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: 

You can find out more about the Participant Panel in our recent Genomics 101 episode which Lisa featured in, titled ‘What is the Participant Panel?’, and you can read about their timeline of achievements over the last 10 years.

“One 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 name”

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.

In this explainer episode, we’ve 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 you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

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.

In this episode, we explore how individualised medicines are evolving from “n=1” treatments (a treatment effective for a single individual) into approaches that could transform care for many people living with rare conditions. 

Advances in genomic medicine are making it possible to design highly targeted treatments based on an individual’s genetic information. While these therapies may begin as bespoke solutions for a single patient, they can often be adapted, refined or reused to benefit others with similar conditions. 

While the research is evolving, the systems needed to deliver these treatments at scale are still catching up. From regulation to access, our guests discuss what needs to change to turn this potential into reality. 

Our host Sharon Jones, is joined by: 

If you enjoyed today’s conversation, please like and share wherever you listen to your podcasts. 

“However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.”

You can download the transcript or read it below.

Sharon: What if treatments once designed for just one person could now help many others? Thanks to advances in genomic medicine, regulations are changing and research is expanding.

This opens up more options for treatments for rare conditions. But what does this mean and how close is real change? I'm Sharon Jones, and this is Behind the Genes.

We look at how genomics is changing healthcare, covering everything from cutting-edge research to real-life stories.

Individualised medicines are a fast-moving area, but there's still a big gap between scientific progress and what's actually happening to patients. You could call it the gap between hype and hope.

Ana Lisa: However rare your condition is, someone has a right to have hope. Everybody should have a hope that we should be able to find a treatment.

Sharon: Coming up, we'll hear from Ana Lisa Tavares, Clinical Lead for Rare Disease Research at Genomics England, and Consultant in Clinical Genetics at Cambridge University Hospital, as well as Mel Dixon, member of the Participant Panel at Genomics England and CEO and founder of Cure DHDDS. Mel opens this chat by explaining why developments in individualised healthcare really matter to her.

Mel: This issue is really personal to me. I have three children, two of whom are affected with an ultra-rare DHDDS gene variant, for which there is currently no treatment. Their condition causes symptoms such as, well, it varies between mild to severe learning difficulties, seizures, tremors, and movement and coordination difficulties.

But the, the most worrying thing for us was that this condition is actually also progressive. So over time it becomes more of a Parkinsonism and some patients experience dementia-like symptoms and psychosis. So for us to get a treatment that targets the genetic cause of, of their condition is, like, the most important thing in, in our lives.

If we could intervene now, they could potentially, at the stage they're at, you know, live an independent life with, with some supports. But if the disease is left to progress, it would be a very different outcome for them.

Sharon: I mean, that sounds so difficult and I can't even imagine how life is for you and your family. And I can see what is driving you to find anything to extend the life of your children and to give them that opportunity to, to have a better quality of life. And then Lisa.

Ana Lisa: It's a huge burden for families to carry. And I think at the moment there's an additional layer of burden, which shouldn't fall on families, to feel like they need to forge a pathway for their child to have a chance of a treatment. That's, that's a lot to bear.

Mel: I think as well, families feel they almost have to become mini scientists in their children's specific condition overnight, because you go to these appointments with the consultants and nobody's heard of the condition and they don't know, they just don't really know what to do with you.

So they're asking you, you know, so tell me about this, this gene change. What, what does it do? What does it mean? So you have to become the mini professor in your child's condition to be able to advocate for them. We've had to really learn on our feet so that we're able to advocate and push for research into DHDDS, because without us doing it, nobody else was going to be.

Sharon: Yeah. So that's, you know, that's partly what we're here and what this podcast is for, it's here to support families to, to understand this stuff. And Ana Lisa, can you just break it down to us, what is individualised medicines?

Ana Lisa: An individualised medicine that's made for one individual person. In reality, sometimes there are other individuals that can also benefit from the same medicines, and sometimes actually, although the medicine is made for one specific person, it might be made using a strategy that other patients could also benefit from, either directly, exactly the same, even, or through tweaking them so that they could work for a different patient.

In the context that they're most often referred to at the moment, they're therapies that are being made based on the genetic information about somebody.

Sharon: Thank you. I mean, that sounds amazing. And now coming to you, Mel, what does receiving a diagnosis mean for a family? And how do you navigate the space between finally having answers and the reality that the treatment may not yet exist?

Mel: So for us, I think, we went down the, the diagnostic route in the hope that we would be able to find a treatment for our children, or there would already be a treatment in place. But unfortunately when we got their diagnosis, we were told that their, their condition was ultra rare, neurodegenerative and also newly discovered. So there was, there was no treatment pathway and actually minimal research happening into it at the time.

