that it’s embedded. So remain in terms of some of the challenges around making sure that we change clinical pathways where genomics means that we can do things much earlier on in a patient pathway and get a definitive result and intervene. This is particularly important in cancer, but it’s not just cancer, it’s also in rare disease.

Secondly, it’s about how do we develop the whole of the NHS workforce. We have 1.3 million people that are directly employed by the NHS. There are another 600 that actually are associated with the NHS through the contracts that they hold. It’s a huge task that we still have to undertake to make sure that genomics is available to all. There are two other elements, one we have to continue to take the public with us, and I think we’ve learnt from COVID that the public does understand now the importance of molecular tests. But there’s still more to do as we use genomic information more broadly across the NHS and to drive treatment decisions that might mean that a patient thought they were going to get one cancer drug but they’re going to get another because their genomic mutation says treatment B might be better for them than treatment A. We have and will continue to have a number of ethical issues that will arise as we consider whether it’s some of the research initiatives that are undertaken or whether it’s some of the decisions that might be made within the NHS Genomic Medicine Service or for the use of genomics.

That’s just a few, but it pulls it together from what we’ve learnt from the 100,000 into the GMS, what else the GMS is doing, and what some of the challenges are that remain.

Rebecca: And a great deal has been done. There are a number of key challenges ahead. As you say, it’s been a learning process, it’s been a navigation process, but it’s been driven by the people, by systems, by people, and they have played a critical role and will continue to play a critical role in ensuring the success going forward. I sit as the Vice Chair of Rare Conditions on The Participant Panel. Rich, if I can come to you next, how has the patient voice, how has The Participant Panel but the wider patient voice been heard and how are their view, their needs being reflected in addressing these four big sort of buckets of challenges and how are we learning these lessons going forward thinking of the new projects? For example, the newborn genome project, The Generation Study, could you give us some examples of how that learning is going forward and we’re learning from the past but preparing for the future?

Rich: I think it comes back to one of the really key words here is transparency and transparency in a number of ways. One of those is about the fact that this is a journey we’re all on together. So, one of the things that was there right from the beginning of the 100,000 Genomes Project before I arrived was putting participants absolutely at the centre of project and the design and then in time that came for us in Genomics England wider in terms of our organisational governance. Establishing The Participant Panel on which you’re a co-chair I think was really important for us early on to make sure that participants whose data it is we hold, it’s no one else’s data, it’s our participants’ data, are there driving and at the centre of the decision-making process, for example, through our Access Review Committee around who accesses the data. Participants sit on various of our governance groups and that’s a template which I think is one that people have seen in various fields as working really well. It’s one that Sue has touched on as being looked at and has provided useful input as to how patient and participant involvement has been set up in the Genomic Medicine Service.

I think recognising that much of this is us all collectively finding the right path forward is how we approach every question that we tackle. Sometimes that’s around really very practical questions. So, for example, Rebecca, you will know we often come to you guys about how we phrase a letter that might go out to participants, because recognising that from the inside of an organisation you see things one way but you might not recognise some of the nuances that are really important. Through to thinking about the really important questions around how we should set up access and safeguards around access that are there and, again, having participants sat on our Access Review Committee is crucial. And on to finding our way in new areas where the Newborn Genomes Programme I think is a really nice example where in many ways it’s quite similar to the 100,000 Genomes Project in that it’s a research study and it’s delivered in partnership with the NHS. It’s asking big questions around whether genomics can be used in a particular setting and if so, how could we use it? I think a really critical part of that and one that’s been, as you know, sat in a number of the different strands and in the overall governance for the programme, Rebecca, having participants guide us, whether those people who like yourself are already part of the national genomic research library or whether they’re people who might join the study themselves, or whether they’re people with a different perspective that is important to include, including that engagement work as well as just with the broader public as part of the study is absolutely crucial.

Before we even started the design of the study we set out with a public dialogue around attitudes to do with genome sequencing in newborns jointly with the National Screening Committee to understand where public views were to allow us to do a bit of a deep dive, not just a superficial vox pop view on what’s your attitude to a one-liner question, but really to work with people on understanding some of the nuances here. There’s a lot of nuance in most of the questions that we’re engaging with, and then through the programme into different elements, whether that’s designing the materials for consent or whether it’s understanding how to practically design the process for contacting families or feeding back findings as part of the study, making that part of the process rather than a separate endeavour I think is really crucial.

One of the words that I often hear people use when talking about challenging questions around how we make advantages in medicine is around explaining what people are doing. I actually think that’s a really interesting word which I don’t like. Most of the time this is about dialogue and it’s about discovering together what we are doing and it’s not people sit in with the best of intentions and with great expert knowledge in a closed room to decide what’s the best approach, which is often an easy way to think about how to design a research study, for example, but this needs to be an active process where there’s genuine dialogue and we learn and find our ways together.

Rebecca: Some great examples there, Rich, of how powerful the participant and the patient is in the designing future services for even more patient and participants going forward and ensuring how needs and views are reflected. But, Sue, it doesn’t just happen in Genomics England, there are patients and participants across the GMSAs as well, which is fantastic to see and I sit on the panel at the East GMSA as well. How important was that for you to establish that as part of establishing the Genomics Medicine Service? How important was that for you to ensure that the patient and participant view was there locally as well?

