Episodes
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A daily low dose of aspirin could significantly reduce the risk of bowel cancer in people with Lynch syndrome, an inherited condition that increases the likelihood of developing certain cancers.
In this episode, we explore the findings from the landmark CaPP3 trial, hear from a participant living with Lynch syndrome, and discuss how genomics could help shift healthcare from treatment to prevention.
Our host, Sharon Jones is joined by:
Dr Katie Snape, Principal Clinician for Population Health at Genomics England Professor Sir John Burn, Professor of Clinical Genetics at Newcastle University Drew Hyde, participant in the Cancer Prevention Programme (CaPP3)Links:
Listen to: How can genomics help us understand cancer?"I think knowing is always a good thing. And obviously, I wish I'd known earlier, and then, I could have taken more measures earlier on. So I think knowledge is definitely a good thing. And it would be great if more people could be tested or could find out if they were carriers at an early age, I think."
You can download the transcript or read it below.
[00:00:00] Sharon: Welcome to Behind the Genes. In today's episode, we'll explore the research which shows how a low dose of aspirin can halve the risk of bowel cancer in people with Lynch syndrome. We'll hear about the real-life impact of living with the condition, and look at how genomics can help shape a more preventative approach to care in the future.
[00:00:20] I'm Sharon Jones, and to help us unpack all of that, I'm joined by our guests, Dr. Katie Snape, principal clinician for population health at Genomics England; Sir John Burn, professor of clinical genetics at Newcastle University; and Drew Hyde, a participant in the Cancer Prevention Programme, which is also known as the CaPP3 trial.
[00:00:42] So to start with the basics, Katie, can you walk us through what cancer is in simple terms?
[00:00:50] Katie: Sure, Sharon. So, our body is made up of cells. Those are the building blocks that, that make us as humans and other creatures and plants. And our cells need to keep dividing throughout our lifetime as our bodies are growing and working normally.
[00:01:06] And so we need to have processes in place in our body where our cells can divide, but then also stop dividing when we don't need them to carry on dividing. What happens in a cancer cell is basically that cell becomes abnormal, and it doesn't follow the normal checks and balances and rules of cell division.
[00:01:23] So it starts to divide and grow uncontrollably, and it can start to invade other tissues and obviously, that can cause serious consequences.
[00:01:33] Sharon: We'll hear a lot more from Dr. Katie Snape in this episode. But before we move on, I just wanted to flag that there was an episode of our Genomics 101 explainer series with Katie dedicated to helping us get to grips with how genomics can help us understand and diagnose cancer.
[00:01:47] Do go and check that out. We'll put a link to that in the episode description.
[00:01:54] So the World Health Organization estimates between 30 to 50% of all cancers are preventable. So, Katie, when we talk about cancer being preventable, what does that actually mean? And what's an example of cancer prevention that people might already know?
[00:02:11] Katie: Yeah. So some cancers are due to chance or just mistakes happening as our cells copy.
[00:02:19] Other cancers are because there has been damage to the genetic information within the cell that can be caused by certain things that can cause damage to DNA. So for example, a sort of obvious answer would be skin cancer. Skin cancers can be caused by sunlight, the, the UV light in the sun, and particularly if we burn our skin or, or get sun damage to our skin, increases the chance of us developing a skin cancer.
[00:02:44] So you can think of lots of other examples such as cigarette smoking and lung cancer, and so we know that there are a number of different risk factors that increase the chance of our cells developing damage and becoming abnormal cells and growing uncontrollably. So when we talk about prevention, we might think, well, could we reduce some of those risk factors and therefore reduce the chance of those cells getting damaged and becoming cancer cells?
[00:03:10] So I gave the example of skin cancer. We might put sun cream on if we're going out in the midday sun, for example. That reduces the damage of the UV light onto our skin cells. Or we might help people to go into a smoking prevention programme or, you know, other risk factors, such as we know that being very overweight can increase the chance of cancer.
[00:03:31] We might help people get into more exercise regimes or improve people's diets. So those are the sorts of things that we might do sort of for environmental risk factors. But we also know, particularly in this context, that sometimes people are born, they carry genetic changes within their cells that they're born with, that are inherited, that run through families, and those can also increase the chance of some cancers developing.
[00:03:56] And for those people at higher genetic risk, then we might look to other ways that we might reduce that risk. We can't change the genetic changes in their cells, but we might be able to put things in place to reduce the risk for those individuals, and that might be medication, it might be surgery, or there could be other things that we might be able to offer.
[00:04:15] Sharon: Yeah, and with that in mind, is there anything more, you know, that you can share about some of those risk factors that someone is more likely to develop cancer?
[00:04:25] Katie: Yeah. So actually, the, the biggest risk factor for developing cancer is age. The older we get, the more times our cells have divided, the more chance there is of a copying mistake that, that, that can cause that cell to become abnormal and start growing uncontrollably.
[00:04:41] And that's why cancer becomes more common the older we get. We obviously can't change our aging process. Then, as I've said, sometimes we're born with certain specific inherited factors that increase the risk. That might be one big high-risk genetic factor, such as having a cancer gene that's important for, for that process of cell division that isn't working properly.
[00:05:04] Or it could be that we have multiple lower genetic risk factors that can kind of add up together to increase the risk. And those often interplay with some of those environmental factors that we've talked about, like smoking, for example, or weight, or alcohol or other things like that. So most cancers are due to aging, and then there's a sort of interplay of genetic factors, but environmental factors as well.
[00:05:30] Sharon: That's really interesting to understand. And the focus of this podcast is sort of looking at kind of Lynch syndrome and what findings have come out around aspirin and having a low dose of aspirin. So I want to kind of explore what Lynch syndrome is and, and then bring in Drew to talk about his experience of having Lynch syndrome and how he got involved in the trials themselves.
[00:05:49] So from what I understand, Lynch syndrome is a genetic condition that can make some people more likely to have the chances of developing into bowel cancer. And Drew, this is your opportunity to sort of talk about what that's been like living with Lynch syndrome. And, you know, I'd like to understand more about your story and how it came about that you discovered that you had Lynch syndrome, and to share with our listeners your journey.
[00:06:13] Drew: Yep. So in my case, I discovered I had the colon cancer before I discovered I was a Lynch syndrome carrier Basically, at the age of 50, I noticed some change in my health. You know, I was becoming a little bit more tired. My bowel movements had changed or whatever. So, I went to the GP and the GP basically said, "Well, you're probably too young for cancer, so let's look at other alternatives."
[00:06:37] And I had blood tests and I had low iron, so I was on iron tablets for three months and whatever. Then eventually I went back and finally the GP said, "Well, let's try a colonoscopy." And the colonoscopy revealed that I did actually have colon cancer. And then very quickly I had surgery and, uh, then following that, I kind of asked the question, "Well, why me?"
[00:06:59] You know, I'm only 50, 51. Yeah. You know, why me?
[00:07:02] Drew: And basically, I was told, "Well, it's probably genetics." And then I was referred to, you know, St George's and Katie and I had the test and discovered that I was actually a Lynch syndrome carrier, and that's why, you know, I'd got the colon cancer at the age of 50, so.
[00:07:17] Sharon: I mean, that's quite a journey. I mean, how did you feel when you're already on one pathway and then having to kind of find out more, you know, what was your experiences? What was the impact on your life? How did you, how did you feel?
[00:07:27] Drew: I think I was lucky in that I had a very good surgeon. I had surgery very quickly, so that was the first hurdle.
[00:07:32] Then I had to go on to chemotherapy, and the chemotherapy obviously is far worse than any surgery or anything else that comes before or after. But having got through that, then I went through the St George's onto the Lynch syndrome system. So, the most important thing then really was to basically identify what that meant for me, but also because it was an inherited characteristic, what it meant for my family.
[00:07:57] One thing that was interesting, and I say, you know, the, the GP was saying, "Well, you're too young to have cancer," is that there wasn't any history of cancer in my family, you know, looking at older relatives. So, you know, to be fair to the GP, that wasn't an obvious marker. So basically, yeah, it was let's, you know, find out what it means now going forward.
[00:08:21] Sharon: So, can you just take us back to when you were diagnosed with Lynch syndrome? What sort of guidance were you given at the time about managing your cancer risk?
[00:08:30] Drew: Well, following the surgery, I was given various statistics which were fairly grim on what your percentage survival rate were in three years, five years, 10 years based on the surgery, whatever.
[00:08:39] And that was kind of a bit harrowing. But, you know, assuming I'd get through five years, I felt it was, my chances were quite good. As for myself living with, living with Lynch syndrome, that, you know, I was aware that having had the colon cancer, I then had increased risk of other cancers. So since then, I've been on a screening programme, and I have colonoscopies or gastroscopies every year or two years.
[00:09:04] So that's been very good. So, I believe now that if any other cancers were to appear, I would probably know very early on because they would be detected through a screening process before they got to a point where they would be, you know, maybe too difficult to resolve, so. So that's-- I think the screening programme, has been very, very good.
[00:09:23] The main issue for me was what it meant for my family, being a genetic thing. So very quickly, my children, who were teenagers at the time, were both tested, and they went through some counselling with Katie beforehand, you know, about what it would mean for them to get a positive or negative result.
[00:09:42] Unfortunately, my daughter was tested as negative, but my son was tested as positive, so he's now on the same cancer screening programme, and has colonoscopies every two years. So yeah. The mystery really, though, is where I inherited it from because my father died when I was very young. My mother was in a care home at the time, and I wanted to get her tested.
[00:10:07] And at the time, her GP wouldn't test her on the basis that she was unable to give consent. But fortunately, I had power of attorney, and we could persuade him to do the test. But she tested negative. So I'm assuming I inherited it from my father's side. But most of my grandparents on that side of the family lived into their nineties without any apparent cancers.
[00:10:32] So it's still a bit of a mystery how I inherited it, but what was important for me was to know which side of the family I'd inherited it from because obviously with cousins and whatever on different sides of the family, I wanted to be able to tell them what the situation was. My brother also tested negative, which was a positive.
[00:10:54] So at the moment, it's just my son and I that have the defective gene.
[00:10:59] Sharon: I'm sorry to hear that about your son, but does it-
[00:11:01] Drew: Well, well, I mean, he, you know, he has to go through a colonoscopy every couple of years, which, you know, obviously is not a pleasant experience. But at least he knows that, you know, the first sign of any problem, the medics will be aware of it, and he'll be able to react.
[00:11:16] Sharon: Has it changed your outlook on life, having this window in possibly knowing stuff or not knowing stuff? How has that affected you and, and your son as well?
[00:11:25] Drew: I think knowing is always a good thing. And obviously, I wish I'd known earlier, and then, I could have taken more measures earlier on. So, I think knowledge is definitely a good thing. And it would be great if more people could be tested or could find out if they were carriers at an early age, I think.
[00:11:42] Sharon: Yeah. That is really important. And moving into about the trial more broadly, scientists have known that there's been a link between cancer and aspirin for some time, with fewer cancers observed in people who take aspirin. So coming to you, John, could you share a bit more about the history of inherited cancer research and how the focus of Lynch Syndrome came about?
[00:12:02] Because this isn't new, is it?
[00:12:06] John: No, absolutely, Sharon. And in fact, this story, my story in this space begins 40 years ago when I was one of the geneticists who set out to try and find the genes that we've just been talking about. At that time, the group of patients who were the most obvious to begin with were young people with a condition called familial adenomatous polyposis, or FAP for short.
[00:12:26] And they'd get thousands of polyps in their bowel, and the only way to treat that was to actually remove the whole bowel when they reached adulthood, which is a fairly extreme intervention. And I was running, I was setting up a registry. We were trying to find the gene at that time, and we'd just found it, in fact, but we also were trying to find all the families.
[00:12:44] And I'd taken over responsibility for all the genetic services in the north of England, in the North East and Cumbria. And we'd, I'd started identifying families with FAP, and we went to visit one of those families, and this was the kind of light bulb moment for me because I walked into the room and mum had had her colon removed, and her son, Jonathan, had just had his first colonoscopy at the age of 12, and it was clear.
[00:13:07] And I was about to give them the good news, but as I walked in, I noticed that he had little bumps on his forehead called osteomas, little bony bumps. His mother had them just the same, and it was one of the features of this condition. So I knew he had the gene even though he hadn't yet got the polyps.
[00:13:21] Sharon: Wow.
[00:13:22] John: And it made me think, wouldn't it be nice if we could do something to prevent these things happening rather than just waiting for an operation? And as it happened at the time, I was leading the English end of a big study, which you'll probably be aware of, which we're, we're, we were doing the vitamin study on women with spina bifida babies, and we were just about to identify folic acid as a way of preventing spina bifida in pregnant women.
[00:13:45] So I had these two thoughts in my head. Maybe we could set up a trial like this folic acid trial, and then one of my friends in Edinburgh said, 'Have you seen this paper from Melbourne?' Gabriel Kuhn had just done a big study looking at people with colon cancer. It seemed that people who took a lot of aspirin didn't seem to get as much bowel cancer in Melbourne as those who didn't. So that was the design set up.
[00:14:08] We were applying to Europe for a concerted action, so we had to think of an acronym that began with CA. So I, I came up with Concerted Action Polyp Prevention. But then in 1993, just as we started that trial, we were involved in finding the first of the genes for Lynch syndrome. We had a big family in Northumberland where there were lots of people like Drew's family, and there were three generations of cancer in the family.
[00:14:31] So CaPP2 was immediately born in my head. In 1999, we had our first recruit, and we recruited until 2005. We found, in total, 1,000 people in 16 countries to join in, and we gave them two aspirins a day or two dummy tablets. Two aspirins is quite a big dose, but back in my day when I was a junior doctor, we used to give many more tablets of aspirin to people with arthritis.
[00:14:57] So two tablets wasn't such a big deal. Nowadays, it's seen as a very high dose. And it worked. Basically, to cut to the chase, when we looked in 2010, the people who were getting the aspirin were getting less bowel cancers. In fact, it was a 50% reduction. So the people who took two aspirins had half as many bowel cancers and fewer cancers of other types as well.
[00:15:19] We realised, although, at this point, immediately we saw that it was working, we knew we'd need to do another trial to see whether a smaller dose of aspirin would be just as effective. So CaPP3 began, and the great news is that what we'll be reporting in the journals in the next few days when it gets published, is that the people who were taking âCaPP3 aspirin in any dose were tracking exactly the same as the 600-milligram group in CaPP2.
[00:15:46] So we're pretty sure that it works. We're pretty sure that the small dose is just as good. And the great news was that we had fewer side effects in that group. And so in fact, no one had to go to hospital for a transfusion or anything, you know, like that. Whereas in the 600-milligram group, we had a few people who needed treatment because, as you know, and everyone knows, if you take aspirin, there's a higher chance of having an ulcer that causes a bleed.
[00:16:10] And that was always the anxiety. But people like Drew were courageous enough to take the chance because they knew we needed to know the answer to this. And of course, when you compare it to the risk of getting cancer, taking an aspirin is a relatively small risk.
[00:16:26] Sharon: So, what were your kind of considerations when you were designing the trial, having that knowledge?
[00:16:32] John: Well, the first thing is it has to be fully informed consent, which means that you have to explain to people what that risk is. The important thing about aspirin is that doctors have a much worse opinion of it than it deserves because if you work in a hospital, you'll often see people coming in who've had a bleed.
[00:16:48] It's not always caused by the aspirin. The thing is, if you're coming with a bleed and you're on aspirin, everyone blames the aspirin. Right. About half of them would've happened anyway. In fact, the, the irritation of the stomach is much more of a problem in older people So in fact, the average age of the people in CaPP2 and CaPP3 was about 45, 46 when they started.
[00:17:08] Drew was a little bit older, but, but people in that sort of middle age group are much, much less likely to get into trouble than people in their 70s and 80s. And it's people also who've had a history of ulcers that have a bigger problem. We also knew that if you had a stomach infection called H. Pylori, which is itself a risk factor for cancer, and about one in six people carry that bug, and we knew that if we fixed that with antibiotics, that would significantly reduce the risk of bleeding as well.
[00:17:37] So it was a manageable risk. It was something we could share with people. They knew they were taking a bit of a chance. But actually a good way of putting it in terms of the risk, for people in middle age, the risk of a low dose of aspirin is about the same as the risk of having a colonoscopy, which is very small, but it isn't completely without risk.
[00:17:56] Sharon: Yeah, and Drew, kind of like hearing this sort of incredible, like, backstory about how we've got to these trials and where we are today What was your experience like as a kind of participant of this trial?
[00:18:08] Drew: I understood I was going to be on 100, 300, or 600, but wouldn't know for at least three years, or was it five years? I can't remember.
[00:18:15] And then sometime later in the post we got these packs, and it was ... I remember at the time thinking it was like a rather dull advent calendar - ... in that you'd have the days of the week- ... with the little, with the little windows, and you'd, you'd pop the tablets out three times a day and take them.
[00:18:31] So I did that. I think, you know, I, I don't think I ever missed a day or whatever. Initially, I thought I must be on a really low dose, because I didn't actually notice any side effects. You know, I remember saying to my wife, I said, "Oh, I think I must be on the lowest dose, because I don't see any side effects."
[00:18:46] It was a surprise years later when I was told actually I'd been taking 600, so.
[00:18:51] Sharon: Wow.
[00:18:52] Drew: It was quite an easy experience really.
[00:18:54] John: We had a lot of problems. We had to pack the aspirin in six-month packs, because it was very expensive to pack this stuff up. It cost... We got the aspirin free from the Bayer company, but it cost us more than a million pounds to actually put it in, in the packs to satisfy the regulations.
[00:19:10] Uh, and a lot of people complained that the packs were a bit big and awkward, but that was just, you know, a constraint. But it was not that big a deal once people got into it. But we did get a lot of complaints about the size of the packets, which we couldn't do anything about that.
[00:19:24] Drew: They came regularly through the post, and, you know, so every three months or whatever I got another supply, and I just carried on taking them.
[00:19:30] Yeah, so.
[00:19:31] Sharon: What was going through your mind when you were kind of waiting for this potential outcome, Drew? Because you, like you say, it was, you know, it was a long time taking part. What was... Especially as you were opening your, you know, your package a day, knowing exactly what you were going to get.
[00:19:44] Drew: Well, I, I kind of knew it would be a long-term thing.
[00:19:47] I think I was committed for five years initially. But I carried on taking the aspirin for another probably five years after that. So yeah, I was just sort of happy to take the aspirin and then sort of wait to see what the results would be. As I say, that I didn't really notice any side effects, so I wasn't really worried that it was having any detrimental effect on me.
[00:20:09] So I was curious to see what the, what the results would be.
[00:20:12] Sharon: Yeah. John, the trial has provided like the evidence that, you know, low-dose aspirin can prevent bowel cancer. But are there any challenges that still exist with translating this research into clinic and ultimately patient care?
[00:20:26] John: Well, yes, and I'm going to hand back to Katie, who's actually leading the charge on, on getting it into practice as well.
[00:20:32] But just to say that I, I'm actually now literally on my other computer finalising my bid to go back to Cancer Research UK because we want to go for three more years. Wow. We said that we would follow people for 10 years after they'd finished their ... or after they'd started, so, you know, for at least 10 years.
[00:20:50] So the last person to join didn't finish until 2024, so we won't get to that person. It's Robin and one of my patients. We won't get to Robin's 10-year anniversary until 2029. Oh, yeah. By which time, obviously, Drew will be even further on. But that will give us at least 10 years of follow-up because we know that there is this delayed effect, and that was seen right back at the beginning when people looked, for example, the nurses study in America, where they followed 86,000 nurses and just asked them if they took aspirin.
[00:21:18] And nothing happened for 10 years, but those who were taking aspirin for more than 10 years saw a benefit. So in the general population, it probably takes that long to kick in. And so we need to keep going for just a while longer. It's not as expensive now because we're not giving people aspirin anymore.
[00:21:33] Sharon: Yeah.
[00:21:34] John: But one of the reasons we g- we made Drew's dose blind was because we wanted to know what the side effects would be when you didn't know how much you were getting There's a danger if you're getting a higher dose, you're more likely to complain. And actually, it did work out that the people on the lowest dose had the fewest side effects, even slight side effects.
[00:21:51] The only thing we can't escape from is if you're taking aspirin, you get bruising more easily because it blocks the platelets, which are the little tiny blood cells which plug up little holes in your blood vessels when they leak. The good news is we now know that platelets turn out to be right, a major factor in triggering cancer.
[00:22:09] And so the aspirin, by blocking the platelets, is actually reducing the risk of cancer, but also reducing the risk of cancer spreading in the body. So this is new research, and we've got another big research project in collaboration with a team in Cambridge who are, uh, pursuing this. Also, the other exciting news is that my other partner, Ruth Langley, is running a big trial of people with cancer, and those who are given aspirin as part of their treatment have less likelihood of getting spreading cancer later on.
[00:22:39] So the aspirin is clearly doing something good at many levels in the system. Surprisingly, and we think it might be partly, partly because we used to have a lot of salicylate in our diet, which is what aspirin's made from. And we think that maybe we're putting back something that the body actually was used to having.
[00:22:57] Yeah. But modern diets don't contain any, any salicylate because of the way we prepare our food. So it may well be that a little bit of aspirin's a good thing for everybody, but obviously, that's a choice that each person will have to make.
[00:23:09] Sharon: Yeah. I mean, it's a real powerhouse of a, of a drug essentially, which you're finding out more about its benefits as, uh, as research goes on.
[00:23:18] So Katie, can you just give us a bit of a broad overview of Genomics England's new adults program, which is kind of looking at this sort of area of work and, and what, how can it benefit people?
[00:23:29] Katie: Yeah. Thank you, Sharon. So, the adults programme at Genomics England is being funded by government, and the government wrote about it in the 10-year NHS Health Plan, the Life Science Sector Plan to run a large-scale genomics population study.
[00:23:44] So looking at how we can obtain genetic information from people in the population and look at more proactive and preventative healthcare, and can we generate evidence on where, how, and why the NHS should start applying genomics into kind of more population health measures. So, there's sort of two sides to this.
[00:24:05] So the first is thinking about pharmacogenomics, which is basically about how genetic factors influence how we respond to drugs. So lots of people have had experiences of having side effects from drugs, we've just been talking about that with aspirin, or for drugs not working so well for them. And we know that there are certain drugs that genetic factors can influence whether you should take the drug at all, or if you do, what dose you should take, whether it's going to work for you or not, whether you might be more likely to get side effects or adverse reactions.
[00:24:34] So part of the programme's looking at that. And then the other half of the programme will be looking at sort of is, are the genetic factors relevant for sort of serious and high-risk conditions in the adult population? So we could take bowel cancer as an example of that, a common condition, breast cancer, you know, common cancers or cardiovascular disease.
[00:24:58] We know there are certain genetic factors for some people that have significantly increased their chance of developing those serious adult onset conditions. Can we find those people in the population and then put measures in place to prevent that? So, you know, even just thinking about Drew's story, he didn't have a family history of cancer.
[00:25:16] The first time that he knew he had Lynch syndrome, he'd already developed bowel cancer. And we know that many people that have Lynch syndrome or other high-risk cancer genes are unaware of their status in the population, and so, um, the idea of this program is to really look at, well, if we were to, to look for some of these very high-risk genes in the general population, could we then put measures in place to reduce the chance of them developing the serious condition as a consequence?
[00:25:44] So instead of Drew presenting with his bowel cancer, we'd actually already picked it up, despite the fact he doesn't have a family history, and we'd offered him, let's say, aspirin if we'd known the information at the time, and we could maybe have prevented him from developing bowel cancer.
[00:25:58] So it's really exploring looking at that a little bit more.
[00:26:02] Where can we get genetic information in the population? Where might there be a really well-evidenced, like all the work John's done over 40 years, is really well-evidenced now. Yeah. Yeah. Where are there these opportunities for us to turn the dial on some of these common adult onset conditions?
[00:26:20] Sharon: What other challenges do you think with getting this out there do you see?
[00:26:25] Katie: Uh, I think there's, there's lots of challenges. I think it's a really com- ... complex programme of work. The first thing is that the risks might be different for people in a population than have a family history. So where I've worked for, for years, and John as well in, in clinical genetics, we've seen the highest risk people, the people with lots and lots of cancer in their family because they're the people that are presented to healthcare services. So we've worked out the risks based on that population. It will be really different when we move to the population setting. We'll find fewer people, and the risks might be lower because there might be other factors that are giving them a lower risk. But that's not to say the risk is zero.
[00:27:05] It's probably still raised. So then what we need to do is we need to consider, okay, well, what can we do to intervene, taking into account this change of context from people that we found through clinical services to people that we see in the population. And aspirin is a great example of this.
[00:27:22] So, you know, if we find that someone has a Lynch syndrome gene, then taking aspirin, unless there's a really good reason for them not to take aspirin, is almost certainly going to be low cost to the NHS and really significantly reduce the chance of them developing bowel cancer with a low risk profile. So where are those opportunities?
[00:27:41] And that isn't clear cut, and that's why we need a large scale research programme that can try to help the NHS answer some of those questions, so it can decide how best to spend its money in, in the people that are most likely to benefit from it with the least amount of risk or harm to them.
[00:27:58] Sharon: That makes sense. And, and so, you know, going to you, Drew, what are your kind of thoughts on some of the challenges that Katie's highlighted? And is there anything else that you think needs to be improved in better supporting people living with inherited risk of cancer in the future?
[00:28:14] Drew: In the brief sort of 10, 15 years or whatever since I've been s- suffering, awareness has increased greatly.
[00:28:21] I mean, for example, my GP now knows about Lynch syndrome, whereas I don't think she did when I was first diagnosed, and I think there is a little bit more awareness out there, but I still think it's a lot less than there would be for, say, for breast cancer. So for example, when a high-profile personality reveals they've got breast cancer, you often get information about inherited risks.
[00:28:44] You don't seem to get that with colon cancer. You know, when it's announced that so-and-so has died or is whatever, you don't get that same, you know, it, it might be a genetic thing. I mean, when I was first told people that I had bowel cancer, the response I got usually was, "Oh, poor diet, was it?"
[00:29:04] And I always felt a bit upset, that, you know, actually my diet was fairly healthy. And that was the assumption that people had. So I think anything that gets the message out there that there is a risk, an inherited risk, I'm not sure what the statistics are now, Katie, is it one in 400 people might be a Lynch syndrome carrier or something like that?
[00:29:24] You know, it's relatively high for something that is, if you know in advance you're at risk, you can do something about it. But like me, you know, I waited until it was too late, because I didn't know, and then had to have the surgery, so anything that promotes the message that there is a risk. I know some people don't want to know about their genetic makeup. Obviously, that's a choice. But I think to give people, as many people as possible, the choice must be a good thing.
[00:29:54] Sharon: Yeah, absolutely. And I think one thing I've noticed through this thread is the sort of theme of funding and what gets funding and the amount of time it takes to, to kind of get that funding.
[00:30:05] Is there anything you wanted to add around the kind of funding model, around why some things get funded, you know, uh, more prominent, like Drew's point, obviously, talks about if someone high profile kind of comes forward and says XYZ, that gets the spotlight shone on it, and there might be research going that direction compared to s- to, to other cancers.
[00:30:23] John: So maybe I could speak at that. So partly because of my experience, I've now been made chairman of the grant committee at Cancer Research UK for prevention and population research. And there is a real drive to push more resource into prevention for the obvious reasons.
[00:30:39] Katie: Yeah.
[00:30:39] John: And also, it's got to be remembered, it's very difficult for the drug companies to fund this because it takes such a long time that the drug's- Mm
[00:30:46] out of its patent before they actually get to use it. So, it's very difficult from a business point of view to fund research into prevention. But they are keen to help us, uh, but we really need sort of central government and the charities to focus on prevention if it's going to make a difference.
[00:31:02] And just on Drew's point on diet, I mean, diet is still important even if you have Lynch syndrome. In our CaPP2 trial, the people who were overweight were more than double the risk of cancer. So it's not like an either/or. If you've got a higher genetic risk and you have a bad diet, then that's, you know, is going to contribute.
[00:31:21] But the other exciting thing is, of course, we now have medical ways of treating obesity in, in people. So, one of the interesting areas is whether we should be, in the same way as we are for other high-risk populations with overweight, we should be giving overweight people with Lynch syndrome, help to lose weight because that will also reduce their risk.
[00:31:41] It's also worth just dropping in at the last moment here is that this is also a good news story in terms of treatment and further prevention. We now have a new class of drugs called immune checkpoint inhibitors, which specifically target the types of cancer that Drew had and are much more effective in curing them And also, we've just been given funding to do a project called LynchVax, which I'll be helping with, but it's led by David Church in Oxford.
[00:32:05] And this is developing a vaccine against cancers in people with Lynch syndrome. The great news is it'll probably work alongside aspirin because we know the aspirin is enhancing the immune response. So the two together may make this a curable condition.
[00:32:18] Sharon: That's actually incredible. I mean, that, it gives so much hope for people.
[00:32:23] And I just wanted to find out if you had any more kind of reflections as we close, because we're going to come to the end of our podcast today. If there's anything more that you wanted to share, anything that has been missed, or anything that you want our listeners to know, and I think I'm gonna come to you, Drew, first, because you're the person who's had to sort of live through this and, and go through this journey along the way.
[00:32:41] Drew: I think just basically, if you're not sure, get tested. Obviously, there are financial constraints. I'm sure that running a DNA test is quite an expensive business. But I think if you've got any history of bowel cancer in the family, you've got any concerns about your health, speak to a GP and see if you can get tested as quickly as possible.
[00:33:00] And then, to get a better message out there that there are risks of inherited colon and other similar cancers, so.
[00:33:11] Sharon: Yeah, so it's getting that, messaging out, um, for people to understand more and make those informed choices. And Katie?
[00:33:18] Katie: I mean, I would say that the power of, of our, you know, NHS and our academia and, and our healthcare system has been collaboration.
[00:33:26] Sharon: Yeah.
[00:33:27] Katie: There's so many moving parts. There's commissioners, there's funding, there's the evidence, there's research, there's healthcare implementation. The UK's a really amazing place to work in genomic medicine, and I think that's partly because of the amazing collaborations that we have, and the way that we can translate research into healthcare as John's team have done with this amazing study.
[00:33:48] So let's all keep working together, please.
[00:33:52] Sharon: Absolutely. And John, it feels like this is your lifetime's work.
[00:33:58] John: Well, I've become aspirin man, it wasn't intended. But Katie's done fantastic work in her role as chair of the Cancer Genetics Group in the UK, so we've now implemented a,
[00:34:06] we're the first in the world to really make this an absolute directive to the GPs and all, to all doctors to say, "People with Lynch syndrome need to be offered aspirin." And so that's a great step forward. But we also need to get it into the British National Formulary, and I'm working with their team so that the GPs are empowered to do this.
[00:34:24] It's actually part of their care package. But I would just say we've still got a long way to go. We've now got a national list of all the people with Lynch syndrome, like Drew, to make sure we offer them all a colonoscopy, but there are only 14,000 people after several years of really pushing.
[00:34:40] Sharon: Right.
[00:34:40] John: We think in the national population in all ages, it's about 1 in 300. That's a lot of people. That means there's about 150,000 people like Drew in the country, and we've only found 10% of them. So we can't just rely on family history for all the reasons Drew explained. You know, I mean, Drew's dad probably died of Lynch syndrome, but we don't know because we've lost that record.
[00:35:02] So now we're checking every bowel cancer to see if it might be caused by Lynch, and that programme is now kicking in, and we're picking up a lot more gene carriers as a result of that. But there's still a long way to go to get co- get people aware of Lynch syndrome, to think of it when someone presents with a cancer, not just of the bowel, but in the womb, in the kidney, in other parts of the body.
[00:35:23] It's not just the bowel, but that's the most important group.
[00:35:26] Sharon: Yeah.
[00:35:26] John: So there's still a long way to go.
[00:35:28] Sharon: Where you've come to now is still an incredible achievement, even though we've still got a long way to go, and I don't think we should ever lose sight of that. So we're going to wrap it up there. Thank you to our guests, Katie Snape, Professor Sir John Burn, and Drew Hyde, for joining me today as we discuss cancer prevention.
[00:35:48] If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app, and thank you for listening. I've been your host, Sharon Jones, and Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan, and Dave Howard at Bespoken Media.
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In this explainer episode, weâve asked Jamie Ellingford, Lead Genomic Data Scientist for Rare Disease, to explain how genomics is helping us better understand rare conditions.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
[00:00:00] Florence: How can genomics help us better understand rare conditions? My name is Florence Cornish, and today I am joined by our Lead Genomic Data Scientist for Rare Disease, Jamie Ellingford, and he is going to be sharing lots more insights about the topic with us.
So, I guess before we begin, Jamie, it might be useful if you could explain what we actually mean by the term 'rare condition'?
[00:00:25] Jamie: Sure. Hi, Florence. So, a rare condition we define as something that impacts one in less than two thousand people, and so that's something that occurs really infrequently in the population. But we know that collectively there's lots of different rare diseases. And so, the estimates are that it's about one in seventeen people in the population that are impacted by some sort of rare disease, of which we think there's over seven thousand.
But research that uses data that we have here at Genomics England as well as other sources is starting to uncover more and more of these individual rare disorders. So collectively, as I just said, one in seventeen individuals, we think, is impacted by a rare disease, and that equates to almost three and a half million people here in the UK.
[00:01:15] Most of these rare conditions, we think, have a genetic basis, and perhaps we'll explain a little bit more about what that means.
[00:01:22] Florence: Yeah, no, it would be great to talk a little bit more about that actually. So as you said, most rare conditions we think have a genetic cause, but I think it might be helpful if you could explain what we mean when we say that something 'has a genetic cause'.
[00:01:35] Jamie: Of course. So maybe we go back to kind of the basics and kind of how a person is first formed. So, at that point of fertilisation, where the sex cells from mum and dad join, we inherit one copy of our genome from mum and one copy from dad, and it's the order and the composition of these letters in our genome which makes it unique to us.
Most of that genome is absolutely identical to anyone else in the human population. And a small fraction of it is unique to us and is a combination of things that we've inherited from our mothers and our fathers. And when we think about genetic causes, largely, we look at those differences. And so, what is it that's different in individuals compared to the wider population that could be driving these rare conditions?
[00:02:23] Florence: So could you maybe explain a little bit more about how people's genetic material, how people's genomes differ from one another?
[00:02:30] Jamie: So there's lots of different ways that we can observe these genetic differences. So some of them impact individual letters, and we, we may swap a single letter for another.
[00:02:41] We can also remove small sections, so it may be that a run of three or four of these letters is deleted from someone's genome. But on the opposite end of the scale, we can also see huge changes in how that genetic material looks.
So perhaps a good way to think about this is as a story. And so if our, if our genome is like any kind of good fiction story that you would read, then we can have spelling mistakes that impact single words,
[00:03:09] that impact whole paragraphs, or some which impact whole chapters. Lots of these different types of genetic causes can give rise to genetic conditions. And so even the smallest changes, the smallest spelling mistakes in words, can still give rise to rare genetic conditions.
[00:03:26] Florence: We actually have a previous podcast episode that explores that topic in a lot more detail. So if listeners want to check that out, it's called "Are genetic conditions always inherited from parents?"
So obviously, Jamie, we spoke quite a lot about DNA and genetic changes there, and this episode is all about how genomics specifically can help us better understand rare conditions.
[00:03:47] Um, but what actually is genomics as a field of study?
[00:03:53] Jamie: So simply put, genomics is the study of the whole genome, or at least as complete a picture of the genome as we can possibly represent. And so in the case of rare disorders, we use genomics to try and understand what the genome looks like from an affected child.
[00:04:12] And, um, in some cases, we're also able to look at the whole genomes of their relatives, so perhaps their mother and their father. And we use this information to best detect and best prioritise variants that we think are giving rise to their genetic condition. But how we've done that has evolved and advanced a lot over time, has gone hand in hand with these remarkable developments in technology.
[00:04:37] And so a decade ago, maybe 15 years ago, the state-of-the-art technologies were to look for single spelling mistakes or to be able to survey complete genes. Nowadays, we can generate data for the whole genome, and we can do that fairly cheaply, we can do it quickly. And we rely on computational algorithms and the development of bioinformatic resources to be able to properly make sense of that data. And so there's, there's three key aspects of bioinformatics, this discipline of integrating informatics, computational technology, with biology.
[00:05:17] And so the first is, having generated some data, can we appropriately find where in the human genome that data should map to? Having done that, can we detect these differences, these small or large changes in the human genome, for that individual? And finally, can we start to make sense of those changes? Can we understand whether they exist frequently in a population or they're unique to this family and predict what potential consequence they have on a gene's function?
[00:05:47] Florence: Mm. So there's obviously lots of different components of genomics, but how can all of them help us better understand rare conditions specifically?
[00:05:59] Jamie: So as we've already touched upon, most rare diseases have a genetic basis, and we think that that estimate could be something like 80% of rare diseases have a genetic component to them. And what we've seen over the past decade and further, is that genomics has really transformed the discovery of new genomic conditions.
[00:06:20] And so being able to look at data from the whole genome has allowed us to understand new genetic, types of genetic changes, changes in new genes, which could cause these rare conditions. And what we've seen recently is that move and that transformation from genomics as a discovery tool to a tool that we use routinely and so essentially, we've moved this technology from research laboratories into the NHS and the UK healthcare system. We've really come a long way, and so, whilst we see that the amount of genetic diagnoses that we can find is really dependent on the specific disorders, broadly, we find genetic diagnoses for somewhere between a quarter and half of the individuals that are referred.
[00:07:10] What that does mean is that there's still 50% of individuals out there that get referred to these services with a rare condition where we don't find an obvious genetic answer through the implementation of genomics within healthcare.
[00:07:24] Florence: Do you have, um, a specific example you could share of where genomics has had a real impact in our understanding of rare conditions?
[00:07:33] Jamie: So I think all of us that have worked in this space for, for a long time have our own individual examples. We're recording this in 2026, and over the past two years, there's been a flurry of discoveries of genes which don't directly encode proteins, that cause a certain type of rare conditions, and so we call these non-coding genes.
[00:07:54] These genes have recently been described as a cause of kind of wide neurodevelopmental disorders, as a cause of genetic blindness, and there's ten at the time of recording, distinct rare conditions another example that I wanted to elaborate on is something that was really personal to me because it happened really early during my development as a, as a researcher and as a, somebody who looks at genomic data very early in my career, and really kind of had a profound impact on how I think about genomics and how it can be applied.
[00:08:28] And so this was an individual who was referred with a certain type of rare condition. And through the analysis of their genomic data, we identified a genetic variant in a certain gene. At the time of testing, they were in their early teenage years, and when we looked at the scientific literature, what this suggested is that other symptoms were going to develop before the age of 20.
[00:08:52] And so at this point, genomic testing had been done in a really critical window for that individual and allowed them to be referred to specialist centres, and to be managed appropriately, and that's really ended up in a good outcome.
And what's becoming more and more frequent is the opportunity for genomics to inform enrolment to clinical trials, the development of targeted treatments, and we hope that in the next decade or so we'll see an increased flurry of those activities.
[00:09:22] Florence: Yeah. So I guess, would the headline be that genomics allows us to see changes in the genome that maybe more traditional genetic tests wouldn't have allowed us to see, and then that in turn helps us with our approaches to rare conditions?
[00:09:37] Would you say that that's accurate?
[00:09:40] Jamie: So it certainly gives us that opportunity.
[00:09:42] Florence: So I think we'll finish there, Jamie. Thank you so much for coming on, for taking the time to speak with us. It's been very insightful.
[00:09:50] Thank you very much. A pleasure to chat.
[00:09:52] Florence: If listeners want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.
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Episodes manquant?
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When people think of midwives, they often think about pregnancy and birth, but the reality of modern midwifery is far broader.
In this episode of Behind the Genes, our guests explore the many different roles midwives play across healthcare, from clinical care and safety improvement to research and genomics.
The conversation looks at how midwives are helping shape the future of maternity care through research, supporting families to make informed decisions about genomic testing, and contributing to studies like the Generation Study.
Our host, Sharon Jones is joined by:
Katie Handley - maternal and child health clinical lead for the Generation Study, Fiona Smith - research midwife for the Generation Study at Rosie Hospital in Cambridgeshire Jess Fletcher - safety and quality midwife at the Rosie Hospital and a participant on the Generation StudyYou can find out more about the Generation Study via the studyâs official website.
ââThe more brave we are as midwives, and the more that we're willing to be curious about what we can do to improve our care, the better we're going to be at our profession. All midwives want to do is to provide safe, effective care that is what is in the best interest of that woman. We are advocates for women and for their families.â
You can download the transcript or read it below.
[00:00:00] Sharon Jones: Welcome to Behind the Genes. How is genomics changing midwifery, and what role are midwives playing in shaping the future of genomic healthcare? Also, do midwives just deliver babies, or is their role much broader than many people realise?
[00:00:16] My name is Sharon Jones, and in this podcast we cover everything from cutting-edge research to real life stories in genomic healthcare.
[00:00:23] Joining me today are Katie Handley, Fiona Smith, and Jess Fletcher. Katie is Maternal and Child Health Clinical Lead for the Generation Study, Fiona is a research midwife for the Generation Study at Rosie Hospital in Cambridgeshire, and Jess is a safety and quality midwife at the Rosie Hospital, and a participant on the Generation Study.