So it was frustrating, upsetting, um, and it felt like quite a hopeless situation at the start, but actually this was just over three years ago. And through a lot of proactiveness on our part in fundraising, we've been able to better understand the condition and we now have treatments in the pipeline. So in that three-year window, from there being nothing, we now have treatments both in terms of potential drug repurposing candidates and also, um, an individualised therapy called an ASO is also in development for them.

So it was hard, but it's given huge benefit to us. Otherwise, we'd just be going, remaining going from specialist to specialist without having any answers or understanding why their symptoms were progressing.

Sharon: I mean, that sounds really, really tough and you know, coming back to you, Ana Lisa, could you talk us through how genomics is changing the way we can treat rare conditions? You know, what types of individualised medicines now exist and how do they even work?

Ana Lisa: Maybe I'll start with how some of these medicines are working.

So with, without going into details, but the sort of principle that these medicines might be able to, to do something called gene editing. So our, our DNA, uh, the instruction manual is made up of genes and it's now can be possible scientifically to change even a single DNA letter code in somebody to try and ameliorate the symptoms of their rare condition. You know that's phenomenal scientific progress to be able to do that.

I think a lot of people have heard about gene therapy, where one is trying to get into the body a gene or part of a gene that might be able to sort of replace the function of a gene that isn't working as it should. There are various other strategies. So our DNA is actually used to send messages to our body, if you like, to, to decode these instructions.

And so there are medicines that target the next step in this process, the RNA, which are the ASO therapies that Mel was referring to earlier. And really what those are doing are either trying to correct for a protein in our body that isn't working as it should, or to try and get rid of one that shouldn't be there.

And so they can act in different ways. And that's actually quite powerful, because you can, theoretically, use these strategies to correct for different genetic rare conditions. So I think going to the sort of first part of your question, maybe if I can phrase it as "directly at source". If you can go upstream and target in a very direct way the cause of a rare condition, then actually you might be able to apply those same principles to many different types of rare condition.

We know that there are, you know, 8,000 as a very ballpark number of rare conditions, and it might be that these strategies could be used I don't want to say for all rare conditions, but for many rare conditions where we find the genetic cause, these strategies could collectively be a very powerful way to treat them.

And traditionally we've had to understand all the underlying biology, find a druggable target, find a drug that could target that, that's safe, effective, et cetera. And that's a lot of work. And that's still very, very valuable. If we were going to do this for these thousands of conditions, it would probably take us hundreds to thousands of years, collectively.

And these strategies provide a lot of hope for being able to do this in a, in a more efficient way, where we can actually use the information used to treat one rare condition and apply those learnings to another rare condition.

Sharon : I mean, that's really helpful to understand. So if the science is there, why aren't more patients benefiting from it yet? You know, what's standing in the way from your perspective?

Ana Lisa: That's a really good question, and it's complex because the, our whole ecosystem is made up of, of many parts that go from finding a potential strategy that could help a rare condition to a patient benefiting from that. And I think one thing that maybe we haven't touched on yet is the fact that rare conditions can be really rare and affect a really small number of people individually, even though we know collectively they affect so many.

You know, in the past it's been easier, if you're taking a condition that's common, that affects thousands of people, it's easier to see and to be sure whether your new medicine is actually working as you think it does and should, and having the benefits that you think. The, the sort of regulators have really clear guidance.

We have lots of knowledge about how to assess treatments and have a randomised clinical trial, for example. How the reimbursement process may work in a public healthcare system. And when you, when you, when you sort of set down into the really rare, this is difficult for each stage of the journey.

The transformation that's needed is a whole, system-wide transformation to be able to regulate in a scalable, equitable way, these therapies that could actually be an N of one treatment for one individual, that actually maybe one day another individual may also benefit, and sometimes even a group of individuals.

It's not just the, the regulator, it's also how do you make it viable. So again, you have to make it scalable, equitable. And even to implement in the NHS down to this very "N equals one" level, and demonstrate that patients could benefit from these treatments, might require sort of fancier ways of assessing these treatments, whether it's statistics, other methodology and I think it's really the system-wide nature that makes this tricky, but is also a fantastic opportunity for, for collaboration, because that, that sort of end goal and benefits could be so, so great.

Sharon: Yeah, absolutely. And I mean, Mel, for your side of things, it must sound, you know, quite frustrating where the people in the rare community to not see the support being made more readily available?

Mel: Yeah, it is particularly difficult for patients and their families. I think in our case, when you're dealing with a neurodegenerative condition, time is of the essence. So when you know that the science is available or it's ready, but you don't have the systems in place to implement them to the patients so that they can access these much-needed therapies, it's worrying and frustrating.