Sue: So, I think we learnt from the 100,000 Genomes Project about the importance of patients and participants being part of the research element of the 100,000 Genomes Project and how that was designed, how the different pathways were put in place. In NHS England the patient is at the centre of everything when we come to our services. In all of our major programmes we have patient representatives, patient for an ongoing discussion with patient groups. This was both building upon what we’d created together with the Genomics England Participant Panel in the 100,000 Genomes Project, but then making sure that it fitted with the new genomic medicine service infrastructure that NHS England commissioned from 2018 onwards. It was making it a key part of that, making sure that coproduction with patients and families and really having a temperature check on an ongoing basis about the experience of patients and families of the genomic medicine service that they were experiencing has been a key component of our infrastructure and how we’ve put the infrastructure together. I always think there is more we can do, there’s more we can do to monitor the experience particularly of services. That having been said, we will continue to drive forward the involvement of patients and families in the future iteration of services, whatever that might look like.

I think if you put patients and families at the centre, that actually helps you determine the type of services that need to be commissioned nationally, the type of concerns that people have of the service and the experience that’s feeding up, but it makes sure that patients and public representatives are part of all the important governance groups. For me, that’s where the conversation needs to happen, it needs to happen both at an individual service level but through all the levels of governance that actually govern a service that is commissioned by the NHS in England for the population that is being served. Even if we haven’t got it totally right, I hope that we’ve got it as a key component of all of the services and set out in commissioning specifications such that it’s a requirement as is having the technology in place to deliver a bunch of genomic tests.

Rebecca: Thank you, Sue. The Genomic Medicine Service is unique in the way that it provides a clinical outcome that is an answer for a patient, and also includes the option of joining the research library which supports further discovery. What are the benefits of this?

Sue: The positive benefit of having the National Genomic Research Library has been through the researchers, scientists who’ve been granted access to the data. To date, we’ve had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they’ve been given or make treatments available. That is a real positive benefit from that pipeline to individual patients. But also the evidence that’s generated enables us to evolve the genomic test directory. It enables us to add to genes if new genes have been discovered to the test directory, changes in eligibility criteria, so it’s this continuous evolving learning system. From patients providing samples and their consent for their data to be used to the research library, to the feedback loop back into the NHS that influences both individual patient care, but also the type of tasks that get offered in the genomic medicine service overall.

In conjunction with Genomics England we have also been working on an NHS Genomic Medicine Service research collaborative that’s enabled us to look at the projects and initiatives that industry or other researchers would like to undertake, would like to have access to samples or to data, and to consider that on the basis of would this support the overall national endeavour in genomics, would it add to the National Genomic Research Library and create that learning system? Is it something that we need to do nationally rather than just locally in a research project? It’s making the infrastructure available for those research projects over and above the ones that are part of Genomics England spending review initiatives or NHS England’s Genomic Networks of Excellence. But enabling us to work with industry and researchers to support their research endeavours in a way that is contained and make sure that we create and continue to create and add to the National Genomics Research Library and this overall learnings infrastructure.

Rebecca: And Rich, anything further to add there?

Rich: I think that creation, that word, that learning infrastructure is the key thing there. I think the process that has taken us here where we’ve worked out how to integrate clinical care and research is so valuable, both for the individual patient and participant and also for the system as a whole, often making the choices that allow us to arrive in the direction actually all point together towards doing the same thing. It’s really constructing things around that central vision and I think that is so important.

Rebecca: Thank you so much. We’ve had a whistlestop tour of genomics over the past decade which and improved and informed the lives of thousands of patients and families. But to finish, let’s look forward. What is your one hope for the future of genomics within the NHS? Rich, perhaps we could start with you?

Sue: I think my wish is a relatively simple one, which is that we maintain this momentum that we’ve got and we’ve built together. We’re on a journey and it’s momentum towards genomics being absolutely part of the day-to-day, the mainstream of healthcare so that wherever you are in the country, whoever you are and often potentially without the clinical teams needing to feel they’re doing anything very genomicsy, if you like, genomics is there and bound into the routine care that one has to deliver. I think when we look and we compare ourselves to other countries, because of that link that we’ve made and that partnership between clinical care and research, we are in a really strong position. It’s therefore about maintaining that momentum and getting us to that place where genomics is just a routine part of everyone’s care.

Rebecca: And Sue, finally over to you, what is your one hope for the future?

Sue: What I’m looking for when we put the patient at the centre is that we adopt all of the genomic technologies that would really enable us both to diagnose a genomic cause for patients that of presenting symptoms, or to inform their more preventative or inform their treatment such that genomics becomes part of everyone’s pathway of care in the NHS, and that we really maintain the NHS Genomic Medicine Service as the most advanced service within the world and that it continues to work to populate a National Genomic Research Library with Genomics England such that patients can benefit from ongoing analysis and interpretation of their data. That we really become the leader across the world of this learning ecosystem and we give as many patients as possible a diagnosis and that we inform as many patients as possible treatment pathways. I believe we’re in the next wave of genomics following the discovery of DNA in 1953, and now it’s how do we make genomics available to everyone across where an inherited disease, across cancer, across common and acquired disease and in pharmacogenomics.