[00:00:42] Together, we'll be exploring how midwifery's evolving, where research fits into clinical practice, and what genomics mean for maternity care now and in the future. We kicked off this one by asking Katie what roles midwives play day to day.
[00:00:56] Kate Handley: I think when people think of midwives, they think of helping a lady to have a baby.
[00:01:01] We're there for the birth, we're there to catch the baby, but it is so, so much more than that. We're there from the moment a woman becomes pregnant or even before that. We can help with prenatal, uh, preconception care. We're there all the way through the pregnancy, for the birth, and then afterwards as well, we'll look after the lady, her family, until, until we hand the baby and, and her over to the health visitor or to whoever's next in her care pathway.
[00:01:25] But that's just looking at clinical midwives for the... that are involved directly in that particular pregnancy. There's midwives doing all sorts of other roles. I think I'm a really good example of that. So I am a clinic- I was a clinical midwife. I am a registered midwife, but now I work as a clinical lead, so I'm using my midwifery background and my midwifery skills in a research environment, but to help people who don't know as much about midwifery to implement a research study, and how we can make a research study real in a clinical environment.
[00:01:59] So that's one example, but there are so many other things, and we have midwives doing screening roles and lots and lots of midwives working in research as well.
[00:02:08] Sharon Jones: That's interesting. I've got a couple of friends who are midwives, and I would never have known, like, the extent and scope of their role.
[00:02:14] Kate Handley: Yeah, I think people might be surprised to hear that you can be a midwife but never actually even see a pregnant person. So we have midwives that are academics, for example, or midwives that are lecturing at universities, midwives that are working behind the scenes in risk and governance and looking after the safety aspect.
[00:02:30] Sharon Jones: That's amazing. I would never have known that. So Fiona, how has your role as a midwife changed over the years? Because you've gone through quite a bit of a transition, haven't you?
[00:02:39] Fiona Smith: I have. Before I even became a midwife, I was, I was nursing. That nursing pathway was not academic, as we now have to undertake academic training to become a midwife.
[00:02:50] So we... the training was very different. It was very hospital-based, and this is what you do, this is what we do. You would do some observation. You'd have a go. You'd get signed off. That really was my nursing background, and then when I started to explore midwifery, and it was much more academic, and that I was going to do the university pathway, I doubted that that would be something that I could actually even contemplate.
[00:03:15] Moving forward 20 years, here I am. I've had various roles: community midwife, running birth centres, and then more recently, the last six years, joining a university hospital which has a, a, a big emphasis on research and academic training, brought in lots of students, medical students, and others. I saw some research that was happening at the hospital and became quite curious, took the plunge, and the last two years I've been working as a research midwife, which was a real surprise to me to find that this is where I am, and to actually be working on a genomic study is an even bigger surprise.
[00:03:57] If you'd asked me 20 years ago that this is where I'd be, I'd probably have laughed and said, "No, that's not something that I could even be contemplating."
[00:04:07] Sharon Jones: That's fascinating. It's fascinating, the journey you've been on and how midwifery and nursing training has evolved more broadly. So Jess, how does that compare with your own journey in midwifery?
[00:04:19] Jess Fletcher: Similarly, actually, like off the back of what Katie and Fiona are saying, you do kind of go into midwifery thinking that your career is going to very much look like providing labour care and catching babies, which is a wonderful part of the job. And that is very much my background, is that I have been, like, a labour and delivery midwife, usually on the birth centre or in the community doing home birth.
[00:04:43] So, and never in my wildest dreams did I think that I would pivot and go into something specialist. I think you k- ... Well, in my case, certainly, I kind of fell into it, quite literally, uh, because I broke my ankle and then had- ... to work from home for quite some time. I was offered to be off sick, and I was working at a new trust, and I kind of wanted to, so to speak, keep my foot in the door.
[00:05:05] And I said, "Oh, I, there must be something I can do from home." And they set me up to do some auditing, which quite frankly, a few years prior I would've ... Yeah, you couldn't have paid me all the money in the world to do auditing. And then, lo and behold, I found it so fascinating, not just the process, but kind of seeing how that then would kind of implement us in clinical practice.
[00:05:28] And now I'm a safety and quality improvement midwife. My office is on a birth centre though, so it does mean that I still very much work clinically. So yeah, so a similar story.
[00:05:38] We're such a highly skilled profession that we can apply it in so many different ways. And now of course, I'm on maternity leave with my third baby.
[00:05:46] Sharon Jones: Congratulations.
[00:05:47] Jess Fletcher: And so taking a little, a little break, but really lovely to talk about it all today actually.
[00:05:52] Sharon Jones: Yeah. Thank you. Thank you for sharing that.
[00:05:53] So as mentioned, alongside clinical care, midwives are, are playing this increasingly important role in research.
[00:06:00] And though it's something that people might not necessarily realise and they might not associate with the profession, I'd love to explore what that actually means in practice and how midwives have become involved in this space. So Katie, where does research fit in with midwifery today, and how do midwives get involved in that space, and is that something that all midwives are engaged with?
[00:06:21] Or is it a more specialist kind of pathway?
[00:06:23] Kate Handley: It can be a specialist pathway, but I think what's really, really important to realise here is that every single midwife is involved in, in research, whether they realise it or not, or midwifery care, has got to be evidence-based. Everything we do is evidence-based, um, because that's what keeps midwifery care as safe as it possibly can be, and we can only get that evidence base from doing research.
[00:06:46] So even if midwives aren't taking part in a research study themselves, if they're not, you know, getting consent from people to do research studies, the care that they are giving comes from research that has been done in some space. Even if that's not within the UK, it's research that has been done. So research is incredibly important.
[00:07:03] That's how we evolve, um, our care, how we evolve our pathways, evolve our guidelines is through that, through that research.
[00:07:11] Sharon Jones: So can you talk to the audience about what is a research midwife versus a clinical midwife?
[00:07:16] Kate Handley: So a clinical midwife generally is somebody that will have hands-on care during the antenatal and intrapartum or, or postnatal period.
[00:07:24] A research midwife, often that will be someone who still works on a ward, in a hospital, but is helping to put research into place. So that may be running a study and taking consent from women to take to be part of that study, and then doing whatever the study needs. Or it can be actually conducting their own research, it can be writing, it can be an academic form of, of midwifery as well.
[00:07:49] It's really, really important, and it really depends on the hospital and on the trust how much that research is incorporated into the clinical care, and sometimes it can be quite separate. But both very, very important. And the Royal College of Midwives are really, really trying to work on making research part of general midwifery care.
[00:08:09] It's something that undergraduates need to do now as part of their, their degree, which all midwives have to do a degree to become a midwife. They have to do research. They have to be involved in research. Midwives in their first year of being qualified should still be having a research role and looking at how research can broaden their clinical skills, and it's something that should be going on throughout their entire career
[00:08:32] Sharon Jones: Yeah, that's great.
[00:08:33] Fiona, what does a typical day look like in your kind of research-focused role?
[00:08:38] Fiona Smith: Firstly, just to say, when I moved from a clinical role into the research role, I thought I was going to miss that kind of adrenaline rush that does come with being a clinical midwife. And so I thought, it-- this is so quiet, it's just a really very different pace.
[00:08:54] But actually, there are deadlines and things like that. So yeah, on a daily basis, it is really... it's a really busy day.
[00:09:02] So we can be answering our emails and inquiries about research. We're liaising with the clinical team, so I'm involved in a screening study, so we, we need to collect samples. So we go and collect samples, we register those samples.
[00:09:19] We're then approaching our patients or ladies that come in to have scans, or they might be in the antenatal ward. We liaise with the community midwives who might have people that want to take part in the study, so we do a lot of communication with the women through that way.
[00:09:38] And having the background as a midwife, having that holistic approach has really, really broadened, you know, and really helped support my role as a midwife. Having-- transferring those skills has been incredible.
[00:09:53] Sharon Jones: So what kind of studies do midwives support?
[00:10:03] Fiona Smith: So apart from the genomic studies, uh, because a, a lot of genetic-based studies are going on within our trust. Where they're looking at trying to understand why things happen and see if there's a genomic h- component that might be attributed to conditions. We've got observational studies where we use lots of questionnaires to ask patients about their experiences. We've got interventional studies, so that could be testing a new drug or an interventions, just testing something that might work and, and might build that into that evidence base to -
[00:10:32] You know, to put into practice. I'm really surprised at the portfolio of, of studies that is available. So they could be, um, not just maternity-based, but the obviously obstetric-based and studies, and we do a lot of gynae studies as well, so we work alongside the gynecologists.
[00:10:51] Sharon Jones: So Katie, genomics is becoming more visible in healthcare. How is that showing up in maternity care more broadly?
[00:10:58] Kate Handley: So I think what's really important to note here is that genomics has always been really important in, um, maternity care.
[00:11:04] It's just that midwives potentially didn't know that they were doing it. Um, so from the very moment that we book a pregnancy, so when, when a woman has her first appointment at, you know, 8-10 weeks, we're already using genomics to plan her, her care. So we're asking about family history. We're asking about a predisposition to, um, heart disease, for example, or heart conditions or diabetes, or things that we will then use to plan a, a pregnancy going forwards.
[00:11:30] We're looking at, yeah, family history. Uh, we're doing screening, antenatal screening, which, uh, some of the tests there are genomic based. And then after the 20-week scan, for example, if we find some sorts of congenital abnormalities, we can use genomic testing then to find out what, what is potentially wrong with the baby and what we can do about it.
[00:11:50] And then moving forward throughout that pregnancy, genomics is also really important in bereavement care. So if there's a history of multiple miscarriages, for example, or if a baby is stillborn, we can use genomic testing to find out any reasons for that and to hopefully improve, um, care for that woman going forwards as well.
[00:12:08] The big thing that's going on at the moment for genomics in maternity and midwifery is, uh, newborn screening At the moment, our newborn screening is looking for, uh, nine or 10 different conditions, um, which are very rare, but do have some treatment if they are caught early. What we're doing with whole genome sequencing, where genomic testing is looking to see whether we can find a much larger range of conditions much earlier in the baby's life to see if we can improve outcomes for those babies.
[00:12:38] And so that's a huge role of genetics. Yeah, absolutely.
[00:12:41] Sharon Jones: So Fiona, how confident do midwives generally feel about discussing genomics with families, even though Katie's just said it's not sort of nothing new and it's always sort of been there, maybe badged differently. How do you feel that midwives feel about talking about it when they are talking to families?
[00:12:59] Fiona Smith: They probably don't feel, you know, very confident speaking about it. And I definitely wouldn't have been able to speak confidently in a comm- as a community midwife, uh role. But what, what is great about the hospital is that we know that they're where to refer to. So we've got the fetal medicine midwives who are available at any point to talk us through what to say to women or to help us, and the screening team are really useful and are on hand to, again, help us navigate that and what to, you know, what to say to parents.
[00:13:36] We've got a really good patient record system as well, so we should, we, you know, the notes are very accurate. We should be able to, uh, follow through from what the parents have been told already, what their journey looks like. So although we're not 100% confident, but I think the students coming through, they're going to have res- acquire a lot more knowledge.
[00:13:59] And also our midwifery standards imply that genomics should be part of that everyday conversation that midwives are having. So although it isn't something that's familiar within our parlance. I think going forward, I think it definitely will become much more mainstay, if you like, just-
[00:14:20] something that we will be naturally talking about because you know, let's face it, genomics is here. I want to say being part of the Generation Study team, because I'm quite visible and everybody seems to know me because I've, I've transitioned from one role to the other, you know, we are visible. I'm stopped quite a lot, and midwives are asking the questions and, "Well, why?"
[00:14:43] You know, "Why is it important?" Just even to be able to talk about, you know, that we've, we're building up a database, data that's going to be used for future reference. Being able to have those conversations with, with the midwives now will really help that confidence. It's something that I didn't think I'd ever have a conversation with.
[00:15:02] I don't have very deep conversations, but I know where there are people if I do need to get those answers.
[00:15:09] Kate Handley: No, um, I think going with what, what Fiona says, I think it's really interesting that pregnancies generally now are becoming a lot more complex. Um, we're seeing a lot more high-risk pregnancies, and I think that we will find that, that women and their families, their knowledge of genomics is probably going to increase as well because we're going to see genomic testing more widely in, in healthcare, and that's going to have to then flow through into maternity and into midwifery knowledge because women are coming in with more of a baseline knowledge as well.
[00:15:40] And when we're dealing with more complex pregnancies and more high-risk pregnancies, genomics is a huge part of that. We, you know- Mm ... because we're going to be looking at things like pharmacogenetics, where we can see what kind of treatments are going to be best for these women and how that can then impact on their pregnancies.
[00:15:56] I think epigenetics is becoming more and more talked about and more interesting in maternity, you know, and it's really important that midwives are aware that we've been speaking for years about the impact of smoking, alcohol, all of the outside factors on a pregnancy. But when we actually consider that from a genetic point of view, and that these genetic changes could potentially then be feeding down through generations, it brings a whole new level to the, to that aspect of maternity that, that midwives do need to know about.
[00:16:27] So I, I think Fiona's right. I think that there is a lack of confidence when you hear the word genomics, but as soon as you explain what genomics actually means, then that confidence can be boosted. And I think that as we go forwards, there's so much work being done in the training and education systems for universities, for midwives that are already practicing.
[00:16:53] We're really trying to, to improve that confidence and competence. Within the Generation Study, that's something that we're working really, really hard on, is to make sure that we're giving all the really appropriate training to the midwives that are involved in it, and that's not just the research teams that are, uh, that are asking consent from the participants, but that's for the wider team as well to, to help the, the midwives who are taking samples, for example, understand why they need to take that particular blood sample, the importance of taking it at the time, and what that means for the family and how that can impact on, on the future.
[00:17:26] Sharon Jones: So it's kind of a whole literacy raising across the piece, isn't it? Just to sort of go back to a couple of things you said there, for those who might not know who are listening, would you mind just explaining about, um, pharmacogenomics and epigenetics? Because I just wanted to make sure that we put it across for everyone who might not know those terms.
[00:17:44] Katie Handley: So epigenetics, for example, that's looking at how environmental factors can influence gene expression. So how the impact of something on the outside can impact what's going on in the inside. And we do know now that, that environmental factors can change the way that your genes in your body work. So that can not only impact the individual, those gene changes can be passed down through to the next generations as well.
[00:18:12] And we know that this can happen across the placenta, so what a mum does in her pregnancy can then change the gene expression of the baby as well. And then we've got pharmacogenetics, which is looking at how certain drugs and certain treatments can be individualised for personal care. So looking at a person's genome, looking at the way their individual genes all work together, and then seeing how specific drugs, specific treatments can be used for that individual rather than as a population level.
[00:18:43] Sharon Jones: That's really helpful. Thank you. So Jess, did being a participant on the Generation study change how you approach conversations as a midwife? 'Cause you're kind of like in both camps, which is a quite rare and interesting position to be in.
[00:18:58] Jess Fletcher: Yeah, it's been a really amazing insight actually. Um, it definitely will, and I think this will kind of, uh, piggyback off of what, uh, Fiona was, and Katie was saying about how confident are midwives when, when they're counselling for studies.
[00:19:10] So, you know, I'm, I'm particularly passionate about, and I mean mostly all midwives are, but I'm very passionate about making sure, ensuring that the people that we're providing care for are making truly fully informed decisions. Like very informed, you know, not, not just signposting, but making sure that they understand, you know, what does this mean for you?
[00:19:31] Like what could these results mean for you and your family? Because I think the, I mean, this is a wonderful approach in some ways, but very often we'll be met with people under our care that go, "Yes, of course. Like sign me up for absolutely everything." Like the, the more we know, the better. Mm. And actually, I think it's- Then having that discussion about, well, actually, knowing things can be very complex because it then opens up a lot more questions for you and your family, and I'm not, not suggesting that ignorance is bliss, but actually, you know, really ensuring that they truly understand what this could mean for them and for their babies.
[00:20:09] And the positives of that as well, what this could, you know, how this could really optimise your, your child's health throughout their life. And so for me, you know, I've always been very passionate about discussing studies with, with the people that I'm caring for. But it was really amazing actually being on the other side and applying that to me and my family and my baby.
[00:20:32] What I talk about this, you know, every day, and actually Fiona's right, they're a very visible team, and it's, and it's amazing because, well, for Fiona, because often if she's on the birth centre and a bell goes, she's often having to get stuck in clinically in emergencies anyway. So you get a little touch of that every now and then, don't you, Fiona?
[00:20:49] But it means that they are very accessible. I felt I had a really good understanding, but suddenly it felt very personal. And I can't quite remember how it went, whether Fiona approached me or I approached her, because we see each other so frequently at work. I think that when my pregnancy became, you know, common knowledge, correct me if I'm wrong, Fiona, it was more of a like,
[00:21:11] "Oh, here we are again meeting in a corridor. Oh, yay, I can do the study," type of thing.
[00:21:16] Fiona Smith: I think you came and sat in my office to do the consent.
[00:21:19] Jess Fletcher: And that was a really interesting part for me because, of course, as a midwife, you know, you don't get to see behind the curtain, so to speak, as much as what I got to do as a participant. So I got to come and sit with Fiona in the office with the team.
[00:21:33] It was wonderful from the perspective as a pregnant person, but also as a midwife, I've learnt quite a lot, and I think that, of course, I'm not at work, you know, currently, but when I return, um, certainly the way in which I signpost and, and the way that I talk about research and this, and the Generation Study in particular, all of that will still be there.
[00:21:54] But I, I do wonder if there's going to be, there's a much deeper understanding on my side And yeah, I think undoubtedly that's probably going to, uh, I will adapt how I then, um, talk to people about the study because I've, you know, had more of an opportunity to delve into, you know, some of the great stories that have come out of it
[00:22:15] and some of the real successes that have been shared from the team. I think there was very recently a case where a genetic condition was found, but it was found so early that actually his quality of life is now going to be, you know, really optimal. And I just found the whole story really fascinating. So I suppose it's opened a bit more of a door for me on a personal side and a professional side to read more, and I found it, you know, that much more intriguing, I suppose.
[00:22:41] Sharon Jones: Yeah, I suppose it piques that curiosity and also just hearing those good news stories. Yeah, kind of showing how, you know, a family's life has been impacted in such a, sort of the early part instead of having that massive journey of finding out what possibly could be the challenges a child is facing and not knowing, having that result so much early on makes such a difference to, to a family.
[00:23:03] Jess Fletcher: Absolutely. And, and also just I think as well, because I work in safety and quality, you know, the, a huge part of my role is looking at patient experience. It's been great to be on the other, I mean, yes, this is third time around, but this was the first time that I had a baby at this current trust that I'm working at.
[00:23:18] So, you know, it was really great being on the other side of that and actually seeing how streamlined it was, how the communication between the research team and myself as the pregnant person, how efficient it was that I was receiving various things in the post and through the kind of patient portal that we use.
[00:23:36] And then how swift the results were as well.
[00:23:39] I mean, that, I'm sure that can vary between participants, but for me, you know, you're so caught up in the, in the newborn weeks that you can almost forget you were part of a study. And then I, and then I got the results through and I went, "Oh my gosh, of course. I mean, what a wonderful thing to participate in."
[00:23:54] And the fact that we're still a part of it really until he's 16 years old and beyond, if he consents. So I just think, yeah, it's been a really great experience to participate, but it will undoubtedly change how I then talk about it moving forward because I've had this personal experience.
[00:24:11] Sharon Jones: Yeah, yeah. Kind of hearing that seamless experience kind of builds on the trust that, you know, you have in the study and, and, you know, the sort of people behind it essentially, which is, is really important when you're kind of giving your genomic data essentially.
[00:24:25] So it's, it's really good to hear that. Yeah. So looking to the future, it's clear that genomics is going to play a growing role in healthcare, so I'm really interested in what that means for midwifery. How might the role evolve, and what does that mean in terms of supporting midwives who need to feel confident in this space?
[00:24:43] Kate Handley: I think that genomics is going to have a huge impact on maternity care, and I think it's going to be really great to see how we can really improve the personalised care that we give to individuals that come through the maternity system. We try really hard as midwives to treat every single woman that comes through our care as an individual, to personalise her care plan, and the more information that we've got about somebody, the more information they want to share, the better we can look after them and the better care plan we can actually put in place.
[00:25:17] So by using any genomic data that we have, we can really improve that, that care. If whole genome sequencing does become part of newborn screening in the future, we can potentially find these babies every day that we think may have a rare condition, and we can do something to improve their quality of life.
[00:25:37] Sharon Jones: Yeah. That's, that's incredible. If the study continues and, and rolls out into healthcare, that will be, um, such an impactful and, like, really game-changing Sort of effect for everyone.
[00:25:49] Kate Handley: It will be really impactful and game-changing as long as we do it properly, and I think what Jessica was saying is really, really important about genomics can have huge implications for families and for people.
[00:26:00] So it is so important that people understand what they're signing up for in any kind of genomic testing, not just in the Generation study. And because of that, the training that we give to midwives in the future, and I say we, I mean that as universities, as midwives teaching each other, as all education bodies, the information and the education that we give to midwives is so important because the only way that we can ensure that the individual signing up for any kind of genomic testing are giving informed consent is by making sure the people taking that consent are fully informed as well.
[00:26:34] As us going forwards, if all midwives can just embrace genomics, everybody will help each other build to a position where we can provide really, really good care.
[00:26:44] Jess Fletcher: From the perspective of, yes, a midwife, but also someone that's fairly freshly postnatal, you know, decision-making during a pregnancy is actually really complex.
[00:26:53] There's a lot of grey areas, and I think that decision-making, that can be really tough if it's your first experience or if you're suddenly dealing with something in a pregnancy that is more complex than you anticipated, and there's no right or wrong answer, and you're having to make decisions with perhaps not quite all of the information.
[00:27:14] I mean, Katie touched on the non-invasive prenatal testing when we are, yes, we're, we're screening in, in early pregnancy for a number of conditions, but the non-invasive prenatal testing, it's not 100%, but it, it gives us a lot more to work with. And I think everyone interprets risk differently, don't they?
[00:27:34] So if you're given a one in something chance that your baby might have a condition, it's very, can be really difficult and, and a very emotional process to make decisions around that. What's my next move going to be? So if we have the ability with genomics to actually provide a lot more information and kind of broaden the decision-making process, then -
[00:27:59] that can only, I think, be a positive thing, or give them the opportunity to then opt out of any further testing, which is equally as important.
[00:28:08] Sharon Jones: Giving you as much agency to choose without pressure and just giving you as much knowledge that you need to make the best decision that you can in that, in that situation.
[00:28:17] Jess Fletcher: Yeah, the situation that's right for, for you and for your family, which is going to look different for every family, isn't it?
[00:28:23] Kate Handley: And midwives are in such a privileged position because of the amount of time that we potentially spend with a woman and to get to know that woman. We have got the ability to actually explain things in a way that, that woman may be able to understand as well, as long as we've got the knowledge.
[00:28:40] So, you know, genomics can be really, really complex. Mm. And it can be really difficult for people to understand, even if we do have all that information. So by using the relationships that we can build with those women, I'm thinking particularly community midwives or people during the labour room that are building these really intense relationships really, really quickly.
[00:28:58] We really need to be able to use that to our advantage when it comes to actually information given to, to patients as well, and to women and their families.
[00:29:06] Jess Fletcher: We're in a really unique position in our profession because we're very highly skilled at having to explain something quickly and under pressure, and try and capture and provide all of the information possible.
[00:29:18] But also we work as part of a multidisciplinary team, so we've got access to a lot of professionals that can provide input and help with educating the patient, but also educating us. So our knowledge is always growing, especially around kind of research and genomics in, in particular. Yes, it's becoming so much more a part of midwifery.
[00:29:41] So I think, yeah, I, I feel really lucky that, you know, we're not just in a profession that, it, you know, we do this day to day and that's it. It just feels like that there's always a chance to learn and to grow as a professional, and then impart that on the people that we're caring for
[00:29:57] Sharon Jones: So coming to my final question, if you could leave our listeners with one message about midwives and research, what would it be?
[00:30:05] Fiona Smith: I'd say even though it does sound like it's a scary subject, I think we need to embrace it. The technology that's there, you know, we've got it. It's here to stay. Yeah, just don't be scared. Be curious and excited.
[00:30:22] Jess Fletcher: Yeah, and I, I do think... I, I think midwives in general, I feel like when we qualify, we also qualify with a bit of an inferiority complex, you know?
[00:30:30] That we worry about what we don't know, and actually, you're right, Fiona, we really mustn't be scared of this. We, we carry so much knowledge. Our profession is, as we've already spoken about, it's so... It's amazing how much we actually do as midwives and, and how broadly we practice, that actually it's absolutely okay if we're not confident in delivering this information, or we're not confident about, you know, where research is going.
[00:30:55] The most important thing is, is, is accessing support so that we can make sure that we are, for ourselves and for the people that we're looking after, we have a- as deep of an understanding as we possibly can.
[00:31:06] Sharon Jones: Definitely, and, and talking about sort of multi-skilling and, and being kind of pretty amazing, Jessica, I'm, I'm very impressed with our guest that has joined us on, on your shoulder
[00:31:26] Jess Fletcher: The generation study baby!
[00:31:28] Sharon Jones: A newborn baby. A Generation Study baby, that you've, uh, done this entire podcast with your baby.
[00:31:32] Jess Fletcher: He's done amazingly well, hasn't he?
[00:31:35] Sharon Jones: Yeah, he's done very well, and that really does, uh, sort of show the power of your, of your skills, not just a midwife, also as a mum, as we know.
[00:31:43] Jess Fletcher: Always a juggle.
[00:31:45] Sharon Jones: It certainly is. Katie, did you want to add any more about leaving our listeners with a, a message about midwives and, and research?
[00:31:50] Kate Handley: Yeah. I, um... Fiona used the word curious, which I think is, is brilliant. I think if we can all be curious about research, we're already onto a winner. And Jessica said about being brave. The more brave we are as midwives, and the more that we're willing to be curious about what we can do to improve our care, the better we're going to be at our profession. All midwives want to do is to provide safe, effective care that is what is in the best interest of that woman.
[00:32:07] We are advocates for women and for their families. We want what they want. But in order to do that, we have to embrace research, along with safeguarding and health and safety, I feel like it needs to be everyone's responsibility. You know, we all have this responsibility to improve care for, for the women that we're looking after, and research is at the heart of that.
[00:32:30] And the more research that we can do, that we can be part of and that we can implement, the better that our profession will be and the safer that our women will be.
[00:32:39] Sharon Jones: Thank you. Thank you to our guests, Katie, Fiona, and Jessica, and Jessica's newborn baby, for joining me today and sharing your insights into the evolving role of midwives.
[00:32:50] It's been fascinating to hear how midwives are not only supporting families day-to-day, but also contributing to research and helping to bring genomic medicine into routine care. If you'd like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening.
[00:33:06] I've been your host, Sharon Jones. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan, and Patrick Wallace at Bespoken Media.
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In this explainer episode, weâve asked Kate Stanbury, research midwife on the Generation Study, to tell us more about the vital role that midwives play.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What does a midwife do? My name is Florence Cornish, and today I'm joined by Kate Stanbury, who is a research midwife working on the Generation Study, and she is going to be explaining the vital role that midwives play.
So, to start off with Kate, I'm sure that most of our listeners will have heard of midwives before or maybe even like come across them in healthcare settings, but it would be good to hear from you more about what a midwife actually does.
Kate: Yeah, absolutely. So, a midwife is someone who provides care and support to birthing people and their families during pregnancy, labour, and after birth as well. A lot of people just think of midwives as delivering babies, but we do a lot of other stuff around that as well.
There are lots of different types of midwives as well, so we've got community midwives that might come out to your home and see you and your baby. We've got specialist midwives who might have a certain medical condition that they're experts in. And then we also have people like myself who are research midwives as well.
Florence: So, you talked about a couple of different types of midwives there. Could you tell me more about the specific type of midwife that you are?
Kate: Yeah, so a research midwife, as the name suggests, does research, so I also look after women during their pregnancy as well. A lot of the research that we do relates to sort of high-risk pregnancies, and so we approach women for specific research studies that might have a particular characteristic that we are investigating.
We also recruit patients to these studies. We look after them during their pregnancies when they're taking part in the studies, and then we follow them up after their birth as well to collect data and see if what we've done as part of the research has had an impact.
Florence: And so you are working on the Generation Study, and if any listeners want to learn more about that, then they can check out our previous Genomics 101 episode, What is the Generation Study?
Kate, could you tell me a little bit more about what led you to become a midwife? Like what was the journey that you took to get to this point?
Kate: Yeah, so I started my degree in midwifery straight out of college. So, I was quite young at the time, I was 18. I went to university, did a three-year degree to get a bachelor's of midwifery.
That is probably the most common route that people go through in terms of to become a midwife, but some people choose to do adult nursing first, and then they can do a conversion course into midwifery, which is about 18 months long as well. So that's usually the most common route.
I was sort of drawn to the occupation because one of my close friends, her mum was a midwife, so I used to see her in their lounge. They used to have lots of cards and things that she would display from patients that she'd looked after, which was really nice.
Florence: And so what makes you passionate about working in the Generation Study and what motivates you in your role?
Kate: I think being able to have an impact on how we can improve care, I think that's really important. Obviously everything that we do is evidence-based, so that's what really drew me to become a research midwife and being able to take part in research studies that we can look back on in the future and say, âoh, I was part of that, and because of that we've been able to improve the lives of families and babies going forward.â
That's really important to me.
Florence: Yeah. And, and just building off of that, have there been any specific moments that have like stood out to you during your time working on the study?
Kate: Yeah, I think being able to see it from its starting point, so as a research midwife as well as working on the Generation Study. I sort of see people in clinics, I tell them about the study and then they might sign up to it.
But then the other half of my role is a re regional results coordinator for the Generation Study. So I might then see that patient come through to me with a condition suspected result, and being able to follow that family through their sort of patient journey, from consent taking part in the study to getting their baby into NHS care, that potentially we might be able to give treatments really quickly for a baby that might have a really rare genetic problem.
And being able to see that that process works really well and improves those outcomes for that baby and that family. That's really, really something that's amazing to see and what I'm really looking forward to in the future as well.
Florence: Yeah, I can imagine that like getting to experience the kind of like end to end, like see it.
Kate: Yeah, absolutely. Yeah.
Florence: Super cool.
Kate: We don't often get to follow the babies up in my line of work, so it's really nice.
Florence: Yeah. Yeah. I'd also be curious to know has being involved in the Generation Study changed how you think about the space? So whether that's genomics or research or even your role as a midwife, do you see any of those things differently now?
Kate: Yeah, absolutely. I think before I started this role with the Generation Study, genomics was sort of there, but I didn't really know the full details and like much in depth knowledge about genomics and how that could impact on people's health and their pregnancies and their health going forward into the future.
But since doing this job, I think it's really opened my eyes to how much of an impact it can have and how much I think it could potentially improve the lives of generations to come.
Florence: Well, thank you so much, Kate. I think we'll finish there, but I really appreciate you taking the time to come on our podcast.
Kate: Thank you. Thanks for having me.
Florence: If you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.
Thank you for listening.
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In this episode, we celebrate 10 years of the Participant Panel and explore how genomic research is being guided by patient and participant voices.
Made up of people who have consented for their genome, or the genome of their loved one, to be included in the National Genomics Research Library, the Panel plays a vital role in shaping how research is designed, how data is used, and how genomics is communicated. From influencing policy discussions to to advising the Genomics England board, their work helps ensure lived experience is embedded from the very beginning.
Over the past decade, the Panel has driven meaningful change. From advocating for greater transparency and accessibility, to challenging how the genomics community talks about genetic conditions. But beyond the impact, this episode focuses on the people behind the work: their motivations, experiences, and the realities of representing a wider community.
Our host, Sharon Jones is joined by:
Kirsty Irvine â Chair of the Participant Panel and member of the NHS Genomic Medical Service People and Communities Forum Lisa Beaton - member of the Participant Panel, panel member for the North East and Yorkshire GMSA and research and development for Harrogate Hospital Foundation Trust Frances Allan â member of the Participant Panel and member of the following: CRUK Women+s Cancers PPIE at CambridgeMHRA Yellowcard BiobankNorthumberland NHS health forumOvacome HealthforumIMPRESS cancer diagnostic tool study participantYou can find out more about the Participant Panel in our recent Genomics 101 episode which Lisa featured in, titled âWhat is the Participant Panel?â, and you can read about their timeline of achievements over the last 10 years.
âOne of the things as participants that we're always really keen to get across, particularly to the scientists, is that behind every piece of data is a face and a nameâ
You can download the transcript, or read it below.
Sharon Jones: This time on Behind the Genes, we'll be celebrating the 10th anniversary of the Participant Panel, and we'll discuss how genomic research is being guided by patient and participant voices. The panel is made up of participants whose data is held in the National Genomic Research Library. They help us to put lived experience at the heart of our work.
My name is Sharon Jones, and in this podcast we cover everything from cutting-edge research to real-life stories in genomic healthcare. Joining me this time are Kirsty Irvine, chair of the Participant Panel, and Frances Allan and Lisa Beaton, who are also both members. Collectively, they wear many hats for a range of organisations, which are listed in the episode description. As you'll hear, this one is all about people power.
So back in 2016, the Participant Panel was in its infancy, with 12 founding members bringing lived experience of rare conditions. The idea was straightforward but radical: that the people whose genomes were being sequenced should have a real say in how the work was done. Over the decade since, the Panel has shaped some significant changes, from pushing for a service that let participants track their own samples, to publishing a language guide that changed how the genomics community talks about genetic conditions and disability. They've navigated the pandemic, welcomed new members and, in 2025, launched their first formal strategy.
This year they mark their 10th anniversary, and today we're hearing from some of the people who've been part of that story. So welcome Kirsty, Frances and Lisa. So what was your reason for joining the Participant Panel? And I will ask Frances that.
Frances Allan: Hi Sharon. I joined the Panel back in 2023 following a cancer diagnosis, and as part of that investigation I was fortunate enough to have a whole genome sequence performed.
And they also asked would I be interested in taking part in a panel who look after this information, and I ticked the box and then thought no more of it. And then a month or so later I heard from the then Chair, Jillian, um, and had a chat about genomics and joined the Panel, and it was a very good decision that I made.
Sharon Jones: Did you have any kind of expectations? What were your early thoughts when you kind of accepted?
Frances Allan: Not many thoughts. So I was in the middle of my chemotherapy treatment, but one of the things that really stood out: when I signed the consent form, I said, well, of course I would do that. And the clinician consenting me, said, actually, not everybody does.
And I thought, well, why would they not want to do that? So I was really interested in finding out about that. I had no idea how influential the Panel was, and that was great to discover as I became part of it. But seeing the breadth of the research and the knowledge already gained, compared to my rudimentary A-level Biology from many, many years ago, gave me incredible hope, um, and really helped me through a very difficult, difficult time.
Sharon Jones: Yeah, that's, that's amazing. It's amazing that you could kind of think in that way whilst you were actually going through the treatment itself. I mean, how did you split yourself in that way?
Frances Allan: I think it gave me a sense of, of purpose. So at the time, I'd, I'd stopped working to have my treatment and I was a, a vet previously, so I was used to thinking about medical things and problem solving, and it, it filled a, a void in my life. I had no idea I'd be able to contribute to it. I thought, well, I'd learn something from it. But, you know, the, the Panel is managed very well. Kirsty's a fantastic Chair. Everybody gets an opportunity to speak, and the attendance can be in person. And I've done most of them in person.
When I was poorly I attended an online meeting, but even that is managed so well that you get a chance to speak up. If you're not feeling well enough, then you can, you can add it to the chat or email. So it's very, very inclusive and a very supportive environment, as well.
Sharon Jones: Yeah, it sounds like a, a very safe space to be in. And Lisa, what was your reason for joining the Participant Panel?
Lisa Beaton: I think it was sort of one of those, bit of a light bulb moment for me thinking, yeah, I could do that. I'm not quite sure why I felt I was qualified to do that, but my reasoning is slightly different than Frances. So I joined the 100,000 Genomes Project back in 2015 in respect of one of my children who has an undiagnosed, thought to be neuromuscular, syndrome.
Um, so myself, my husband and our daughter recruited for genetic sampling, and over the years I've sort of taken a keen interest in all things genetic and genomic related, followed on kind of various social media platform. And I think if memory serves, I saw an announcement or an advert stating, do you want to be part of the Participant Panel, clicked on the link and thought, this is something that really resonates with me.
I've served with different hats on different kind of participant groups and speaking events, and it's something I feel really, it's an overused phrase, but I do feel really passionate and strong about it because, you know, we are the people who are the front and centre of this, because it's our genetic information.
So I applied, did a bit of a kind of resume of myself, um, then had huge imposter syndrome and thought, oh, that'll be the last I'll ever hear of that. And uh, actually had a really lovely interview with some of the then, uh, members of the Panel and must have said a few of the right things, 'cause here I am, three years down the line.
Sharon Jones: That's amazing. Has it lived up to your expectation? How has it, how has it helped you get through what sounds like a really challenging time?
Lisa Beaton: It's, it probably sounds wrong to say I, I didn't really have an expectation, but I joined it really just wanting to kind of know more and see if I could find out more details, more information, kind of more genomic discovery, and hope that I could give something back, if that doesn't sound too cringey.
I think one of the things I'm always really keen to say is that you don't need to be a geneticist. You don't need to be a scientist. You don't need to kind of have lots of scientific information. And I will confess that the very first meeting I went to, I did come away thinking, I think I probably only understood about one word in three. But three years down line as I say, I'm still here, and it's been good to challenge myself and to explore kind of things that I don't know information about, but also I found that there are areas that I can definitely bring lived experience to and, and hopefully a voice for people like myself and my family.
Sharon Jones: Yeah. That's so important. It sounds like you've become a bit of an expert by, uh, experience there. Has your vocabulary improved in the last three years? Do you know more words now?
Lisa Beaton: Yes. Uh, I've, I have to remind myself not to use an acronym. It's one of my pet peeves. You know, when you're, you're in a, a meeting and terminology or, or vernacular, that is not necessarily something that people would use day-to-day, and I think lots of you know, you don't, don't have to be genomics or genetics to, um, using acronyms for things.
It's something we all need to remind ourselves that just because you know that expression, somebody else doesn't. So it's really important to kind of keep that at a, a lay explanation so that everybody understands it. Um, I think particularly with quite heavy subject matter such as genomics and genetics, there can be a tendency otherwise for people to feel that it's not for them. And of course it is, because it's about our own personal data.
Sharon Jones: Yeah, absolutely. And, um, and coming to you, Kirsty, what were your kind of motivations for, for joining the Participant Panel?
Kirsty Irvine: Well, it's been quite a long journey for me to find myself on the Participant Panel, so I and my family, we were all consented into the a 100,000 Genomes Project back in 2015.
But from that point, I then spent nearly 10 years chairing committees at NHS Digital and then NHS England, focusing on health data access. And I remember talking about the 100,000 Genomes Project at my interviews for those roles. I then went down a different path. And in those roles I was very much wearing my solicitor's hat.
So I was thinking about governance and risk and were we complying with the precise wording of the legislation. And then when the chair role came available, I had a number of people sort of forward it to me saying, I think this would suit you. I think this would suit you. And at that stage, I was aware of the Panel because I'd met the fantastic former chair, Jillian.
Um, so I'd seen Jillian at various conferences and meetings and things, so I was well aware of what the Panel did. I was well aware of the Panel's standing. It was probably the only participant panel that I was aware of in my work with NHS Digital, NHS England. And then I realised, you know, I wanted to be closer to the people behind the data and I wanted to do something more active.
I wanted to bring a bit more of myself. Because when you're chairing a very formal committee, at NHS England, you, you can't talk about the time that you resuscitated your child at home, you know? And on the Panel, you know, my very first meeting, I, I met someone, someone whose child had, you know, been fed with an NG tube for a number of months.
You know, I met someone else who had resuscitated their child, you know, and all of a sudden I could bring more of myself to my colleagues and, and find a real community. So for me, joining the participant panel was a way of shifting the perspective, but to also bring that experience with me because I, the roles at NHS England, you know, from a governance perspective, I couldn't continue chairing those, you know, board subcommittees forever.
But I didn't want that knowledge to just sort of disappear. So for me, I'm really delighted that I've, what I hope, what I hope is a good fit. I feel it's a good fit. So that, that's been my journey to the Panel.
Sharon Jones: Yeah, that's, that's so interesting. And I guess having that space to kind of be yourself, and having understanding because of your lived experience, brings a lot of value to the role that you're doing now in a way that kind of is different when you're in your previous roles of NHS Digital, because you had to be a bit more, kind of stand back from it and, yeah. That's so interesting.
So, what has it been like being part of these groups? You know, the ones that you kind of, you're involved in a lot of things, and we'll list them in the, in the web description. And how has it kind of affected your life, essentially, because it's not the kind of average thing that people are involved in.
Frances Allan: So it's been an incredible, I think as Lisa alluded to, incredible learning curve. We've learnt so much. But the team at Genomics England are endlessly patient and very skilful at passing that information on. And we have access to the leading researchers, the clinicians that are involved in genomics. And they're happy to take any question.
And the questions, however silly, there's no silly question. They're happy to answer that. And so we learn every time we attend a meeting, we have quarterly meetings and that can be in person or online. Um, but we also have regular lunch-and-learns. So if there's somebody we want to speak to or find more about their specialist area, they'll come and have a, a chat with us.