And also I see our children are affected with, with, you know, one of these N of few conditions that there's, you know, there's only 59 confirmed cases of DHDDS worldwide, and we've seen how the system firsthand doesn't fit ultra-rare patients. We can't, when we were looking at drug repurposing, we can't do a traditional clinical trial because we don't have the patient numbers and we don't have the funding. So a placebo-controlled trial just wouldn't be possible for us when there's only, I think, seven confirmed patients in the UK and, um, four that we're actually in, in, in touch with.

So it does feel, I think, as Ana Lisa was saying, that we really need a system rethink, um, and refit so that it does start to accommodate these ultra-rare conditions, especially now as there's therapies which are showing huge benefit to patients.

Sharon: And so with like all of these challenges, where are you seeing things shift and what does meaningful progress really look like for you?

Mel: At the end of last year, the MHRA announced that they were rewriting the regulatory framework for rare conditions, and that fills us with lots of hope for the future. They're recognising that the traditional systems don't work for particularly ultra-rare conditions, and now that we do have these therapies in the pipeline, we, we want to get the patients to be able to access them. And we're also seeing innovation in how evidence is generated and measured.

We witnessed this firsthand with our son as he was undergoing baseline tests for his ASO therapy. You know, the use of digital biomarkers, of real-world evidence, how they're increasingly being used for these N of one or N of few populations.

And how the individual receiving the treatment becomes their own comparator. So you're not relying on these big natural history studies of the disease or placebo controls. It's you're looking specifically at that individual, getting a really strong baseline and then looking, once they're dosed with the medication, is that improving or stabilising symptoms?

So I think this shift in focus is really meaningful for the ultra-rare community and also for them to be part of the decision-making process of what, what benefits do they want from a drug? Like what is meaningful to them? I think there's much more talk about the patients and how the, what will benefit them most.

It's not necessarily what the scientists would think or research would think would most benefit, but what, what would make a meaningful difference to the patient?

Sharon: I mean, that's good to know because it's kind of putting the person at the centre of, you know, this is what it's all about, isn't it? It's not just the science. We're trying to treat people and it's putting people, people first.

Ana Lisa: Just to build on that, it's exactly that, that awareness that is, is growing, I think, that there are so many people affected by a rare condition and, and however rare your condition is, someone has a right to have hope and that the system should be able to cater for many rare conditions, you know, whether they're an ultra-rare or an actually almost common rare condition, everybody should have a hope that we should be able to find a treatment.

And it's not a hopeless situation that it's, you know, never going to happen or be too difficult. It's quite powerful, hope. If you can solve for the truly individualised medicine, then you at the same time may also be helping everyone in-between a really common condition and a really rare condition, because right now the system works for common conditions. And if you can take it right down to the sort of radical of, example of an individualised medicine made for one person, then you are also forcing the system to a change for everybody else. And I think that's one of the great benefits of thinking about it as a joined-up system.

Sharon: So how do you each navigate between hype versus hope when it comes to rare therapies? Mel?

Mel: I like to focus on hope, because when we got our diagnosis, we felt really hopeless and that's a really dark place for a family to be.

But as we learnt more about their condition and the rare condition landscape and genomics, we actually learned of all these new therapies that were in the pipeline. We were hearing about, you know, recently, conditions like Huntington's Disease that you never, never previously had any disease-modifying treatment, how they're now being able to be treated with gene therapy with really positive effects.

Similarly for other neurodegenerative conditions that have been treated with ASOs, how they're seeing not just disease stabilisation, but improvements. So I know it's, it's still, like, relatively early days with these technologies and therapies, but I think it, it allows families to have hope, which is, which is really, really important, because that statistic, you know, of the, of 95% of rare conditions not having a treatment, it's, it's a really brutal one, uh, to be told at the outset or to learn at the outset.

So, you know, if, if these therapies can, can make a huge dent in that, that would be life-changing. It would make a profound difference to many, many families, and I think there's a lot of reason to have hope, taking all of that into consideration.

Sharon: And then Lisa?

Ana Lisa: I think to work in this area, one needs to be full of hope and optimism because there are so many, um, challenges to overcome as a community. Uh, but I think that means that people are also incredibly collaborative, because they know that we need to work together for this to succeed. And no one, you know, one individual, one organisation can do it on their own.

It truly has to be a crosscutting, collaborative endeavour. The fact that we, in the UK, have resources like the National Healthcare System,Genomics England in partnership with the NHS runs a National Genomic Research Library. And so the fact that you could look at, at tens of thousands of, of genomes for many, many individuals with rare conditions.

That gives me hope because it means that if a treatment is made for another person, it could be in a different country in the world, and if we could find another patient, it doesn't matter what specialty they're under, where they are, we should be able to find them and connect with their clinical team if, you know, if they've consented for the National Genomic Research Library.