Rebecca: Thank you to our guests, Professor Dame Sue Hill and Dr Rich Scott, for joining me today. It’s been great to talk to you and understand the journey so far and what’s ahead for genomic healthcare. Happy 10th birthday, Genomics England, and happy 75th birthday, NHS. Here’s to the next decade of supporting patients and more scientific research and genomic discovery to drive home. If you’d like to hear more like this, please subscribe to the G Word on your favourite podcast app. I’ve been your host, Rebecca Middleton. This podcast was edited by Mark Kendrick at Ventoux Digital and produced by Naimah Callachand. Thank you for listening.

 

Amanda Pichini, Jonathan Roberts and Emma Walters: How can Genetic Counsellors improve care through research?

Genetic Counsellors play an important part in healthcare and research. This Genetic Counsellor Awareness Day we focus on the role genetic counsellors have in research, to help improve care for patients and families.

On this episode of the G Word, Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Emma Walters, member of the Participant Panel at Genomics England, and Jonathan Roberts, NHS Genetic Counsellor and Clinical Content Developer at Genomics England. Emma shares her personal story and our guests delve into the impact of not having access to genetic counselling. They explore how research priorities can be defined by bringing together both the genetic counsellors and what they're doing in their healthcare roles and the patients themselves and their experiences together.

Johnathan will also be talking to genetic counsellors throughout this episode from the recent World Congress on Genetic Counselling.

You can download the transcript here.

"I think another way in which research can really push that agenda forward is understanding who isn't accessing that [genetic] counselling. So when people get through the door and they experience genetic counselling, often that can be really valuable and they can suddenly start to make sense of all this testing, this family history. They can have a chance to talk about how they feel about it."

 

With special thanks and acknowledgements to World Congress on Genetic Counselling and Wellcome Connecting Science for their contribution to this podcast including Genetic Counsellors, Manisha Chauhan, Alison McEwen, Jared Warde-Jospeh, Nour Chanouha, Jehannine Austin and Kennedy Borle.

Dr Mie Rizig, Sir John Hardy, Candice King and Will Townley: Why is diversity in Parkinson’s research so important?

Unfortunately, please note you may be able to hear some background noise or static during some parts of the recording.

In this episode of the G Word, Candice King, Patient and Public Engagement Manager and Will Townley, Cohorts Manager who both work at the Diverse Data initiative at Genomics England, are joined by Dr Mie Rizig and Sir John Hardy, who both work at University College London (UCL).

This podcast delves into a new paper published by Mie and John in the Lancet Neurology. The paper describes a novel African ancestry Parkinson's disease genetic risk factor. Our guests discuss the need for diversity in genetic research, the key findings from their study, and opportunities for future research in Parkinson's disease.

 

You can read the full transcript here: Diversity-in-Parkinsons-research.docx

 

“The number of people [in genomic research studies] from a white background, Northern Europeans, is about 95%. The number of people from an African background is only 0.2%. This is a significant disparity. When [clinicians] want to translate this into clinical practice, [they] think about: How will be able to test those people sufficiently enough?”

 

The study was conducted by scientists from the UCL Queen Square Institute of Neurology, London, the National Institutes of Health, and the University of Lagos, Nigeria as part of the Global Parkinson's Genomic Program (GP2). GP2 is supported by the Aligning Science Across Parkinson's (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson's Research (MJFF). The paper mainly included cohorts from:

1. The Nigerian Parkinson Disease Research Network, which is part of the International Parkinson's Disease Genomics Consortium (IPDGC) Africa, a collaboration of cohorts across 12 countries to increase the scientific understanding of Parkinson's disease in Africans. IPDGC Africa is funded in part by MJFF.
2. The BLAAC PD study is a cross-sectional study that collects blood or saliva samples and clinical data from Black and African Americans. It is funded by ASAP and implemented by MJFF.
3. Most of the control participants were obtained from 23andMe, a personal genetics company that has assembled a sizable cohort of individuals who have consented to contribute their data for use in various research studies.

Vivienne Parry and David Bick: Which conditions will we look for initially in the Generation Study?

The Newborn Genomes Programme is delivering the Generation Study in partnership with the NHS. The study will explore the possibilities of whole genome sequencing in newborn babies, including to identify a wider range of rare genetic conditions current NHS newborn blood spot test. To do this, we have undertaken significant engagement work to identify the genetic conditions that should be looked for and fed back to families.

In this episode of the G Word, Vivienne Parry, Head of Public Engagement at Genomics England, speaks to David Bick, Principal Clinician for Newborn Genomes Programme at Genomics England. They discuss the process behind determining the provisional list of over 200 conditions caused by genetic changes in more than 500 different genes and how this list may change during the course of the study as new evidence emerges.

 

You can read the transcript here: Conditions-list-for-the-Generation-Study.docx

You can also find a short explainer video explaining the conditions list on our YouTube channel.