And then we have half of it, them chatting to us and half us, us. Us asking them questions and, and challenging them. Um, so it's very, very informative and then learning from each other. And as Kirsty was saying, you know, this is a, a group of people who've, who've dealt with an awful lot of unique situations and they're happy to, to share that and pass on the information. It's a, it's a great place of learning.
Sharon Jones: Lisa, would you agree with that? How it been for you?
Lisa Beaton: Yeah, I would definitely echo everything that Frances has actually said there, and I think it's a very humbling experience, as well. Ostensibly, we are a, a collection of individuals who have all been brought together, um, purely because of, uh, our genomic interests.
And whether that's for our families, you know, as, as parents, as in my case, or in somebody like Frances' case, who's obviously a participant in her, in her own right. And although there are kind of many differences in our stories, there's also a lot of similarities. But I think what's really interesting, very precious, is that the staff at Genomics England, obviously they range from, you know, there, there's so many different kind of areas from the, the comms, the scientists, etc., but everybody is really interested. They want to know your story, who you are, why you are there. There's a real kind of inclusion focus on that.
And one of the things as participants that we're always really keen to get across, particularly to the scientists, is that, you know, behind every piece of data is a face and a name. And I think they really make that felt when they're chatting to us. You know, we go in and, and there, there's people who are there from governance sides for how the data is accessed by other parties.
There's people there who are the science technicians, etc. There's people who are dealing with the administrative side of things, but every single person that I've encountered wants to know more about you, what you are there for. And that is, is very, very precious. And as Kirsty also alluded to, a lot of us have been through some really quite traumatic experiences.
It, it's not my place to speak of others' journeys, but you know, there, there are, uh, bereaved parents and family members among us. And so we are sharing very precious raw material, emotions, experiences, and that is very powerful, as well. And I, I think the Genomics England staff never forget that. They seem to bear that at the forefront of their, their communications with us, always.
Um, and certainly Kirsty and Adam and previous chairs, uh, of the panel, that inclusivity was entirely throughout every dealing we had with them.
Sharon Jones: It's very humanising and I think that it's humbling for us who work here that that's always at the forefront of our mind, that this is why we kind of get up and go to work every day, because of that human element.
And it's not just a data point. There is a whole family, a story, a history, and that's, that's so important to us in the work that we do. Kirsty, did you want to add your point on this as well?
Kirsty Irvine: I've probably got two points I wanted to raise. One was just to draw out what Lisa was saying, is that it can be complex being a Panel member, because the story you're bringing often isn't just your own.
In my family, we've got a real, we've got a whole range of genetic differences and conditions that, you know, across the extended family. And so when I speak, I'm often drawing on experiences that aren't solely mine to share, and, you know. So I think that's something that for some on the Panel, we're sort of, we're, we're being quite careful to think about what we're saying, and if we're speaking in the public domain, we might be talking about it in more general terms.
So that's, you know, but there's not a single right way, and there's room on the Panel, everyone, for the people who can and, and as Lisa talked about, you know, the, the most acute situation is where someone's bereaved, you know. And it's, so everyone's got different, you know, different experiences. But that, that, again, coming back to the positive side of things, one of the biggest things to me about being on the Panel, what it means to me, is being part of a wider community.
I mean, one of the other things that, Sharon, I don't know if I can sort of segue onto this about, you know, the opportunities that have arisen?
Sharon Jones: Yeah, absolutely. I'd love to hear more about that.
Kirsty Irvine: So one thing that really stands out for me was the opportunity to speak directly with, um, Associate Health Minister Ahmed about, and his policy team.
So we went to the department, Adam and I went to the Department of Health, and it was about the use of GP data in consented research cohorts. So getting the GP data into the National Genomic Research Library. So even though there's consent, up until now, that GP data, that tranche of really rich data, hasn't, hasn't gone into the NGRL. So I'll use that abbreviation now that I've used it in full. And so what was really unique for me was that I'd seen it from multiple angles because I'm participant in the 100,000 Genomes Project, so I'm a cohort member.
I then worked on the consent review for NHS England. I then sat on a, the consent review assessment committee with, you know, a multiparty group. And then, because I was on the panel, I got to see things full circle. I was then invited to, to go and meet with, um, Minister Ahmed and, and advocate for the use of this GP data. And that really matters because something, you know, there's such important information sitting in that GP data and it wasn't a given, it was not a given that the government was going to the direction that allowed that data to go into the NGRL.
And so we were able to talk about how we really wanted that data to be used. And now, going forward, you know, something as simple as BMI or for example, if a, if an individual's coded for a neuro, neurodevelopmental condition like autism, sometimes that data actually only sits in the GP health record. It's in primary care only, so it's not necessarily in the hospital records or other records.
And so this is really, really valuable data for, for researchers. And so that was something that was a really special experience, just being able to see that come full circle. And I felt like it's a really tangible example of how the participant voices really helped strengthen that conversation, you know, with the DH policy team, you know, and the government ministers.
Sharon Jones: Yeah, I mean that's, that's really powerful and it, it just sort of shows how these opportunities can arise from being involved in a participant panel in a way that you wouldn't have necessarily had that power if you hadn't been involved. And you know, obviously you are wearing lots of different hats in that, in that position, Kirsty.
And um, it just sort of shows what can be done when you're, unfortunately, you know, you're in this group for a reason and it's not necessarily the, the most cheeriest reasons, but it, you still leverage that opportunity to create something positive, you know, with it.
Frances Allan: So we've given all sorts of opportunities and we seek to get involved with as many things as we can to speak and have our voice heard.
Um, and one of the things I did last year was, um, do a short presentation to open a stage at the Genomics England Research Summit, which was quite a challenge for me, but I felt very exhilarated having done it. And then a couple of people came up afterwards and just said, oh, thank you for sharing your story.
And a researcher who was slightly older than I, so very experienced, been in his field a long, long time, and he said his clinical years were long behind him, and now he researches within a lab. And actually for someone to say, you know, thank you for, for looking, thank you for finding, had a very profound experience on him.
And he knew there was a clinical benefit; his research was very clinically led. But he said he hadn't thought about the recipients of those findings. And I pointed out every time you have that chat with somebody, come to an event like that, have a network, spend a bit longer in the lab, look for something that you might not find, even if it's a negative finding, there will be somebody eventually that benefits from that.
And I've been a direct recipient of other people putting forward their whole genome sequence, and then a common change was noted in people with the type of cancer that I have, and that then qualified me for a treatment that otherwise I wouldn't have been eligible for, and I wouldn't have been, I wouldn't have been here now.
So it's a very, you know, profound thanks to all the people that are involved from everybody within Genomics England, all the researchers, all the other patients that speak up. We each have a contribution to make.
Sharon Jones: Yeah, that's amazing. That must have been quite a poignant experience when you, you met him at the, um, Summit, of just kind of the other side of the, the world that you don't often see. And they obviously don't see our side of the world, and it's kind of interesting to join those dots and kind of come full circle.
So moving on. In terms of like, collectively, there's a lot of impact that you have and there's a noticeable shift in organisations where people with lived experience are playing, you know, a much bigger role in decision making. Can you help our listeners understand how people are getting involved in governance and shaping research?
Lisa Beaton: From my perspective, it comes back to that word "embedding". I think historically, perhaps there's been an, an almost about-face. Um, it's kind of come at it very backwards, that that embedding has almost happened as an afterthought, which is sort of a bit of a misnomer way of explaining it.
When you're talking about embedding, obviously it should be the foundation. Historically, at least both from the parent, parental perspective, I've seen that with clinicians, for example, that historically I've been made perhaps to feel a bit of a thorn in someone's side, that even though we're there for an appointment about our young person, when I'm asking questions that they don't necessarily want to answer, you know, I'm almost the, the add-on rather than the reason that we're there.
And I think there has been a paradigm shift in everybody's approach to that. So thinking much more about, you know, the, the what's, the wherefores, the whys. How do we ensure that right from the get go, that patient or participant voice is heard, and it shapes the question. And one of our other Panel members frequently uses the phrase, "nothing about us without us", because that is front and centre of why, you know, genomics exists in the first place, really.
Without that data, the conversation ceased to exist. It, it's so vitally important, not just for us as an individual, not just for our family members, but for the greater good, if that doesn't sound too grandiose.
Sharon Jones: No, not at all. And, and, and Frances?
Frances Allan: I think having raised that value of patient advocacy: what we have to say. So it started off, people felt that they should have some, so they included it, but actually once they started to include it, they thought, this does contribute to our study.
And starting at the very beginning of the research project, so what is reasonable to ask participants and patients to do? Is it something that there is benefit from? And trying to see that end goal right at the beginning. And we might help shape a research study that actually goes in a beneficial direction, rather than the researchers starting alone, and then actually getting into the study, and the procedure is, is too painful to endure, there's no clinical benefit, it's not something that can be translated into clinical practice, and it gets abandoned.
So start us right at the very beginning, and our perspectives may not be what, what researchers or clinicians think. Uh, with that lived experience, however empathetic you are, the lived experience is a very unique lens and position to look from.
Sharon Jones: Yeah, it absolutely is. So, given that you are part of a small group and you know, you're representing a much wider community, essentially, like, what are the considerations that you, you have to bear in mind?
Lisa Beaton: I think we can only speak, obviously, to our own individual experience and we are very aware that, you know, diversity, ethnicity, inclusion is something that is a much bigger conversation and certainly something that we want to broaden in, in the panel itself.
And I know there's kind of lots of work and thought going into how that can widen those perhaps more diverse communities that historically... It's not that, there's, there's been a terminology that, you know, they're difficult to access, but actually the question is wrong there. The statement is wrong. It's not that they're difficult to access, it's just that we've been asking that incorrectly.
And we need to ensure that they are, uh, empowered to bring their stories forward and find ways to push forward for their inclusion. We need to ensure that everybody's voices are heard, otherwise the data set is wrong from the off. So I think that's something that we're all very minded when we speak about, and definitely want to, to diversify the pools of data that come in. That, that has huge resonance for, you know, shaping genomic and genetic policies moving forward, for sure.
Sharon Jones: Yeah, definitely. Frances, sort of broadening out that question. Does it feel like a lot of pressure and a lot of responsibility, kind of representing, you know, in this kind of small group where you are almost speaking on behalf of, you know, a lot of people?
Frances Allan: I think it mainly feels like a, a privilege, Sharon, to be in that position, to have a say. And back to my, one of my motivators for joining is why would people not choose to do this? And actually understanding why that is. And is it the, you know, the lack of knowledge of genomics? And there is a lot of, of fear about what can be discovered. But understanding the immense benefits from that so people don't miss out on those opportunities.
Our genomes contain the, the blueprint to us, but also how we would respond in certain situations, and you want everybody to be using those leverage points. You know, cancer's a really difficult disease to manage, and anything you can do to make it slightly easier, slightly more comfortable, slightly more successful, we want to do that.
So every time we speak out and we advocate for the benefits of genomics, we might gain one more person who's going to feel that a successful outcome.
Sharon Jones: Yeah, and who knows what, what that can mean for their family and, and sort of further down the line. So have you got any advice for, or encouragement, or any tips for, you know, potential participants who are thinking of getting involved in, in groups?
You know, it doesn't necessarily mean the Participant Panel, but just generally, sort of groups related to their conditions or their family's conditions.
Frances Allan: Yeah, I think the value of the one's personal experience: don't underestimate that. Everybody has an individual journey and they can comment and reflect on that.
And anybody interested in, in joining our panel, you can include in the, the copy or description, ways they're getting in touch with us and speak to us about what that, what that involves. And uh, Lisa said at the, the beginning, you come and it's a huge learning curve, but there are people to support you and guide you through that way.
And the learning is, is just fascinating. And there's a position for everybody and everybody's point of view to be heard, and you will be heard.
Sharon Jones: Thank you. Lisa?
Lisa Beaton: Yeah, I think I might steal a phrase or two actually from some, uh, well-known brands. But, um, one would be "just do it" and the other would be "feel the fear and do it anyway" because, you know, you are amongst friends, first and foremost. We all, we do tailor our experiences, and clearly we self-censor at times because that's necessary to protect the privacy and dignity of not necessarily ourselves, but as we've already alluded to in our chats, but you know, our family members, the wider people that you are aware will be hearing this.
And you don't necessarily want certain medical information about your family members out there, because it's not your information to share. But in terms of joining the panel and, you know, having a voice, giving more voices, giving more diverse data, we, we need as many people as possible to come. We need more voices.
We need to get our genetic, genomic information out there, uh, in front of the researchers and, and all involved with Genomics England, um, and other patient advocacy groups, as well, because that will only benefit the greater public.
Sharon Jones: Thank you. And Kirsty?
Kirsty Irvine: I'm just thinking about sort of general tips building on what Lisa and Frances have said. You don't need to be a seasoned public speaker. I think that's something, absolutely not. We've got some fantastic speakers in the group. Um, but then we've got people in the group who've got, who have got different skills, so don't think that you need to be ready to give a TED Talk at the first meeting, be that the Participant Panel or whatever group you might be motivated to join.
We, we just need good listeners. I've chaired meetings in the past where people, uh, wanted to contribute via the chat function, and that worked absolutely fine. They would put their incredibly insightful, erudite comments in the chat, and then I would relay them to the group, and that was how we got that person's input, because we realised that they weren't necessarily going to speak up in the forum.
So whatever your communication style, we can accommodate it at the Participant Panel and we would be delighted to hear from you.
Sharon Jones: That's great. Thank you. Um, final question. So what do you hope the next 10 years of participant involvement will look like?
Kirsty Irvine: I think if I could use a little catchphrase, which I'm sure is not mine, but I would like to see us fully integrated as partners, not participants.
I'll put that out there. I mean, Sharon, I wonder if I could sort of also open things up to how are things going to look in another 10 years, because there's been some statistics that have really struck me, uh, at presentations that, that we've heard. One of them being that in the next, you know, within 10 years, around about half the data in the National Genomics Research Library will be from, I don't know if this is the best name for it, the general population.
So that's people who aren't necessarily seeking an answer, or have a diagnosis or a condition. These are people who have donated their genomic data through being part of, you know, research projects. And, as a panel, so Genomics England's evolving and the panel will be evolving. And in 10 years time, the panel will need to be, I believe, true to the original route.
So, 100,000 Genomes Project. Uh, the people who've had their whole genome sequencing through cancer diagnoses. You know, there's a significant COVID cohort, but also people of the gen, general population. So how do we advocate for and look after everyone in that broad group of people. So I think that, that's both a challenge, that's a challenge for us, but it's also really exciting to think how we can meet that challenge.
Sharon Jones: Yeah, definitely one, definitely an opportunity and a challenge, and one that will take a lot of thinking in the next few years. Frances?
Frances Allan: Yeah, thanks Sharon. I think looking forward to that, that 10-year period is how genomics just becomes a normal part of everybody's healthcare, so we all fully understand the benefits of it.
People are willing to participate in it and then using lots of different types of data to go into the National Genomics Research Library. So at the moment, it's mainly genomics material, but there's been a lot of work done with the cancer cohort, putting in diagnostic images, pathology slides, other clinical data, written notes, and this can then be accessed under the strict criteria of the access review committee.
It can be accessed by clinicians, researchers across the world. And we want our research library to be the premium source of that information and to have collaboration with researchers, clinicians, participants, worldwide, to speed up the generation of that information and those positive outcomes. It's a, a very, very rich data source now, and it'll only get bigger as we include people from the general population.
Sharon Jones: That'd be amazing and have some quite incredible global, um, outcomes. Lisa?
Lisa Beaton: I just had a little image actually pop into my head that I, I almost look at it a little bit like we're doing one of those, I think they might be called an "impossipuzzle" where actually we don't have the picture on the box, but we have lots and lots of little pieces that are all going in together and they're making up a really creative, wonderful, fantastic, woven story, a tapestry as you were, of different information that's coming through. And how incredible, you know what, what a wonderful legacy we're building, you know, and this amazing picture that's going to evolve and change and develop over the years to come.
Sharon Jones: That's a wonderful note to end on, so we're going to wrap it up there.
Thank you for listening. A special thanks to our guests, Kirsty, Frances, and Lisa, for joining me today as we discussed how lived experience can shape health research. If you'd like to hear more like this, please subscribe to the Behind the Genes on your favourite podcast app. And if you want to know more about the Participant Panel, you can head to the Genomics England website and listen to our 10-minute explainer podcast, Genomics 101.
Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan and Dave Howard at Bespoken Media.
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In this explainer episode, weâve asked Lisa Beaton, Panel Member and Parent Representative for SWAN UK, to tell us about the Participant Panel.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What is the Participant Panel at Genomics England? My name is Florence Cornish and today I'm joined with Lisa Beaton, who is a Parent Representative for Syndrome Without a Name, Swan UK, and a member of the Participant Panel. And we have a special episode today because it is to celebrate the 10th anniversary, so a decade of the Participant Panel at Genomics England.
Lisa, I think it would be good to start with a quick rundown of what the Participant Panel is. If you had to describe it in a few sentences, what would you say?
Lisa: Ooh, that's tricky actually, to cram all our wealth of expertise and knowledge into that, I guess in just a few sentences. But essentially, we are a group of lay people who have all contributed by way of being on genomic studies, such as the 100,000 Genome, for our data to be held in the NGRL, the National Genomic Research Library.
We may have joined because our children or another family member have a disorder or a syndrome or a condition that requires further genetic testing. So, there are panel members who represent from different cancer communities, there's panel members who have connections with rare disease, and then there's panel members like myself who come from the undiagnosed community, where we joined to essentially try and find a diagnosis in respect of our daughter.
The majority of us don't have any kind of medical background. We're all just individuals who collectively are really interested in where genomics and genetics is going to take us in the future. But probably most importantly, we all feel a sense of responsibility to ensure that there's equity of access, to diversify, to basically ensure that the lived experience of real-life people become more than just the data point to the scientific and research community. We, we are real people.
Florence: Yeah. And could you explain a little bit more about the practical role of the panel? So what you aim to do as a group and what it involves to be a part of it?
Lisa: Certainly. So as a panel, we meet either in person or on Teams approximately four times a year. So quarterly. We also get to listen to what we call 'Lunch and Learns', which have been absolutely fascinating. It's different people from different areas of the scientific and research community who will come along and talk to us about their latest discovery or what new things have been found. What's in pipelines, what we can be looking forward to.
There's all sorts of different aspects of that. So currently a project that's been quite well known in the news is the Generation Study, the study of newborns. There have been research interviews and meetings around cancer studies. It's really exciting actually because every time there's something kind of new to learn or to see where progress is going, and that is just, I guess that's what most of us are there for, really just to see it in action.
The role of the panel really is there to hold accountability, to ensure that, you know, data is being kept in a safe and secure manner, to ask any questions that we have about that.
I think probably, we are all just members of the public, so our interests are widely there to ensure, you know, we're representing what we feel we would want to know, and therefore, hopefully in connection with what other members of who have kindly donated their genetic information and material towards studies so we, we can hold that agency for them and just to get more information, knowledge, share that out there with power.
Power to the people, as it were!
Florence: I'm interested if there's anything in particular that comes to mind that the panel has achieved that you are especially proud of, or that you are the most proud of.
Lisa: Again, I think to squash that into just kind of one or two sentences is probably impossible, because there's so many things that panel members are proud of.
One of the things that has definitely, we feel made a huge difference is the Plain Language Guide. We are absolutely adamant that, you know, everything should be as clear and easy to understand as possible. It's all very well having all the, the science and researchers who, you almost speak like a different language. For us, to get that passionately back to everybody who, who can be involved at different levels.
You know, if you've contributed your time, your information, your DNA to research, then everybody who's done that, whether they speak English as a first language or second language, or if they have any kind of say, learning disability or just different socioeconomic experience, et cetera, it's really key that across the board everybody can, can access the language and terminology that is used around genetics.
To summon up a point that has been used time and again, but is so, so crucial: nothing about us, without us.
Florence Cornish: I can confirm, I'm a very big fan of the Language Guide. I use it all the time, I share it all the time. It's amazing, and you should be very proud of it.
Lisa: Well, we definitely are. When I first joined the panel, one of the things I found really hard was I came into a room and I already had a bit of imposter syndrome.
There were lots of terms being flung around in kind of, and acronyms. It's something we all do in everyday life, and you know, the more used to them you are the more you use them. But actually it's to go back and remind ourselves what those are. You don't want to be sort of 10 steps behind because you're constantly having to go back and, and look something up.
So if you've got that guide there with you, if we ensure that everything is written as plainly and simply, whilst not dumbing anything down, just ensuring that it is accessible, that's incredibly important.
Florence: Yeah, completely. So it's been really great to hear about what the panel does and, and the vital role that they play, and you've given a really great example there.
But I thought it might also be nice to hear about what being part of the panel has meant for you and how it's impacted you just as a person, I guess, if you feel comfortable to share more about that.
Lisa: Yes, definitely. So as I said, when I joined the panel, I did have a bit of imposter syndrome.
Um, I don't have a medical background. I've gained 17+ years of medical experience because of our undiagnosed child, and I suppose I've gleaned quite a lot of information along the way, but clearly I'm not a geneticist. I'm not a doctor. I know what I know and I'm comfortable with that.
I think joining the panel for me gave me back some of who I am as a person. Over the years, I've been 'mum' a lot of the time. Medical professionals in particular face-to-face, utilise that term. And I know it's not meant in any kind of patronising way, but being part of the panel has, has made me become sort of myself as a person again, I'm more than just 'mum'. It's enabled me to meet with fellow parents and caregivers and kind of share that common bond.
Although we all come from different pathways and walks of life, be that the cancer pathway or the rare disease pathway, or the undiagnosed pathway, or in our case a combination of rare and undiagnosed, we share so many different things in common and our experience of commonalities, even if we've come about it from a different pathway, and that gives agency and strength, I think to us as individuals.
We know what we are going through, that lived experience, that real voice really brings it back and I know from chatting to members of Genomics England and being at different networking events that they really hear us when they meet us, we are so much more than just the data.
Florence: Yeah. Thank you for sharing that. And in connection to that, I just wanted to finish off by giving you the opportunity to say, is there one thing that you wish people knew about patient advocacy in general?
Lisa: Yes, come and join us would be my message. We need more people. We definitely need more diversity. We want to hear from everybody and anybody, you know, genetics, genomics affects all of us.
By 2035, I think it is, that it's predicted that more than 50% of medical such encounters will be with a genomic connection. And so to ensure that, you know, we are representing all members of communities across the board, we need more and more people particularly people of different backgrounds, would be something that I would be very keen to see the panel kind of move and diversify into.
Florence: And so, for anyone listening that does want to get involved, how would they go about doing that?
Lisa: So, I think there's probably quite a number of ways. I personally saw some information on Facebook. They're across different social media - X, Instagram, et cetera. So, there's definitely more information there.
Obviously type in their website, Genomics England, and there's different links on the pages there. And come, come and join us. We're a very friendly bunch.
Florence: Thank you so much, Lisa, for sharing more about the Participant Panel and the vital role they play and have done for the last 10 years.
Lisa: Thank you so much for inviting me to be a part of this.
Florence: If you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. Thank you for listening.
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In this episode, we explore how individualised medicines are evolving from ân=1â treatments (a treatment effective for a single individual) into approaches that could transform care for many people living with rare conditions.
Advances in genomic medicine are making it possible to design highly targeted treatments based on an individualâs genetic information. While these therapies may begin as bespoke solutions for a single patient, they can often be adapted, refined or reused to benefit others with similar conditions.
While the research is evolving, the systems needed to deliver these treatments at scale are still catching up. From regulation to access, our guests discuss what needs to change to turn this potential into reality.
Our host Sharon Jones, is joined by:
Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England Mel Dixon, Participant Panel member and CEO and Founder of Cure DHDDSIf you enjoyed todayâs conversation, please like and share wherever you listen to your podcasts.
âHowever rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.â
You can download the transcript or read it below.
Sharon: What if treatments once designed for just one person could now help many others? Thanks to advances in genomic medicine, regulations are changing and research is expanding.
This opens up more options for treatments for rare conditions. But what does this mean and how close is real change? I'm Sharon Jones, and this is Behind the Genes.
We look at how genomics is changing healthcare, covering everything from cutting-edge research to real-life stories.
Individualised medicines are a fast-moving area, but there's still a big gap between scientific progress and what's actually happening to patients. You could call it the gap between hype and hope.
Ana Lisa: However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.
Sharon: Coming up, we'll hear from Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, and Consultant in Clinical Genetics at Cambridge University Hospital, as well as Mel Dixon, member of the Participant Panel at Genomics England and CEO and founder of Cure DHDDS. Mel opens this chat by explaining why developments in individualised healthcare really matter to her.
Mel: This issue is really personal to me. I have three children, two of whom are affected with an ultra-rare DHDDS gene variant, for which there is currently no treatment. Their condition causes symptoms such as, well, it varies between mild to severe learning difficulties, seizures, tremors, and movement and coordination difficulties.
But the, the most worrying thing for us was that this condition is actually also progressive. So over time it becomes more of a Parkinsonism and some patients experience dementia-like symptoms and psychosis. So for us to get a treatment that targets the genetic cause of, of their condition is, like, the most important thing in, in our lives.
If we could intervene now, they could potentially, at the stage they're at, you know, live an independent life with, with some supports. But if the disease is left to progress, it would be a very different outcome for them.
Sharon: I mean, that sounds so difficult and I can't even imagine how life is for you and your family. And I can see what is driving you to find anything to extend the life of your children and to give them that opportunity to, to have a better quality of life. And then Lisa.
Ana Lisa: It's a huge burden for families to carry. And I think at the moment there's an additional layer of burden, which shouldn't fall on families, to feel like they need to forge a pathway for their child to have a chance of a treatment. That's, that's a lot to bear.
Mel: I think as well, families feel they almost have to become mini scientists in their children's specific condition overnight, because you go to these appointments with the consultants and nobody's heard of the condition and they don't know, they just don't really know what to do with you.
So they're asking you, you know, so tell me about this, this gene change. What, what does it do? What does it mean? So you have to become the mini professor in your child's condition to be able to advocate for them. We've had to really learn on our feet so that we're able to advocate and push for research into DHDDS, because without us doing it, nobody else was going to be.
Sharon: Yeah. So that's, you know, that's partly what we're here and what this podcast is for, it's here to support families to, to understand this stuff. And Ana Lisa, can you just break it down to us, what is individualised medicines?
Ana Lisa: An individualised medicine that's made for one individual person. In reality, sometimes there are other individuals that can also benefit from the same medicines, and sometimes actually, although the medicine is made for one specific person, it might be made using a strategy that other patients could also benefit from, either directly, exactly the same, even, or through tweaking them so that they could work for a different patient.
In the context that they're most often referred to at the moment, they're therapies that are being made based on the genetic information about somebody.
Sharon: Thank you. I mean, that sounds amazing. And now coming to you, Mel, what does receiving a diagnosis mean for a family? And how do you navigate the space between finally having answers and the reality that the treatment may not yet exist?
Mel: So for us, I think, we went down the, the diagnostic route in the hope that we would be able to find a treatment for our children, or there would already be a treatment in place. But unfortunately when we got their diagnosis, we were told that their, their condition was ultra rare, neurodegenerative and also newly discovered. So there was, there was no treatment pathway and actually minimal research happening into it at the time.
So it was frustrating, upsetting, um, and it felt like quite a hopeless situation at the start, but actually this was just over three years ago. And through a lot of proactiveness on our part in fundraising, we've been able to better understand the condition and we now have treatments in the pipeline. So in that three-year window, from there being nothing, we now have treatments both in terms of potential drug repurposing candidates and also, um, an individualised therapy called an ASO is also in development for them.
So it was hard, but it's given huge benefit to us. Otherwise, we'd just be going, remaining going from specialist to specialist without having any answers or understanding why their symptoms were progressing.
Sharon: I mean, that sounds really, really tough and you know, coming back to you, Ana Lisa, could you talk us through how genomics is changing the way we can treat rare conditions? You know, what types of individualised medicines now exist and how do they even work?
Ana Lisa: Maybe I'll start with how some of these medicines are working.
So with, without going into details, but the sort of principle that these medicines might be able to, to do something called gene editing. So our, our DNA, uh, the instruction manual is made up of genes and it's now can be possible scientifically to change even a single DNA letter code in somebody to try and ameliorate the symptoms of their rare condition. You know that's phenomenal scientific progress to be able to do that.
I think a lot of people have heard about gene therapy, where one is trying to get into the body a gene or part of a gene that might be able to sort of replace the function of a gene that isn't working as it should. There are various other strategies. So our DNA is actually used to send messages to our body, if you like, to, to decode these instructions.
And so there are medicines that target the next step in this process, the RNA, which are the ASO therapies that Mel was referring to earlier. And really what those are doing are either trying to correct for a protein in our body that isn't working as it should, or to try and get rid of one that shouldn't be there.
And so they can act in different ways. And that's actually quite powerful, because you can, theoretically, use these strategies to correct for different genetic rare conditions. So I think going to the sort of first part of your question, maybe if I can phrase it as "directly at source". If you can go upstream and target in a very direct way the cause of a rare condition, then actually you might be able to apply those same principles to many different types of rare condition.
We know that there are, you know, 8,000 as a very ballpark number of rare conditions, and it might be that these strategies could be used I don't want to say for all rare conditions, but for many rare conditions where we find the genetic cause, these strategies could collectively be a very powerful way to treat them.
And traditionally we've had to understand all the underlying biology, find a druggable target, find a drug that could target that, that's safe, effective, et cetera. And that's a lot of work. And that's still very, very valuable. If we were going to do this for these thousands of conditions, it would probably take us hundreds to thousands of years, collectively.
And these strategies provide a lot of hope for being able to do this in a, in a more efficient way, where we can actually use the information used to treat one rare condition and apply those learnings to another rare condition.
Sharon : I mean, that's really helpful to understand. So if the science is there, why aren't more patients benefiting from it yet? You know, what's standing in the way from your perspective?
Ana Lisa: That's a really good question, and it's complex because the, our whole ecosystem is made up of, of many parts that go from finding a potential strategy that could help a rare condition to a patient benefiting from that. And I think one thing that maybe we haven't touched on yet is the fact that rare conditions can be really rare and affect a really small number of people individually, even though we know collectively they affect so many.
You know, in the past it's been easier, if you're taking a condition that's common, that affects thousands of people, it's easier to see and to be sure whether your new medicine is actually working as you think it does and should, and having the benefits that you think. The, the sort of regulators have really clear guidance.
We have lots of knowledge about how to assess treatments and have a randomised clinical trial, for example. How the reimbursement process may work in a public healthcare system. And when you, when you, when you sort of set down into the really rare, this is difficult for each stage of the journey.
The transformation that's needed is a whole, system-wide transformation to be able to regulate in a scalable, equitable way, these therapies that could actually be an N of one treatment for one individual, that actually maybe one day another individual may also benefit, and sometimes even a group of individuals.
It's not just the, the regulator, it's also how do you make it viable. So again, you have to make it scalable, equitable. And even to implement in the NHS down to this very "N equals one" level, and demonstrate that patients could benefit from these treatments, might require sort of fancier ways of assessing these treatments, whether it's statistics, other methodology and I think it's really the system-wide nature that makes this tricky, but is also a fantastic opportunity for, for collaboration, because that, that sort of end goal and benefits could be so, so great.
Sharon: Yeah, absolutely. And I mean, Mel, for your side of things, it must sound, you know, quite frustrating where the people in the rare community to not see the support being made more readily available?
Mel: Yeah, it is particularly difficult for patients and their families. I think in our case, when you're dealing with a neurodegenerative condition, time is of the essence. So when you know that the science is available or it's ready, but you don't have the systems in place to implement them to the patients so that they can access these much-needed therapies, it's worrying and frustrating.
And also I see our children are affected with, with, you know, one of these N of few conditions that there's, you know, there's only 59 confirmed cases of DHDDS worldwide, and we've seen how the system firsthand doesn't fit ultra-rare patients. We can't, when we were looking at drug repurposing, we can't do a traditional clinical trial because we don't have the patient numbers and we don't have the funding. So a placebo-controlled trial just wouldn't be possible for us when there's only, I think, seven confirmed patients in the UK and, um, four that we're actually in, in, in touch with.
So it does feel, I think, as Ana Lisa was saying, that we really need a system rethink, um, and refit so that it does start to accommodate these ultra-rare conditions, especially now as there's therapies which are showing huge benefit to patients.
Sharon: And so with like all of these challenges, where are you seeing things shift and what does meaningful progress really look like for you?
Mel: At the end of last year, the MHRA announced that they were rewriting the regulatory framework for rare conditions, and that fills us with lots of hope for the future. They're recognising that the traditional systems don't work for particularly ultra-rare conditions, and now that we do have these therapies in the pipeline, we, we want to get the patients to be able to access them. And we're also seeing innovation in how evidence is generated and measured.
We witnessed this firsthand with our son as he was undergoing baseline tests for his ASO therapy. You know, the use of digital biomarkers, of real-world evidence, how they're increasingly being used for these N of one or N of few populations.
And how the individual receiving the treatment becomes their own comparator. So you're not relying on these big natural history studies of the disease or placebo controls. It's you're looking specifically at that individual, getting a really strong baseline and then looking, once they're dosed with the medication, is that improving or stabilising symptoms?
So I think this shift in focus is really meaningful for the ultra-rare community and also for them to be part of the decision-making process of what, what benefits do they want from a drug? Like what is meaningful to them? I think there's much more talk about the patients and how the, what will benefit them most.
It's not necessarily what the scientists would think or research would think would most benefit, but what, what would make a meaningful difference to the patient?
Sharon: I mean, that's good to know because it's kind of putting the person at the centre of, you know, this is what it's all about, isn't it? It's not just the science. We're trying to treat people and it's putting people, people first.
Ana Lisa: Just to build on that, it's exactly that, that awareness that is, is growing, I think, that there are so many people affected by a rare condition and, and however rare your condition is, someone has a right to have hope and that the system should be able to cater for many rare conditions, you know, whether they're an ultra-rare or an actually almost common rare condition, everybody should have a hope that we should be able to find a treatment.
And it's not a hopeless situation that it's, you know, never going to happen or be too difficult. It's quite powerful, hope. If you can solve for the truly individualised medicine, then you at the same time may also be helping everyone in-between a really common condition and a really rare condition, because right now the system works for common conditions. And if you can take it right down to the sort of radical of, example of an individualised medicine made for one person, then you are also forcing the system to a change for everybody else. And I think that's one of the great benefits of thinking about it as a joined-up system.
Sharon: So how do you each navigate between hype versus hope when it comes to rare therapies? Mel?
Mel: I like to focus on hope, because when we got our diagnosis, we felt really hopeless and that's a really dark place for a family to be.
But as we learnt more about their condition and the rare condition landscape and genomics, we actually learned of all these new therapies that were in the pipeline. We were hearing about, you know, recently, conditions like Huntington's Disease that you never, never previously had any disease-modifying treatment, how they're now being able to be treated with gene therapy with really positive effects.
Similarly for other neurodegenerative conditions that have been treated with ASOs, how they're seeing not just disease stabilisation, but improvements. So I know it's, it's still, like, relatively early days with these technologies and therapies, but I think it, it allows families to have hope, which is, which is really, really important, because that statistic, you know, of the, of 95% of rare conditions not having a treatment, it's, it's a really brutal one, uh, to be told at the outset or to learn at the outset.
So, you know, if, if these therapies can, can make a huge dent in that, that would be life-changing. It would make a profound difference to many, many families, and I think there's a lot of reason to have hope, taking all of that into consideration.
Sharon: And then Lisa?
Ana Lisa: I think to work in this area, one needs to be full of hope and optimism because there are so many, um, challenges to overcome as a community. Uh, but I think that means that people are also incredibly collaborative, because they know that we need to work together for this to succeed. And no one, you know, one individual, one organisation can do it on their own.
It truly has to be a crosscutting, collaborative endeavour. The fact that we, in the UK, have resources like the National Healthcare System,Genomics England in partnership with the NHS runs a National Genomic Research Library. And so the fact that you could look at, at tens of thousands of, of genomes for many, many individuals with rare conditions.
That gives me hope because it means that if a treatment is made for another person, it could be in a different country in the world, and if we could find another patient, it doesn't matter what specialty they're under, where they are, we should be able to find them and connect with their clinical team if, you know, if they've consented for the National Genomic Research Library.
And so to me, that feels, that whilst there's, there is a lot of hype in the sense that some of the really well-publicised cases, really had a lot of people working on them and a lot of resources to make it happen. But that gives hope to everybody else that follows that actually it is doable and if we can make better systems, and having these national resources that we do, the fact that, there are a lot of guidelines being written at the moment, both international and national.
And again, they show that the sort of scaffolding is starting to be in place to apply these in an equitable scalable way. It might not be that you're so much looking for a specific rare condition as for a particular type of genetic variant that could be targeted in the same strategic way, and that therefore you could look across many different rare conditions.
So again, all these sort of pieces of the puzzle are, are filling me with, with, with hope.
Sharon: You touched upon, um, inequity there. Now, you know, is there a risk of inequity given what we've talked about in terms of those challenges?
Ana Lisa: I think we, we always have to have the lens of equity in everything we, we do.
And that, and that really does apply to healthcare and, and in fact, probably the whole rare disease community are, are, are not well served in terms of therapies at the moment. There are so few, um, therapeutic options and so I think there's a massive inequity in that this, our systems are not geared, uh, towards rare conditions.
I suppose, you know, different countries have different healthcare systems and some of the sort of first personalised therapies may require a lot of money behind them to, to happen, but they will be pioneers in leading the way for how this can be done. And I think in the UK we have a lot of the infrastructure and the, a sort of a strong, that's very equitable, I think. And so we could do this in a, in a much more open and equitable way.
Sharon: Mel?
Mel: Cost is always, unfortunately, and it, when it's your family that's affected you, you know, you hate the thought that things are coming down to cost and, and money. But I, I think as Ana Lisa said, if, if the system absorbs the initial cost.
You know, it seems that those longer-term costs could come down significantly. We already see with our very small DHDDS community that an ASO, which is an allele specific that was made personally for one, for one child, can actually also benefit my son, even though they have a different variant.
So if the cost of the ASO is 1.2 million per person, but if you suddenly find actually one other person can share that, that's almost halving the, the cost.
And then if then you're finding out that actually, oh no, 3, 4, 5, 10 people can all have that same ASO, suddenly it becomes much more cost-effective and more sustainable. So I think, as we have to think about cost, I think that also allows us to have more hope that these therapies can, the cost of these therapies that are obviously hugely expensive at the moment, can be brought down in the longer term.
Ana Lisa: There are a lot of things that people want to do in the NHS. People can be working under quite hard circumstances, so to talk about making a therapy for one individual can be difficult and people can sometimes, I think, think that it's a pie-in-the-sky conversation.
However, I think that, you know, all the clinicians I know who work with families with rare conditions, what they'd most like to be able to do is to be able to offer a therapy.
And so I think a lot of people see this as a, as a big opportunity, despite these initial hurdles. One thing I often think about is my grandfather, when he was alive, every phone conversation, he would start with, "How many lives have you saved today?" And so I think that's the, that's our challenge.
Sharon: Wow. That's, that's really powerful.
Mel: Just echoing really what Ana Lisa was saying, I feel the, um, inequity lies in rare conditions as a, as a whole, from the point of diagnosis to the lack of pathway, um, to, to the lack of system in place for them. You wouldn't have a patient with a life-changing cancer diagnosis receive that information in a telephone call, and that is the stark reality for many rare disease patients. That's how they receive the, that's how they often receive the news. That was certainly our, our experience. And, and from that point, there was then no pathway. It's just this horrendous feeling of isolation.
And I think now that there are these treatments in place and therapies in, in place, it's about time we change that because often the rare, the rare condition community, and certainly those with ultra-rare conditions as well, they're probably like some of the most underserved members of the community in that it's their parents and their families that have to advocate. Otherwise, without that, they, they often wouldn't stand a chance of understanding the disease, let alone finding a treatment.
So I think the whole system needs to have a reset, to think about these rare condition patients and, put them at the heart as they do for more common conditions.
Ana Lisa : I completely agree. And you mentioned cancer, and there are actually quite a few parallels. So there might be really common cancers that affect a lot of people that are being, uh, subsetted down into different groups depending on the genetics that are related to that particular cancer and therefore what treatments might be most effective.
And so I think there's, there's a lot we can each learn from each other between the rare disease and cancer communities. Perhaps as in rare disease we scale up to apply the same strategies to many different rare conditions and patients. Even if they're being tweaked for their particular genetic variant and cancer, sometimes one is subsetting down to treat specifically that, exactly that cancer subtype.
So there's a lot we can learn and I completely agree that the, the rare disease community deserves the same chance at at treatments, and the hope that that comes with.
Sharon: Thank you. It feels like there needs to be some kind of seismic system change along with this piece around collaboration and how, you know, the science is there, but it's how do we bring it to families who are facing these difficulties with it, you know, their children and, and rare conditions.
We'll wrap it up there. Thank you to our guests, Ana Lisa Tavares and Mel Dixon, for joining me as we discussed the evolving landscape of individualised medicines. And thank you for listening.
If you'd like to hear more like this, please subscribe on your favorite podcast app. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan and Patrick Wallace at Bespoken Media.
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In this explainer episode, weâve asked Georgia Chan, Senior Data Wrangler at Genomics England, to explain what de-identified data is.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What do we mean by de-identified data?