And so to me, that feels, that whilst there's, there is a lot of hype in the sense that some of the really well-publicised cases, really had a lot of people working on them and a lot of resources to make it happen. But that gives hope to everybody else that follows that actually it is doable and if we can make better systems, and having these national resources that we do, the fact that, there are a lot of guidelines being written at the moment, both international and national.

And again, they show that the sort of scaffolding is starting to be in place to apply these in an equitable scalable way. It might not be that you're so much looking for a specific rare condition as for a particular type of genetic variant that could be targeted in the same strategic way, and that therefore you could look across many different rare conditions.

So again, all these sort of pieces of the puzzle are, are filling me with, with, with hope.

Sharon: You touched upon, um, inequity there. Now, you know, is there a risk of inequity given what we've talked about in terms of those challenges?

Ana Lisa: I think we, we always have to have the lens of equity in everything we, we do.

And that, and that really does apply to healthcare and, and in fact, probably the whole rare disease community are, are, are not well served in terms of therapies at the moment. There are so few, um, therapeutic options and so I think there's a massive inequity in that this, our systems are not geared, uh, towards rare conditions.

I suppose, you know, different countries have different healthcare systems and some of the sort of first personalised therapies may require a lot of money behind them to, to happen, but they will be pioneers in leading the way for how this can be done. And I think in the UK we have a lot of the infrastructure and the, a sort of a strong, that's very equitable, I think. And so we could do this in a, in a much more open and equitable way.

Sharon: Mel?

Mel: Cost is always, unfortunately, and it, when it's your family that's affected you, you know, you hate the thought that things are coming down to cost and, and money. But I, I think as Ana Lisa said, if, if the system absorbs the initial cost.

You know, it seems that those longer-term costs could come down significantly. We already see with our very small DHDDS community that an ASO, which is an allele specific that was made personally for one, for one child, can actually also benefit my son, even though they have a different variant.

So if the cost of the ASO is 1.2 million per person, but if you suddenly find actually one other person can share that, that's almost halving the, the cost.

And then if then you're finding out that actually, oh no, 3, 4, 5, 10 people can all have that same ASO, suddenly it becomes much more cost-effective and more sustainable. So I think, as we have to think about cost, I think that also allows us to have more hope that these therapies can, the cost of these therapies that are obviously hugely expensive at the moment, can be brought down in the longer term.

Ana Lisa: There are a lot of things that people want to do in the NHS. People can be working under quite hard circumstances, so to talk about making a therapy for one individual can be difficult and people can sometimes, I think, think that it's a pie-in-the-sky conversation.

However, I think that, you know, all the clinicians I know who work with families with rare conditions, what they'd most like to be able to do is to be able to offer a therapy.

And so I think a lot of people see this as a, as a big opportunity, despite these initial hurdles. One thing I often think about is my grandfather, when he was alive, every phone conversation, he would start with, "How many lives have you saved today?" And so I think that's the, that's our challenge.

Sharon: Wow. That's, that's really powerful.

Mel: Just echoing really what Ana Lisa was saying, I feel the, um, inequity lies in rare conditions as a, as a whole, from the point of diagnosis to the lack of pathway, um, to, to the lack of system in place for them. You wouldn't have a patient with a life-changing cancer diagnosis receive that information in a telephone call, and that is the stark reality for many rare disease patients. That's how they receive the, that's how they often receive the news. That was certainly our, our experience. And, and from that point, there was then no pathway. It's just this horrendous feeling of isolation.

And I think now that there are these treatments in place and therapies in, in place, it's about time we change that because often the rare, the rare condition community, and certainly those with ultra-rare conditions as well, they're probably like some of the most underserved members of the community in that it's their parents and their families that have to advocate. Otherwise, without that, they, they often wouldn't stand a chance of understanding the disease, let alone finding a treatment.

So I think the whole system needs to have a reset, to think about these rare condition patients and, put them at the heart as they do for more common conditions.

Ana Lisa : I completely agree. And you mentioned cancer, and there are actually quite a few parallels. So there might be really common cancers that affect a lot of people that are being, uh, subsetted down into different groups depending on the genetics that are related to that particular cancer and therefore what treatments might be most effective.

And so I think there's, there's a lot we can each learn from each other between the rare disease and cancer communities. Perhaps as in rare disease we scale up to apply the same strategies to many different rare conditions and patients. Even if they're being tweaked for their particular genetic variant and cancer, sometimes one is subsetting down to treat specifically that, exactly that cancer subtype.

So there's a lot we can learn and I completely agree that the, the rare disease community deserves the same chance at at treatments, and the hope that that comes with.

Sharon: Thank you. It feels like there needs to be some kind of seismic system change along with this piece around collaboration and how, you know, the science is there, but it's how do we bring it to families who are facing these difficulties with it, you know, their children and, and rare conditions.