My name is Florence Cornish, and today I'm here with Georgia Chan. Georgia is Senior Data Wrangler here at Genomics England, which just means that she cleans up and adds structure to complicated data so that it becomes usable, and she is going to be telling us much more about the topic of de-identified data.
Georgia, I think it would be a good place to start by talking about the National Genomic Research Library, which is the library that we at Genomics England store data in. So maybe you could explain more about that and what kind of data is in there.
Georgia: Sure. Thanks Florence. So, we have genomic data.
Genomic data is information that comes from a person's DNA. It helps us understand how the body works and why disease happens. This can include whole genome sequencing data, variants found in genes, small differences that make each of us unique, and information about how genes function or how they differ between people.
Genomic data does not include a person's name or who they are. It's biological information, not identity, and it's used to understand health and disease. It's really important to note that by nature, it's nature, genomic information is incredibly rich. We all have millions of common genetic variants, but your whole genome is unique to you. So although genomic data alone can't directly identify you, it still counts as personal data under data protection.
We also have clinical data. Clinical data provides real world context for the genomic data. It shows what's happening in someone's health. This can include diagnosis of a disease or a symptom, treatments that have been received, health outcomes over time, such as remission or progression, and this clinical data that help researchers see how genetic differences relate to symptoms, treatment response, and long-term outcomes.
So, we have both of these kinds of data. Genomic data on its own can be hard to interpret, and clinical data on its own only tells part of the story. Together, they allow researchers to better understand how diseases develop, helps them discover new or more targeted treatments, and it helps them improve diagnosis, care, and outcomes.
And this is why both types of this data are used together in the National Genomic Research Library.
Florence: And so, both of these data types, both clinical and genomic, we say that they are de-identified. But what exactly does that mean?
Georgia: Yes, good question. De-identified data means that information which directly identifies a person has been changed or removed from a health record before researchers can access it.
And in practice, it means that researchers cannot see who the person is. The data cannot be used to contact individuals, and a person's identity is protected by design, which means that necessary safeguards are embedded into every stage of a service or process. So, researchers work with the data, but not with people's identities.
Florence: Could you tell me a little bit more about why it's so important to de-identify data in this way?
Georgia: Sure. De-identification creates a safe middle ground. It means that data can be used to improve healthcare whilst people's privacy and trust is respected. So, without de-identification, every new research question would require individual contact and large-scale, long-term research would be extremely difficult.
With de-identification, we reduce the risk of someone being identified. We prevent inappropriate use of data, and we ensure that data is used only for approved research.
And it's important to note also that it sits alongside a list of other safeguards, so that helps ensure data is used responsibly, such as secure Research Environment, strict access control, independent ethical and governance approvals. And all of those safeguards are provided in Genomics England's Research Environment.
Florence: I think a common question that people might have, or a question that I definitely had when I first heard the term, is how de-identified data is different from anonymous data.
Georgia: Yes, it is a good question. So, anonymised data cannot be linked back to an individual and is no longer considered personal data, whereas de-identified anonymised data, it has identified as hidden from researchers, but it can still be relinked by a trusted authorised organisation if needed.
So, in healthcare research, de-identification is often preferred because it allows long-term follow up. It also allows updates as new health information becomes available, and also allows corrections or withdrawals when they occur and when they're appropriate.
Florence: So say a researcher did find something in the data that they might want to feedback, how can we re-identify that participant? What does that process look like?
Georgia: Researchers cannot re-identify participants themselves. At Genomics England, if researchers do make a new discovery that could help an individual, for example, a possible diagnosis for a rare condition, we have an in-house clinical team who can link back to that individual's details and work with their NHS clinicians to establish if this new insight can be fed back.
So if something clinically important is discovered, research is reported through a formal governance process, and then a trusted authorized team, not the researchers who re-identify the participant, and this ensures that researchers never know who the participant is and individuals remain protected.
Whilst important findings can still benefit patients, and this would only happen when it's ethically approved and clinically appropriate.
Florence: Great. Well, I think we'll finish there. Thank you so much, Georgia, for taking the time to talk us through the meaning of de-identified data and why it is so important to protect participants.
Georgia: Thank you, Flo. And let's remember that de-identified data isn't about hiding information. It's about using it responsibly.
Florence: Absolutely. If you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. Thank you for listening.
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Blood cancers are the fifth most common group of cancers in the UK. But for a small number of people, the condition may have an inherited genetic cause.
In this episode of Behind the Genes, we explore the role of genetics in blood cancer, and what an inherited risk means for patients and their families. Our guests explain what blood cancer is, how inherited factors can increase risk, and why multidisciplinary teamwork is key to supporting families. They also look ahead to future advances, from whole genome sequencing to prevention trials.
Our host Amanda Pichini, Clinical Director at Genomics England, is joined by:
Dr Katie Snape, Principal Clinician at Genomics England and Consultant Cancer Geneticist Bev Speight, Principal Genetic CounsellorDr Sarah Westbury, Consultant HaematologistâBy doing whole genome sequencing we get all of the information about all of the changes that might have happened, we know whether any are inherited, but importantly, weâre certain of the ones that have just occurred in the cancer cells and can help guide us with their treatment.â
You can download the transcript or read it below.
Amanda: Hello, and welcome to Behind the Genes.
Sarah: When we think about blood cancers, itâs a whole range of different conditions and when you talk to patients who are affected with blood cancers or are living with them, their experiences are often really different from one another, depending in part on what kind of blood cancer they have. We also know that blood cancers affect not just the cell numbers but also the way that those cells function, and so the range of symptoms that people can get is really variable.
Amanda: I am your host, Amanda Pichini, clinical director at Genomics England and genetic counsellor. Today Iâll be joined by Dr Katie Snape, principal clinician at Genomics England and a consultant cancer geneticist in London, Bev Speight, a principal genetic counsellor in Cambridge, and Dr Sarah Westbury, and haematologist from Bristol. Theyâll be talking about blood cancers and the inherited factors that increase blood cancer risk. If you enjoy this episode, weâd love your support, so please subscribe, rate and share on your favourite podcast app. Letâs get started.
Thanks to everyone for joining us today on this podcast, weâre delighted to have so many experts in the room to talk to us about blood cancer. Iâd love to start with each of you introducing yourself and telling us and the listeners a little bit about your role, so, Sarah, could we start with you?
Sarah: Sure. Itâs great to be here. My nameâs Sarah Westbury, and Iâm a consultant haematologist who works down in Bristol. And my interest in this area is Iâm a diagnostic haematologist so I work in the laboratories here in the hospitals, helping to make a diagnosis of blood cancer for people who are affected with these conditions. And I also look after patients in clinic who have different forms of blood cancer, but particularly looking after families who have an inherited predisposition to developing blood cancer. And in the other half of my job, I work as a researcher at the University of Bristol. And in that part of my job, Iâm interested in understanding the genetic basis of how blood counts are controlled and some of the factors that lead to loss of control of those normal blood counts and how the bone marrow functions and works.
Amanda: Thank you. Thatâs really interesting, weâll be looking forward to hearing more about your experience. Bev, weâll come to you next.
Bev: Thank you. Hello everyone, Iâm Bev Speight, Iâm a genetic counsellor, and I work at Addenbrookeâs Hospital in Cambridge. I work with families with hereditary cancers in the clinical genetic service, and for the last six years or so have been focused on hereditary blood cancers. So weâve been helping our haematologists across the region to do genetic tests and interpret the results, and then in my clinic seeing some of the onward referrals that come to clinical genetics after a hereditary cause for blood cancer is found. Iâm also part of the Council for the UK Cancer Genetics Group.
Amanda: Thank you, Bev. And Katie, over to you.
Katie: Hello, Iâm Katie Snape. Iâm a genetics doctor and I am a specialist in inherited cancer. So we look after anyone who might have an increased chance of developing cancer in their lifetime due to genetic factors. I am the chair of the UK Cancer Genetics Group, so thatâs a national organisation to try and improve the quality of care and care pathways for people with inherited cancer risk in the UK. And I have a special interest in inherited blood cancers through my work at Kingâs College Hospital, I work in the haematology medicine service there seeing individuals who might have or have been diagnosed as having an inherited component to their blood cancers. So itâs great to be here.
Amanda: Excellent, thank you for those introductions. Iâd like to then dive right in and understand a little bit more about blood cancers. So, Sarah, could you tell us a little bit more about what blood cancer is?
Sarah: Yes, sure. The term blood cancer is used to describe a whole range of different kinds of cancer, all of which affect some part of the blood or sometimes parts of the immune system that kind of gets represented as part of the blood. So itâs really describing a big group of conditions rather than one single kind of condition or entity itself. But like any form of cancer, we understand blood cancers as being conditions where because cells as part of the blood system are rapidly dividing and normally doing so under really well controlled circumstances to produce just the right balance of blood cells and just the right number of those cells. In a cancer affecting those cells, we see that that loss of control results in either too many of one type of blood cell being produced or too few, or that balance being lost. And like any form of cancer, this is because of genetic changes that happen in individual cells that then go on to grow in a way that is not controlled and well regulated.
And because when we talk about blood cancer weâre talking about such a wide range of different kinds of cancer affecting different cells within that blood system, thereâs a really wide range of different conditions. From conditions that we might think of as being like a form of acute leukaemia, so something that produces often symptoms and signs in patients very quickly and they can often feel quite unwell quite soon and then get picked up with having this condition because they present feeling unwell. All the way to chronic and slow growing cancers that can be found completely by chance and serendipity when blood tests are done for other reasons. So when we think about blood cancers, itâs a whole range of different conditions. And when you talk to patients who are affected with blood cancers or are living with them, their experiences are often really different from one another, depending in part on what kind of blood cancer they have.
We also know that blood cancers affect not just the cell numbers, but also the way that those cells function. And so the range of symptoms that people can get is really variable, again depending on which of the blood cells are really affected by that. And it may be that during the course of some of the conversations we have today in this podcast, weâll perhaps focus on particular kinds of blood cancer. But like any cancer, itâs that disruption of the normal growth and development of cells that means that the number and function of those blood cells has been disrupted in some way.
Amanda: Thank you so much for explaining that, Sarah, thatâs really helpful. In terms of across the range of blood cancers, is that something that people can get at any age, and how common is it?
Sarah: It does depend, as we were sort of talking about that really wide range of different disorders that make up that group of blood cancers. And individually each of those blood cancers is reasonably uncommon compared to cancers that we might typically think of, like breast cancer or colon cancer. But actually, if you group blood cancers together, they make up quite a sizeable proportion, and theyâre actually as a group the fifth most common form of cancer thatâs diagnosed in people in the UK. In adults in particular we think that perhaps people diagnosed with leukaemia would make up about 3% of the new diagnosis of cancer made in any year.
Amanda: So coming to you, Bev, when we talk about inherited blood cancers, what are the differences between those and blood cancers more generally?
Bev: So at point of diagnosis, it may not be obvious that somebody with a new blood cancer diagnosis is one of the minority of people in that big group as Sarah has described, who has an inherited cause. So it may not be immediately obvious. However, in the last few years certainly, itâs become more and more routine to do quite broad genetic testing. Often on a bone marrow sample or blood, because that is done looking for genetic changes, which are part of all cancer and we find within cancer cells, that can help with treatment planning. It can also find that there is an inherited cause to that new blood cancer diagnosis. Sometimes that might not be clear cut, sometimes that might be inferred from the genetic tests that are done on the blood or the bone marrow. And the proportion of blood cancers in that huge group which do have an inherited cause is fairly small, the actual proportion will depend a bit on the age of the patient and the specific subtype of blood cancer.
Amanda: Okay, and could you talk us through how some of those inherited genetic factors can increase the chance of a person developing blood cancer, how does that work?
Bev: Yes, so if we know that there is an inherited cause for blood cancer, then what we mean by that most of the time is that a change in a single gene has been found. And that there is enough research evidence and enough known about that specific change in that gene to say to the person whoâs been diagnosed, there is at least in part or perhaps a full explanation for why that blood cancer has developed and this could be shared in the family. So at that point itâs information that not only has implications for the person in treatment, but also their relatives. Depending on what sort of gene alteration it is and which gene itâs found in, there are different inheritance patterns, and that changes the sorts of information that we give about risks for relatives. So for lots of the genetic tests that detect an inherited cause in adults when theyâre diagnosed, thatâs most often what we would call an autosomal dominant inheritance pattern. Essentially that means you only need to have one gene alteration which is in that personâs normal non-cancerous DNA inherited from a parent and can be passed onto a child. And for people in the family who have inherited this one genetic change, then they are likely to be at increased risk of developing blood cancer.
Sometimes with particularly the childrenâs blood cancers, if an inherited cause is found, it can be a different pattern, which we call autosomal recessive. And thatâs where two gene changes are found and one has been inherited from each parent. So parents might be what we call carriers and have one each just by chance, both have been passed onto a child who has developed blood cancer either in childhood or possibly later on, and thatâs the pattern we call autosomal recessive. There are other inheritance patterns too. The third one that we come across being X-linked, and so that has a gender component. Thatâs where thereâs a change on the X chromosome, women have two Xâs, and men have one X and one Y. So sometimes with the X-linked conditions weâre more likely to see the clinical signs of a condition in boys and men because theyâve only got that one X chromosome. But those are less common in the context of talking about hereditary blood cancers.
Amanda: Thank you. Thatâs really helpful to understand. So it sounds like you're saying that these forms of blood cancers that are caused by a single gene are relatively rare. And also by having one of these changes, itâs not a given that that person will develop a blood cancer, but it makes them more likely, and how likely that is might depend on the inheritance pattern or the type of condition.
Bev: Thatâs right. So what weâre saying is it can give either part of full explanation for the blood cancer diagnosis, and it could confer a risk to family members, but that doesnât mean they definitely will develop it. Weâre talking about an increased risk compared to the population risk.
Amanda: Right. I can imagine for those families to some extent it might be helpful to know the underlying reason why they had that blood cancer, but again, thatâs just a small proportion. So, Katie, could I come to you next? What about the rest of all the blood cancers, how do they occur?
Katie: Yes, thanks, Amanda. So most blood cancers will occur just by chance. We also know that there are some environmental factors that can increase the risk of blood cancers, so, for example, serious radiation exposure, something like that. What Bev has described is where there is this sort of quite rare condition where there is a kind of single gene thatâs really important for the blood cells in terms of keeping those control mechanisms that Sarah described. And thatâs not working properly, which has increased the risk of a blood cancer. But we also sometimes see some families where there is more blood cancer, or the same type of blood cancer in that family than we might expect by chance. We think thatâs probably not due to a single high risk genetic factor, but might be due to kind of multiple lower risk genetic factors that are sort of shared by close family members and can add up together to increase the risk a little bit. And we call that familial risk or polygenic risk.
We donât have a test for that at the moment. We wouldnât offer usually any extra screening or testing to those families, but we would just suggest obviously family members are aware of any signs of symptoms of blood cancers and seek any advice if theyâre concerned. But, you know, the majority of blood cancers are not due to genetic factors, and itâs sort of environmental or chance or bad luck.
Amanda: Okay, so itâs clear that obviously blood cancer is almost an oversimplification, within that category thereâs so many different types, so many ways that it could happen in a person. So, Bev, if weâre dealing with that type of blood cancer that is inherited or has some heritability, can you tell us more about what that means for the family? What kind of impacts do you see that having for them?
Bev: Yes, of course. So clearly this is another layer of information thatâs often coming at a family during a time where somebody is often recently diagnosed with blood cancer of one sort or another and is having to take in a lot of information about treatment and all of the uncertainty and anxiety that goes with that. So for this minority of patients and families where there is new information about an inherited cause, that needs conveying in a timely but sensitive way, bearing in mind what else is happening. And for some people it can come as a major shock and really an additional burden at that time. I think the reaction to that will of course depend on lots of factors. And what we also see is that this question about a new cancer diagnosis of any sort, including blood cancers, can generate the question in peopleâs mind, particularly if theyâve got children, about does this change the risk for relatives? So sometimes this new information that, actually, there is an inherited cause is an answer to a question that families have already got. And that might be because of what Katieâs described as familial clustering, there might already have been this known history in the family.
So sometimes this information can feed into that and actually be quite a helpful answer. But itâs quite normal for families to feel quite mixed about this and for different family members to have a different approach to it. When thereâs the offer of what we would call predictive testing, if we found a change in a single gene in somebody with blood cancer which weâre saying is a hereditary cause for that, that might open the door for relatives to access predictive testing. I.e., the opportunity to discuss and possibly take up a genetic test for themselves when they haven't had cancer themselves, but thereâs an opportunity to try and quantify whether or not theyâre at increased risk. We know in families the uptake of those kinds of tests is different, and a lot of it is to do with timing and the way people respond to this in families might depend on their response to the cancer diagnosis in their relative, and of course what else is going on in their life at the time.
This aspect for the family is where clinical genetic services come in, because these initial tests in the person with blood cancer are done in their haematology/oncology setting, and normally the results about an inherited cause has been found are conveyed through that service. Thatâs when a referral to clinical genetics happens. And in our specialist service weâre addressing those additional concerns for the family which arise because of this diagnosis.
Amanda: Thanks, Bev, for explaining that. Sarah, coming back to you. Could you tell me then if someone has an inherited blood cancer does it also change the way that the patient is treated?
Sarah: Well, it certainly can do, and again, it does depend a little bit on the specific circumstances of that particular person and the form of inherited blood cancer predisposition that they have. But certainly if we think about treatment as a whole, then for a lot of people it does affect the way that we might recommend treatments or look after them and their families. So, for example, for some patients who have a diagnosis of an inherited form of blood cancer, we know that some treatments might be more or less effective for their particular set of circumstances. And so that can sometimes influence the specific treatment recommendations that we would make, particularly thinking about, for example, the risks that the cancer might come back again after itâs been treated. Or thinking about whether or not some of the typical drug regimes that might be used might be perhaps more likely to cause them side effects or problems with tolerating that treatment. So it can certainly make some changes in that respect.
For some people, to be fair a minority of people with blood cancers, they may need a stem cell transplant as part of their treatment to hopefully cure them of their blood cancer. And this as I say is a treatment thatâs required for a minority of patients as a whole who have a diagnosis of a blood cancer. But for those people who have got an inherited predisposition and who might be recommended a stem cell transplant as part of their treatment, then knowing about a familial risk for this condition can also be really important. For making sure that if a family member is being considered as a donor for example that weâre being really careful to make sure that weâre not choosing a donor that might also be affected by the same underlying blood cancer predisposition. Because this can obviously cause problems for the person thatâs receiving the stem cells if it turns out that the person theyâre receiving them from actually has the same inherited condition as them. So in that respect knowing about the underlying predisposition and genetic cause for their cancer can be helpful.
But in a more sort of general sense, yes, the other thing that it can have a big difference for is that some of these inherited cancer predispositions and syndromes also have other health conditions associated with them. So it might be that that genetic diagnosis predisposes somebody not only to a form of blood cancer but to other health conditions as well. And so actually knowing about that diagnosis can help their haematologist then make sure that theyâre linked in with the right other medical teams to make sure that those other health conditions are identified if theyâre present and taken care of. And then I think really coming back to what Bev has already touched on, thereâs the sort of bigger picture of just how people are looked after in their own right but also as part of their family unit. And making sure that theyâre given the right information and advice about their health, but also thinking about other family members. And particularly for younger patients who perhaps either are just starting their own families or for whom thatâs not yet a consideration, making sure that theyâve got the information to understand what might be relevant for future family members, if that makes sense.
So itâs not necessarily true to say that for every individual patient knowing that thereâs an inherited blood cancer present will necessarily directly affect the way that the treatment is offered. But you can see that as a part of a bigger picture for a lot of patients, it will make a difference to their care as a whole.
Amanda: And you can really see how the impact is very sort of multigenerational and is going to affect people at all ages and stages of their life, so thatâs really interesting. Katie, Bev spoke a little earlier about the fact that there are genetic tests that can help tell us if blood cancer is inherited. Could you tell us more about what the tests involve, and some of your experience taking families through this?
Katie: Thereâs sort of two main different ways that we might identify somebody has an inherited cause for their blood cancer through testing. So traditionally what has happened, as Bev and Sarah sort of discussed before, is that when a person is diagnosed with a blood cancer, we either take a sample of their blood or bone marrow. To try and look at what are the changes within those cells that have driven that cell to become a cancer cell and have driven this blood cancer to develop. And a lot of the time, as weâve said, itâs not inherited, itâs not genetic, so theyâre what we call acquired changes, theyâre changes that have just happened in the bone marrow or to the blood cells that have caused that kind of particular cell to become a cancer cell. And itâs really important that we look at those because that can help both diagnose the blood cancer, it can give us information about how serious that blood cancer might be, and it can also help us guide our treatments and therapies.
And so if we do those testings, theyâre primarily done within haematology for those sort of diagnostic or prognostic or treatment purposes. We do sometimes see then a change that looks a bit suspicious that it might be inherited for various reason. And if we see something that is in the cancer and it looks like thereâs a potential it could be inherited, we would go on and do a second test. So usually because we canât do a blood test because the cancerâs in the blood, we would take a skin biopsy. And then we would look and see, well, is this change also present in the skin? And if it is, then that indicates that that change is in all of the cells of the body, because itâs in both the blood cancer and itâs in the skin, and therefore itâs likely to be inherited. So thatâs one thing that we do.
And I think that that can be quite challenging for patients. Because they go in to have a test for their blood cancer and then suddenly were being told, âWell, actually, weâve also found something that might be inherited,â and it is something then that other members of the family might have. And as Sarah said, potentially that means that even if your relative was offering to be a bone marrow donor for you, they might not be able to if they also carry the same thing. And so that can be quite tricky just in terms of making sure that weâre guiding the patient and their family members through that process.
And then thinking about the work that Genomics England does, particularly with whole genome sequencing, and this is particularly offered for children and young adults in the paediatric setting. But I think weâre also increasingly, as we progress weâll perhaps talk about this a bit, moving towards whole genome sequencing for adult blood cancers more routinely as well, that that is offered as a sort of standard of care. And what whole genome sequencing is, is it is looking at the entire genetic instruction manual in both the blood cancer cells and in the cells that weâre born with, to look at the inherited or germline genome as well. And the reason that we look at both the cancer cells and the inherited or germline genome is because what weâre trying to understand is firstly, are there any inherited changes that have led to the blood cancer developing? But also, what are the changes that have just occurred in the cancer cells that are going to help us to diagnose and treat that blood cancer?
So by doing whole genome sequencing we get all of the information about all of the changes that might have happened, we know whether any are inherited, but importantly, weâre certain of the ones that have just occurred in the cancer cells and can help guide us with their treatment. And so, again, when weâre talking to patients, we have to explain to them that weâre going to be looking at their entire genetic information. And whatâs interesting about that is it might find things that are not only relevant to blood cancer, but very rarely other findings, incidental findings as well, or we might find things that we donât know about. But I think certainly thatâs something that patients often feel very comfortable with having because it gives them the maximum amount of information.
Amanda: Thanks, Katie. So it really sounds like thereâs a lot of advancements that are being made in genetic technology which potentially brings a lot of new things for you and Bev as genetic specialists, but also for you, Sarah, as a haematology specialist. What does that kind of change for you, and I assume itâs really important then for you all to be working together as a multidisciplinary team?
Katie: Yes, I mean, I think for clinical genetics, we were not involved in sort of haematology pathways for a really long time, and the haematologists are absolute experts in the genomic factors that drive blood cancers. And certainly in my practice, itâs really only been as the technology advanced that we really started finding more and more of these inherited factors, particularly in the adult setting. Because I think in the paediatric and childhood setting, the haematologists again have been managing those conditions very well for years. And I think thereâs places that we really interface and we really need to work together as a multidisciplinary team, understanding the genetic information, really understanding when something that weâve seen in the blood cancer or the bone marrow could be inherited. Do we need to check that? What should that pathway look like? But I think as youâve said, a lot of these are actually really quite new conditions, particularly in the adult setting. And we donât yet 100% know why do some people get blood cancer and some people donât when they have the same inherited factor. Whatâs the actual risk? Are there any other factors modifying it? What makes some people progress to develop a blood cancer and some people not?
And for that we really need to work together to try and gather the data and sort of capture people that have these inherited changes. And hopefully develop a system and an infrastructure that we can follow it long-term and get a lot of information about long-term outcomes, both for individuals with cancer but also their families. And also from looking at doing population studies. Because I think we know that lots of people in the general population might carry some of these inherited changes and never develop a blood cancer as a result of this, certainly ones that seem a bit lower risk. So we really need to work together to understand all of that. But Iâd be really interested in Sarahâs views on that as well.
Sarah: Yes, sure. So I think, as you say, Katie, haematologists have got a long history of understanding and interpreting genetic findings in the sort of acquired or somatic changes that we know are what occurs in some blood cells to drive the cancer forming in the first place. But this kind of newer integration of that with the germline testing is something that is becoming much more mainstream in haematology now, and I think something that people have had to sort of acquire new skills in this area to interpret that alongside. I think as you say, that multidisciplinary working, where weâre able to benefit from both sides of our expertise and knowledge and put that together is so valuable, particularly in those circumstances where there is some uncertainty. And I think as a haematologist, one of the things that I really find a benefit both personally and professionally to help me navigate these tricky questions but that I also think patients benefit from is your expertise and ability to have those really quite tricky conversations with people who are not haematology patients, if that makes sense.
So they may be the relatives of patients who have a haematological diagnosis for example. Who at the moment are entirely well and were just going about their daily business, and theyâre now told that they may or may not potentially have this inherited predisposition. And I think that as haematologists, weâre very used to dealing with potentially quite poorly patients, potentially quite scared patients who find themselves, you know, the recipient of all this quite difficult information. But weâre not necessarily so skilled and experienced at holding conversations with people who donât yet have that diagnosis. And I think that thatâs a really rich area of mutual aid to one another as haematologists and genetic doctors, if that makes sense. And I think your points about understanding actually the real risks and the nature history, as we would call it, of what happens to people who carry these variants that predispose them to blood cancers is something that we can probably only work out by working together. And of course, working with the patients and families that are affected by these conditions so that hopefully for both sides in the future weâll be able to give much better advice to patients and their families.
Amanda: So, Bev, from your experience and as a genetic counsellor, what do you feel are the important things that patients and their families should know as theyâre going through this testing and diagnosis process?
Bev: The things I think families where there is a hereditary cause found should know is that with this new information comes a whole new referral to a dedicated service. Who want to help patients and their family members at risk to navigate this, to adjust the information, and to make decisions that fit with them, about whether to have testing and the timing of that. As we already said, where there is a hereditary blood cancer risk, that risk in family members is rarely 100%. Depending on what the hereditary predisposition is in the family, we may be able to quantify that risk, sometimes we canât always. And the other thing to know which links to that is that there is growing interest in research in this area. That will really help us to improve care in terms of, for example, being able to quantify the risk of developing a blood cancer in relatives who are perfectly well that may have inherited these predisposition gene changes. Or, for example, the other obvious place where we want to make improvements in terms of some sort of evidence-based surveillance for those people who want to find out that they have inherited the genetic change and are at increased risk.
Amanda: Thank you. And overall thereâs been a lot I think weâve been covering today thatâs probably going to be very new to many people. Why do you think itâs important to raise public awareness of inherited blood cancers?
Bev: There have been lots of public awareness campaigns about other cancers, as listeners probably can think about, in terms of for women checking their breasts and breast cancer awareness. And perhaps thereâs been a bit less of that in general for blood cancers. As weâve already talked about, clinical genetics were not so involved in all of the genetic testing happening in blood cancers. Because it wasnât so long ago in the history of how we think about inherited cancers in general that our suspicion of inherited causes in leukaemia was much lower than it is now. So I think that awareness in the public probably will take a bit more effort to bring up. But clearly public awareness about blood cancers in general, symptom awareness, and the fact that occasionally it can be something that is running in the family, clearly better public awareness of that means that people are empowered to ask the right questions. And the questions that might already be in some way going through their minds of their haematology doctors or perhaps of their GP, if theyâve got a family history but are not affected themselves.
Amanda: Wonderful. So, looking now to the future, Katie, what genomic advancements are we seeing or are we likely to see that could impact on the care of people with an increased genetic risk of blood cancer?
Katie: We touched a little bit, I think that whole genome sequencing is expanding. And as we can turn that test around and get it back more quickly that might become more commonplace. And I know Genomics England and the UK Haemato-oncology Network of Excellence have been doing a lot of work in that area. We are very lucky now we have a national inherited cancer predisposition register that NHS England have set up with the National Disease Registration Service. So that will enable us to capture individuals that have these sort of rarer but single gene disorders or conditions that increase the chance of developing blood cancers. And that will enable us to do that sort of longer-term follow-up and get really more information. Weâve touched on this already but I think thereâs really amazing research happening, why do some people develop blood cancers and some people donât, even though everyone carries the same underlying change that increases the risk?
And then I think really importantly, weâre seeing now in some conditions, clinical trials of certain medications to see if that can actually prevent people who carry these inherited changes from progressing to developing blood cancers. So I think all of those things are really exciting and will give us lots more information that we can then help patients and their families, particularly the sort of treatment and trials aspects.
Amanda: And, Sarah, on treatment and trials, how do think genomics might improve the treatment, but also the diagnosis of people with inherited blood cancers in the future?
Sarah: I think, you know, hopefully when we are able to accrue more information about these underlying genetic predispositions and how they actually then affect peopleâs likelihood of developing blood cancer, weâll be able to build on what we have so far to make that just feel much more robust and evidence based. And it feels like at the moment there are many of us struggling to bring together small threads of evidence that have been accrued in the UK but in other centres around the world that are also interested in understanding this inherited blood cancer risk. In such a way that we can actually give patients and their families more clear information and advice about what that means to them. And I think that in terms of the diagnosis of blood cancer, I think this is something that Bev alluded to. If we could better understand who might benefit for example from having regular screening or monitoring blood tests performed to see whether we can detect an emerging blood cancer. Versus identifying those people who actually, the chances of them developing a blood cancer are so small that doing those tests is likely to do them more harm than good. Perhaps by just causing them to be anxious or have other sort of unintended consequences of that kind of testing.
So understanding something more about that natural history, as weâve already alluded to, will hopefully improve our ability to go from the diagnosis of the predisposition condition to working out how to then diagnose the blood cancer on the back of that. And with time, I think as Katie has alluded to, thinking about more specific treatments and more tailored treatments to the individual predisposition condition and the blood cancer. So whether itâs that you're intervening before the blood cancer has developed to try and reduce that happening, or whether itâs that you're then treating the blood cancer after itâs developed. Understanding the genetic basis and what it is that causes that transition would be really helpful and I think that is something that will come but will take time.
And I think on a sort of national level what I would really hope to see over time is that weâre able to use that improvement in evidence base to then be able to bring together perhaps more defined patient pathways. So that if you're diagnosed with a particular condition, one of these leukaemia predisposition syndromes or another form of blood cancer predisposition, thereâs a recognised strategy and set of steps that should be taken for all of those patients. To make sure that theyâre getting equity of care and make sure that everything is being done in a way that feels safe, sensible and appropriate across the country. While still then enabling us to give really personalised treatment to that individual person and what that diagnosis means for them. But I think until weâve gathered more information and more evidence we are just in the process of trying to do that to then bring about those changes.
Amanda: If you enjoyed todayâs episode, weâd love your support. So please subscribe, share and rate us on wherever you listen to your podcasts. Iâve been your host, Amanda Pichini. This podcast was produced by Deanna Barac and edited by Bill Griffin at Ventoux Digital. Thank you for listening.
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In this explainer episode, weâve asked RĂ©ka Novotta, Research Ethics Operations Manager at Genomics England, to explain what informed consent is.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What do we mean by informed consent? My name is Florence Cornish, and today I'm here with RĂ©ka, who is Research Ethics Operations Manager here at Genomics England, and she's going to be telling us much more about it.
I think it would first be helpful RĂ©ka, if you could explain the word consent.
RĂ©ka: The broad definition of consent is that it's the voluntary agreement given by an individual to participate in a particular activity.
We all probably give consent to a lot of different things each day without really realizing it. So, you go on to read the news in the morning, and the website asks for your consent to process cookies. You maybe go to a routine GP appointment later, and you stick your arm out for them to measure your blood pressure. Maybe you even go to a podcast and you give consent to a host to record your voice. So, these are all based on affirmative action made by you while taking into consideration the information that's available to you.
The technical definition of consent often includes that it's freely given, meaning that you are not coerced. That itâs specific, meaning when you stick your arm out for your doctor, you're only agreeing to that part of the examination, and perhaps most importantly, that person needs to be adequately informed for the consent to be meaningful.
Florence: So you gave lots of really interesting examples there. I think it would be good to understand what we mean by informed consent and where this distinction comes in. How does it differ?
RĂ©ka: By informed consent, we mean that the person consenting has been provided with all relevant and necessary information about the activity, in a format that is accessible and understandable for them.
And that latter part of the sentence is really important, because if you go to the doctor and the doctor speaks to you in French, if you speak French, then wonderful, you have all the information that you need. But if you don't, even though the information is technically there, you not understanding it makes it impossible for your consent to be informed.
Similarly, if you think about maybe an older person who's not familiar with technology, if they see a QR code, they might not necessarily know what to do with it, even if it would technically lead to all of the information that they would ever want to know about Genomics England.
Florence: So you mentioned Genomics England, obviously we both work for Genomics England, this is a Genomics 101 podcast. So what do we mean by informed consent in the context of genomics? Where does it come into play?
RĂ©ka: So if we think about informed in a traditional research study, they test a drug, the treatment either works or it doesn't work, and there's analysis of that data, and that's sort of the end of the process.
With genomics, there's a huge amount of information that gets generated and analysed, and the field itself is rapidly evolving. So we may not have an answer today, but we might do tomorrow, which puts our participants' data in the research resource that we manage in a really unique position.
Because of that, it's even more important perhaps for this consent to be ongoing. Consent is often incorrectly considered a tick box exercise, where you receive information, you consider the information, you make a decision, and that's sort of it. Whereas for genomics, it's important that it is an ongoing conversation and it doesn't just stop at the signing of a form.
We also employ what's called a broad consent model. Genomics England manages the National Genomic Research Library, which rather than being a single study, is a resource for a wide range of research uses. It allows us to gain permission via the informed consent conversations for the storage and the use of data and samples for upcoming studies that we don't yet know about.
And this eliminates the need to reconsent each participant every time a researcher starts to use their data for a new research project, and in turn, and this also feeds back to the need for ongoing conversation, a fully informed consent is very hard to achieve at the time of consenting.
Florence: So you mentioned the National Genomic Research Library, and we actually did a previous explainer podcast episode about this. So, if listeners would like to learn more about it, you can check out our previous Genomics 101 episode: What is the National Genomic Research Library?
RĂ©ka, I'd be interested to know, are there any challenges related to informed consent that are specific to the field of genomics?
RĂ©ka: Yeah, so thereâs many fascinating challenges. There's one that I really want to highlight, which is the family aspect. It's a lot more pronounced in genomics than it is in traditional medicine. The information that you receive, it doesn't only affect you, but it also affects your parents, your siblings, your existing, or even your future children, which is quite unique, and there's a challenge in how we articulate that without causing further anxiety.
Florence: So speaking of the challenges there, the family aspect and the fact that genomics as a field is rapidly evolving, I think this highlights how important it is that we embed informed consent into our practices.
Could you tell me a bit about how we're doing this at Genomics England?
RĂ©ka: We follow best practice in informed consent called information layering, where we provide materials for our research in different formats. And this can ensure that participants can get the depth of understanding that they need, without feeling overwhelmed by a massive amount of information from the outset.
So this includes longer and shorter information sheets, providing materials and training for healthcare professionals so that they can have conversations with potential participants. We also have lots of different copy on our website. We have videos, and this podcast as well.
And it's all part of what we call patient and public involvement and engagement or PPIE, which means that we co-produce our materials involving members of the public and patients in the design of our materials, making sure that they present accessible and understandable information.
It is really important for us not to, as you say, mark our own homework. What makes sense to one person might not make sense to another, and it's important to get lots of different perspectives. And I just wanted to shout out the Participant Panel who's a committee of wonderful people who help us, and also keep us accountable in everything that we do.
Florence: What would happen if say, somebody gave informed consent for their data to be stored in the National Genomic Research Library, but then they change their mind and they want to take it back? What would happen then?
RĂ©ka: So we offer 2 types of withdraw from a resource. There is an option to withdraw partially or to unsubscribe, which means that you can leave your de-identified donated data for researchers to analyse, but not receive any updates or contact from us going forward.
You can also decide to withdraw your participation fully, and that's where we make your data unavailable for future research. One of the key pillars in informed consent and the consent model that Genomics England employs, is that research participants can withdraw their consent to participate at any time without giving us a reason.
So, it doesn't matter if you submit your request on a website or on a paper form or if you call us, we will respect your decision with no questions asked.
Florence: Thank you so much for coming on and for walking us through the meaning of informed consent, and why it's so important in the context of healthcare and research.
If you want to learn more about terms we use in genomics, check out our other podcasts at www.genomicsengland.co.uk, or, wherever you get your podcasts. Thank you for listening.
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In this special episode, recorded live at the 2025 Genomics England Research Summit, host Adam Clatworthy is joined by parents, clinicians and researchers to explore the long, uncertain and often emotional journey to a genetic diagnosis. Together, they go behind the science to share what it means to live with uncertainty, how results like variants of uncertain significance (VUS) are experienced by families, and why communication and support matter just as much as genomic testing and research.
The panel discuss the challenges families face when a diagnosis remains out of reach, the role of research in refining and revisiting results over time, and how collaboration between researchers, clinicians and participants could help shorten diagnostic journeys in the future.
Joining Adam Clatworthy, Vice-Chair for the Participant Panel, on this episode are:
Emma Baple â Clinical geneticist and Medical Director, South West Genomic Laboratory Hub Jamie Ellingford â Lead genomic data scientist, Genomics England Jo Wright â Member of the Participant Panel and Parent Representative for SWAN UK Lisa Beaton - Member of the Participant Panel and Parent Representative for SWAN UKLinked below are the episodes mentioned in the episode:
What is the diagnostic odyssey? What is a Variant of Uncertain Significance?Visit the Genomics England Research Summit website, to get your ticket to this years event.
You can download the transcript, or read it below.
Sharon: Hello, and welcome to Behind the Genes.
My name is Sharon Jones and today weâre bringing you a special episode recorded live from our Research Summit held in June this year. The episode features a panel conversation hosted by Adam Clatworthy, Vice-Chair of the Participant Panel.
Our guests explore navigating the diagnostic odyssey, the often-complex journey to reaching a genetic diagnosis. If youâd like to know more about what the diagnostic odyssey is, check our bitesize explainer episode, âWhat is the Diagnostic Odyssey?â linked in the episode description.
In todayâs episode you may hear our guests refer to âVUSâ which stands for a variant of uncertain significance. This is when a genetic variant is identified, but its precise impact is not yet known. You can learn more about these in another one of our explainer episodes, âWhat is a Variant of Uncertain Significance?â
And now over to Adam.
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Adam: Welcome, everyone, thanks for joining this session.
Iâm always really humbled by the lived experiences and the journeys behind the stories that we talk about at these conferences, so Iâm really delighted to be hosting this panel session. Itâs taking us behind the science, itâs really focusing on the people behind the data and the lived experiences of all the individuals and the families who are really navigating this system, trying to find answers and really aiming to get a diagnosis â that has to be the end goal. We know itâs not the silver bullet, but it has to be the goal so that everyone can get that diagnosis and get that clarity and what this means for their medical care moving forwards.
So, today weâre really going to aim to demystify what this diagnostic odyssey is, challenging the way researchers and clinicians often discuss long diagnostic journeys, and weâll really talk about the vital importance of research in improving diagnoses, discussing the challenges that limit the impact of emerging research for families on this odyssey and the opportunities for progress. So, weâve got an amazing panel here. Rather than me trying to introduce you, I think itâs great if you could just introduce yourselves, and Lisa, Iâll start with you.
Lisa: Hi, Iâm Lisa Beaton and I am the parent of a child with an unknown, thought to be neuromuscular, disease. I joined the patient Participant Panel 2 years ago now and Iâm also a Parent Representative for SWAN UK, which stands of Syndromes Without A Name.
I have 4 children who have all come with unique and wonderful bits and pieces, but itâs our daughter whoâs the most complicated.
Adam: Thank you. Over to you, Jo.
Jo: Hi, Iâm Jo Wright, I am the parent of a child with an undiagnosed genetic condition. So Iâve got an 11-year-old daughter. 100,000 Genomes gave us a VUS, which weâre still trying to find the research for and sort of what Iâll talk about in a bit. And Iâve also got a younger daughter.
I joined the Participant Panel just back in December. Iâm also a Parent Rep for SWAN UK, so Lisa and I have known each other for quite a while through that.
Adam: Thank you, Jo. And, Jamie, youâre going to be covering both the research and the clinician side and you kind of wear 2 hats, so, yeah, over to you.
Jamie: Hi, everyone, so Iâm Jamie Ellingford and, as Adam alluded to, Iâm fortunate and I get to wear 2 hats. So, one of those hats is that Iâm Lead Genomic Data Scientist for Rare Disease at Genomics England and so work as part of a really talented team of scientists and engineers to help develop our bioinformatic pipelines, so computational processes.
I work as part of a team of scientists and software engineers to develop the computation pipelines that we apply at Genomics England as part of the National Health Service, so the Genomic Medicine Service that families get referred to and recruited to, and we try to develop and improve those.
So thatâs one of my hats. And the second of those is I am a researcher, Iâm an academic at the University of Manchester, and there I work really closely with some of the clinical teams in the North West to try and understand a little bit more about the functional impact of genomic variants on kind of how things happen in a cell. So, we can explore a little bit more about that but essentially, itâs to provide a little bit more colour as to the impact that that genomic variant is having.
Adam: Great, thank you, Jamie. Over to you, Emma.
Emma: My nameâs Emma Baple, Iâm an academic clinical geneticist in Exeter but Iâm also the Medical Director of the South West genomic laboratory hub, so thatâs the Exeter and Bristol Genomics Laboratory. And I wear several other hats, including helping NHS England as the National Specialty Advisor for Genomics.
Adam: Thank you all for being here. I think itâs really important before we get into the questions just to ground ourselves in like those lived experiences that yourself and Jo and going through.
So, Lisa, Iâm going to start with you. The term âdiagnostic odysseyâ gets bandied around a lot, we hear about it so many times, but how does that reflect your experience that youâve been through and what would you like researchers and clinicians to understand about this journey that youâre on, essentially?
Lisa: So I think ours is less an odyssey and more of a roller-coaster, and I say that because we sort of first started on a genetic journey, as it were, when my daughter was 9 weeks of age and sheâs now 16Âœ â the halfâs very important â and we still have no answers.
And weâve sort of come a bit backwards to this because when she was 6 months old Great Ormond Street Hospital felt very strongly that they knew exactly what was wrong with her and it was just a case of kind of confirmation by genetics. And then they sent off for a lot of different myasthenia panel genes, all of which came back negative, and so having been told, âYes, itâs definitely a myasthenia, we just need to know which one it is,â at 4 years of age that was removed and it was all of a sudden like, âYeah, thanks, sorry.â
And that was really hard actually because we felt weâd had somewhere to hang our hat and a cohort of people with very similar issues with their children, and then all of a sudden we were told, âNo, no, thatâs not where you belongâ and that was a really isolating experience.
I can remember sort of saying to the neuromuscular team, âWell is it still neuromuscular in that case?â and there was a lot of shrugging of shoulders, and it just⊠We felt like not only had we only just got on board the life raft, then weâd been chucked out, and we didnât even have a floaty. And in many ways I think I have made peace with the fact that we donât have a genetic diagnosis for our daughter but it doesnât get easier in that she has her own questions and my older children â one getting married in August whoâs already sort of said to me, you know, âDoes this have implications for when we have children?â And those are all questions I canât answer so thatâs really hard.
Adam: Thank you, Lisa. Yourself, Jo, how would you describe the odyssey that youâre currently experiencing?
Jo: So my daughter was about one when I started really noticing that she was having regressions. They were kind of there beforehand but, I really noticed them when she was one, and thatâs when I went to the GP and then got referred to the paediatrician.
So initially we had genetic tests for things like Rett syndrome and Angelman syndrome, which they were all negative, and then we got referred on to the tertiary hospital and then went into 100,000 Genomes. So we enrolled in 100,000 Genomes at the beginning of 2017, and we got our results in April of 2020, so obviously that was quite a fraught time.
Getting our results was probably not as you would want to do it because it was kind of over the phone and then a random letter. So, what I was told in that letter was that a variant of uncertain significance had been identified and they wanted to do further research to see if it might be more significant. So we were to be enrolled into another research project called Splicing and Disease, which wasnât active at the time because everything had been put on hold for COVID, but eventually we went into that. So, I didnât know what the gene was at that point, when I eventually got the form for going to get her bloods done⊠So that went off and then that came back and the geneticist said, âThat gives us some indication that it is significant.â
So, since that point itâs been trying to find more information and research to be able to make it a diagnosis. There have been 2 sort of key things that have happened towards that but weâre still not there. So one of the things is that a research paper came out earlier this year so thatâs kind of a little bit more evidence, itâs not going to give us a diagnosis but it kind of, you know, sits there. And the other thing is that my geneticist said, âActually, yeah, it looks like itâs an important change.â Thatâs as far as weâve got. So weâve still got work to do to make it a diagnosis or not. Obviously if it is a diagnosis, it is still a one-of-a-kind diagnosis, so it doesnât give me a group to join or that kind of thing.
But now Iâve got that research paper that Iâve read and read, and asked ChatGPT to verify that Iâve understood it right in some places, you know, with the faith that we put into ChatGPT (laughs), Iâve got a better understanding and Iâve got something now that I can look back on, the things that happened when my daughter was one, 2, 3, 4 and her development was all over the place and people thought that I was slightly crazy for the things I was saying, that âActually, no, I can see whatâs happening.â
So, itâs like the pictureâs starting to come into focus but thereâs work to do. I havenât got a timeframe on that, I donât know when itâs going to come together. And I always say that Iâm a prolific stalker of the postman; ever since our first genetic tests youâre just constantly waiting for the letters to drop through the door. So a diagnostic odyssey to me is just waiting for random events.
Adam: I think what youâve both kind of really clearly elaborated on is how youâre the ones that are having to navigate this journey, youâre the ones that are trying to piece this puzzle together, and the amount of time youâre investing, all whilst navigating and looking after your child and trying to cope with the daily lived experience as well.
And something youâve both touched on that Iâd love to draw out more is about how exactly was the information shared with you about the lack of diagnosis or the VUS or whatâs going on, because in our case you get this bit of paper through the post that has all these numbers and itâs written in clinical speak and we had no conversation with the geneticist or the doctors.
You see this bit of paper and youâre reading it, scared for what the future will hold for your child, but Iâd love to know like how were you communicated whilst all this is going on, how did you actually find out the next steps or any kind of future guidance.
Lisa: So I think in our case we kept sort of going onto neuromuscular appointments, and I think for probably the first 5 years of my daughterâs life I kind of had this very naĂŻve thought that every time we turned up to an appointment it would be âthe oneâ and then⊠I think it wouldâve been really helpful actually in those initial stages if they had said to us, âActually, we donât know when this is going to happen, if itâs even going to happen, you need to kind of prepare yourself for that.â
It sounds fairly obvious to say but you donât know what you donât know. And in some ways we were getting genetic test results back for some really quite horrible things and they would tell us, âOh itâs good news, this mitochondrial disorder hasnât come up,â and so part of you is like, âYay!â but then another part of you is thinking, âWell if itâs not that what is it?â And weâve very much kind of danced around and still donât really have an answer to whether itâs life-limiting.
We know itâs potentially life-threatening and we have certain protocols, but even that is tricky. We live in North Yorkshire, and our local hospital are amazing. Every time we go in, if itâs anything gastro-related, they say to me, âWhatâs the protocol from Great Ormond Street?â and I say, âWe donât have oneâ (laughs) and that always causes some fun. We try to stay out of hospitals as much as we absolutely can and do what we can at home but, equally, thereâs a point where, you know, we have to be guided by where weâre going with her, with the path, and lots of phone calls backwards and forwards, and then is it going to be a transfer down to Great Ormond Street to manage it.
And actually the way I found out that nothing had been found from 100,000 Genomes was in a passing conversation when we had been transferred down to Great Ormond Street and weâd been an inpatient for about 6 weeks and the geneticist said to me, âSo obviously with you not having a diagnosis from the 100,000 GenomesâŠâ and I said, âSorry? Sorry, what was that? Youâve had the information back?â And she said, âWell, yes, did nobody write to you?â and I said, âNo, and clearly by my shock and surprise.â
And she was a bit taken aback by that, but it happened yet again 2 years later (laughs) when she said, âWell you know everythingâs been reanalysedâ and I said, âNo.â (Laughs) And, so thatâs very much, it still feels an awful lot like Iâm doing the heavy lifting because weâre under lots of different teams and even when theyâre working at the same hospital they donât talk to each other. And I do understand that theyâre specialists within their own right, but nobody is really looking at my daughter holistically, and there are things that kind of interrelate across.
And at one of the talks I attended this morning they were talking about the importance of quality of life, and I think that is something that has to be so much more focused on because itâs hard enough living without a diagnosis, but when youâre living with a bunch of symptoms that, I think the best way I can describe it is at the moment weâve got the spokes of the umbrella but we donât have the wrapper, and we donât know where weâre going with it. We canât answer her questions, we canât even necessarily know that weâre using the most effective treatments and therapies for her, and sheâs frustrated by that now, being 16, in her own right, as well as we are.
And Iâm panicking about the navigation towards Adult Services as well because at the minute at least we have a clinical lead in our amazing local paediatrician but of course once we hit and move into that we wonât even have him and thatâs a really scary place to be, I think.
Adam: Jo, is there anything you wanted to add on that in terms of how youâve been communicated to whilst all this is going on?
Jo: Yeah, so I think part of what makes it difficult is if youâre across different hospitals because theyâre not necessarily going to see the same information. So obviously it was a bit of a different time when I got our results, but I got our results on a virtual appointment with a neurologist in one hospital, in the tertiary hospital, and because he could see the screen because it was the same hospital as genetics, and he said, âOh youâve got thisâ and then the letter came through later.
When I had my next appointment with the neurologist in our primary hospital, or secondary care, whatever itâs called, in that hospital, he hadnât seen that, so Iâm telling him the results, which isnât ideal, but it happens quite a lot.
What I think is quite significant to me is the reaction to that VUS. I have to give it, the doctors that look after my daughter are brilliant, and Iâm not criticising them in any way but their reaction to a VUS is âIâm so grateful for the persistence to get to a diagnosis.â
Neurologists are a bit more like âOh itâs a VUS so it might be significant, it might be nothing.â Actually, as a patient, as in a parent, you actually want to know is it significant or not, âDo I look at it or not?â And, I mean, like I said, there were no research papers to look at before anyway until a few months ago so I didnât have anything to look at, but I didnât want to look at it either because you donât want to send yourself off down a path. But I think that collective sort of idea that once someone gets a VUS we need a pathway for it, âWhat do we do with it, what expectation do we set the patients up with and what is the pathway for actually researching further?â because this is where we really need the research.
Adam: Thank you, Jo. So, Emma, over to you in terms of how best do you think clinicians can actually support patients at navigating this odyssey and whatâs the difference between an initial diagnosis and a final diagnosis and how do you then communicate that effectively to the patients and their family?
Emma: So I think a key thing for me, and itâs come up just now again, is that you need to remember as a doctor that the things you say at critical times in a patientâs or parentâs journeys they will remember â theyâll remember it word for word even though you wonât â and thinking about how to do that in the most sensitive, empathetic, calm, not rushed way is absolutely key.
And there are some difficulties with that when youâre in a very high-pressure environment but it is absolutely crucial, that when you are communicating information about test results, when youâre talking about doing the test in the first place, youâre consenting the family, youâre explaining what youâre trying to do and those conditions, you balance how much information you give people.
So, you were talking earlier about âSo you havenât got this diagnosis, you havenât got that diagnosis,â I often think itâs⊠Weâre often testing for numerous different conditions at the same time, I couldnât even list them all to the parents of the children or the patient that Iâm testing. Itâs key to try and provide enough information without overwhelming people with so much information and information on specific conditions you are just thinking about as a potential. Sometimes very low down your list actually but you can test for them.
Because people go home and they use the internet and they look things up and they get very, very worried about things. So, for me itâs trying to provide bite-sized amounts of information, give it the time it deserves, and support people through that journey, tell them honestly what you think the chance of finding a diagnosis is. If you think itâs unlikely or you think you know, sharing that information with family is helpful.
Around uncertainty, I find that a particular challenge. So, I think weâve moved from a time when we used to, in this country, declare every variant we identified with an uncertain significance. Now, if we remember that weâve all got 5 million variants in our genome, weâve all got hundreds and hundreds⊠thousands and thousands, in fact, of variants of uncertain significance in our genetic code. And actually, unless you think a variant of uncertain significance genuinely does have a probability of being the cause of a childâs or a patientâs condition, sharing that information can be quite harmful to people.
We did a really interesting survey once when we were writing the guidelines for reporting variants of uncertain significance a few years ago. We asked the laboratories about their view of variants of uncertain significance and we asked the clinicians, and the scientists said, âWe report variants of uncertain significance because the clinicians want themâ and the clinicians said, âIf the labs put the variant of uncertain significance on the report it must be important.â And of course, if youâre a parent, if the doctorâs told you the variant is a variant of uncertain significance of course you think itâs important.
So, we should only be sharing that information, in my opinion, if it genuinely does have a high likelihood of being important and there are things that we can do. And taking people through that journey with you, with the degree of likelihood, the additional tests you need to do and explaining to them whether or not you think you will ever clarify that, is really, really key because itâs very often that they become the diagnosis for the family. Did I cover everything you thinkâs important, both of you?
Lisa: I think the one thing I would say is that when you are patient- or parent-facing, the first time that you deliver that news to the parent⊠you may have delivered that piece of news multiple times and none of us sit there expecting you to kind of be overcome with emotion or anything like that but, in the same way that perhaps you wouldâve had some nerves when, particularly if it was a diagnosis of something that was unpleasant, you know, to hold onto that kind of humanity and humility. Because for those patients and parents hearing that news, that is the only time theyâre ever hearing that, and the impact of that, and also, theyâre going on about with their day, you donât know what else theyâre doing, what theyâre juggling.
Weâre not asking you all to be responsible for kind of, you know, parcelling us up and whatnot but the way information is imparted to us is literally that thing we are all hanging our hats on, and when weâre in this kind of uncertainty, from my personal experience Iâm uncomfortable, I like to be able to plan, Iâm a planner, Iâm a researcher, I like to sort of look it up to the nth degree and that, and sitting in a place without any of that is, itâs quite a difficult place to be. And itâs not necessarily good news for those parents when a test comes back negative, because if itâs not that then what is it, and that also leaves you feeling floundering and very isolated at times.
Adam: Yeah, and you touched upon the danger of like giving too much information or pushing families down a particular route, and then you have to pull them out of it when itâs not that.
You talked about the experience you had, you felt like youâd found your home and then itâs like, âWell, no, no, sorry, actually we donât think itâs that.â And youâve invested all of your time and your emotion into being part of that group and then youâre kind of taken away again. So itâs to the point where you have to be really sure before you then communicate to the families, and obviously in the meantime the families are like, âWe just need to know something, we need to know,â and itâs that real fine line, isnât it?
But, Jamie, over to you. Just thinking about the evolving nature of genomic diagnosis, what role does research play in refining or confirming a diagnosis over time?
Jamie: So itâs really, really difficult actually to be able to kind of pinpoint one or 2 things that we could do as a community of researchers to help that journey, but perhaps I could reflect on a couple of things that Iâve seen happen over time which we think will improve things. And one of thatâs going back to the discussion that weâve just had about how we classify genetic variants. And so, behind that kind of variant of uncertain significance there is a huge amount of effort and emotion from a scientistâs side as well because I think many of the scientists, if not all, realise what impact thatâs going to have on the families.
And what weâve tried to do as a community is to make sure that we are reproducible, and if you were to have your data analysed in the North West of England versus the South West that actually youâd come out with the same answer. And in order to do that we need guidance, we need recommendations, we need things that assist the scientists to actually classify those variants.
And so, what we have at the moment is a 5 point scale which ranges from benign to likely benign, variant of uncertain significance, unlikely pathogenic variant and pathogenic variant. Itâs objective as to how we classify a variant into one of those groups and so itâs not just a gut feeling from a scientist, itâs kind of recordable measurable evidence that they can provide to assist that classification.
So in many instances what that does is provide some uncertainty, as weâve just heard, because it falls into that zone of variant of uncertain significance but what that also does is provide a framework in which we can generate more evidence to be able to classify it in one direction or another to become likely pathogenic or to become likely benign. And as a research community weâre equipped with that understanding ââ and not always with the tools but thatâs a developing area â to be able to do more about it.
What that doesnât mean is that if we generate that evidence that it can translate back into the clinic, and actually thatâs perhaps an area that we should discuss more. But kind of just generating that evidence isnât always enough and being able to have those routes to be able to translate back that into the hands of the clinicians, the clinical scientists, etc, is another challenge.
Adam: And how do you think we can drive progress in research to deliver these answers faster, to really try and shorten those diagnostic journeys, like what are the recommendations that you would say there?
Jamie: So being able to use the Genomics England data thatâs in the National Genomic Reference Library, as well as kind of other resources, has really transformed what we can do as researchers because it enables teams across the UK, across the world to work with data that otherwise they wouldnât be able to work with.
Behind that thereâs an infrastructure where if researchers find something which they think is of interest that can be reported back, it can be curated and analysed by teams at Genomics England and, where appropriate, kind of transferred to the clinical teams that have referred that family. And so having that pathway is great but thereâs still more that we can do about this. You know, itâs reliant on things going through a very kind of fixed system and making sure that clinicians donât lose contact with families â you know, people move, they move locations, etc. And so, I think a lot of it is logistical and making sure that the right information can get to the right people, but it all falls under this kind of umbrella of being able to translate those research findings, where appropriate, into clinical reporting.
Adam: Thank you. And, Emma, is there anything you would add in terms of like any key challenges that you think need to be overcome just to try and shorten the journeys as much as possible and find the answers to get a diagnosis?
Emma: I think trying to bridge that gap between some of the new technologies and new approaches that weâve got that we can access in a research context and bringing those into diagnostics is a key area to try to reduce that diagnostic odyssey, so I really want to see the NHS continuing to support those sorts of initiatives.
Weâre very lucky, as Jamie said, the National Genomic Research Library has been fundamental for being able to reduce the diagnostic odyssey for large numbers of patients, not just in this country but around the world, and so trying to kind of look at how we might add additional data into the NGRL, use other research opportunities that we have in a more synergistic way with diagnostics I think is probably key to being able to do that.
We are very lucky in this country with the infrastructure that weâve got and the fact that everything is so joined up. Weâre able to provide different opportunities in genomics for patients with rare conditions that arenât so available elsewhere in the world.
Adam: Great, thank you. I think weâre it for time, so thank you very much to the panel. And Iâd just say that if you do have any further questions for ourselves as participants then weâre only too happy to pick those up. Thank you for lasting with us âtil the end of the day and hope to see you soon.
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Sharon: A huge thank you to our panel, Adam Clatworthy, Emma Baple, Jo Wright, Lisa Beaton and Jamie Ellingford, for sharing their insights and experiences.
Each year at the summit, the Behind the Genes stage hosts podcast style conversations, bringing together researchers, clinicians and participants to discuss key topics in genomics. If youâre interested in attending a future Genomics England Research Summit, keep an eye out on our socials.
If youâd like to hear more conversations like this, please like and subscribe to Behind the Genes on your favourite podcast app. Thank you for listening.
Iâve been your host, Sharon Jones. The podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac.
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In this special end-of-year episode of Behind the Genes, host Sharon Jones is joined by Dr Rich Scott, Chief Executive Officer of Genomics England, to reflect on the past year at Genomics England, and to look ahead to what the future holds.
Together, they revisit standout conversations from across the year, exploring how genomics is increasingly embedded in national health strategy, from the NHS 10-Year Health Plan to the governmentâs ambitions for the UK life sciences sector. Rich reflects on the real-world impact of research, including thousands of diagnoses returned to the NHS, progress in cancer and rare condition research, and the growing momentum of the Generation Study, which is exploring whether whole genome sequencing could be offered routinely at birth.
This episode offers a thoughtful reflection on how partnership, innovation, and public trust are shaping the future of genomic healthcare in the UK and why the years ahead promise to be even more exciting.
Below are the links to the podcasts mentioned in this episode, in order of appearance:
How are families and hospitals bringing the Generation Study to life?How can cross-sector collaborations drive responsible use of AI for genomic innovation?How can we enable ethical and inclusive research to thrive?How can parental insights transform care for rare genetic conditions?How can we unlock the potential of large-scale health datasets?Can patient collaboration shape the future of therapies for rare conditions?https://www.genomicsengland.co.uk/podcasts/what-can-we-learn-from-the-generation-studyâThere is this view set out there where as many as half of all health interactions by 2035 could be informed by genomics or other similar advanced analytics, and we think that is a really ambitious challenge, but also a really exciting one.â
You can download the transcript, or read it below.
Sharon: Hello, and welcome to Behind the Genes.
Rich: This is about improving health outcomes, but itâs also part of a broader benefit to the country because the UK is recognised already as a great place from a genomics perspective. We think playing our role in that wonât just bring the health benefits, it also will secure the countryâs position as the best place in the world to discover, prove, and where proven roll out benefit from genomic innovations and we think itâs so exciting to be part of that team effort.
Sharon: Iâm Sharon Jones, and today Iâll be joined by Rich Scott, Chief Executive Officer at Genomics England for this end of year special. Weâll be reflecting on some of the conversations from this yearâs episodes, and Rich will be sharing his insights and thoughts for the year ahead. If you enjoyed this episode, weâd love your support, so please subscribe, rate, and share on your favourite podcast app. So, letâs get started.
Thanks for joining me today, Rich. How are you?
Rich: Great, itâs really good to be here.
Sharon: Itâs been a really exciting year for Genomics England. Can you tell us a bit about whatâs going on?
Rich: Yeah, itâs been a really busy year, and weâll dive into a few bits of the components weâve been working on really hard. One really big theme for us is itâs been really fantastic to see genomics at the heart of the governmentâs thinking. As weâll hear later, genomics is at the centre of the new NHS 10-year health plan, and the governmentâs life sciences sector plan is really ambitious in terms of thinking about how genomics could play a role in routine everyday support of healthcare for many people across the population in the future and it shows a real continued commitment to support the building of the right infrastructure, generating the right evidence to inform that, and to do that in dialogue with the public and patients, and itâs great to see us as a key part of that.
Itâs also been a really great year as weâve been getting on with the various programmes that weâve got, so our continued support of the NHS and our work with researchers accessing the National Genomic Research Library. Itâs so wonderful to see the continued stream of diagnoses and actionable findings going back to the NHS. Itâs been a really exciting year in terms of research, publications. In cancer, some really exciting publications on, for example, breast cancer and clinical trials. Really good partnership work with some industry partners, really supporting their work. For me, one of the figures we are always really pleased to see go up with time is the number of diagnoses that we can return thanks to research thatâs ongoing in the research library, so now weâve just passed 5,000 diagnostic discoveries having gone back to the NHS, it really helps explain for me how working both with clinical care and with research and linking them really comes to life and why itâs so vital.
And then, with our programmes, itâs been great to see the Generation Study making good progress. So, working with people across the country, more than 25,000 families now recruited to the study, and weâre beginning to hear about their experiences, including some of the families whoâve received findings from the programme. Itâs really nice to see and hear from Freddieâs family, who talked to the press a bit about the finding that they received. Freddie was at increased risk of a rare eye cancer, and really pleasingly, it was possible to detect that early through the screening that was put in place. Again, it really brings to life why weâre doing this, to make a difference and improve health outcomes.
Sharon: Thatâs an incredible 12 months. Diving into that Generation Study piece and for listeners who donât know what that is, itâs a research study in partnership with the NHS that aims to sequence the genomes of 100,000 newborn babies. On an episode from earlier in the year, we had mum, Rachel Peck, join the conversation, whose baby Amber is enrolled on a study. Letâs year from Rachel now.
Rachel: From the parentsâ point of view, I guess thatâs the hardest thing to consent for in terms of you having to make a decision on behalf of your unborn child. But I think why we thought that was worthwhile was that could potentially benefit Amber personally herself or if not, thereâs the potential it could benefit other children.
Sharon: Consent has been such a big area of focus for us, Rich, and Rachel touches on that complexity, you know, making a decision on behalf of her unborn child. Can you talk a bit about our approach to consent in the Generation Study and whatâs evolving in that model?
Rich: Yeah. Itâs been for the whole study, really, starting out asking a really big question here, what weâre aiming to do is generate evidence on whether and if so, how whole genome sequencing should be offered routinely at birth, and thatâs responding to a really ill need that we know that each year thousands of babies are born in the UK with treatable rare conditions. We will also need to see if whole genome sequencing can make a difference for those families, but we realise to do that, as with all screening, that involves testing more people than are going to benefit from it directly themselves. So, you have to approach it really sensitively. Thereâs lots of complicated questions, lots of nuance in the study overall. One of them is thinking really carefully about that consent process so that families can understand the choices, they can understand the benefits and risks. This is still a research study. Weâre looking to understand whether we should offer this routinely. Itâs not part of routine care at this point. The evidence will help decision-makers, policymakers in the future decide that.
At the beginning of the programme, we spent a lot of time talking to families, talking to health professionals who understand the sorts of decisions that people are making at that time of life, but also are experts in helping think about how you balance that communication. That involved, as I say, a lot of conversations. We learnt a lot, lots of it practical stuff, about the stage of pregnancy that people are at when we first talk to them about the study, so that people arenât hurried and make this decision. What weâve learnt in the study, right from the outset, is talking to people from midway through the pregnancy so that they really have time to engage in it and think about their choice. So, itâs an important part of getting the study design right so that we run the study right. Itâs also a really crucial element of the evidence that will generate from the study so that we can understand if this is something thatâs adopted, how should we communicate about it to families. What would they want to know? Whatâs the right level of information and how do we make that accessible in a way that is meaningful to people from different backgrounds, with different levels of interest, different accessibility in terms of digital and reading and so on. Thereâs a lot that weâve learnt along the way and thereâs a lot that weâre still learning. And as I say, important things that weâll present as evidence later on.
Sharon: Thank you. Itâs fascinating there are so many moving parts and a lot to consider when youâre building the design of a programme like this or study like this.
Earlier in the year you had a great conversation with Karim Beguir about the developments of AI in genomics. Letâs revisit that moment.
Karim: We live in an extraordinary time. I want to emphasise the potential of scientific discovery in the next two or three years. AI is going to move, letâs say, digital style technologies like coding and math towards more like science and biology. In particular, genomics is going to be a fascinating area in terms of potential.
Sharon: So, Karim talks about AI moving from maths and coding into biology. Why is genomics such a natural area for AI?
Rich: Itâs really fascinating. I think it links a lot to how we think about genomics and how you get the most value in terms of health benefit and sort of the progress that we can see could come through genomics more generally. So, your genome, which is your DNA code, written in 3 billion little letters across each one of us, one copied from mum, one copied from dad, even just our genomic code of one person is a large amount of data. That is just part of the story because weâre not just interested in DNA for DNAâs sake, this is about thinking about health and how we can improve health outcomes. So, itâs also thinking about the other sorts of information that needs to link to genomic data to make a difference. Whether thatâs just to provide routine healthcare with todayâs knowledge, or whether itâs about continuing to learn and discover.
As I mentioned at the beginning, I think a really important part of this whole picture is weâve learnt a lot in the last 20/30/40 plus years about genomics. Itâs incredible how much progress has been made, and weâre really just scratching the surface. Take rare disease and the progress thatâs been made there, itâs wonderful how many more families weâre able to help today. We know that many thousands of families we still canât find a diagnosis for when we know that there is one there for many of them. That theme of ongoing learning is at the centre of all of our work, and that will continue as we look about broader uses of genomics in other settings beyond rare conditions and cancer. Itâs also that ongoing learning, but also the amount of, at the moment, manual steps that are required in some of the processes that we need to, for example, find a diagnosis for someone or to make sure the tools that we use are the most up to date, the most up to date with the medical literature, for example. AI is a tool that weâre, as the whole of the society, weâre beginning to see how it can play a role. We see it as important today for some of the just really practical things. I mentioned it, staying up to date with the medical literature, making sure that we and our systems are aware of all of the knowledge thatâs coming in from around the world. Itâs got real potential there.
I think the biggest bottom line here is that itâs got the potential to be a really important tool in terms of our ongoing learning and improvement. Iâm a doctor by background, the human intelligence alone is fantastic, itâs moved us a long way, but we know it also has tremendous blind spots. AI has the potential to complement us there. I guess another thing to really call out here, AI isnât a panacea, itâs not suddenly going to answer all of the questions. And, just like human intelligence, it will have its own biases, have its own strong points, and less strong points.
One of the things weâre really committed to is working with people like Karim, and many others, to understand where AI could make a difference, to test it, to generate evidence on how well it works and an understanding in all sorts of ways about how that might play out. And, make sure that as AI becomes a tool, that we in genomics, but also in other areas, we understand its strong points and where we need to be more careful and cautious with it. Thatâs a really important part of what weâre going to be doing in the coming years here, is making sure that we can maximise the impact of it, but also be confident, so that we can explain to people whose data we might use it on how weâre doing it and what itâs bringing.
Sharon: Thanks Rich. Itâs definitely a fast-moving conversation of which we really want to be part of. One of the things thatâs come up again and again this year is participation and co-production. Letâs hear quote that really captures that.
Bobbie: In an earlier conversation with Paul, which you might find surprising that itâs stuck with me so much, he used the word âextractiveâ. He said that heâd been involved in research before and looking back on it, he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it, and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants.
Sharon: That was Professor Bobbie Farsides talking about moving away from extractive research towards true co-production. How are we making that shift in practice here at Genomics England?
Rich: Itâs a great question. Itâs one of the areas where I think weâve learnt most as an organisation over the years about how really engaging from the beginning with potential participants in programmes, participants who join our programmes, people who are involved in delivering our programmes and healthcare is so important at the beginning. I mentioned earlier the work to think about the consent process for the Generation Study, and thatâs one of the areas where I think from our first programme, 100,000 Genomes Project, we learnt a lot about how to do that well, some of the pitfalls, some of the bits that are most challenging. And really, right from the start of our programmes, making sure that people who will potentially benefit from the programmes, potentially join them, can be part of that engagement process, and really part of the design and the shaping of the research questions, the parameters around research, but also the materials and how people will engage with them. And thatâs one of the key capabilities we have internally as an organisation, so we work with partners externally, but also itâs a really key part of the team that we have at Genomics England.
Sharon: So, whilst Bobbie talked about moving away from research that can feel one-sided and towards true collaboration, in another episode, Lindsay, a parent of a child with a rare condition, reflected on what that change really means for families and how itâs empowering to see their voices and experiences shaping future treatments.
Lindsay: Historically, thereâs been a significant absence of a patient voice in rare disease research and development. And knowing that thatâs changing, I think thatâs really empowering for families. To know that professionals and industry are actually listening to our stories and our needs and really trying to understand, that offers much greater impact on the care and treatments of patients in the future.
Sharon: So, what role do you see participants as partners in shaping the next phase of Genomics Englandâs work?
Rich: So, as you probably detected from my last answer, we see it as absolutely vital. One of the really exciting things here at Genomics England, weâve had a participant panel from very early in our life as an organisation. Thatâs one really important route to us at the heart of our organisation, part of our governance, making sure that participants representing all sorts of parts of our programme, but rare conditions being a really large focus for us. And I think, whatâs so striking as someone with a medical and a research background can see how I think historically medics and researchers have sometimes not known, sort of maybe been a bit scared about knowing how to involve participants from the outset. Often, because theyâre worried that they might ask the wrong questions in the wrong way, they just donât have the tools.
One of the things I often say now to people we work with is one of the most empowering and positive experiences we have at Genomics England is the power of our participants helping to, right from the beginning, shape what the questions are that we should be asking. Realise some of the challenges that you canât possibly, if youâre not in their shoes, understand are the most important to really shape how we prioritise our work internally, the problems that we need to solve first, how we think about some of the practical impacts on peopleâs lives that, again, without hearing from their voice you just wouldnât know. And again, to help our researchers, people accessing data in the National Genomic Research Library, helping them make sure that they involve participants in their work and the confidence and tools to do that.
Sharon: Thatâs great, thank you. Another big theme this year has been collaboration across the NHS, academia, and industry. Dr Raghib Ali puts this really well.
Raghib: There are areas where academia and the NHS are very strong, and there are areas where industry is very strong, and why working together, as we saw, you know, very good examples during the pandemic with the vaccine and diagnostic tests, etc., a collaboration between the NHS, academia, and industry leads to much more rapid and wider benefits for our patients and, hopefully, in the future for the population as a whole in terms of early detection and prevention of disease.
Sharon: So, how does collaboration fit into the 10-year health plan and whatâs next for 2026 in that space, Rich?
Rich: I think one of the most enjoyable parts of my role at Genomics England and our role as an organisation is the fact that we see ourselves very much as part of a, sort of team across the UK and in fact internationally in terms of delivering on the potential we see for genomics. So, we have a vision as an organisation, which has been the same the last 5 or so years, which is a world where everyone can benefit from genomic healthcare. In fact, that vision is now shared by the NHS from a genomics perspective, and really demonstrably, the 2 parts of the system absolutely pointing in the same direction. And when weâve been thinking, looking forward with that 10-year lens on it, what we always like to do, and I think itâs a real privilege to be able to do, because weâre here in the UK, because we have a National Health Service, because thereâs been that long-term commitment from government on genomics and really taking a long-term investment view there, and because of so many other parts of the ecosystem, other experts who access data in the National Genomic Research Library, research organisations like Our Future Health, UK Biobank, all teaming together, and the expertise thatâs there in genomics more broadly. So weâve, if you like, worked back from what the UK could do as whole, and in the 10-year health plan, as I said earlier, genomics is at the heart of that.
Thereâs a double helix on the front cover and, in fact, on the watermark on almost every page. And, thereâs this view set out there where as many as half of all health interactions by 2035 could be informed by genomics or other similar advanced analytics. And we think that thatâs a really ambitious challenge. We see a really important role for us, as Genomics England, in contributing to that, but itâs very much a team effort. Our role is around where we have the biggest capabilities, so around building and running digital infrastructure at a national scale for healthcare delivery and for research, to building evidence to inform future policies, so running programmes like the Generation Study to inform future policy. And really, as part of that, that evidence piece, being driven by engagement, ethics, and work on equity, to really make sure that evidence that future policy can be built on is informed by a fully rounded view. We think if we do that right that we could as a country with others, the NHS, research organisations, many others could live up to that ambition thatâs set out there in the 10-year plan.
And the 10-year plan is really clear, and government is really clear that this is about improving health outcomes. But itâs also part of a broader benefit to the country because the UK is recognised already as a great place from a genomics perspective. We think playing our role in that wonât just bring the health benefits, it also will secure the countryâs position as the best place in the world to discover, prove and where proven role out benefit from genomic innovations. And we think itâs so exciting to be part of that team effort.
Sharon: So, Genomics Englandâs refreshed mission and direction of travel is really setting out how we move from research to routine care, and how we embed genomics across the health system. Carlo Rinaldi captured the idea perfectly, imagining a future where diagnosis and hope arrive hand in hand.
Carlo: My dream is that in five to ten yearsâ time an individual with a rare disease is identified in the clinic, perhaps even before symptoms have manifested. At that exact time the day of the diagnosis becomes also a day of hope, in a way, where immediately the researcher, the genetic labs, flags that specific variant, that specific mutation. We know exactly which is the best genetic therapy to go after.
Sharon: And Rich, what are your thoughts on that?
Rich: I think Carlo captures it really well. And for us, I think a really big theme is for that potential for genomics to make a difference, a continued and in fact increased difference for people with rare conditions and cancer, areas where itâs already making a difference, but also with the potential to make a much broader impact for people across the population. The real theme is embedding genomics into routine care, making it something that you donât need to know that youâre seeing an expert in genomics to benefit from it, really make sure that those benefits can be felt as just part of routine care. Itâs not something separate where we recognise that the best healthcare is healthcare thatâs supported by all sorts of inputs, with genomics being a key part of that, and that we can continue to learn as we do that. So that with peopleâs consent, with their understanding of how their data is being used, we know that if we donât have the best answer for them today, we give the best answer we can today, and we can continue to learn, and they can benefit from that in the future.
Iâm a rare disease doctor by background, and one of the really most enjoyable parts of my job is seeing that come to practice. In the last year or so Iâve had a number of families where Iâve been seeing the family for years, and a researcher accessing data in the National Genomic Research library has found an answer that weâve not been able to find for maybe their childâs whole life, and then finally weâre able to feed it back. Seeing that come to life is just so wonderful, and I think gives us a bit of a blueprint for how things could work more generally.
Sharon: Thatâs great. I mean, what a feeling for those families who do get those answers. As we look ahead to 2026 and beyond, the conversation is starting to include prevention, using genomics not just to diagnose conditions but to predict and treat and even prevent them. Alice Tuff-Lacey summarised this nicely in an episode about Generation Study.
Alice: This is quite an exciting shift in how we use whole genome sequencing, because what weâre talking about is using it in a much more preventative way. Traditionally where weâve been using it is diagnostically where we know someoneâs sick and theyâve got symptoms of rare condition, and weâre looking to see what they might have. What weâre actually talking about is screening babies from birth using their genome to see if theyâre at risk of a particular condition. And what this means is this raises quite a lot of complex ethical, operational, and scientific and clinical questions.
Sharon: Rich, when you think about 2026, whatâs your biggest hope for where weâll be this time next year?
Rich: I think itâs a really exciting time. As you can tell from how weâve been speaking, Iâm really excited about the direction of travel and how over the next 5 and 10 years we can really make a transformational shift because of how well placed we are in the UK from a genomics perspective. Where we are with todayâs knowledge, where we could be because of the continued government and NHS commitment to genomics being at the heart of this, if we build the right infrastructure, if we generate the right evidence to inform whatâs adopted, I think weâre in a really exciting place.
From a 2026 perspective, I think what weâre really committed to is continuing to do the work, the day-by-day-by-day work that is to build that incrementally. So, a really big focus for us is continuing to support the NHS and making sure researchers can access data, so that flow of answers for families can continue and grow, accelerate, to continue delivering the Generation Study because itâs a really important part of that wider jigsaw to generate the evidence that can inform future policy on whether this is something thatâs adopted and offered routinely to every child when theyâre born.
I think a really important time now that the governmentâs provided the opportunity for us as a team, as a UK genomics and life sciences ecosystem, is to really put in place some of the next steps, the building blocks that can take us towards that 10-year vision. So for us also, a really important part of the year is beginning the design process for an adult population genomics programme, where weâre looking at what evidence itâs important that we can provide thatâs complementary to different work around by others in the ecosystem that needs to be there if weâre going to think about that potential broader use of genomics.
Sharon: Thatâs great. It sounds like another exciting year ahead. So, weâre going to wrap up there. Thank you to Rich Scott for sharing your reflections on the key milestones this year, and for your thoughts on the year ahead. Thanks, Rich.
Rich: Thanks very much for having me.
Sharon: If you enjoyed todayâs episode, weâd love your support, so please subscribe, share, and rate us on wherever you listen to your podcasts. Iâve been your host, Sharon Jones. This podcast was produced by Deanna Barac and edited by Bill Griffin at Ventoux Digital. Thank you for listening.
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In this explainer episode, weâve asked Dr Katie Snape, principal clinician at Genomics England, cancer geneticist, and specialist in inherited cancer, to explain how genomics can help us understand cancer.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Flo: How can genomics help us understand cancer?
I'm Florence Cornish, and today I'm joined with Katie Snape, who is Principal Clinician here at Genomics England, lead Consultant for Cancer Genetics at the Southwest Thames Centre for Genomics, and Chair of UK Cancer Genetics Group.
So Katie, it's probably safe to say that everyone listening will have heard the word cancer before. Lots of people may have even been directly affected by it or know someone who has it or who has had it, and I think the term can feel quite scary sometimes and intimidating to understand. So, it might be good if you could explain what we actually mean when we say the word cancer.
Katie: Thanks, Florence. So, our bodies are made up of millions of building blocks called cells. Each of these cells contains an instruction manual, and our bodies read this to build a human and keep our bodies working and growing over our lifetimes. So, this human instruction manual is our genetic information, and it's called the human genome.
Throughout our lifetime, our cells will continue to divide and grow to make more cells when we need them. And this means that our genetic information has to contain the right instructions, which tell the cells to divide when we need new cells, like making new skin cells, for example as our old skin cells die, but they also need to stop dividing when we have enough new cells and we don't need anymore. And this process of growing but stopping when we don't need anymore cells, keeps our bodies healthy and functioning as they should do.
However, if the instructions for making new cells goes wrong and we don't stop making new cells when we're supposed to, then these cells can grow out of control, and they can start spreading and damaging other parts of our body. And this is basically what cancer is. It's an uncontrolled growth of cells which don't stop when they're supposed to, and they grow and spread and damage other tissues in our body.
Florence: So, you mentioned there that cancer can arise when the instructions in our cells go wrong. Could you talk a little bit more about this? How does it lead to cancer?
Katie: Yeah. So the instructions that control how our cells should grow and then stop growing are usually called cancer genes. So our body reads these instructions a bit like we might read an instruction manual to perform a task.
So if we imagine that one of these important cancer genes that has a spelling mistake, which means the body can't read it properly, then those cells won't follow the right instructions to grow and then stop growing like they should. So if our cells lose the ability to read these important instructions due to this type of spelling mistake, then that's when a cancer can develop. As these spelling mistakes happen in cancer genes, we call them genetic alterations or genetic variants.
Florence: And so, when you're in the clinic seeing somebody who has cancer, what kinds of genomic tests can they have to help us find out a little bit more about it?
Katie: So the genetic alterations that can cause cancer can happen in different cells. So that's why cancer can affect many different parts of the body. If a genetic alteration happens in a breast cell, then a breast cancer might develop. If the alteration happens in a skin cell, then a skin cancer could develop. We can take a sample from the cancer. This is often known as a biopsy, and then we can use this sample to extract the genetic information to read the instructions in the cancer cells, and when we do this, we are looking for spelling mistakes in the important cancer genes, which might of course, those cells to grow out of control.