We'll wrap it up there. Thank you to our guests, Ana Lisa Tavares and Mel Dixon, for joining me as we discussed the evolving landscape of individualised medicines. And thank you for listening.

If you'd like to hear more like this, please subscribe on your favorite podcast app. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan and Patrick Wallace at Bespoken Media.

In this explainer episode, we’ve 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 you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

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. 

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: 

“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, we’re certain of the ones that have just occurred in the cancer cells and can help guide us with their treatment.” 

You can download the transcript or read it below.

Amanda: Hello, and welcome to Behind the Genes. 

Sarah: When we think about blood cancers, it’s 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 I’ll 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.  They’ll be talking about blood cancers and the inherited factors that increase blood cancer risk.  If you enjoy this episode, we’d love your support, so please subscribe, rate and share on your favourite podcast app.  Let’s get started. 

Thanks to everyone for joining us today on this podcast, we’re delighted to have so many experts in the room to talk to us about blood cancer.  I’d 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.  It’s great to be here.  My name’s Sarah Westbury, and I’m a consultant haematologist who works down in Bristol.  And my interest in this area is I’m 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, I’m 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.  That’s really interesting, we’ll be looking forward to hearing more about your experience.  Bev, we’ll come to you next. 

Bev: Thank you.  Hello everyone, I’m Bev Speight, I’m a genetic counsellor, and I work at Addenbrooke’s 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 we’ve 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.  I’m also part of the Council for the UK Cancer Genetics Group. 

Amanda: Thank you, Bev.  And Katie, over to you. 

Katie: Hello, I’m Katie Snape.  I’m 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 that’s 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 King’s 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 it’s great to be here. 

Amanda: Excellent, thank you for those introductions.  I’d 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 it’s 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 we’re talking about such a wide range of different kinds of cancer affecting different cells within that blood system, there’s 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, it’s 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, we’ll perhaps focus on particular kinds of blood cancer.  But like any cancer, it’s 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, that’s 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 they’re actually as a group the fifth most common form of cancer that’s 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, it’s 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 who’s 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 it’s 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 it’s 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 they’re diagnosed, that’s 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 person’s 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 children’s blood cancers, if an inherited cause is found, it can be a different pattern, which we call autosomal recessive.  And that’s 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 that’s 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.  That’s where there’s a change on the X chromosome, women have two X’s, and men have one X and one Y.  So sometimes with the X-linked conditions we’re more likely to see the clinical signs of a condition in boys and men because they’ve only got that one X chromosome.  But those are less common in the context of talking about hereditary blood cancers. 

Amanda: Thank you.  That’s 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, it’s 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: That’s right.  So what we’re 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 doesn’t mean they definitely will develop it.  We’re 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, that’s 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 that’s really important for the blood cells in terms of keeping those control mechanisms that Sarah described.  And that’s 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 that’s 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 don’t have a test for that at the moment.  We wouldn’t 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 they’re concerned.  But, you know, the majority of blood cancers are not due to genetic factors, and it’s sort of environmental or chance or bad luck.

Amanda: Okay, so it’s clear that obviously blood cancer is almost an oversimplification, within that category there’s so many different types, so many ways that it could happen in a person.  So, Bev, if we’re 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 that’s 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 people’s mind, particularly if they’ve 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 Katie’s 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 it’s quite normal for families to feel quite mixed about this and for different family members to have a different approach to it.  When there’s the offer of what we would call predictive testing, if we found a change in a single gene in somebody with blood cancer which we’re 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 there’s an opportunity to try and quantify whether or not they’re 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.  That’s when a referral to clinical genetics happens.  And in our specialist service we’re 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 it’s 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 that’s 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 we’re being really careful to make sure that we’re 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 that’s receiving the stem cells if it turns out that the person they’re 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 they’re linked in with the right other medical teams to make sure that those other health conditions are identified if they’re present and taken care of.  And then I think really coming back to what Bev has already touched on, there’s 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 they’re 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 that’s not yet a consideration, making sure that they’ve got the information to understand what might be relevant for future family members, if that makes sense. 