We can also look for patterns of alterations in the cells, which might tell us the processes that led to those genetic alterations occurring. For example, we can look at patterns of damage in the genetic information caused by cigarette smoke, or sunlight, or problems because the cell has lost its ability to mend and repair its genetic information.
And we can also count the number of different alterations in the cancer cell, which might tell us how different that cancer cell is from our normal cells, and that can be important because we might be able to use medications to get our immune system to attack the cancer cells.
So where we see genetic alterations in a cancer cell, we call them acquired or somatic alterations because we weren't born with them, but they've happened in a cell in our body at a later stage, and they've caused those cells to become uncontrollable and to keep growing.
Sometimes people can be born with a genetic alteration in a cancer gene that significantly increases the chance of them developing cancer in their lifetime. This type of genetic alteration can be inherited, and so these changes can be shared by relatives. If we see more cancer in a family than we would expect by chance, or unusually young cancers or patterns of cancer, or there are other signs that a cancer patient might have an inherited cancer gene causing their cancer, then we can offer a test to check for this as well.
Florence: And so, when we do these tests, what are we looking for specifically? What is it that we're trying to find out about a person's cancer that could help us to treat it as effectively as possible?
Katie: So all of these genetic tests are helping us understand why a cancer has developed and what are the underlying changes that cause the cells to grow out of control. If we understand why the cancer developed, we can choose medications to try and treat the cancer and these specifically target the underlying problems in the cell, and hopefully attack the cancer cells, but not the normal cells in the body.
We call this precision or personalised medicine. Many newer cancer drugs specifically target the changes that have occurred in the cancer cells as part of this process for becoming cancer, and they kill those that carry specific genetic changes which have caused those cells to grow uncontrollably.
Florence: I wanted to ask you now about inherited cancer risk. So by this we mean if a parent has a change in one of their genes that increases their risk of developing cancer, there's a possibility that they can then pass this gene along to their children. Is there anything we can do to manage these inherited risks?
Katie: If a person has an inherited change, increasing cancer risk, we can offer them programs to help reduce that risk. There are different things that we might offer them. So, for example, for some conditions we have preventative medication. There is a condition called Lynch syndrome, which is due to a change in some cancer genes, and people who have Lynch syndrome have a high chance of developing bowel and womb cancers, amongst others.
For people with Lynch syndrome, they can take a daily low dose aspirin, and this reduces their chance of developing a bowel cancer by about a half. Or in other cases, we can offer extra screening and that will allow us to catch any cancers that do occur at an earlier stage when they're more likely to be more effectively treated. So for example, if someone has a high risk of breast cancer, we could offer them extra and more frequent screening of their breast.
Another option is we could offer risk reducing surgery. So, for example, if someone had a higher chance of developing ovarian cancer after the age of 50, we could offer removal of the tubes and ovaries as their chance of cancer starts to increase, and that would significantly reduce their risk of developing cancer in the future.
Florence: And, working in this space, you and I know that research groups are working all the time to try and better understand cancer and how we might be able to treat it more effectively. Could you tell me about how genomics in particular is helping to advance the detection and treatment of cancer?
Katie: Genomics is helping develop both our understanding of how and why cancer develops, and as well as that, it's also helping us find new cancer treatments all the time.
There are already many drugs that are available to cancer patients that specifically target the genetic changes found in their cancer. In addition to that, there are many clinical trials now for cancer patients, which use the information from genomic sequencing to help guide new research into better treatments based on the genetic alterations in the cancer cell.
We are increasingly using genetic testing to identify more at-risk people with inherited changes in the population as well, so that we can make sure if they have a higher chance of developing cancer in their lifetime, that they get the best prevention and screening programs available. our understanding of genomics is really impacting both our understanding of what causes cancer, how we treat it, and how we can prevent it as well.
Florence: So, I think we'll finish there. Katie, it's been so great to talk to you and to learn more about why genomics is proving to be so important in helping us to understand cancer.
If listeners want to hear more, explain episodes like this, you can find them on our [email protected].uk or wherever you get your podcasts. Thank you for listening.
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In this explainer episode, weâve asked Amanda Pichini, clinical director at Genomics England and genetic counsellor, to explain what a genetic counsellor is.
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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What is a genetic counsellor? I'm Florence Cornish, and today I'm joined with Amanda Pichini, a registered genetic counsellor and clinical director for Genomics England, to find out more.
So, before we dive in, lots of our listeners have probably already heard the term genetic counsellor before, or some people might have even come across them in their healthcare journeys. But for those who aren't familiar, could you explain what we mean by a genetic counsellor?
Amanda: Genetic counsellors are healthcare professionals who have training in clinical genomic medicine and counselling skills. So they help people understand complex information, make informed decisions, and adapt to the impact of genomics on their health and their family. They're expert communicators, patient advocates, and navigators of the ethical issues that genomics and genomic testing could bring.
Florence: Could you maybe give me an example of when somebody might see a genetic counsellor?
Amanda: Yes, and what's fascinating about genetic counselling is that it's relevant to a huge range of conditions, scenarios, or points in a person's life.
Someone's journey might start by going to their GP with a question about their health. Let's say they're concerned about having a strong family history of cancer or heart disease, or perhaps a genetic cause is already known because it's been found in a family member and they want to know if they've inherited that genetic change as well.
Or someone might already be being seen in a specialist service, perhaps their child has been diagnosed with a rare condition. A genetic counsellor can help that family explore the wide-ranging impacts of a diagnosis on theirs and their child's life, how it affects their wider family, what it might mean for future children. You might also see a genetic counsellor in private health centres or fertility clinics, or if you're involved in a research study too.
Florence: And so, could you explain a bit more about the types of things a genetic counsellor does? What does your day-to-day look like, for example?
Amanda: Most genetic counsellors in the UK work in the NHS as part of a team alongside doctors, lab scientists, nurses, midwives, or other healthcare professionals. Their daily tasks include things like analysing a family history, assessing the chance of a person inheriting or passing on a condition, facilitating genetic tests, communicating results, supporting family communication, and managing the psychological, the emotional, the social, and the ethical impacts of genetic risk or results.
My day-to-day is different though. I and many other genetic counsellors have taken their skills to other roles that aren't necessarily in a clinic or seeing individual patients. It might involve educating other healthcare professionals or trainees, running their own research, developing policies, working in a lab, or a health tech company, or in the charity sector.
For me, as Clinical Director at Genomics England, I bring my clinical expertise and experience working in the NHS to the services and programmes that we run, and that helps to make sure that we design, implement, and evaluate what we do safely, and with the needs of patients, the public, and healthcare professionals at the heart of what we do.
My day-to-day involves working with colleagues in tech, design, operations, ethics, communications, and engagement, as well as clinical and scientific experts, to develop and run services like the Generation Study, which is sequencing the genomes of 100,000 newborn babies to see if we can better diagnose and treat children with rare conditions.
Florence: So, I would imagine that one of the biggest challenges of being a genetic counsellor is helping patients to kind of make sense of the complicated test results or information, but without overwhelming them. So how do you balance kind of giving people the scientific facts and all the information they need, but while still supporting them emotionally?
Amanda: This is really at the core of what genetic counsellors can do best, I think. Getting a diagnosis of a rare condition, or finding out about a risk that has a genetic component, can come with a huge range of emotions, whether that's worry, fear, or hope and relief.
It can bring a lot of questions, too. What will this mean for my future or my family's future? What do you know about this condition? What sort of symptoms could I have? What treatments or screening might be available to me? So genetic counsellors are able to navigate all of these different questions and reactions by giving an opportunity for patients and families to discuss their opinions, their experiences, and really trying to get at the core of understanding their values, their culture, their expectations, their concerns, so that they can help that individual make an informed decision that's best for them, help them access the right care and support, adjust or find healthy coping strategies, or maybe even change their lifestyle or health behaviours. So it's really finding that balance between the science, the clinical aspects, the information, and the support.
Florence: So obviously working in this space, I get to read about lots of incredible research all the time, and it feels like genetics and genomics seems to be changing and advancing day by day. So, I'd be interested to know what this means for you and for other genetic counsellors, what's coming next?
Amanda: Yeah, so as we continue to see advances in genetics and genomics, there's, I think, a really increasing need for genetic counselling expertise to help shape how these technologies are used and with giving the right consideration for the challenges around what this means for families and for wider society.
Genomics is also still growing the evidence base it needs to provide a consistent and equitable service. We're seeing digital tools being increasingly available to give people information in innovative ways, seeing huge advancements in targeted treatments and gene therapies, that are changing fundamentally the experiences of people living with rare conditions and cancers. And we're using genomics more and more to predict future health risks and how people might respond to certain medications. So, there's a huge amount that we're seeing sort of coming for the future.
What's interesting is the 10-Year Health Plan that the government has set out for the NHS provides, I think, huge opportunities for genomics. For example, we'll see healthcare brought closer to local communities, genomics being used as part of population health, reaching people closer to where they are and hopefully providing greater access.
But I think the key thing in all of this is knowing that genomics is really just a technology. It requires people with the right skill sets to use it safely and to be able to benefit everyone, and genetic counsellors are a huge part of that.
Florence: And finally, in case anyone listening has been inspired by this conversation and wants to build a career like yours, what advice would you have to offer somebody hoping to become a genetic counsellor in the future?
Amanda: To train as a genetic counsellor in the UK, you usually need an undergrad degree in biological sciences, psychology, or being a nurse or midwife. The background can be varied, but usually driven by a common thread, a desire to sort of improve healthcare experiences for patients and make genomic healthcare widely accessible and safely used for everyone.
You can apply for the 3-year NHS scientist training programme, or there's also master's degrees offered through Cardiff University, for example. In general, I'd encourage people to check out the website for the Association of Genetic Nurses and Counsellors, and reach out to genetic counsellors to ask about their career and their journey as much as possible, as well as seeking opportunities to really understand the experiences of people living with rare genetic conditions, because that will help you understand the ways in which genetic counselling can have an impact.
Florence: We'll finish there. Thank you so much, Amanda, for all of those insights and for explaining what it means to be a genetic counsellor. If any listeners want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.
Thank you for listening.
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In this explainer episode, weâve asked Dr Emily Perry, research engagement manager at Genomics England, to explain what the Genomics England Research Environment is.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
You can listen to the previous episodes mentioned in this podcast
How has a groundbreaking genomic discovery impacted thousands worldwide?What is the National Genomic Research LibraryIf youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What is the Genomics England Research Environment? My name is Florence Cornish and I'm here with Emily Perry, Research Engagement Manager at Genomics England, to find out more.
So Emily, before we dive into the Research Environment, let's set some context. Could you explain what Genomics England is aiming to do as an organisation?
Emily: So, Genomics England provides genome sequencing in a healthcare setting for the National Health Service in England. As we sequence genomes for healthcare, the benefit is that we can also put that genomic and clinical data out for research in a controlled manner, and then that can also feed back into healthcare as well. So, it's really, this kind of cyclical process that Genomics England is responsible for.
Florence: And so, what do we mean when we say Research Environment?
Emily: So, the Research Environment is how our researchers can get access to that clinical and genomic data that we get through healthcare. So, it's a controlled environment, it's completely locked down, so it's kind of like a computer inside a computer. And in there, the researchers can access all of the data that we have and also a lot of tools for working with it in order to do their research.
We refer to the data as the National Genomics Research Library, or the NGRL. The NGRL data is provided inside the Research Environment
Florence: So you mentioned the National Genomic Research Library. If any listeners want to learn more about this, you can check out our previous Genomics 101 podcast: What is the National Genomic Research Library?
And so Emily, could you talk about what kind of data is stored in this library?
Emily: So the library is made up of both genomic data and clinical data, which the researchers use alongside each other. The genomic data includes what we call alignments, which is where we match the reads from sequencing onto a reference sequence, and variants, which is where we identify where those alignments differ from the reference sequence, and this is what we are looking for in genomic research.
The clinical data includes the data that was taken from our participants at recruitment, so details of the rare disease, the cancer, that they have, but also medical history data. So, we work with the NHS and we're able to get full medical history for our participants as well.
This is all fully anonymised, so there's no names, there's no dates of birth, there's no NHS numbers. It's just these identifiers which are used only inside the Research Environment and have no link to the outside world.
Florence: And so how is this clinical and genomic data secured?
Emily: So, as I said there's no names, there's no NHS numbers, there's no dates of birth. And we have very strict criteria for how people can use the data. So researchers, in order to get access to the Research Environment, they have to be a member of a registered institution, they have to submit a project proposal for what it is that they want to study with the data.
There's also restrictions on how they can get the data out, so they do all their research inside, there's no way that they can do things like copy and paste stuff out or move files. The only way that they can get data out of the Research Environment is going through a process called Airlock, which is where they submit the files that they want to export to our committee, who then analyse it, check that it's in accordance with our rules and it protects our participants' safety and that only then would they allow them to export it.
Florence: Who has access to the Research Environment?
Emily: We have researchers working with the Research Environment all over the world. There's 2 kind of major groups. One of them is academia, so this will be researchers working in universities and academic institutions. The other side of it would is industry - so this will be biotech, startups, pharma companies, things like that.
Florence: And finally, can you tell us about some of the discoveries that have been made using this data?
Emily: There's lots of really cool things that have come out of the Research Environment. A recent story that came out of the Research Environment was the ReNU syndrome, it was initially just one family that they identified this in, and they were able to extend this discovery across and identify huge numbers of individuals who had this same disorder because they had their genomes within the Research Environment.
Florence: You can hear more about this research in our previous Behind the Genes podcast: How has a groundbreaking genomic discovery impacted thousands worldwide?
So, we'll wrap up there. Thank you so much, Emily, for sharing more about what we mean by the Genomics England Research Environment.
If you'd like to hear more explain episodes like this, you can find them on our website, at www.genomicsengland.co.uk or wherever you get your podcasts.
Thank you for listening.
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In this episode, we step inside the NHS to explore how the Generation Study is brought to life - from posters in waiting rooms to midwife training. We follow the journey of parents joining the study at the very start of their babyâs life, and hear from those making it happen on the ground.
Our guests reflect on the teamwork between families and hospitals, the importance of informed consent, and the powerful insights this study could unlock for the future of care and research.
Our host Jenna Cusworth-Bolger, Senior Service Designer at Genomics England, is joined by:
Tracie Miles, Associate Director of Nursing and Midwifery at the South West Genomic Medicine Service Alliance, and Co-Investigator for the Generation Study at St Michaelâs Hospital in BristolRachel Peck, parent participant in the Generation Study and mum to AmberIf you enjoyed todayâs conversation, please like and share wherever you listen to your podcasts.
For more on the Generation Study, explore:
Podcast: How has design research shaped the Generation Study Podcast: What can we learn from the Generation Study Podcast: What do parents want to know about the Generation Study Blog: Genomics 101 - What is the Generation Study Generation Study official websiteâI think from a parentâs point of view I guess that's the hardest thing to consent for, in terms of you having to make a decision on behalf of your unborn child. But I think why we thought that was worthwhile was that could potentially benefit Amber personally herself, or if not, there's a potential it could benefit other children.â
You can download the transcript, or read it below.
Jenna: Hi, and welcome to Behind the Genes.
Rachel: I think if whole genome sequencing can help families get answers earlier, then from a parent perspective I think anything that reduces a long and potentially stressful journey to a diagnosis is really valuable. If a disease is picked up earlier and treatment can start sooner, then that could make a real difference to a child or even Amberâs health and development.
Jenna: My name is Jenna Cusworth-Bolger and today I have the great pleasure to be your host. Iâm a senior service designer at Genomics England specifically working with the hospitals involved in delivering the Generation Study. In March 2023 we started with our very first hospital, St. Michaelâs in Bristol. I am today joined by Tracie Miles who I had the utter pleasure of working closely with when they were setting up. And we also have Rachel Peck, one of the mums who joined the study in Bristol. Regular listeners to this podcast may already be familiar with the Generation Study but for those who are not, the Generation Study is running in England and aims to sequence the genomes of 100,000 newborn babies from a cord blood sample taken at birth. The families consented to take part will have their babies screened for over 200 rare genetic conditions most of which are not normally tested for at birth. We expect only 1% of these babies to receive a condition suspected result, but for those 1,000 families that result could be utterly life changing as it could mean early treatment or support for that condition.
Would you like to introduce yourselves and tell us what it means to you to have been that first hospital open in this landmark study. Tracie, Iâll come to you first.
Tracie: Hi Jenna, lovely to be with you all this morning. And for those who are listening it is early in the morning, we get up early in the morning because we never know when these babies are going to be born on the Generation Study and we have to be ready for them. So, my name is Tracie, I am the Co-Investigator with the wonderful Andrew Mumford, and we work together with a huge team bringing this study to life in Bristol. I am also the Associate Director of Nursing and Midwifery at the South West Genomic Medicine Service Alliance.
Jenna: Thanks Tracie. Weâre also joined today by Rachel. Would you like to introduce yourself and your baby, and tell me when you found out about the Generation Study?
Rachel: Hi, thank you for inviting me. My nameâs Rachel, Iâm based in Bristol. My baby is Amber; she was born four months ago in St. Michaelâs hospital in Bristol. I first heard about the Generation Study when I was going to one of my antenatal appointments and saw some of the posters in the waiting room. Amber is napping at the moment, so hopefully sheâll stay asleep for long enough for the recording.
Jenna: Well done, that's the perfect mum skill to get a baby to nap whilst youâre busy doing something online. So, Rachel, you said you heard about the study from a poster. When you first saw that poster, what were your initial thoughts?
Rachel: I thought it was really interesting, I havenât come across anything like that before and I thought the ability to screen my unborn baby at the timeâs whole genome sounded really appealing.
Jenna: Fantastic. So, what happened after the poster?
Rachel: If I remember correctly, I scanned the QR code on the poster which took me to the website. I filled out a few simple questions online and then I was contacted by one of the research team where I arranged a formal consent conversation. That was done by Zoom I think in the evening because Iâve already got a toddler at home so post bedtime works best for me. So, we had about a forty-minute conversation on the phone where I could ask all the questions that I needed to ask and if I was happy which I was. I then gave my consent and then I believe my maternity records were kind of highlighted to say that I signed up for the Generation Study and that when my baby was born then a sample was going to be taken, and I would be given the results in due course.
Jenna: And did all that go smoothly, that youâre aware of?
Rachel: Yeah, as far as Iâm aware. It was genuinely really simple to do. After that initial consultation where I signed the consent form there wasnât any follow-up appointments so the next thing I knew, I think it was just chance, but one of the research nurses actually came down to see me on the day which was really nice. Just to say, âOh, just to let you know that the team are aware.â And then, other than that, the next thing I knew was getting the results through by post.
Jenna: Sure. So, behind the scenes your babyâs blood was collected from the umbilical cord, that would have been registered, packaged, sent off and went on a whole journey for you to ultimately get your result. It all sounds very simple, but I think weâre going to dig into a lot of the mechanisms that kind of went behind the scenes to make something that seems simple come to life. Tracie, we met in the summer of 2023 I believe. I came to St. Michaels with a suitcase full of our materials which we had started to bring to life, including that poster. Weâve sat together and we were trying to figure out exactly how this was going to come to life in our very first hospital and how, what Rachel described, was actually going to become real. Tracie, can you tell me what you remember about those conversations and the thinking that you did as a team ahead of getting that green light to go ahead and start recruiting?
Tracie: Listeners, just to let you know that Rachel hasnât been primed to say that it was a seamless journey from delivery to getting results. Iâm delighted to hear that it was. And I think the reason that weâve achieved that in Bristol and across England now with the other teams that Jenna and the team have helped roll out, is teamwork. And part of our team is our mum, in this case Rachel. If you hear me or Jenna describing our mums as "Mia", that's the name, the significant name or the identifier we give for our participant. So, yeah, Jenna, I think the thing was it was about those first conversations. It was about teamwork and who shall we involve? We involved everybody didnât we, Jenna? So, I know that the team, by the time they came to us they'd already been planning for two years. So, in fact what came to us in Bristol was a wealth of work and information, and two years of behind the scenes of the team working. We involved every midwife. Now a midwife is a cover all term.
We involve community midwives, research midwives, antenatal midwives, post-natal midwives. They all do different things for the mum pathway. Not forgetting dad as well, he is involved in all of this and Rachel Iâm sure will testify later to the fact that when she was offered the consent, her partner was offered to come along too. UHBW, thatâs United Hospital Bristol and Western, that our maternity hospital as part of, have got a fantastic R&D department and they were on straightaway with the rule book checking that we knew what we were doing. So, for those of you that arenât in the medical world, that's making sure weâve got the right governance, that weâre doing things by the rule book. Andrew went out and spoke to lots of different clinicians that would be involved in the pathway after the results were back, for those babies where we found a condition suspected. So, essentially Jenna, I think the list that was fairly long, grew longer and longer.
Jenna: I think that was something that I was really struck by when I came back and visited you repeatedly after that. You were particularly good at getting some of those staff members that you might not even think about involved in the study, like the receptionist on your sonography department who you had recruited to make sure that they gave out the leaflet and the participant information sheet to all the mums coming in for their twenty-week scans etc. All that thinking was really valuable and something that Iâve passed on and taken out on my trips to other hospitals along the way. We heard from Rachel that she heard about this study from the poster. Now that youâve been going for just over a year, what are all the different ways that people hear about the study, is it just the poster?
Tracie: No, itâs not just the poster. So, essentially when we first opened, we had lots of material. We had banners, we had posters. A short leaflet that you might often pick up at the GP, a little one that you can unfold into three pieces, and then a bigger patient information leaflet which actually described the whole study and also signposted the mums and dads to go and have a look on the website to hear more about it. What we did was we literally walked the mumâs journey as she came into the hospital through antenatal and placed those posters and leaflets in the places where we knew she would see them. Now we had to be very careful about that as well because we couldn't just distribute them everywhere, we wanted to make sure that mum was getting sight of them, or mum and dad if they were coming together, at a place where their pregnancy was in hopefully, a safe position. So, that's around about 20 weeks onwards.
We didnât want to be giving that information out in the early days of pregnancy when actually mum and dad are getting flooded with lots of information, but we wanted them to feel secure in their pregnancy and for us to feel clinically secure. That worked really well and really effectively, but there's nothing like people pairing. So, in fact getting our ultra sonographers. So, for those of you that have been through pregnancy will remember at around about twenty weeks you have a scan, itâs often called a dating scan or an anomaly scan, and we would get our receptionist to physically hand out a leaflet then.
What we have evolved over the last year working with the team from Genomics England to make sure that we keep the wording right so that we can share with all the other sites across England, because itâs good to have consistency. And also, as this evolves if this becomes standard of care, if this proves that actually this is useful for future-proofing for all of us in the public, if this study becomes something in real clinical terms, weâve actually started sending out what we call, a signposting email. So, this is an email that goes to all of our prospective parents at 20 weeks plus, once weâve checked that the pregnancy is safe and healthy. That has absolutely paid dividend and actually plays into the NHS future promise of analogue to digital to using those quick smart ways of working to reach our families. So, that has created a huge influx of recruits for us, Jenna.
Jenna: Thatâs really interesting. Weâve sort of observed that same sort of thing. As we go through the hospitals now there's kind of three main ways that people are finding out the study. We call it like the passive way. So, that's what Rachel did which is the posters, the banners, but that doesnât work for everyone. In hospitals poster blindness is real. And also, youâre coming for your twenty-week scan, youâve got other things on your mind. Youâre not really looking around wanting to pick up leaflets and things and obviously weâve also got to think about our non-English speakers. Or even an English speaker who sees the poster, but their literacy isnât very high, or their health literacy isnât very high. So, reading a message that says something about genomics and testing, it can be quite overwhelming for people and not something that they would respond to.
So, then weâre signposting as our other kind of keyway and that's trying to get exactly what Tracie described, all the different staff involved. Who could be physically putting this leaflet in somebodyâs hand? Who could be mentioning it albeit briefly, just, you know, this is something you might like to consider. Rachel, I want to ask you what Tracie was describing there about the message kind of being better to be given later in pregnancy or after that 20-week scan point, because of all that information overload you get earlier in your pregnancy. Does that resonate with you?
Rachel: Yeah, I think that sounds about right. For lots of people when there's so much uncertainty in early pregnancy and I think some people are quite almost superstitious and don't want to sign up for things that potentially might not happen. So, I think from a personal perspective and from other friends who havenât been quite as fortunate, I think actually waiting until a little bit later when youâve got a little bit more headspace and mental capacity for that sounds about right. I think there's too many things early on. It sounds like youâre aiming at the right spot.
Jenna: Absolutely. I think one of the other interesting aspects of all of this is the fact that Amberâs cord blood was taken on the day that Amber was born, and Iâm interested to understand a little bit about how that baton was passed from the moment that you consented, Rachel, to make sure that that sample was taken. I know it sounds like Rachel; you were in hospital at a point that the staff were there so they actually popped down to your bedside to see you but that doesnât always happen. Our teams donât work 24/7 and babies do get born at 2:00 a.m. over a bank holiday weekend. But Tracie, how do you make sure that that kind of message is passed through at St. Michaels, and what's worked well and what have the challenges been?
Tracie: So, a bit like how did we get the message through, is there one way? And the answer is no. There are posters, there are emails, etc. What we do do is first and foremost we encourage our mum, like Rachel here, and the dad, it might be two mums coming in together, to advocate for themselves. To say, âIâm on the Generation Study.â We donât expect that to be the only signal however because if a mum is coming in in full labour having done that a couple of times myself, I might forget. Now Genomics England have made some great bag tags, some stickers, all sorts of different visual identifiers that some hospitals around England are using, some arenât. We in fact actually donât get our mums to carry them, that may change. There are lots of different ways of doing it and every hospital maternity unit will find their fit. So, visual clues that mum and dad, or mum and mum, advocating for themselves as they come in, but also making sure that we have spoken with the delivery suite midwives and the theatre midwives.
Because in our hospital, which it seems to be the same sort of ratio around the country, sometimes up to about 40% of deliveries are done in theatre. So, we need to make sure we talk to our theatre staff and the people there as much as our central delivery or labour ward, for listeners who arenât familiar with the terms. So, we make sure that we went and walked the floor in the delivery labour ward and theatre on a regular basis. So, the task for us was to make sure that our midwives, all 200 of them know that if a mum is in the Generation Study and coming in for delivery, that they know that sheâs on the study. So, ways we do that is research midwives are an absolute ally, they do walk the floor. They do pop down to delivery suite and they do alert the team that there is a potential that a mum might be coming in that week with a planned Caesarean section, that's one easy. That actually can be an email. But we still do that by word of mouth, or they have a big board up in the delivery suite, which I gather is quite often the way across a lot of the country.
Also, really, really key and this once again fits with our NHS plans, analogue to digital. The majority of our sites now are taking on electronic records. So, we put a key flag on the electronic record to say that this mum is on a research study. Staff are used to that because itâs not the only research study that is happening. Now it doesnât have to just be an electronic note, it can be done on the retro paper notes as well. So, for those of you that have got paper notes or if weâve got mums who are holding paper notes, fear not, there is an area on the notes where we can put that too. So, itâs basically anywhere where we know the delivery midwife has sight of the babiesâ notes we will put a sticker, we will say something. So, itâs one size doesnât fit all.
Jenna: Yeah, what youâve described there is just so lovely and so true about itâs got to be belt and braces. The research team, the study team and the hospital might be a small number of people working Monday to Friday. Your people you completely rely on are those huge numbers of delivery midwives that need to have that message transmitted to them potentially over a 20 week timespan from the time the consent has happened to that day that that baby is born. So, what was really key as my role as service designer was going to the sites. Iâm still doing this to this day, onboarding new sites all the time. We go and we speak to the sites, help them envisage how they might deliver this, how itâs actually going to work. Whatâs the nitty-gritty of all that mechanism thatâs going to happen but making sure that what they really understand is, what's the outcome? What do we want to happen? We want as many babies as possible to have those cord bloods taken and not missed.
How you actually send that message whether itâs through a paper note, a sticker on a paper note, giving a pack to the family to bring in so theyâve got something physical to hand over to their delivery midwife as a physical memento. Magnets that are put on the handover boards, or any or all of these things, in lots of ways the hospitals that have still got paper notes actually find it easier because that can staple a bag with the bottle that we use for our cord blood samples and this mum is part of the Generation Study to the front of the notes. Itâs more obvious than it would be as a digital flag.
Tracie: I totally agree with that, itâs all about that visual cue that we were talking about earlier. We actually fund a midwifery support worker, her nameâs Lauren. Hello Lauren, if youâre listening. And what Lauren does is actually she makes sure that in all the rooms where women deliver that there are little set bags with all the equipment needed to take that cord blood. She also came up with a brilliant idea and again, a visual clue and Genomics England help us to design it, a poster. We would put on the outside of the door of mum and dad when they said they were on the study. So, if youâve got a changeover of midwives then those midwives know that theyâre going into a room to support and deliver a mum that's got a baby on the study.
Jenna: And I think that's something that's really key is what you said there about Lauren and her bright idea to create that poster and things like that, and that's been really key to how weâve worked from Genomics England as a kind of service design kind of wrapper if you like around all of these hospitals. I have taken on the role of chief pollinator, so Iâve flown from hospital to hospital taking all the best ideas. So, Laurenâs idea of the poster, I came along and I took a photograph of that poster. That poster is in a slide and that slide gets shown when I go and do onboarding and training sessions with future hospitals.
Bristol were really key because as our first site and as the first early days check in we did, the photographs I took at your hospital at Birmingham Womenâs and at the Rosie in Cambridge which were the first three hospitals, you still to this day make up a large percentage of what we show because you were the first to have all those great ideas and we share those out. But we donât go round all the other hospitals, and we have found new ideas all the time and they are put together in our service design manual which is all available for all the sites. Something that St. Michaelâs can refer back to to see what new things they could be thinking about. But basically, raising up the best and allowing hospitals to borrow from each other. Before we just move on from how it all works, I just want to ask Rachel, did you notice any of that or were you very busy having a baby? And did you remember to kind of advocate to yourself and mention the study?
Rachel: I did remember to advocate for myself, also it was one of the jobs that I allocated to my husband as well as a, well, if I forget which is likely, can you make sure that you mention to them. I had a caesarean section. For other people who have had caesarean sections, there's quite a lot of waiting round time. So, when we were in the theatre getting ready, having a chat with the anaesthetist it was a nice opportunity to be able to take my mind off the impending surgical procedure and just mention about the Generation Study. But incidentally, they knew about it anyway. I think I remember seeing some kind of sticker or maybe the blood tubes or something on my theatre records. But see them taking the sample, I wasnât aware, I had other things on my mind at that point.
Jenna: Absolutely. You were cuddling Amber for the first time probably.
One of the things that you touched on Tracie, was you had to go round all of your delivery suite midwives and make sure they all knew how much blood to take, what tube to put it in. The fact that they had to invert it 10 times, put it in a particular fridge so that you knew where to find it. All of those are really important training messages that you had to pass on. But for you to be able to pass them on, we had to train you in the first place. So, my memory was that we came down to you one cold December day and spent a whole day with you down at St. Michaels trying our best to train you as seamlessly as we could. My memory of that day is it wasnât terribly slick because it was our first and weâre always learning. Iâd like to think weâve got it a lot more slick now, but what do you remember about that day? And just in general kind of learning what you needed to do on the study and what kind of worked well for you, and what worked less well?
Tracie: I do remember that day, it was very cold. I think what's changed Jenna is on that December day the whole team felt that they were having to take on the whole of the journey. They now as the work has developed, realise and learn the part of the journey that they need to be involved in and don't have to be concerned about the rest of the journey.
Jenna: I learnt an awful lot and I think itâs really true that itâs really important that people who are taking the samples, they just need to know their role. But they do need to know a little bit about what the study is, why itâs worthwhile, why this mum has signed up and what value itâs going to bring to that family. I think the other thing that we learnt when we came to your training as well was in the same way that we went a bit too deep for some people in their role, we didnât go deep enough for your team that were actually going to be doing these consent conversations. At that, at end of that training day, you still felt trepidatious about doing those conversations and so we really took that on board and then developed our informed choice cards which are like scenario cards that allow teams to kind of practice, rehearse and think through how theyâre going to answer those common questions.
And weâve taken those into a session that allows people who are just doing the consent conversation to go even deeper, so we do that online in a webinar now which we run monthly and that allows any new members of staff to go that little bit deeper in terms of what is this consent conversation? What is it that I need to get people to understand and be fully informed about before they come into this study?
A key objective of the Generation Study which after all is a research study, is to understand if the NHS and families would benefit if screening for conditions via whole genome sequencing was something that became part of NHS standard care. Rachel, can I ask you as a mum, is that something that youâve reflected on at all and how would you feel about it?
Rachel: Yeah, Iâve thought about quite a bit. I think if whole genome sequencing can help families get answers earlier then from a parent perspective, I think anything that reduces a long and potentially stressful journey to a diagnosis is really valuable. If a disease is picked up earlier and treatment can start sooner, then that could make a real difference to a child or even Amberâs health and development. So, I think that would be potentially very advantageous. I guess in a resource limited NHS that we have, there are, you know, clear challenges in rolling out whole genome sequencing for everyone. But Iâm guessing that the Generation Study will provide the evidence to help understand if this is feasible or worthwhile. And clearly the Generation Study needs to show that the screening of these 200 or so conditions is as good as the existing screening that already exists. From a parent perspective, if itâs shown to be equally as good at doing that, plus all these other disorders then it seems like a win-win.
I think for me the main advantage and the main reason why I was keen to enter for Amber was if she were at risk of getting one of these rare disorders then there's an advantage to picking that up earlier for her. Because Iâm aware that lots of people if they have a rare disorder, it can take a long time to get to that diagnosis and that can be really stressful for you as the parent but also for the child. Anything I think to minimise their suffering is worthwhile. So, it sounds fantastic, if it works.
Jenna: Absolutely and I think that's whatâs really nice about being involved in something like this is that the study itself is set out to find out those things. Itâs not set out to find out how we could do whole genome sequencing in the NHS, itâs whether we should. As part of the study, you also consented to have Amberâs data go through into the National Genomic Research Library which leads us to one of the secondary objectives of the Generation Study which is to understand the implications of keeping a babyâs genomic data over their childhood, or even over their lifetime.
Amber will be contacted when she is 16 by Genomics England to find out whether she herself is happy for her data to be kept. But keeping that data for that length of time offers up opportunities for further screening for other conditions later in Amberâs life. Or using that data with your consent of course, to do further research into genes and health. And so over the next few years you may be contacted by Genomics England to invite you to take part in future studies. And, I was just wondering about how much you have been told about the potential for that and again, how you feel about that kind of aspect of being part of this study.
Rachel: Yeah, that was definitely discussed quite a lot in the consent conversation that I had with Siobhan, and we were told that Amberâs data would be stored long term and that there might be future opportunities for the team to kind of get in touch or do additional testing. And I think from a parentâs point of view I guess that's the hardest thing to consent for in terms of you having to make a decision on behalf of your unborn child. But I think why we thought that was worthwhile was that could potentially benefit Amber personally herself, or if not, there's a potential it could benefit other children. So, I think that whole kind of for the greater good, that kind of prevailed.
And I think the other, not concern as it were, but other thing we wanted to discuss with that consent was the security of that data. And certainly, when I was discussing it with my husband that was his kind of main point to kind of clarify, if the data is being stored long term and if that was safe. And in terms of the safety, thinking about could future employers or can insurance companies, you know, get hold of that data? As a parent, the last thing you want to do is accidentally prevent your daughter from getting a job that she wants to get. But it was all explained that that wouldn't happen, but I think that was something that was us for us personally important to clarify.
Jenna: I think that's really where that depth of the consent conversation is so key and why we do that sort of additional training to allow staff who may be very used to doing research and doing research consent, but never before have done a genomic consent where itâs about keeping genomic data and the implications of keeping it for that really long time. What else do you remember about that consent conversation, Rachel? Is there anything else that kind of stands out that you had to sort of really dig into with Siobhan on that day?
Rachel: Iâm just trying to think back because it was a little while ago. The main kind of points that I want to discuss was the security of the data and then what would happen if for whatever reason the umbilical cord blood sample wasnât taken and if that meant that we could still be part of the study or not. It was explained that yes, there is a way, they would do an initial heel prick blood sample. But that was reassuring to know that if for whatever reason if there was some kind of emergency and it didnât happen the way we wanted. So, I think that was the other kind of practical thing that was discussed.
Jenna: It sounds like Siobhan sort of had by that point all of the answers at her fingertips, but that kind of links back I guess to how important it is for all the training and all of the materials, because quite a lot of the answers to those questions are in the participant information sheet. Quite a few of them are covered in the participant video which is a sort of a four-minute-long video, itâs meant to make the understanding a little bit more accessible. But itâs not relying on one route of information, itâs the conversation and that face to face you have with someone. Itâs the written information and itâs those videos and other materials.
So, we need to go as far as we can to kind of get the word out. One of the limitations that we had, certainly back in the day when we just had St. Michaelâs and a couple of other hospitals on board was that trying to get the word out about the study widely was also going to disappoint quite a lot of people who werenât able to take part because their hospital wasnât in it. Weâve talked a lot about this consent conversation, and I think something that's really important, underpinning for the whole study is the ethics thatâs been involved and all the work that's been done around that area.
As the study is free and optional and taking part involves a commitment from families to have babiesâ data held for at least 16 years, the consent conversation and getting that right is so vital. We touched upon this in a previous episode with my colleague Mathilde Leblond where we talked about all the design research that our team did in the build up to launching this study, so that we could really deeply understand what families wanted and needed as part of their experience. So, Tracie, weâve heard from Rachel the things that she was concerned around, but what were your reflections as a team in St. Michaels around the ethical aspects of the study? And what has been particularly tough about that in relation to you guys in Bristol?
Tracie: I would say informed consent is something that we all take as healthcare professionals, and we all hold dearly the governance. So, I was mentioning earlier that actually consent may not be a one-off situation. So, for example, Rachel had forty minutes with Siobhan. That was the conversation that she had where Rachel felt that she was enabled and informed enough to take consent, and Siobhan listening to her having that conversation with Rachel felt that that was appropriate at the time. So, consent was achieved between the two of them. Now, that wasnât the only part of Rachelâs consent is Rachel was telling us there's the patient information leaflet that she read, so that's also part of the informed consent. And we have to be sure that our mums and the other parent of the baby have read that information.
And one of the things that I was very worried especially about at the beginning was itâs a superb information leaflet, itâs quite long, it needs to be. It signposts the parents of the unborn baby to a website which is fantastic. Do they all look at it? Not always. Would I? Probably not. So, there's no criticism of the parents here. So, one of the things that I was really concerned about from the genomics perspective of this and the data protection because this is not a one-off, this is a longitudinal study. Amber when sheâs 16 years old will decide whether or not she wants to continue, so itâs not a one-off moment that her lovely mum and dad have consented her for. There's a lot thatâs been consented for. All great and all appropriate and all future-proofing for future Ambers. But my concern was actually, are we getting that information across to all the mums and dads as they sign up? So, it was really important that when we were training our midwives and our genomic practitioners, those that were consenting, to make sure that they were really cognisant of the enormity of the wealth of science we were signing our parents and their babiesâ futures up to.
Jenna: Indeed, and very well said and I think you touched on something that is really close to our hearts as well that weâve thought a lot about but still continue to do work to get right, which is the patient information leaflet if you have the health literacy and written language literacy to be able to sit and read a 16-page document, great, but not everybody does. As Iâve gone place to place and hospital to hospital, Iâm always struck by the different communities that surround different hospitals and the different challenges that they might have. So, if you compare somewhere like Royal London which is in the heart of Whitechapel, I think around 40% of their birthing parents there are first generation Bengali women who have little to no English. Also, whose health literacy is quite low as well. So, engaging them takes a very different approach to an approach you might take elsewhere. So, itâs definitely not a one size fits all. Tracie, how have you adapted some of your approaches to your local communities in Bristol?
Tracie: So, we have a fairly diverse population, not as diverse as the Whitechapel example that you gave, but in fact we were aware, a bit like the team in London that we have a population of Somali potential birthing parents. What weâve done is weâve worked with community leaders and elders from the Somali population to develop a day, or it might be a couple of mornings, for us to talk about and workshop to explain about the study. So, we have all of the information. We have the translations that have been done by Genomics England. And hat we are doing is we are working with the community elders for them to tell us the right fit. Should it be a whole day? Probably not. Should it be a coffee morning or a tea morning? Probably. Should it be where we get a guest speaker in? That was their idea. What is the key condition suspected, one of those 200 conditions that the study is looking at that is prevalent in that community? Letâs ask the community elders what they think, and weâll do what weâre told. So, itâs been fabulous actually doing that.
Jenna: Itâs really, really great to hear about that. I think weâve got little pockets of work like that popping up all over the country now which is really exciting to start seeing. I think at first, we were very much about getting the study up running and out there. And now weâre starting to make sure we get that reach and we get that equity, and the opportunity for all pregnant people to decide whether this is right or wrong for their family. Itâs about informed choice and you canât make an informed choice whether that's an informed yes or an informed no if you don't have the information.