So it’s not necessarily true to say that for every individual patient knowing that there’s 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 that’s 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: There’s 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 we’ve said, it’s not inherited, it’s not genetic, so they’re what we call acquired changes, they’re 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 it’s 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, they’re 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 there’s a potential it could be inherited, we would go on and do a second test.  So usually because we can’t do a blood test because the cancer’s 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 it’s in both the blood cancer and it’s in the skin, and therefore it’s likely to be inherited.  So that’s 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, “Well, actually, we’ve also found something that might be inherited,” 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 we’re 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 we’re also increasingly, as we progress we’ll 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 we’re 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 we’re 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, we’re certain of the ones that have just occurred in the cancer cells and can help guide us with their treatment.  And so, again, when we’re talking to patients, we have to explain to them that we’re going to be looking at their entire genetic information.  And what’s 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 don’t know about.  But I think certainly that’s 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 there’s 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 it’s 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, it’s 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 there’s 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 we’ve 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 you’ve said, a lot of these are actually really quite new conditions, particularly in the adult setting.  And we don’t yet 100% know why do some people get blood cancer and some people don’t when they have the same inherited factor.  What’s 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 I’d be really interested in Sarah’s 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 we’re 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 they’re now told that they may or may not potentially have this inherited predisposition.  And I think that as haematologists, we’re 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 we’re not necessarily so skilled and experienced at holding conversations with people who don’t yet have that diagnosis.  And I think that that’s 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 we’ll 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 they’re 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 can’t 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 there’s been a lot I think we’ve been covering today that’s probably going to be very new to many people.  Why do you think it’s 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 there’s been a bit less of that in general for blood cancers.  As we’ve already talked about, clinical genetics were not so involved in all of the genetic testing happening in blood cancers.  Because it wasn’t 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 they’ve 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.  We’ve touched on this already but I think there’s really amazing research happening, why do some people develop blood cancers and some people don’t, even though everyone carries the same underlying change that increases the risk? 

And then I think really importantly, we’re 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 people’s likelihood of developing blood cancer, we’ll 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 we’ve 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 it’s that you're intervening before the blood cancer has developed to try and reduce that happening, or whether it’s that you're then treating the blood cancer after it’s 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 we’re 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, there’s a recognised strategy and set of steps that should be taken for all of those patients.  To make sure that they’re 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 we’ve 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 today’s episode, we’d love your support.  So please subscribe, share and rate us on wherever you listen to your podcasts.  I’ve been your host, Amanda Pichini.  This podcast was produced by Deanna Barac and edited by Bill Griffin at Ventoux Digital.  Thank you for listening. 

In this explainer episode, we’ve asked Réka 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 you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

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 Réka, 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 Réka, if you could explain the word consent.  

Réka: 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 it’s 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? 

Réka: 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? 

Réka: 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?  

Réka, I'd be interested to know, are there any challenges related to informed consent that are specific to the field of genomics? 

Réka: Yeah, so there’s 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? 

Réka: 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? 

Réka: 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.  

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:

Linked below are the episodes mentioned in the episode: 

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 we’re 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 you’d like to know more about what the diagnostic odyssey is, check our bitesize explainer episode, ‘What is the Diagnostic Odyssey?’ linked in the episode description.

In today’s episode you may hear our guests refer to ‘VUS’ 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, “What is a Variant of Uncertain Significance?”

And now over to Adam.

--

Adam: Welcome, everyone, thanks for joining this session.

I’m always really humbled by the lived experiences and the journeys behind the stories that we talk about at these conferences, so I’m really delighted to be hosting this panel session. It’s taking us behind the science, it’s 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 – that has to be the end goal. We know it’s 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 we’re really going to aim to demystify what this diagnostic odyssey is, challenging the way researchers and clinicians often discuss long diagnostic journeys, and we’ll 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, we’ve got an amazing panel here. Rather than me trying to introduce you, I think it’s great if you could just introduce yourselves, and Lisa, I’ll start with you.

Lisa: Hi, I’m 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 I’m 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 it’s our daughter who’s the most complicated.

Adam:  Thank you. Over to you, Jo.

Jo:  Hi, I’m Jo Wright, I am the parent of a child with an undiagnosed genetic condition.  So I’ve got an 11-year-old daughter. 100,000 Genomes gave us a VUS, which we’re still trying to find the research for and sort of what I’ll talk about in a bit.  And I’ve also got a younger daughter.

I joined the Participant Panel just back in December. I’m 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, you’re 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 I’m Jamie Ellingford and, as Adam alluded to, I’m fortunate and I get to wear 2 hats. So, one of those hats is that I’m 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 that’s one of my hats. And the second of those is I am a researcher, I’m 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, it’s 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 name’s Emma Baple, I’m an academic clinical geneticist in Exeter but I’m also the Medical Director of the South West genomic laboratory hub, so that’s 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 it’s 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, I’m going to start with you. The term ‘diagnostic odyssey’ gets bandied around a lot, we hear about it so many times, but how does that reflect your experience that you’ve been through and what would you like researchers and clinicians to understand about this journey that you’re 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 she’s now 16½ – the half’s very important – and we still have no answers.

And we’ve 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, “Yes, it’s definitely a myasthenia, we just need to know which one it is,” at 4 years of age that was removed and it was all of a sudden like, “Yeah, thanks, sorry.”

And that was really hard actually because we felt we’d 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, “No, no, that’s not where you belong” and that was a really isolating experience.

I can remember sort of saying to the neuromuscular team, “Well is it still neuromuscular in that case?” 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 we’d been chucked out, and we didn’t even have a floaty. And in many ways I think I have made peace with the fact that we don’t have a genetic diagnosis for our daughter but it doesn’t get easier in that she has her own questions and my older children – one getting married in August who’s already sort of said to me, you know, “Does this have implications for when we have children?”  And those are all questions I can’t answer so that’s really hard.

Adam:  Thank you, Lisa. Yourself, Jo, how would you describe the odyssey that you’re 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 that’s 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 wasn’t active at the time because everything had been put on hold for COVID, but eventually we went into that. So, I didn’t 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, “That gives us some indication that it is significant.”

So, since that point it’s 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 we’re still not there. So one of the things is that a research paper came out earlier this year so that’s kind of a little bit more evidence, it’s not going to give us a diagnosis but it kind of, you know, sits there. And the other thing is that my geneticist said, “Actually, yeah, it looks like it’s an important change.”  That’s as far as we’ve got. So we’ve 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 doesn’t give me a group to join or that kind of thing.

But now I’ve got that research paper that I’ve read and read, and asked ChatGPT to verify that I’ve understood it right in some places, you know, with the faith that we put into ChatGPT (laughs), I’ve got a better understanding and I’ve 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 “Actually, no, I can see what’s happening.”

So, it’s like the picture’s starting to come into focus but there’s work to do. I haven’t got a timeframe on that, I don’t know when it’s going to come together. And I always say that I’m a prolific stalker of the postman; ever since our first genetic tests you’re 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 you’ve both kind of really clearly elaborated on is how you’re the ones that are having to navigate this journey, you’re the ones that are trying to piece this puzzle together, and the amount of time you’re investing, all whilst navigating and looking after your child and trying to cope with the daily lived experience as well.

And something you’ve both touched on that I’d love to draw out more is about how exactly was the information shared with you about the lack of diagnosis or the VUS or what’s going on, because in our case you get this bit of paper through the post that has all these numbers and it’s written in clinical speak and we had no conversation with the geneticist or the doctors.

You see this bit of paper and you’re reading it, scared for what the future will hold for your child, but I’d 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 daughter’s life I kind of had this very naïve thought that every time we turned up to an appointment it would be ‘the one’ and then…   I think it would’ve been really helpful actually in those initial stages if they had said to us, “Actually, we don’t know when this is going to happen, if it’s even going to happen, you need to kind of prepare yourself for that.”

It sounds fairly obvious to say but you don’t know what you don’t know. And in some ways we were getting genetic test results back for some really quite horrible things and they would tell us, “Oh it’s good news, this mitochondrial disorder hasn’t come up,” and so part of you is like, “Yay!” but then another part of you is thinking, “Well if it’s not that what is it?” And we’ve very much kind of danced around and still don’t really have an answer to whether it’s life-limiting.

We know it’s 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 it’s anything gastro-related, they say to me, “What’s the protocol from Great Ormond Street?” and I say, “We don’t have one” (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, there’s a point where, you know, we have to be guided by where we’re 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 we’d been an inpatient for about 6 weeks and the geneticist said to me, “So obviously with you not having a diagnosis from the 100,000 Genomes…” and I said, “Sorry?  Sorry, what was that?  You’ve had the information back?”  And she said, “Well, yes, did nobody write to you?” and I said, “No, and clearly by my shock and surprise.”

And she was a bit taken aback by that, but it happened yet again 2 years later (laughs) when she said, “Well you know everything’s been reanalysed” and I said, “No.”  (Laughs)  And, so that’s very much, it still feels an awful lot like I’m doing the heavy lifting because we’re under lots of different teams and even when they’re working at the same hospital they don’t talk to each other. And I do understand that they’re 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 it’s hard enough living without a diagnosis, but when you’re living with a bunch of symptoms that, I think the best way I can describe it is at the moment we’ve got the spokes of the umbrella but we don’t have the wrapper, and we don’t know where we’re going with it. We can’t answer her questions, we can’t even necessarily know that we’re using the most effective treatments and therapies for her, and she’s frustrated by that now, being 16, in her own right, as well as we are.

And I’m 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 won’t even have him and that’s a really scary place to be, I think.

Adam: Jo, is there anything you wanted to add on that in terms of how you’ve been communicated to whilst all this is going on?

Jo: Yeah, so I think part of what makes it difficult is if you’re across different hospitals because they’re 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, “Oh you’ve got this” and then the letter came through later.

When I had my next appointment with the neurologist in our primary hospital, or secondary care, whatever it’s called, in that hospital, he hadn’t seen that, so I’m telling him the results, which isn’t 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 I’m not criticising them in any way but their reaction to a VUS is “I’m so grateful for the persistence to get to a diagnosis.”