We are proud that we go further than most research studies in terms of our accessibility, in terms of translations and we know that not English speaking is not the only barrier to access, there's lots of cultural barriers as well. But with the translated materials we support 10 languages as far as our professionally translated participant information leaflet. I was also really pleased when I found out at first that our website team had built the website in such a way that it worked not only with screen readers. So, somebody with a visual impairment could âreadâ, in inverted commas, the website but that also it translates via Google into the 160 languages that Google support, which we know Google translations arenât perfect but theyâre better than nothing.
And going back to what Tracie sort of said, the website doesnât have to do everything, itâs about a conversation at the end of the day. Itâs a consent conversation that can be supported by a professional interpreter but itâs about getting that initial message out there so they even get as far as having that conversation with an interpreter.
We heard from Rachel around her reflections for the future, Tracie, about the study potentially becoming NHS standard care and about that potential of us having Amber and 99,999 other babiesâ data in the National Genomic Research Library and the potential that gives us for further research. Or for potentially re-screening those children as they grow up. When you look to the future and think about the Generation Study and what it might pave the way for, what are your hopes or perhaps fears?
Tracie: So, my belief working in the genomics field is genomics is everybodyâs business. So, itâs the 3 of us talking today, weâre all very keen about genomics but there is a fear around genomics. Actually, I feel that this landmark study is absolutely fantastic. It makes genomics everybodyâs business. And it actually helps the whole healthcare community looking after these parents and the unborn babies as they go through the journey learn about the positivity of genomics. I think this landmark study is an absolutely win-win. It speaks to the whole family.
Jenna: Thank you, Tracie. Iâm also particularly excited about what the future could hold. I think as the service designer that's been working so closely with the hospitals, Iâm really excited around what weâve learned through this study in terms of reaching families and getting genomic information and options out to them. As you say, it is everybody. I continue to enjoy meeting new hospitals and seeing their kind of innovative take on that and kind of pollinating that back to other trusts so that we can reach as many families as possible and get that equity of access for everybody. Iâm also particularly excited that weâre moving into a phase where weâre going to be learning more from the parents themselves that are taking part.
So, I think weâll wrap up there. Thank you to our guests Rachel, Tracie for joining me today as we discuss the rollout and impact of the Generation Study at St. Michaelâs Hospital in Bristol. If youâd like to hear more about this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iâve been your host Jenna Cusworth-Bolger. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac.
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In this explainer episode, weâve asked Dr Nour Elkhateeb, clinical fellow at Genomics England and clinical geneticist for the NHS, to explain the role of a clinical geneticist.
The previous episode mentioned in the conversation is linked below.
What is the diagnostic odyssey?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 youâve got any questions, or have any other topics youâd like us to explain, let us know on [email protected].uk.
You can download the transcript or read it below.
Florence: What is a clinical geneticist? My name is Florence Cornish and I'm here with Nour Elkhateeb, clinical geneticist for the NHS and fellow at Genomics England, to find out more.
So, Nour, before we dive into talking about clinical geneticists, could you explain what we mean by the term genetics?
Nour: Hi Florence, so at its heart, genetics is the study of our genes and how they are passed down through families. Think of your genome as a huge, incredibly detailed instruction manual for building and running your body. This manual is written in a specific language, DNA, which is made up of millions of letters arranged in a specific order.
And here is the interesting part, we all have tiny differences in our genetic spelling, which is what makes each of us unique.
But sometimes a change in the instructions, a spelling mistake in a critical place, can affect health. Genetics is all about learning to read that manual, understand how changes in it can cause disease, how it's passed down through families and finding ways to help.
Florence: And so, what kind of thing does a geneticist actually do?
Nour: Well, the term geneticist can cover a few different roles, which often work together. Crudely speaking, you can think of two main types, laboratory geneticists and clinical geneticists.
Laboratory geneticists are the incredible scientists who work behind the scenes. When we send a blood sample for genomic sequencing, they are the ones who use amazing technology to read the billions of letters in that person's instruction manual. The job is to find the one tiny spelling mistake among those billions of letters that might be causing a health problem.
Clinical geneticists like me are medical doctors specialised in the field of genetics, and we work face-to-face with patients and families in a hospital or a clinic setting. You can think of us as the bridge between the incredibly complex science of the genomics lab and the real-life health journey of the person in front of them. We diagnose, manage and provide support for individuals and families who are affected by or at risk of genetic conditions. And we translate that complex genetic information into meaningful information for the patient, the family and the other doctors as well.
Florence: So, let's talk a little bit more about clinical geneticists. What stage of someone's genomics journey are they likely to see you? What are some typical reasons they might get referred, for example?
Nour: That's a really good question. So, people actually can be seen by clinical geneticists at almost any stage of life, and for many different reasons. Let me give you some examples.
We see a lot of babies and children. A family may be referred to us if their baby is born with health problems that do not have a clear cause, or if a child is not developing as expected. And sometimes families may have been searching for answers for years, or what we call a diagnostic odyssey, but no one has been able to find a single unifying diagnosis to explain their challenges. And our job is to see if there is a genetic explanation that can connect all the dots.
Florence: You touched there on the diagnostic odyssey, and I know we don't have time to dive into that right now, but if listeners want to learn more about this, then they can check out our previous Genomics 101 podcast: What is the Diagnostic Odyssey?
So, Nour, we know that you see children and families in their genomics journeys. Do you see adults as well?
Nour: Yes, indeed. We also see many adults who develop certain health conditions, such as cancer or certain types of heart disease, and their clinicians suspect they might be having an underlying inherited genetic cause, or it could be actually someone who is healthy themselves, but have a family history of a particular condition, and want to understand their own risk or the risk for their children and other family members.
A classic example is in cancer genetics. A woman with breast cancer at a young age, or who has several family members who have also had it, she would be investigated to see if she carries a gene change that increases the risk of breast cancer and other cancers, and finding that actually would be critical for the treatment choices, and it has huge implications for her relatives.
Also, a major part of our work is in the prenatal setting, so we might see a couple during a pregnancy if the antenatal ultrasound scan, for example, shows that the baby has abnormalities. And the obstetrician might refer them to us to investigate if they have an underlying genetic reason for that. And this can help the couple and the medical team prepare for any challenges after birth and also make informed decisions about the pregnancy.
And clinical genetics is unique in that we don't see just individual patients, we often work with entire families, and if there is an inherited condition in the family, it's not unusual for several relatives across different generations to be seen by our team.
This family-wide approach helps us piece together the inheritance pattern and offer the right tests to the right people, and also ensure that everyone who might benefit from information or screening has the opportunity to access that.
Florence: So if someone has a suspected genetic condition, will they always come to you first?
Nour: Actually no, the way people come to us is changing. It used to be that you would always see clinical geneticists first, but now with genetic testing becoming more common, other clinicians like a cardiologist, a neurologist, or a paediatrician, might order a genetic test themselves.
But these tests can produce a huge amount of data, and the results are not always a simple yes or no. Sometimes the lab finds something called a variant of uncertain significance, which means a gene change that we are not certain whether it is the cause of health problems or not. And in these cases, a specialist will refer the patient to us to help put the uncertain result into the context of the patient's specific health problems, and family history, and to help also work out what it really means for them and their family.
Florence: So, you mentioned a couple of other healthcare professionals there, paediatricians and neurologists for example. Are there any other roles that you work closely with as a clinical geneticist?
Nour: Well, genetics is never a one-person job, and it's rather like a team sport, so we never work in isolation. We work in what we call a multidisciplinary team, where clinical geneticists, genetic counsellors, genomic practitioners, scientists and other specialists, all bring our knowledge and expertise together. We also work directly with other specialists across the hospital and the NHS.
Let's say if it's a genetic heart condition, a cardiologist would be a key part of this multidisciplinary team for the patient. And this 360-degree view ensures that we are giving the best possible holistic care.
Florence: And finally, before we wrap up, I'm sure lots of our listeners may have heard or even come across genetic counsellors. Could you explain how this role is different from a clinical geneticist?
Nour: So, our role as a clinical geneticist is distinct from that of a genetic counsellor, but we work side by side. Clinical geneticists, as the medical doctors on the team, we're often focused on the diagnosis, and we will perform a physical examination of the patient, looking for subtle clues. We will review their medical history, and piece together the whole medical puzzle. And based on that, we decide which genetic test is the most appropriate, and we'll have the best chance of finding an answer.
A genetic counsellor is a healthcare professional with highly specialised training in both genetics and counselling. They are communication experts, they spend time helping families understand results, process the information, and think through what it means for them and their relatives.
They are incredibly skilled at explaining complex genetic concepts in a way that is easy to understand, and also at providing support. They help families navigate the emotional impact of what can be life-changing news, and also discuss the implications for the wider family. And genetic counsellors are not only there after the diagnosis is made, they can also play an active role in the diagnostic process.
So in many situations, they are the ones taking the detailed family history, recognising patterns that suggest a genetic condition, and arrange the most appropriate genetic tests. They work closely with laboratory scientists and clinical geneticists to interpret the results and guide the next steps for the patient.
And a family will often see both of us as our roles complement each other.
Florence: So, we'll finish there. Thank you so much, Nour, for sharing what you do as a clinical geneticist.
If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk, or wherever you get your podcasts. Thank you for listening.
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In this episode of Behind the Genes, we explore how Artificial Intelligence (AI) is being applied in genomics through cross-sector collaborations. Genomics England and InstaDeep are working together on AI and machine learning-related projects to accelerate cancer research and drive more personalised healthcare.
Alongside these scientific advances, our guests also discuss the ethical, societal and policy challenges associated with the use of AI in genomics, including data privacy and genomic discrimination. Our guests ask what responsible deployment of AI in healthcare should look like and how the UK can lead by example.
Our host, Francisco Azuaje, Director of Bioinformatics Genomics England is joined by
Dr Rich Scott, Chief Executive Officer at Genomics England
Karim Beguir - Chief Executive Officer at InstaDeep
Harry Farmer â Senior Researcher at Ada Lovelace InstituteIf you enjoyed todayâs conversation, please like and share wherever you listen to your podcasts. And for more on AI in genomics, tune in to our earlier episode: Can Artificial Intelligence Accelerate the Impact of Genomics?
"In terms of what AIâs actually doing and what itâs bringing, itâs really just making possible things that weâve been trying to do in genomics for some time, making these things easier and cheaper and in some cases viable. So really itâs best to see it as an accelerant for genomic science; it doesnât present any brand-new ethical problems, instead what itâs doing is taking some fairly old ethical challenges and making these things far more urgent."
You can download the transcript, or read it below.
Francisco: Welcome to Behind the Genes.
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Rich: The key is to deliver what we see at the heart of our mission which is bringing the potential of genomic healthcare to everyone. We can only do that by working in partnership. We bring our expertise and those unique capabilities. Itâs about finding it in different ways, in different collaborations, that multiplier effect, and itâs really exciting. And I think the phase weâre in at the moment in terms of the use of AI in genomics is weâre still really early in that learning curve.
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Francisco: My name is Francisco Azuaje, and I am Director of Bioinformatics at Genomics England. On todayâs episode I am joined by Karim Beguir, CEO of InstaDeep, a pioneering AI company, Harry Farmer, Senior Researcher at the Ada Lovelace Institute, and Rich Scott, CEO of Genomics England. Today we will explore how Genomics England is collaborating with InstaDeep to harness the power of AI in genomic research. We will also dive into the critical role of ethical considerations in the development and application of AI technologies for healthcare. If youâve enjoyed todayâs episode, please like, share on wherever you listen to your podcasts.
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Letâs meet our guests.
Karim: Hi Francisco, itâs a pleasure to be here. I am the Co-Founder and CEO of InstaDeep and the AI arm of BioNTech Group, and Iâm also an AI Researcher.
Harry: Iâm Harry Farmer, Iâm a Senior Researcher at the Ada Lovelace Institute, which is a think-tank that works on the ethical and the societal implications of AI, data and other emerging digital technologies, and itâs a pleasure to be here.
Rich: Hi, itâs great to be here with such a great panel. Iâm Rich Scott, Iâm the CEO of Genomics England.
Francisco: Thank you all for joining us. I am excited to explore this intersection of AI and genomics with all of you. To our listeners, if you wish to hear more about AI in genomics, listen to our previous podcast episode, âCan Artificial Intelligence Accelerate the Impact of Genomicsâ, which is linked in this podcast description. Letâs set the stage with what is happening right now, Rich, there have been lots of exciting advances in AI and biomedical research but in genomics itâs far more than just hype, can you walk us through some examples of how AI is actually impacting genomic healthcare research?
Rich: Yeah, so, as you say, Francisco, it is a lot more than hype and itâs really exciting. Iâd also say that weâre just at the beginning of a real wave of change thatâs coming. So while AI is already happening today and driving our thinking, really weâre at the beginning of a process. So when you think about how genomics could impact healthcare and peopleâs health in general, what weâre thinking about is genomics potentially playing a routine part in up to half of all healthcare encounters, we think, based on the sorts of differences it could make in different parts of our lives and our health journey. There are so many different areas where AI, we expect, will help us on that journey. So thinking about, for example, how we speed up the interpretation of genetic information through to its use and the simple presentation of how to use that in life, in routine healthcare, through to discovery of new biomarkers or classification that might help us identify the best treatment for people.
Where itâs making a difference already today is actually all of those different points. So, for example, thereâs some really exciting work weâre doing jointly with Karim and team looking at how we might use classification of the DNA sequence of tumours to help identify what type of tumour - a tumour that we donât know where itâs come from, so what we call a âcancer of unknown primaryâ - to help in that classification process. Weâre also working with various different people who are interested in classification for treatment and trials, but thereâs also lots in between recognising patterns of genomic data together with other complex data. So weâve been doing a lot of work bringing image data together with genomic data and other health data so that you can begin to recognise patterns that we couldnât even dream of. Doing that hand in hand with thinking about what patients and participants want and expect, how their data is used and how their information is held, bringing it all together and understanding how this works, the evidence that we need before we can decide that a particular approach is one that policymakers, people in healthcare want to use, is all part of the conversation.
Francisco: Thank you, Rich, for speaking of cutting-edge AI applications and InstaDeep. Karim, could you give us a glimpse into your work and particularly how your technologies are tackling some of the biggest challenges in genomic research?
Karim: Absolutely, and I think whatâs exciting is weâve heard from Rich and, you know, this is like the genomics expertise angle of things and I come from the AI world and so do most of the InstaDeep team. And really whatâs fascinating is this intersection that is being extremely productive at the moment where technologies that have been developed for like multiple AI applications turn out to be extremely useful in understanding genomic sequences.
This is a little bit, our journey, Francisco. Back in 2021/2022 we started working on the very intriguing question at the time of could we actually understand better genomic sequences with the emerging technologies of NLP, natural language processing. And you have to put this in context, this was before even the word âgenerative AIâ was coined, this was before ChatGPT, but we had sort of like an intuition that there was a lot of value in deploying this technology. And so my team, sort of like a team of passionate experts in research and engineering of AI, we tackled this problem and started working on it and the result of this work was our nucleotide transformer model which we have open sourced today; itâs one of the most downloaded, most popular models in genomics. And whatâs interesting is we observed that simply using the technologies of what we call âself-supervised learningâ or âunsupervised learningâ could actually help us unlock a lot of patterns.
As we know, most of genomics information is poorly understood and this is a way actually, with using the AI tool, to get some sense of the structure thatâs there.
So how do we do this? We basically mask a few aspects of the sequence and we ask the system to figure them out. And so this is exactly how you teach a system to learn English, you know, you are teaching it to understand the language of genomics, and, incredibly, this approach when done at scale - and we train a lot on the NVIDIA Cambridge-1 supercomputer â allows you to have results and performances that are matching multiple specialised models. So until then genomics and use of machine learning for genomics was for a particular task, I would have developed a specific model using mostly supervised learning, which is, I am showing you a few examples, and then channelled these examples and tried to match that, and so essentially you had one model per task. Whatâs really revolutionary in this new paradigm of AI is that you have a single model trained at very largescale, the AI starts to understand the patterns, and this means that very concretely we can work with our partners to uncover fascinating relationships that were previously poorly understood. And so there is a wealth of potential that we are exploring together and itâs a very exciting time.
Francisco: What youâre describing really highlights both the potential and the opportunities but also the responsibility we have with these powerful tools, its power, and this brings up some important ethical considerations. And we have Harry⊠Harry, we have talked about ethics frameworks in research for decades but AI seems to be rewriting the rulebook. For your work at the Ada Lovelace Institute what makes AI fundamentally different from previous technologies when it comes to ethical considerations and how does this reshape our approach to ensuring these powerful tools benefit society as a whole?
Harry: So I think when you are considering these sorts of ethical questions and these sorts of ethical challenges posed by AI and genomics it really depends on the sort of deployment that youâre looking at. From the conversation weâve had so far, I think whatâs been hinted at is some of the diversity of applications that you might be using AI for within the context of genomics and healthcare. So I think thereâs obviously big advances that have been alluded to in things like drug discovery, in things like cancer and cancer diagnosis, also these advances around gene editing, all of which have been on steroids, by artificial intelligence and particularly machine learning and deep learning.
The area that we have been looking at at the Ada Lovelace Institute, and this was a project that we were doing in collaboration with the NCOB, the Nuffield Council on Bioethics, was looking at what we were calling âAI-powered genomic health predictionâ, which is very related to a technique called âpolygenic scoringâ, for those who might be interested. And thatâs looking at the emerging ability to make predictions about peopleâs future health on the basis of their DNA, and it was thinking about what that ability might mean for UK society and also for how we are thinking about and delivering healthcare in the UK.
Now, thinking about what the ethical challenges might be for that, I think you need to think about what specifically AI is bringing to that technique, so what itâs bringing to genomic health prediction. I think with some of the other deployments, the list of things that AI is bringing is quite similar, so itâs helping with data collection and processing, so speeding up and automating data collection and preparation processes that otherwise are quite slow and very labour-intensive. AIâs also helping with the analysis of genomic and phenotype data, so helping us to understand the associations between different genomic variations and between observable traits, and this is something which without AI can often be prohibitively complex to do, and itâs also sometimes suggested that on the deployment end AI can be a tool that can help us use genomic insight in healthcare more widely. So one example of this might be using an AI chat bot to explain to a patient the results of a genomic test. Thatâs something thatâs only been mooted and I donât think there are current examples of that at the moment but thatâs one of the downstream applications of AI in the context of genomics.
So in terms of what AIâs actually doing and what itâs bringing, itâs really just making possible things that weâve been trying to do in genomics for some time, making these things easier and cheaper and in some cases viable. So really itâs best to see it as an accelerant for genomic science; it doesnât present any brand-new ethical problems, instead what itâs doing is taking some fairly old ethical challenges and making these things far more urgent. So in terms of what those problems actually are, some of the big ones will be around privacy and surveillance, genomic health predictions produce a lot of intimate sensitive data about people and generating those insights requires the collection and the storage and the processing of a lot of very sensitive data as well. We also have issues related to privacy around genomic discrimination, so this is the worry that people will be treated differently and in some cases unfairly on the basis of health predictions made about them. And one of the really typical examples here is the worry that people might face higher insurance costs if theyâre found through genomic testing to be more likely to develop particular diseases over their life course.
And then you also have a bunch of issues and questions which are more structural, so these are questions about how the availability of this kind of insight into peopleâs future health might change or put pressure on existing ways of thinking about health and thinking about healthcare and some extreme cases thinking about the social contract. So these are questions like does the viability of genomic health prediction lead to a radically more preventative approach to healthcare and what might this mean for what the state demands of you as a user of healthcare and as a recipient of that. And there are also some important questions about the practicalities of delivering genomic medicine in the NHS, so questions like how does the NHS retain control and sovereignty over genomic analysis and data capacities, how do we test their efficacy at a public health level, and also â and this is something that we might talk about a bit later â whatâs the best deployment model for these capacities. So thatâs some of the ethical and I think policy challenges that we need to be dealing with in this space.
Francisco: Thank you, Harry. And those principles you have outlined provide a solid foundation for discussing different types of applications.
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Letâs talk about the InstaDeep and Genomics England partnership that is investigating the application of InstaDeepâs powerful foundation model, the nucleotide transformer, and other cutting edge techniques to address several challenges in cancer research. I have the privilege of working closely with this partnership and the potential here is immense. Karim, could you break down for our listeners what you are working on together and what innovations you are aiming for?
Karim: Absolutely, Francisco. Actually, we are very excited by the collaboration with Genomics England. Genomics England not only has one of the best data assets in the world when it comes to genomics, like a very well curated dataset but also a wealth of expertise on these topics, and on my side the InstaDeep team brings fundamental knowhow of machine learning models but also, as you mentioned, like powerful developed models already, such as our nucleotide transformer and others.
The culture of InstaDeep has always been to build AI that benefits everyone â this is literally in our mission â and so in particular, specifically on like current topics, really like the goal is to try to identify partners between genomic sequences of patients and the particular phenotypes or approaches. And one of the key projects, which I mentioned that, is the one of cancer of unknown primary origin. So when you have situations where you are not sure where a particular cancer emerged from it is critical to be able to extract this information to have the best potential care, and this is actually something where understanding of genomic sequences can bring this capability. And so weâve been getting some successful results in the collaboration but in many ways this is just the beginning. What we are seeing is a great wealth of possibilities linking genotypes, so the information which is on the sequences themselves, the genomic sequences, and phenotypes, like the particular state of the patient, and the fact that the Genomics England team has those joint datasets creates incredible opportunities. So we are looking at this really like identifying together what are the most useful âlow-hanging fruitsâ, if you want, in terms of like potentially improving a patientâs care and moving forward from that.
Francisco: And this collaborative approach you are describing raises questions about accelerating innovation in general. When two organisations like Genomics England and InstaDeep come together itâs like a multiplier effect in terms of expertise, data, and other resources. Could you both share how this partnership is accelerating discoveries that might have taken years?
Rich: Yeah, I mean, I think this⊠Francisco, you frame it really nicely because this is what makes it so exciting to be in our position at Genomics England because what we do is we bring the particular understanding and expertise, digital infrastructure and custodianship of the National Genomic Research Library together, but actually the key is bringing the potential of genomic healthcare to everyone. We can only do that by working in partnership, we bring our expertise and those capabilities. And, as you say, itâs about finding it in different ways, in different collaborations, that multiplier effect, and itâs really exciting. And I think the phase weâre in at the moment in terms of the use of AI in genomics is weâre still really early in that learning curve.
And so, as youâve heard already through what Karim and I have said and also what Harry has said, there are multiple different aspects that we need to look at together, bringing different angles and understandings, and we see ourselves⊠We often describe ourselves as a âdata and evidence engineâ, that final word âevidenceâ is really important and it comes in the round. So Harry really eloquently talked about a number of different considerations from an ethical perspective that need to be there. What we need if weâre going to move genomics forwards in terms of its potential to make a difference for peopleâs lives, we need evidence around clinical efficacy of different approaches, thatâs absolutely a given and everyone always jumps at⊠so itâs almost first in line. We need understanding about the health economics, you know, how much difference does it make for a particular investment, is it worth that investment. Critically, it also is founded on, you know, how you might use this technology in different ways, how you use it in clinical pathways, you know, is it something that actually is addressing the particular questions which really hold back the delivery of better care. Also in that evidence piece is an understanding of patientsâ and participantsâ expectations on how their data might be used, their expectations on privacy, the expectations that we have on understanding how equitable the use of a particular approach might be, or at least our understanding of how confident we are about the equity of the impact, and itâs bringing together those different perspectives. And thatâs one of the things that helps us construct the team at Genomics England so we have the expertise to help others access the data in the National Genomic Research Library for purposes our participants support but also help generate that sort of rounded package of evidence that will end up moving the dial. So that itâs not just about proving a cool widget, because thatâs great on its own, what drives Karim and the team is to make a difference in terms of outcomes, and thatâs exactly what drives us and our participants too.
Francisco: And this and other partnership approaches brings up important questions about responsible innovation, and this naturally leads us to the next question for Harry, how do we harness these powerful tools when protecting our communities?
Harry: Yeah, so if we are thinking about over-surveillance and the ways that vulnerable groups might be affected by the use of genomics and healthcare, I think weâre talking about at least two different things here. So one problems around the representativeness of data is it does lead to issues which you could classify as issues of differential accuracy. So in the context of genomic prediction what you have is genomic predictive tools being more accurate for white Europeans and those with white European ancestry compared to other population groups. And this is a product of the fact that genomic datasets and genomic predictions, the terminologies donât port well between different populations, which means if you train a genomic predictive tool on a bunch of people with white European ancestry the predictions you might make using that tool for other groups wonât be as accurate as for the white Europeans. And this can be actively harmful and dangerous for those in underrepresented groups because you are making predictions about people which just wonât have the accuracy that you would expect in the context that you were deploying it.
And I already mentioned this a bit in my previous answer, you have worries about discrimination, and there are a few different things here. So with some historically marginalised groups and marginalised groups now there are longstanding historical sensitivities about being experimented on, about particular fears about eugenics and about being categorised in particular ways. And itâs worth saying here that there is obviously a racial dimension to this worry but I think thereâs also a class dimension, by which I mean youâre far more vulnerable to being categorised unfavourably if youâre poor or if you donât have a particular kind of status within society. There is also within discrimination the idea that genomics might be used to explain away differences between different groups which in fact have a political or an economic basis. So one example of this was during the COVID-19 pandemic, there were attempts by some commentators to explain away the fact that non-white communities had worse rates of mortality from COVID to try and attribute a genetic or a genomic basis to those differences rather than looking at some of the socioeconomic factors behind that. So those are some worries as well.
Now, when it comes to protecting particular groups I think there are a few things that can be done fairly straightforwardly. So, one is work to improve the diversity and the representativeness of datasets. Obviously, thatâs easier said than done, though itâs a very clear thing that we can aspire towards and there is good work, Iâm aware, that is going on in this space, some of which is being spearheaded by Genomics England, amongst other groups. Another is just being very careful about how the results of population level genomic studies are communicated to avoid giving that impression of explaining away differences between different groups simply as things determined by genomics about which we can do nothing rather than things which have historical or socioeconomic bases. But I also think the broader lesson is that some of these harms and these forms of discrimination are things that could theoretically affect anyone; theyâre not just limited to affecting marginalised groups.
Genomic health predicting can produce bases for all of us to be discriminated against, things that have nothing to do with our race, our class, our sex or any other protected characteristic. So I think there has to be thinking about how we establish or sure up more universal protections against genomic discrimination. One thing that we can do here is simply stronger data protection law, and one of the things that we talk about in some of our reports is that how data protection law as it stands could do with being less ambiguous when it comes to how it treats genomic data and phenotype data produced as a result of genomic analysis.
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Francisco: Harry, you are in a unique position at the Ada Lovelace Institute where you bridge this gap between AI developers, researchers, policymakers and the public. Your recent report on AI in genomics with the Nuffield Council on Bioethics offers an important blueprint for responsible AI innovation in general, so based on this cross-sector perspective, what guiding principles do we need to embrace as we navigate this intersection of AI and genomics?
Harry: So I think in addition to the specific recommendations we set out in the final report of that work - which is called âPredicting the Future of Healthâ and which you can find on our website and also on the NCOB website â I think one of the biggest messages was the importance of finding a deployment model for genomic health prediction that respects that technologyâs strengths, what it can actually do, because there are limitations to this technology, and also which avoids circumstances in which the associated risks are difficult to deal with. So another way of putting this is that we need a deployment model that, as well as making sure that weâre ready to cope with the risks of genomic health prediction, the things like law, regulation and governance also proactively tries to design out some of those risks and finds ways of deploying this technology such that those risks donât present themselves in either as extreme a manner or donât present themselves in ways which makes them difficult to deal with.
So one question that we posed in our research was whether some ways of integrating genomic health prediction may present more challenges regarding privacy, discrimination and then these other challenges that weâd identified around dependency and fragility and others. And having looked at some of the different broad approaches to using genomic health prediction within the NHS and within the UKâs health system, we found that one presented by far fewest of the risks identified above, while still presenting some of the most certain benefits of genomic health prediction. And this was using it really primarily as a targeted diagnostic tool - and this is a vision in which the NHS uses genomic health prediction quite sparingly in the first instance - and in situations to improve treatment and outcomes for those who are seriously ill or who have been identified as needing to take particular precautions regarding their health. We think the more situational vision has a few advantages. So one, is it allows patient and people using the health service to retain greater control over data. We think that can also have a positive knock-on effect for worries about discrimination. And here what you have is the absence of those pressures to share your data. It means that itâs easier for you as the user of the healthcare system to resist genomic discrimination simply by keeping your data private. And there are some cases where that option⊠it shouldnât be the only option but where that option is really important.
And then also one of the features of this vision is that the smaller scale of the use of genomic health prediction, presumed, can make outsourcing to third parties, which the NHS is probably likely to need to do in some cases. Itâs also a vision, I think, that overall allows you to capture some of the more certain benefits to genomic health prediction which are about improvements to accuracy in predictions about peopleâs future health at the margin, and therefore this is a deployment of this technology which is deploying it principally to people who will benefit and we know will benefit from marginal improvements in accuracy to predictions made about their future health rather than wanting to deploy those marginal improvements to the vast majority of the population where the benefit is less certain. So this is a vision we hope sets out a way of getting some of the more certain benefits of this technology while minimising some of those broader more systemic risks.
Francisco: Thank you, Harry. Karim?
Karim: Totally agree with Harry about the need for smart regulation in the field so that we make sure we have good uses of the technology but avoid the potential pitfalls. I wanted to emphasise two points which I believe are important. First, we are really in a fast-moving situation when we look at like AI progress. We have seen incredible improvements over the last ten years and in particular what we call âartificial general intelligenceâ, which is essentially systems that are matching human cognitive abilities, are now around the corner. This might sound surprising but literally the last obstacles to reach AGI are being solved right now, and this means that in the next 12-24 months you will have systems that are incredibly capable. So this emphasises the need for the type of measures and type of smart approach that Harry has described. And I would say when you look at the intersection of AI and genomics this is a particularly important one and why itâs the case, because so far in genomics our obstacle has not been data, it has been interpretation of a flood of data. The progress that AI is making, like I just described now, means that very soon extraordinary capabilities will be available to improve patientsâ outcomes. I want to inject a sense of how important is our conversation today, given what is happening, an exponential progress in AI, exponentially growing data in genomics and relatively exponential potential to build the technology for good. But, like in other fields, we see that AI is an extremely powerful technology and we need to make sure it is used for good in fact and this is why the conversation that we have today is so important.
Harry: Obviously I agree with the conclusion to all of this, is that we need to think very hard about the way that artificial intelligence and its deployment in healthcare and also just in many different walks of life is going to be affecting the way we think about public service delivery, affecting the way that we think about scientific development. Itâs worth noting, though, that I think one of the biggest challenges from a policy perspective on artificial intelligence is being able to distinguish the wheat from the chaff. There are obviously areas where AI has made huge and incredibly impressive progress over the past few years and where we reasonably expect that to continue over the next few years, but there are also areas where some of the stories being told about the capabilities of future systems probably wonât be matched by the reality, but there is I think a really big and very live debate about exactly what we can reasonably expect from these technologies and therefore what the deployments of them are.
Francisco: Thank you. We are approaching the end of the episode and Iâd like to conclude with a couple of questions. Genomics England has built quite an ecosystem of industry partnerships, how do collaborations like the one with InstaDeep fit into your broader mission for the company?
Rich: So linking this to the conversation that weâve just been having, which is AI is making a real difference in terms of technologies that we can test, we can develop evidence on, and that is rightly creating excitement, I think our approach⊠The expectation of our participants is that our role is to sit there and help people develop evidence and you can make judgments on policy based on those and that is what will drive adoption. I think the thing that really excites me for the UK, most particularly in genomics, is our ability to be the place in the world where you can come with a new technology, whether itâs genomic sequencing technology, whether itâs a genomic AI approach to train that to develop evidence on its efficacy, and, if itâs proven to be effective to be worth the bang for the buck to perform to the expectations that patients, the public, would have of it in terms of equity and so forth also to deploy it. I think there is a real reason for excitement around that and itâs a real opportunity that the government has highlighted and that we absolutely buy into that the UK can be the best place to do that for academics and for industry. And our participants see real opportunity and are eager for that work to be done so that we have the evidence on which to decide what should be deployed and where. We see opportunities in all sorts of different areas, so certainly in terms of drug discovery and all the way through to simplifying tasks which at the moment just limit the rate at which the existing uses of genomics in healthcare can happen.
So I think thereâs opportunities across the whole length, if you like, the sort of end to end, and the breadth of opportunity, and industry, companies like InstaDeep and others that we work with, are really crucial to that. And what we do is think about the digital infrastructure we need to, you know, have those teams able to interact with within the National Genomic Research Library carrying out their approved research projects. Also what support they need, and that comes in different shapes and sizes, depending on the ask and also the company. So sometimes sort of leaning in more, particularly at the start of programmes, to help people shape the question, working with our participants, thinking about the wider evidence that you might need, for example, those sort of things that Harryâs touched on, but also thinking about what hands-on support companies need, because not every company is anywhere close to Karim and InstaDeepâs expertise. Sometimes this is also about supporting people to have some of those tools that they donât have or some of the knowhow thatâs very specific to areas of genomics, so itâs absolutely crucial to it. And I think that point of the UK being the place to come and develop that evidence in its full breadth so that policy decisions can be made not based on hype but on evidence in the round, on what will make a difference.
Francisco: And, Karim, looking ahead, also in retrospect, what have been your key learnings about making this cross-sector partnership work?
Karim: We live in an extraordinary time and I want to emphasise the potential of scientific discovery in the next two or three years. AI is going to move from, letâs say, digital style, you know, technologies like coding and maths towards more like science and biology. In particular, genomics is going to be a fascinating area in terms of potential, and I agree with Rich and Harry, itâs all in the end about proving on the ground the potential of those capabilities. And at InstaDeep we are passionate about the tech â I think you might have felt that â but weâre also passionate about the applications. The best results come when you bring expertise from multiple domains; machine learning and AI experts will require the expertise of genomic experts, biologists, healthcare practitioners, to be able to translate the potential of those technologies in concrete outcomes. And weâve seen this on multiple successful projects weâve done with Genomics England but really this suggests that we are going to have in the next 3-5 years way more progress than we had in the last five and really my wish is that collectively we seize this opportunity and we do it in a responsible and thoughtful manner.
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Francisco: Weâll wrap up there. Thank you to our guests, Karim Beguir, Harry Farmer and Rich Scott, for joining me today as we discuss the role of AI in genomics research. If you wish to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Francisco Azuaje. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.
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In this episode of Behind the Genes, we explore the hopes, concerns and complex questions raised by the idea of a lifetime genome â a single genomic record used across a personâs life to guide healthcare decisions. Drawing on conversations from Genomics Englandâs Public Standing Group on the lifetime genome, our guests explore what it might mean for individuals, families and society to have their genome stored from birth, and how it could transform healthcare.
The discussion reflects on the potential for earlier diagnoses, better treatments and long-term prevention, alongside pressing ethical concerns such as data security, consent, and the impact on family dynamics. Participants share their views and discuss the future role of genomic data in medicine, with insights into how trust, equity and public dialogue must shape this evolving field.
Our host for this episode, Dr Harriet Etheredge, is joined by Suzalee Blair-Gordon and Gordon Bedford, two members of the Genomics Englandâs Public Standing Group on the lifetime genome, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that helped to facilitate this work. Together, they consider the broader societal implications of lifetime genomic data, and how public involvement can help guide policy and practice in the UK and beyond.
This conversation is part of our ongoing work through the Generation Study, exploring how genomics can be used responsibly and meaningfully from birth onwards. You can listen to some of our Generation Study episodes by following the links below.
What can we learn from the Generation Study?How has design research shaped the Generation Study?What do parents want to know about the Generation Study?"This isnât just a science project, itâs about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction."
You can download the transcript, or read it below.
Harriet: Welcome to Behind the Genes.
Suzalee: I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms.
Harriet: My name is Harriet Etheredge, and I am the Ethics Lead on the Newborn Genomes Programme here at Genomic England. On todayâs episode Iâm joined by 3 really special guests, Suzalee Blair and Gordon Bedford, who are members of Genomics Englandâs Public Standing Group on Lifetime Genomes, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that has helped us to facilitate this work.
Today weâll be discussing the concept of the lifetime genome. What do we mean when we say, âlifetime genomeâ? How can we realise the promise of the lifetime genome to benefit peopleâs healthcare whilst at the same time really appreciating and understanding the very real risks associated? How do we collectively navigate ethical issues emerging at this genomic frontier?
If you enjoy todayâs episode, we would really love your support. Please share, like and give us a 5-star rating wherever you listen to your podcasts. And if thereâs a guest that youâd love to hear on a future episode of Behind the Genes, please contact us on [email protected].uk.
Letâs get on with the show. Iâll start off by asking our guests to please introduce yourselves. Suzalee, over to you.
Suzalee: Thanks, Harriet. So I am a proud mum of two kids, teacher of computing at one of the best academic trusts in the UK, and I am also a sickler, and for those who donât know what that means, I am living with sickle cell disease.
Harriet: Thank you so much, Suzalee. Gordon, over to you.
Gordon: Iâm Gordon Bedford, Iâm a pharmacist based in The Midlands. Iâve worked in hospital and community pharmacy. I have a genetic condition, which I wonât disclose on the podcast but that was my sort of position coming into this as Iâm not a parent of children, but it was coming in from my perspective as a pharmacist professional and as a member of society as well.
Harriet: Thank you so much, Gordon. And, last but certainly not least, Suzannah.
Suzannah: So, yes, Suzannah Kinsella. I am a social researcher at Hopkins Van Mil, and I had the pleasure of facilitating all of the workshops where we gathered together the Public Standing Group and working on reporting the outcome from our discussions, so delighted to be coming in from South London.
Harriet: Thank you so much, everyone, and itâs such a pleasure to have you here today. So, many regular listeners to Behind the Genes will now that Genomics England is currently undertaking the Generation Study. Iâm not going to speak about it in much detail because the Generation Study has already been the subject of several Behind the Genes podcasts and weâll put some links to these in the show notes for this episode. But briefly, the Generation Study aims to analyse whole genomes of 100,000 newborn babies across England, looking for 250 rare conditions. We have a view to getting these children onto treatments earlier and potentially enhancing their lives.
The Generation Study is a research project because we donât know if the application of this technology will work. And as a research project we can also answer other important questions, such as questions about a lifetime genome. When we invite parents to consent to the Generation Study on behalf of their newborn babies, we ask to store babiesâ genomic data and linked healthcare data in our trusted research environment. This helps us to further research into genes and health.
But a critical question is âwhat do we do with these data long term?â And one of the potential long-term uses of the data is to revisit it and re-analyse it over a personâs lifetime. We could do this at critical transition points in life, like adolescence, early adulthood or older age, with the aim of using the genomic data to really enhance peopleâs health. But this is a very new concept. Thereâs been little work on it internationally, however I am pleased to say that interest seems to be picking up.
In the Generation Study, whilst we are at the present time doing no lifetime genomes work, we are looking to explore the benefits, risks and potential uses of the lifetime genome. This Public Standing Group on lifetime genomes was our first foray into this area. So, Iâd like to start off by inviting Suzannah to please explain a bit more about what the Public Standing Group is, why it was created and how a group like this helps us to generate early deliberation and insight.
Suzannah: So, the first thing I should talk about is who were these 26 people that formed part of this group, and the first thing to say is that they were a wide range of ages and backgrounds from across England, so some from Newcastle, some from London and everywhere in between. And these 26 people all had one thing in common, which is they had all taken part in a previous Genomics England public dialogue, either the whole genome sequencing for newborn screening which took place in 2021, or in a more recent one in about 2022/23 which was looking at what should Genomics England think about in terms of research access to data thatâs drawn from the Generation Study.
So, the great thing was that everybody had already some previous knowledge around genomics, but the concept of a lifetime genome was completely new. So these 26 people met on 5 occasions over the period of 2024, mostly meeting face to face, and really the task that they were given was to look at the lifetime genome and look at it from every angle; consent, use, information sharing and all sorts of other aspects as well.
Harriet: Gordon and Suzalee, you were participants in our Public Standing Group, Iâd love to hear from you what your roles in the Standing Group were and what you found most interesting, but also for you which bits were the most challenging. Suzalee, shall we start with you?
Suzalee: For me the most interesting bits were being able to learn about oneâs genome and, through Genomics England and their possible use of pharmacogenetics, could determine the specific medication that could be prescribed for a new health condition instead of expensive and possibly tonnes of adverse side effects trial and error medications.
Additionally, as a person living with sickle cell disease, I got the chance to share my story and to give voice to people living with the same condition or similar to myself, and how the potential of the genomics newborn programme could help our future generation.
There were some tricky bits, and the most challenging bit was to initially discuss and think about the idea of whether or not a parent might choose to know or not to know the potential of their newborn developing or prone to develop a certain condition based on the data received from the programme. My thought went back to when I gave birth to my first child 16 years ago and I was adamant to know if my child would inherit the sickle cell disease, what type, if it would be the trait. In my mind I knew the result, as my haemoglobin is SC and their dad is normal, but I wanted to be sure of my childâs specific trait. But then I asked myself, âWhat if my child was part of the Newborn Genomes Programme, then the possibility exists that other health conditions could be detected through the deep analysis of my childâs genome. Would I really want to know then? What would be the psychological effect or, in some cases, the social impact of what I have to learn?â
Harriet: Thank you so much, Suzalee. And I think itâs just wonderful to hear about the personal impacts that this kind of work can have and thank you for bringing that to us. Gordon, Iâll hand over to you. Iâd be really interested in your thoughts on this.
Gordon: So my role in the Public Standing Group was to give my section of society my experiences in life to bring them together with other people, so experiences like Suzalee and the 24 other people that joined us on the study, to bring our opinions together, to bring our wide knowledge and group experiences of life. And itâs important to have a wide group, because it forces us to wrestle with differences of opinion. Not everybody thinks like I do. As a pharmacist, I can see the practical side of genomics, like pharmacogenomics, where we could use a babyâs genome to predict how theyâll respond to drugs over their lifetime. Thatâs a game-changer for avoiding adverse reactions or ineffective treatments, but not everybodyâs sold on it.
Some in our group worried about privacy, who gets this data, or ethics, like whether itâs fair to sequence a baby who canât say yes or no. I get that. I donât have children, but I hear those things clearly. The most interesting bits for me, the pharmacogenomics discussion in meeting two stood out, everyone could see the tangible benefits of tailoring medicines to a personâs genome, making treatments more effective, and in Meeting 5 designing our own lifetime genome resource was also fascinating. Ideas like it for public health research showed how far-reaching this could be. Some of the challenging sides of things that I came across, the toughest part was grappling with unknowns in Meeting 4, like how to share genetic info with your family without damaging relationships. Those risks felt real, and it was hard to balance them against the benefits, especially when trust from groups like minority ethnic communities is at stake.
Harriet: Thank you so much, Gordon. I think from you and Suzalee itâs so fascinating to hear how you were grappling, I think, with some of your personal and professional feelings about this and your deeply-held personal views and bringing those first of all out into the open, which is something that is very brave and we really respect and admire you doing that, and also then understanding that people do hold very different views about these issues. And thatâs why bring these issues to an engagement forum because itâs important for us to hear those views and to really understand how people are considering these really tricky ethical issues.
So, Suzalee, Iâm wondering from your perspective how do you feel we can really be respectful towards other peopleâs points of view?
Suzalee: Yes, Harriet. In spite of the fact that we had different viewpoints on some topics discussed, every member, researcher, presenter and guests were respectful of each otherâs point of view. We all listened to each other with keen eyes, or sometime squinted eyes, with a hand on the chin which showed that what was being said was being processed or interpreted. All our views were recorded by our researchers for further discussion and analysis, therefore I felt heard, and I believe we all felt heard.
Harriet: Do you have any examples that you can recall from the groups where there were differing points of view and how we navigated those?
Gordon: Where we had screening at age 5, but we agreed on an opt-out model, because it could help spot issues early. But some worried - psychological impacts, knowing too much too soon. But we looked at an opt-out model rather than an opt-in model because itâs easier to say to somebody, âIf you donât want to continue with this, opt outâ rather than trying to get everybody opting in at every different age range. So, as we reach the age of 5, 10, 15, 20, whatever, itâs easier to get people to opt out if they no longer want to be part of that rather than trying to get them to opt in at each stage throughout their life.
Harriet: Suzannah, do you have anything to add there as a facilitator? How did you feel about bringing these different points of view together?
Suzannah: Yeah, you asked about where are the tensions, where do people maybe agree a bit less or agree and hold different views, and I think what stands out is particularly⊠There was an idea floated by one of the speakers about you could have your DNA data on an NHS app and then, letâs say if youâre in an emergency, a paramedic could have access to it or others. And that really I think brought out quite a wide range of perspectives of some in the group feeling, âYou know what, anyone who has an interest, anyone that can help my health, let them have access to it as and when, completely fine,â and others took a more cautious approach saying, âThis is my DNA, this is who I am, this is unique to me, my goodness, if someone, some rogue agent manages to crash the system and get hold if it goodness knows what nightmare scenario it could result in,â and so had a much more keep it locked down, keep it very limited approach to having access to your lifetime genome data and so on. So that was a really interesting example of people going, âYep, make it freeâ and others going, âNo, just for very specific NHS roles,â which I thought was fascinating.
Harriet: Yeah, thank you so much, Suzannah. And I think itâs a real tangible challenge that those of us working in this area are trying to grapple with, is finding the middle ground here with all of the challenges that this involves, for instance, our data infrastructure and the locations at which data are held.
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Harriet: I think this brings us really nicely onto looking at some of the ethical, legal and social issues that we need to think through when weâre considering the lifetime genome. Iâm wondering if we can expand on some of these and the importance of addressing them. Gordon, would you like to give us your thoughts?
Gordon: Sure, thank you. Our job was to dig into how a babyâs genome could be used over the lifetime, think pharmacogenetics for better drugs, early childhood screening for conditions or carrier testing to inform family planning. We saw huge potential for individual health like catching diseases early, but also broader impacts like reducing NHS costs through prevention. Weighing the risks and benefits. The benefits like earlier diagnosis or research breakthroughs grew clearer over time with ratings rising from 4.1 to 4.7 - thatâs out of, I believe, a figure of 5, but risks like data breaches and family tensions over shared genetics stayed significant. We agreed the benefits could outweigh the risks but only with mitigations like transparent governance and strong security. And what are the global implications moving forward? What we discussed isnât just for the UK, itâs feeding into the global conversation about newborns in genomic research. That responsibility made us think hard about equity, access, and how to build public trust.
Harriet: Thank you, Gordon, I think thereâs so much there to unpack. And one point I think in particular that youâve mentioned, and this came out really strongly as one of our main findings from these groups, was the way that a lifetime genome and the way that we might deliver that information could really impact family dynamics in ways that we might not have really thought of before or in ways that we really have to unpack further. And, Suzalee, Iâd love to hear from you about this, how might diverse family dynamics need to be considered?
Suzalee: Harriet, as it relates to diverse family dynamics a burning legal issue, which is then triangulated into being considered an ethical issue as well as a social issue, was the question can siblings of sperm donors be informed of life-threatening genomic discoveries? Whose responsibility is it? Will policies now have to be changed or implemented by donor banks to take into consideration the possibility of families being part of the new genomes programme?
Harriet: Yeah, thank you, Suzalee. I think thereâs so much there that we have to unpack and in the Generation Study weâre starting to look at some of those questions, but going forward into potential risks, benefits and uses of the lifetime genome, all of these new technologies around human reproduction are things that weâre going to have to consider really, really carefully through an ethical and legal lens. Suzannah, I wondered if you have anything to add to these as major ethical issues that came out in these groups.
Suzannah: I think, as you say, people were so fascinated by the idea of this information landing in a family, and where do you stop? Do you stop at your siblings, your direct family, the brothers and sisters of a child? Do you go to the cousins? Do you go to the second cousins? Itâs this idea of where does family stop. And then people were really interested in thinking about who does the telling, whose job is it? And we had this fascinating conversation â I think it was in Workshop 3 â where this very stark fact was shared, which is the NHS doesnât know who your mother or your father or your siblings are; your NHS records are not linked in that way.
And so that presented people with this challenge or concern that âActually, if I get quite a serious genetic condition diagnosed in my family whose job is it to share that information, what support is there to do that and how far do we go?â So, I think people were really fascinated and hopeful that Genomics England will really be at the vanguard of saying, âHow do we as we move into an era of more genetic data being used in our healthcare, howâs that managed and howâs it shared?â
Harriet: Yeah, thank you so much, Suzannah. So I think that whatâs coming out through everything that youâre all saying is the huge breadth of issues that came up here. And of course weâre seeing, very encouragingly, so many nods to the potential benefits, especially around things like pharmacogenomics, but we are seeing some risks. Gordon, I wondered if youâd like to elaborate a bit further.
Gordon: So, something that came up, and it divided the group quite considerably, carrier status divided us. Some saw it as reducing disease prevalence and others feared it could fuel anxiety or stigma amongst the family or other families. It showed how personal these choices are and why families need control over what they learn.
Harriet: Yeah, itâs a very good point, and carrier status is something that could be a conceivable use of our lifetime genome record. Suzannah?
Suzannah: Just building off what Gordon was talking about, I remember there were also discussions around are we getting into a state where this is about eradication of so many different conditions, and actually how does that sit with a society that is more embracing, accommodating and supportive of people with different health needs. So, I think that was quite a big ethical discussion that was had, is, and particularly where we think about what we screen for in the future over time and so forth, people really being conscious that âActually, where are we going with this? Are we risking demonising certain conditions and saying we donât want them on the planet anymore and what are the consequences of that?â
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Harriet: And I think came to a point in our final meeting where we were asking our participants, so Suzalee and Gordon and everybody else in the room, whether you might consider having a lifetime genome for yourself and what that would look like. Weâd love to share your views about that, and Suzalee, Iâm wondering if you can share your thoughts on that with us first.
Suzalee: Definitely. I would wholeheartedly be interested in the lifetime genome programme if it was offered to me right now. I believe that the pros for me are phenomenal. I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms.
Harriet: Thank you, Suzalee. And, Gordon, how did you feel about it?
Gordon: Being part of the group showed me how genomics is both thrilling and daunting. Iâd lean towards âyesâ for a lifetime genome resource for the chance to detect conditions early, but I get why some people may say ânoâ over the data fears or ethical lines. This isnât just a science project, itâs about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction. Laws would have to be enacted regarding the storage, use and availability of genetic data. We havenât yet seen as well, how AIâs complete benefits in medicine will develop over time.
Harriet: Thank you so much, Gordon and Suzalee, for sharing that. And, Suzannah, I know that at the end of the Public Standing Group we generally asked all of our participants whether they would choose to have a lifetime genome, the same sort of question Iâve just asked Suzalee and Gordon. I wondered if you could just briefly give us an overall sense of how the Public Standing Group participants felt about that.
Suzannah: Yes, so itâs interesting to see that actually not everyone said, despite spending a year or almost a year discussing this, not everyone said, âSign me up,â 6 said, âNoâ or âMaybe.â And the reasons they gave, this idea, âWell, all this data, could a government sell it off? What guarantees have we got?â So that was a reason. Somewhat of a concern also about breaches but also this idea of âWhat do I really want to know? Do I want to have a lifetime resource that can tell me whatâs going to happen next in my health?â and some say, âLet me deal with it when the symptoms start coming and thatâs the way I want to handle it.â So, yeah, about 20 said, âIâd be really interested,â similar to Suzalee and Gordon, 6 on the fence or firmly, âNo thanks.â
Harriet: Thank you so much, Suzannah. I think your point about uncertainty there is so relevant and important to us. We see uncertainty across genomics and weâre layering that here with uncertainty about futures, weâre layering that with uncertainty about health. And I hope that this has served to really illustrate the magnitude of the challenge weâre looking at here and I think also why for us as Genomics England this is just something weâre exploring. Thereâs so much to unpack, thereâs so much still to be done.
In terms of our next steps for Genomics England, it feels like we could speak about this for a week but Iâm going to have to wrap it up here. So, for us what are our next steps? We hope really that as we publicise the findings of this Public Standing Group and when we start combining some of our work and looking at it in harmonisation with the work that others are doing across the world, we might be better positioned to understand the potential future directions that a lifetime genome could take.
Thatâs obviously very, very exciting because we expect to see this area of enquiry expanding significantly over the coming years. And weâre already hearing about a number of other countries who are also doing birth cohort studies like we are who might hope to use similar applications of the lifetime genome going forward. So, thereâs a real opportunity for us here to collaborate and itâs really heart-warming that the voices of our participants in this Public Standing Group can be used to facilitate that level of engagement. For us at the Generation Study, weâre already looking at the next iteration of our lifetime genomes work and weâre being led by the findings of this Public Standing Group as we move forward, specifically in that weâre going to be starting to take some of these emerging themes to the parents of our Generation Study babies to really find out how they would feel about them.
Harriet: Iâd like to extend my sincere gratitude to all for being my guests today, Suzannah Kinsella, Suzalee Blair and Gordon Bedford. Thank you so much for your time and joining me in this discussion of the lifetime genome. If youâd like to hear more content like this, which I am sure you would, please subscribe to Behind the Genes on your favourite podcast app. Thank you so much for listening. Iâve been your host, Dr Harriet Etheredge. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac for Genomics England.
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In this episode of Behind the Genes, we explore how ethical preparedness can offer a more compassionate and collaborative approach to genomic medicine. Drawing on insights from the EPPiGen Project, our guests discuss how creative storytelling methods, like poetry, have helped families and professionals navigate the complex emotional, ethical and practical realities of genomics.
Our guests reflect on the power of involving patients and families as equal partners in research, and how this can lead to more inclusive, empathetic, and effective care. The conversation explores how ethics can be a tool for support, not just regulation, and how creating space for people to share their stories can have a lasting impact on healthcare delivery.
Our host for this episode, Dr Natalie Banner, Director of Ethics at Genomics England is joined by Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics and Dr Richard Gorman, Senior Research Fellow, both at Brighton and Sussex Medical School, and Paul Arvidson, member of the Genomics England Participant Panel and the Dad's Representative for SWAN UK.
Paul shares his poem 'Tap tap tap' from the Helix of Love poetry book and we also hear from Lisa Beaton and Jo Wright, both members of the Participant Panel.
"The project gave us the tools to find a different way to get at all of those things inside of all of us who were going through that experience... Itâs almost like a different lens or a different filter to give us a way to look at all those things, almost like a magnifying lens; you can either hold it really close to your eye and it gives you like a blurry view of the world that goes on and you can relax behind that and find a way to explore things in a funny way or an interesting way, but you can also go really close into the subject and then youâve got to deal with the things that are painful and the things that are difficult and the things that have had an impact."
You can download the transcript, or read it below.
Natalie: Welcome to Behind the Genes.
Bobbie: In an earlier conversation with Paul, he used the word âextractive,â and he said that heâs been involved in research before, and looking back on it he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it, and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants. Our participants now have a variety of ways in which they can transport their voices into spaces that they previously found maybe alienating, challenging, and not particularly welcoming.
Natalie: My name is Natalie Banner, Iâm the Director of Ethics at Genomics England and your host on todayâs episode of Behind the Genes. Today Iâll be joined by Paul Arvidson, a member of the participant panel at Genomics England, Professor Bobbie Farsides, Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School, and Dr Rich Gorman, Senior Research Fellow, also at Bright and Sussex Medical School.
Today, weâll be exploring the ethical preparedness in genomic medicine or EPPiGen Project. This project examined how the promise and challenges of genomic medicine are understood and experienced by the people at the heart of it, both the clinicians providing care and the patients and families involved. A big part of the EPPiGen Project explored using creative methods of storytelling and poetry to explore the experiences of parents of children with rare genetic conditions. Weâll discuss why the idea of ethical preparedness is crucial in genomic medicine to acknowledge the challenges and uncertainties that often accompany the search for knowledge and treatment in genomic healthcare, and to help professionals develop the skills to navigate the complex ethical considerations.
If you enjoy todayâs episode weâd love your support. Please like, share and rate us wherever you listen to your podcasts. Is there a guest youâd really like to hear on a future episode? Get in touch at [email protected].uk.
So, Iâm going to ask our fantastic guests to introduce themselves. Paul, would you like to go first?
Paul: Hi, Iâm Paul Arvidson. As well as my Genomics England hat, Iâve got a SWAN hat as well, Iâm the dadsâ rep for SWAN UK, and Iâm on the poets from the EPPiGen Project.
Natalie: Brilliant to have you hear today. Thanks, Paul. Rich?
Rich: Hi, Iâm Rich Gorman, Iâm a Senior Research Fellow at Brighton and Sussex Medical School and Iâve been working on some of the research on the EPPiGen Project that looks at peopleâs social and ethical experiences of genomic medicine, and particularly familiesâ lived experiences of genomics.
Natalie: Brilliant. Really looking forward to hearing from you. And Bobbie?
Bobbie: Hello, Iâm Bobbie Farsides, Iâm Professor of Clinical and Biomedical Ethics at Brighton and Sussex Medical School and co-PI with Professor Anneke Lucasson of the Wellcome Trust funded EPPiGen Project, and itâs been my pleasure and privilege to be involved in the work that weâre going to talk about today.
Natalie: Really fantastic to have the 3 of you here today. So, weâre going to take a slightly unusual approach to starting the podcast today and weâre going to begin with Paul whoâs going to read us a poem from the book Helix of Love. Paul, over to you.
Paul: This is called Tap, Tap, Tap.
âTap, tap, tap, I hold the egg to my ear. There it is again, tap, tap, tap. Run to get a torch and light through the shell, to see whoâs tapping from within. Chickenâs home from work these days just for fun and the odd egg. Market stalls swapped for medicines, cash boxes for cough machines. We kept the apron though. Profound learning disability is our life now, most of it, learning about it, learning from it, surviving with it, despite. Itâs a subtle egg though, this. The shell is there, invisible, but thereâs a person inside, tap, tap, tap. What are you trying to tell us about what the worldâs like for you? Are you bored? Do you hurt? Is your sister a love or a pain? Tap, tap, tap. I wish I could set you free.â
Natalie: Thank you, Paul. Such beautiful and powerful words. I wonder if you wouldnât mind telling us a little bit about that poem and your journey and maybe touch on what the EPPiGen Project has meant for you.
Paul: Wow, thatâs a lot to unpack in one go. I suppose the oddness of the metaphor is probably worth a mention. The way the project worked is that Bobbie and Rich collected together a proper poet, Dawn Gorman, and she led us through the process of kind of, she basically taught us all to be poets from scratch, it was⊠When you say it like that it was a hugely audacious project really to just collect all these randoms together in a room and throw a poet at them and see what happened.
And they trusted us, I suppose, and trusted Dawn that there was going to be something came out of this. But one of Dawnâs techniques was that like each week we did⊠I think we did⊠Did we do 6 weeks, chaps? Which felt like a huge amount of time, but it went in milliseconds. But what she did every week was that she gave us either a poetic form to work with, like, you know, âThis week weâre going to learn how to do a haiku, or a sonnet,â or whatever, or sheâd gone away and thought of a particular poem that she thought might resonate with us and then sheâd bring that to the session. And sheâd read a poem out and then say, âRight, what did you make of this? Go away and write what it inspires you to write.â
So, the poem that I wrote was, the inspiration for that session was a poem called The Egg by Richard Skinner. His poem was more about the form of the object itself, so, although that sounds really abstract, it really, really helped. So, every week it would be like Dawn threw this object into the group and said, âRight, okay, hereâs your new prompt, bosh, off you go.â And although that sounds like the most obscure way to deal with anything, because you get a structure around which to organise your thoughts it was just this like hugely powerful thing for everybody.
And so, the thing that came to mind for me was the metaphor of the egg rather than the egg itself and it just kind of chimed with all of us. Like we used to run the egg stall in Minehead farmersâ market and so, I married into a country girl and so she had like 200 laying hens at one point, and so we had this whole market stall antics but also it spoke to so many things in one hit. So we gave up that part of our lives as our daughter Nenahâs condition became more and more complex.
She was always, once we knew what her genetic condition was one of the few things that we knew from the get-go was that it was progressive. So we knew in advance that that was the case, but we didnât know what that meant. And so slowly but surely one of the things we had to do was give up our working life, you know, one week and one hour at a time, it felt. So part of the poemâs about that as well, the shift in the poem from the comedy bit to the beginning to the more serious bits at the end, and it kind of felt like we gave those things up day by day but the poem kind of got to speak to that.
And then thereâs also the metaphor. Once youâve got a good metaphor itâs always good to run with it, you know? And so the idea of the metaphor of somebody whoâs got profound learning disabilities and canât speak being inside this shell and as parents youâre always kind of peeking in from the outside to see whatâs going on within or to try and find ways, the idea of when youâre checking to see if youâve got a chick inside your shell, and you do this thing called âcandleâ where you hold the light to it, that I describe in the poem, and you like hold it to your ear and hear if thereâs movement going on inside. And you kind of, I donât know, I felt with a profoundly learning-disabled child that you always feel like youâre doing that as a parent as well to see if what youâre doing is, you know, if youâre still communicating while youâre trying to be a parent.
Natalie: Fantastic. Thank you so much for sharing that with us, Paul, both the poem and also your exploration of how you got to that point in writing that poem. Tremendously powerful to kind of understand and hear about that experience. Bobbie, if I can come to you. Paul referred to that project as kind of audacious, can you tell us a little bit about the origins of the Helix of Love but also why storytelling, especially through poetry, was so important for the EPPiGen Project?
Bobbie: Yes, of course, Natalie. But can I start by saying I was so pleased that you got Paul to speak for a while after because I always have to compose myself after hearing these poems because they really do hit so powerfully, however many times you hear them. And I think that is part of what we wanted to achieve with this project, we wanted to use innovative research methods, we wanted to be⊠I love the word âaudaciousâ; Iâm going to borrow that. We wanted to be audacious; we wanted to be courageous, and let me tell you, our Ethics Committee were a little bit worried about the sorts of things we told them we wanted to do. But we knew because we live and work in Brighton that the world is full of creative people and weâd already had such wonderful partnerships with people over the years, we knew that we could draw people into this project who would help us to work with this fabulous group of parents ,in a way that would give them, as Paul says, an opportunity to explore their own feelings and their own experience and share it as they wished.
In an earlier conversation with Paul, which he might find surprising that itâs stuck with me so much, he used the word âextractiveâ and he said that heâd been involved in research before and looking back on it he had felt at times it could be a little bit extractive. You come in, you ask questions, you take the data away and analyse it and it might only be by chance that the participants ever know what became of things next. One of the real principles of this project was always going to be co-production and true collaboration with our participants, and the poetry project probably wouldnât have come about if it hadnât been for the passion of one of our participants who was sort of finding a love for poetry herself and said, âCan we try this next?â So, you know, it means so much to Rich and I that we ended up with this amazing book, but itâs not our book, itâs our poetsâ, as we like to refer to them, book.
So, one of the things that we are so pleased about in this project is that our participants now have a variety of ways in which they can transport their voices into spaces that they previously found maybe alienating, challenging, and not particularly welcoming. And I think another wonderful upshot from this project has been how receptive people have been to the work. And itâs a sort of commonly held myth that your average philosophy article has a readership of 3.4 people. Rich created a wonderful map to show how Helix has travelled round the world and touched thousands of people â I donât think thatâs an exaggeration â and we couldnât be more grateful for that as researchers because we feel as passionately about these subjects as our participants and it is they who have really got this project on the map. Paul, you were going to come in, I hope.
Paul: I feel like the one thing that this project really did was, I know PPIE is a phrase thatâs bandied round but this project kind of stripped that theme apart and took the âIâ bit, this project is like built around inclusion and because it felt like, if weâd have just been jumping in a room with Dawn and told to get on with it, I donât think it wouldâve worked as well. The idea that it was kind of curated by Bobbie and Rich, we very much felt like our hands were held through the process, and after them having had to kick down doors in the Ethics Department to be able to get the project through at all, itâs like âWhat are you going to do to these poor parents?â having gone through that process themselves behind the scenes, then to kind of feel like we were guided through this process. And we were guided and held, and they were super-aware of all of us. And the fact that every time you tell these stories as a parent whoâs gone through them thereâs a cost. And weâve had this discussion with the panel before and the communication group, about the fact that every time you come to a parent and say, âTell us your storyâ thereâs a cost.
And so, they were aware of that, and they held that in both of their hands and so it couldnât have been anything other than this collaborative project by the time weâd finished.
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Natalie: Weâre going to hear a clip from Lisa Beaton, a member of the participant panel at Genomics England, who shares what it has meant for her to take part in the project.
Lisa: It was an amazing opportunity. I had a huge sense of imposter syndrome actually when I as invited to join, because I was aware of some of the people whoâd already taken part in the project and although I can bring lived experience to the table I donât really consider myself as a creative writer or anything like that, although I do enjoy it. When I first started in the group, we were just doing free-flowing writing. It was really cathartic, and I didnât expect that in any way, shape or form. To put pen to paper without necessarily having any strategy in mind, just letting the thoughts come out and ramble away, I didnât really know what was going to come blurting out onto my notepad, and reading some of it back was moving but it was frustrating. It was moving, it was everything really, that opportunity just as a safe space, knowing I didnât have to share it with anybody if I didnât want to but I could, and I could just, I suppose I would call it almost like a brain fart, it just rambled away and maybe it was a way of downloading some of the emotions that I was carrying.
As the project went on and we explored different creative mediums I really enjoyed that and found different skills that I wouldnât have thought about. And it was very thought-provoking, being able to go back and think about some of our very early experiences, which is, not that Iâve buried them but itâs just you move on to deal with the here and now, and it brought me back to some of those very raw emotions of the first days which I think are, I hope, helpful to certainly the medical community in terms of thinking about how they talk to new parents going through similar situations. I was very grateful.
Natalie: Rich, Iâd like to come to you now. As Bobbie and Paul have both mentioned, the outputs for this project have really spread far and wide and maybe beyond the kind of academic circles that you might typically think. Iâd really like to hear from you about how you think the project has helped healthcare professionals, particularly really enabling them to understand a little bit more about what it means to be part of a genomic healthcare service and the journey that patients and families go through. Would you share a little bit about your experience in the project, particularly for healthcare professionals?
Rich: Yeah, I mean, that was one of the things that when Bobbie and I set out to do this, that was one of the real aims, was to sort of help healthcare professionals have a bit more of an insight into what it means to access genomic medicine services from a patient or family perspective. And, as Bobbie said, there were 2 ways we could have gone and done this; we couldâve done some sort of conventional social science interviews, written that up in a lovely social science or philosophy journal article and no one wouldâve probably read it, but instead we thought about the power of the arts to actually change in terms of how we were sort of collecting and collating peopleâs stories and then how we were sharing and disseminating those stories as well. And I think the medium by which stories are told affect the kind of stories that get told, as Paul was sort of hinting at earlier.
When we ask patients to tell us their story, you know, thereâs a level of expectation there about what people are being asked to say in a form in a way, and certainly we didnât get people in a room and say, âYou must write about genomics.â So many of the poems in the collection arenât really about sequencing or big data, theyâre about these kind of much wider themes of everyday life. And I think thatâs been really powerful in allowing healthcare professionals to sort of understand for patients obviously genomics is really important but itâs not the be all and end all of everything thatâs going on in their lives, you know, there are so many other pressures, so many other hopes and desires, and people want an opportunity to express some of those positive aspects of their life with their loved ones and it not just be medicalised all of the time.
Again, as Bobbie said, itâs also opened up our research travelling really well and just become something thatâs really accessible for people to pick up and read through, and Iâve had conversations with healthcare professionals that have said, âOh I read through the book of poetry and itâs made me realise all of these things.â Language particularly has been a really prominent theme that people have reported, telling us theyâve learnt a lot about it, and thinking about how they write their letters and how they communicate with people. And obviously this isnât new, you know, bioethicists for years have been talking about the need to communicate very carefully, very precisely and in a caring way, but I think thereâs something about communicating those messages through a really powerful art form like poetry through patientsâ own words that allows clinicians and healthcare professionals to sort of really get the impact of that in a very, very powerful way.
Natalie: Thanks, Rich, really helpful insights there. I really want to pick up on your point about language and come back to Paul on that because I know thatâs a topic area that can often be, you know, hugely sensitive to families that the medicalisation, the terminology thatâs used, especially, you know, complex areas like genomics, coming back to this term we mentioned earlier about being sort of alienating. How have you found that the work through the EpiGen project and Helix of Love, has it potentially helped the way that families can think about the right sorts of language and enable health professionals to sort of approach some of these questions in a slightly more human way?
Paul: Difficult to say. Itâs a very, very live topic all the time. Thereâs like a backchat communications channel with the Genomics England panel where, because we all go along and do this thing, but we all share that genomics common thread in our lives. One parent was breaking their heart about the fact that theyâd had sight of genetic science reports that basically described their child, and children like them as âlumped togetherâ in a project, and she was gutted about it. And we all were as well, and we were all open-mouthed about it. The whole idea of kind of separating the science and the science language out from the people who are involved, it is our job, isnât it, you know, our job as the panel members is to remind people that those are people, not statistics. But itâs a really live subject and the more people, the more professionals who can be reminded of that on a daily basis and the more we can find kind and open ways to deliver that message to professionals, and every single day that we do that makes a difference, I think. If one parent has to get less of a letter like that or one professional thinks more carefully about how they phrase stuff before it goes out the door, then thatâs one less parent whoâs got to go through that.
Natalie: Absolutely. And Iâm thinking about that insight. I suppose the anticipation and the realisation to healthcare professionals about the impact of the way they approach things, the language they use, the kind of mindset they might adopt with parents and families, one really important aspect of the project was to do sort of preparedness and the idea that you should be able to anticipate and plan for and acknowledge some of the ethical challenges that might come through when youâre dealing with questions of genomic healthcare where there may be lots of uncertainty, there may be a long journey to go through.
Bobbie, can I come to you to help us unpack this notion of ethical preparedness as a core theme for EPPiGen? Help us understand what that means in kind of simple terms and why does it matter for those who are working in the genomic medicine and healthcare space.
Bobbie: I think the way in which most people will have heard of this concept of preparedness is in relation to disaster planning. We know that some of the good things we try and do in life are also potentially fraught with challenges and difficulties just because of their complexity and because of the wide range of people and organisations that will be involved. Can we take this idea of preparedness and almost say, âYou have a moral responsibility to be ethically prepared when, for example, you embark upon a really dramatic change in healthcare delivery or an introduction of fantastic new healthcare innovationâ?
And genomics seemed to be the perfect case study for this. We then had to say, âWhat does that actually mean in practice?â And I think here we wanted to move away from the idea that you can ethically prepare people by putting a small albeit very expert and clever group of people in a room to write guidance and regulations, those things are needed and theyâre useful. But itâs actually much more important to almost recruit everybody, to bring everybody up to speed, so that the ethical challenges arenât a complete shock to those who are delivering the service in the frontline, so that those who plan systems actually think whilst doing so of the ethical challenges that can be posed by the tasks theyâre attempting to achieve.
And I was a sort of founder member of the Ethics Advisory Committee at Genomics England, and it was so interesting in those early days because there were no patients, there were no participants. We were sitting alongside people whilst they designed and put in place basic processes, strategies and ethics was a part of that. And a really important part of that to me, at those meetings, was hearing what the potential participants had to say about it because, again, the Participant Panel was involved. And I found that those were my people, those were the people who were worrying about, concerned about the same things as I was.
So, I think to be prepared we have to take on the responsibility of giving people who work in ethically challenging areas opportunities to come together to acknowledge the complexity of the task, to share strategies and tools, but also, very importantly, to not become divorced from the people that they are attempting to serve, because in fact we feel that this part of our project, and our project is much bigger than this and weâve done some fantastic things working with healthcare professionals, medical scientists, etc, etc, but this part of the project is an attempt to say, âWe can better prepare families as well by ensuring that we tell them that their voices are valuable, that theyâre important, and they help rather than hinder healthcare professionals in doing their jobs.â
Natalie: Thatâs a really important point around the idea that this approach can help, can be positive. Because I think sometimes you think about preparedness and, and quite often with ethics itâs about risk, itâs about, you know, âHow do we avoid the risks?â but thereâs a very positive story to tell about taking a more preparedness-type approach to thinking through ethical complexities, challenges and so on, both for health professionals and, as you say, for families. I wonder if you could just talk a little bit more about the kind of positive aspects that that can bring to everyone in that genomics healthcare journey, both the health professionals and the families. Because I think sometimes itâs easy just to think that itâs mostly about sort of avoiding the risks and the pitfalls, and that might be harder to engage with people if you take that sort of risk-based approach.
Bobbie: Yeah, itâs an interesting one. I think the ability to confront risk and uncertainty is a sign of maturity. And we find medical students, for example, hate any sense of uncertainty; they want to be told how to do something and they want to know that theyâll be able to do that thing and get it right. And our job is often to say, âWell itâs not going to be as easy as that, in fact it might be impossible, and hereâs what you have to do instead and hereâs how you allow yourself to fail or to not achieve in the way that you want but still do something really meaningful for the people that youâre caring for.â
So, I think thereâs that aspect of saying, âItâs part of medical education, itâs part of how we should think in organisations that wherever you take risks, wherever you try to push frontiers, blur boundariesâŠâ I mean, genomic medicine has done something really interesting in terms of blurring the boundary between scientific research and clinical care. Wherever you do these things there are going to be challenges but those challenges, theyâre fascinating, theyâre interesting, they can bring us together. If weâve got a shared will to get through them, you know, to make things work, then itâs enlivens what youâre doing; itâs not a barrier.
I sort of began teaching and working in the space of bioethics right back in the â80s, which is a shock to you, Iâm sure, but in those days Iâm afraid that ethics was seen as a block, a barrier, a hurdle that people had to get over or through. And I think thereâs still a sensitivity, and certainly, I myself have been sort of challenged on critiques that I have offered to say, âOh thatâs a bit harsh.â But I think what ethics attempts to do now, and certainly through really putting a positive spin on this idea of working together to establish ethical preparedness in important spaces, is to show that actually ethics can be very facilitative, it can be very supportive, and it can help people. Itâs not a surveillance mechanism, itâs actually another clinical tool and something that, you know, people should seek support around.
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Natalie: Rich, if I could come to you thinking about that reframing, I suppose, in your own research practice as an early career researcher, whether youâre seeing that maturity in approach in thinking about some of these really complex, knotty ethical questions in genomics, are you seeing a greater appreciation for those? And where do you think youâre going to take your research as a result of this project in that space?
Rich: Yeah, thanks, thatâs a great question. Yeah, I think so, and I think one of the things thatâs really been revealing in this is the appetite for this kind of work in the sort of genomics sector, an appetite for thinking about the sort of complex ethical issues, for engaging with kind of arts-based research, for sort of finding new language and new spaces to involve patient and family perspectives and stories and think about how we can learn from them.
I think in the highly scientific, highly technical space of genomics we often assume that everyone wants numbers and hard data but actually I think the way that this work has travelled, the amount of invitations weâve had to sort of exhibit this work and talk to healthcare professionals and scientists about this work shows that thereâs this really rich appetite for thinking about this complexity and doing that work of ethical preparedness, as Bobbieâs talked about, and I think itâs fascinating. And I know a lot of the participants who joined in our project have also sort of had opportunities from being involved in our work and found that there are people that want to listen to their voices and hear from them and learn from them as well. So thatâs been really exciting, and I hope it will continue and I hope thereâs opportunities for much more interdisciplinary collaboration in the genomics space with philosophers, with social scientists with ethicists, with artists and, importantly, with patients.
Paul: You mentioned the idea that certainly the poetry at the very least has allowed those voices to get into different spaces, and I think when those things first started happening it was when we at least as the people whoâd written the poems felt that there was a huge big impact from this stuff. And I wasnât the first one to read one of these poems out loud, and in a way the collection of poetry became bigger than the sum of its parts in a funny kind of a way. And I canât remember but somebody read one of the poems at a conference somewhere and they said at the end of it that you couldâve heard a pin drop, and it was just that thought that actually with a big audience expecting kind of quite dry subject matter about genetics, to have felt that moment where the poem got launched off the stage and then it impacted on the audience and then, the way they described it, you could almost kind of feel them describing the ripples of the poem just like spreading out amongst this kind of silent audience and everyone kind of taking this kind of mental sigh of like âOh thatâs what it feels like.â And the idea of that happening was when, for me anyway, when we knew that what weâd created was bigger than the sum of its parts and had its own legs, Bobbie and Rich had been the Dr Frankensteins of this kind of amazing, beautiful monster.
Natalie: Obviously the poetryâs got into your soul, Paul, the metaphors are fantastic. But just to make sure we bring in even more participant voices and perspectives into this weâre just going to hear now from Jo Wright, whoâs another member of the participant panel, whoâs going to share what the project and the participant in it has meant for her.
Jo: So being part of the EPPiGen Project, it helped me to find my voice in an area that was relatively new to me, and also it was a way to take control of my own experiences rather than feel like Iâm being swept along by a lot of systems.
And there were things that I really value that I thought contributed to making the project so successful. One was that they asked the question âWhat is this experience like for you, the experience of being part of a research project, the 100,000 Genomes experience of waiting, the experience of having your data in the library?â And no one had asked that before. You go to your appointments and youâre in the system and, you know, itâs kind of, everyone was finding their way to some extent because it was new for all the clinicians as well, but the fact that they asked, because no one asked that before, I donât have an outlet for that.
And then the other thing was that it was completely open so there was no research interview or questionnaire to answer, no expectation about what it was going to look like at the end. And I think working that way really strengthened the connection between us as parents of children with rare conditions and then also our relationships with Bobbie and Rich as the researchers and with the wider clinical community when they started to see our work and respond to it. So it was a way to understand peopleâs individual experiences but it also made us feel connected and empowered through sort of like shared human experience, and that could be between us as the participants but also shared experiences between us and the researchers or us and clinicians and scientists that were looking at what weâve done.
Natalie: So weâve heard lots about the experience of participating in this fantastic EPPiGen Project, the kind of creative storytelling methods, the audacious methods that have been used, and some fantastic impacts beyond the kind of typical what could be quite dry sort of academic circles that this kind of work has spread out to. Iâd be really interested to hear from each of you about the takeaways, what youâve learned, whatâs changed for you and what youâd like our listeners to really understand about this project and the work, and the sort of outputs from it and the ways it might continue to have resonance and impact going into the future, so whether people are patients, families, clinicians, researchers. What would you like people to remember and whatâs affected you most about the project?
Bobbie, I might start with you.
Bobbie: I think we have to always be very careful when we get excited about something - and the âweâ here are the people in the health community, the education community, etc - to remember. As Rich said earlier, that this is only ever going to be quite a small part of other peopleâs lives. You know, weâve all devoted big parts of our careers, our enthusiasm, to thinking about genomics, to working in this space. I would really like people to pick up the book and work to understand a bit better about the everyday lives, the hopes, the expectations, the fears of the families who may or may not get a diagnosis, may or may not get on a good treatment path, all of whom want the best for themselves and everybody else from this venture.
But, as Paul knows better than most, it wonât come to everybody, and we donât want anybody to be forgotten along the way. The people that signed up for Genomics England as participants were pioneers alongside medics and the scientists, and in these early years we want their experience to be recognised, and their experience goes much beyond their interaction with Genomics England and, unfortunately, all the work that weâve produced shows how many challenges families have to face to secure a good life for their children, and I just want us all to just keep that in mind.
Natalie: Incredibly important to maintain that focus, that awareness. And, as you say, Bobbie, thereâs an interesting balance where there is a need for the drive and the innovation and the ambition to help ensure that we are pushing at the forefront of medical research but not leaving people behind and not ever forgetting, as you say, the experience of people who are actually at the forefront of this research and of genomic healthcare.
Paul, could I ask for your perspectives on this, and particularly how you see patient voices being involved in the future of genomic medicine, especially in light of your experience in the EPPiGen Project?
Paul: I think the biggest surprise and biggest takeaway for me was the project gave me, I mean, I canât speak necessarily for all the other poets, but you only need the evidence in the book itself. They gave us the tools, the project gave us the tools to find a different way to get at all of those things inside of all of us who were going through that experience. So it gave us a way to talk about all of those things and a way that was I suppose slightly removed to start with. Itâs almost like a different lens or a different filter to give us a way to look at all those things, almost like a magnifying lens; you can either hold it really close to your eye and it gives you like a blurry view of the world that goes on and you can relax behind that and find a way to explore things in a funny way or an interesting way, but you can also go really close into the subject and then youâve got to deal with the things that are painful and the things that are difficult and the things that have had an impact.
But, because youâve got that tool and youâre used to using it or youâre familiar with using it, it then gives you that safety. Thatâs how I felt about it anyway, it was a massive tool to be able to get behind all of these things that I didnât even know I was feeling, or I knew they were making me uncomfortable, but I didnât know what they were or what name to give them. So the poetry gave us a chance to get behind all of that. Having read the poems, it feels like itâs that for everybody but obviously youâd have to speak to them to know, but it certainly felt like that for me.
Natalie: And, Rich, your perspective. What are you taking forward from the project, so what would your sort of key takeaway be?
Rich: I think it shows what is possible under that PPIE acronym. And there are many ways to do that involvement and engagement, it doesnât have to be a sort of dry tick-box exercise, there are much more creative ways to bring peopleâs lived experiences and perspectives into conversations with genomics. So really, I suppose itâs a call for other people to explore working in this way as well and think about what other kind of creative outputs could work here. I mean, weâve had huge success, and I think a really interesting impact from working in this way.
And certainly as an early career researcher itâs been really formative in my sort of academic journey, you know, reaffirmed that this is the kind of work that I want to do, working in this really co-productive way. And I think itâs possible, it can be done, and, you know, ultimately itâs just been a real privilege to do this kind of research, to sort of be trusted to sort of hold a space together for sharing peopleâs stories and give people a platform to share some really powerful profound stories. And going back to what Paul was saying earlier, I think he hit the nail on the head, as he very often does, this is about evoking peopleâs experiences, not just explaining peopleâs experiences, and allowing those stories to travel. And we donât know where stories will travel, we donât know how stories will travel, we donât know how stories will be received, but we know that they do sort of travel and they do have legacy and they stay memorable to people, they have emotional resonance. So, the impact of this work can often be hard to sort of pin down really specifically, but we know those stories are out there and people are listening and changing their practice as a result.
Natalie: Weâll wrap up there. Iâd like to thank our guests, Paul Arvidson, Professor Bobbie Farsides and Dr Rich Gorman, for joining me today as we discuss the EPPiGen Project. We heard some powerful insights from patients and families about their experiences, and why ethical preparedness is so important in the context of genomic medicine. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iâve been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.
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