Neurologists are a bit more like “Oh it’s a VUS so it might be significant, it might be nothing.” Actually, as a patient, as in a parent, you actually want to know is it significant or not, “Do I look at it or not?” And, I mean, like I said, there were no research papers to look at before anyway until a few months ago so I didn’t have anything to look at, but I didn’t want to look at it either because you don’t 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, “What do we do with it, what expectation do we set the patients up with and what is the pathway for actually researching further?” 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 what’s 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 it’s come up just now again, is that you need to remember as a doctor that the things you say at critical times in a patient’s or parent’s journeys they will remember – they’ll remember it word for word even though you won’t – 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 you’re in a very high-pressure environment but it is absolutely crucial, that when you are communicating information about test results, when you’re talking about doing the test in the first place, you’re consenting the family, you’re explaining what you’re trying to do and those conditions, you balance how much information you give people.   

So, you were talking earlier about “So you haven’t got this diagnosis, you haven’t got that diagnosis,” I often think it’s…  We’re often testing for numerous different conditions at the same time, I couldn’t even list them all to the parents of the children or the patient that I’m testing. It’s 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 it’s 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 it’s unlikely or you think you know, sharing that information with family is helpful.  

Around uncertainty, I find that a particular challenge. So, I think we’ve 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 we’ve all got 5 million variants in our genome, we’ve 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 child’s or a patient’s 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, “We report variants of uncertain significance because the clinicians want them” and the clinicians said, “If the labs put the variant of uncertain significance on the report it must be important.” And of course, if you’re a parent, if the doctor’s told you the variant is a variant of uncertain significance of course you think it’s 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 it’s very often that they become the diagnosis for the family.  Did I cover everything you think’s 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 would’ve 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 they’re ever hearing that, and the impact of that, and also, they’re going on about with their day, you don’t know what else they’re doing, what they’re juggling.   

We’re 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 we’re in this kind of uncertainty, from my personal experience I’m uncomfortable, I like to be able to plan, I’m a planner, I’m 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, it’s quite a difficult place to be. And it’s not necessarily good news for those parents when a test comes back negative, because if it’s 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 it’s not that.  

You talked about the experience you had, you felt like you’d found your home and then it’s like, “Well, no, no, sorry, actually we don’t think it’s that.” And you’ve invested all of your time and your emotion into being part of that group and then you’re kind of taken away again. So it’s 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, “We just need to know something, we need to know,” and it’s that real fine line, isn’t 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 it’s 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 I’ve seen happen over time which we think will improve things. And one of that’s going back to the discussion that we’ve 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 scientist’s side as well because I think many of the scientists, if not all, realise what impact that’s going to have on the families.  

And what we’ve 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 you’d 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. It’s objective as to how we classify a variant into one of those groups and so it’s not just a gut feeling from a scientist, it’s 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 we’ve 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 we’re equipped with that understanding –– and not always with the tools but that’s a developing area – to be able to do more about it.  

What that doesn’t mean is that if we generate that evidence that it can translate back into the clinic, and actually that’s perhaps an area that we should discuss more. But kind of just generating that evidence isn’t 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 that’s 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 wouldn’t be able to work with.  

Behind that there’s 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 there’s still more that we can do about this. You know, it’s reliant on things going through a very kind of fixed system and making sure that clinicians don’t lose contact with families – 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 we’ve 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.  

We’re 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 we’ve got and the fact that everything is so joined up. We’re able to provide different opportunities in genomics for patients with rare conditions that aren’t so available elsewhere in the world. 

Adam: Great, thank you. I think we’re it for time, so thank you very much to the panel. And I’d just say that if you do have any further questions for ourselves as participants then we’re only too happy to pick those up. Thank you for lasting with us ‘til 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 you’re interested in attending a future Genomics England Research Summit, keep an eye out on our socials.

If you’d like to hear more conversations like this, please like and subscribe to Behind the Genes on your favourite podcast app. Thank you for listening.   

I’ve been your host, Sharon Jones. The podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac.

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 government’s 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: 

“There 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.” 

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 it’s 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 won’t just bring the health benefits, it also will secure the country’s position as the best place in the world to discover, prove, and where proven roll out benefit from genomic innovations and we think it’s so exciting to be part of that team effort. 

Sharon: I’m Sharon Jones, and today I’ll be joined by Rich Scott, Chief Executive Officer at Genomics England for this end of year special. We’ll be reflecting on some of the conversations from this year’s episodes, and Rich will be sharing his insights and thoughts for the year ahead. If you enjoyed this episode, we’d love your support, so please subscribe, rate, and share on your favourite podcast app. So, let’s get started. 

Thanks for joining me today, Rich. How are you? 

Rich: Great, it’s really good to be here.  

Sharon: It’s been a really exciting year for Genomics England. Can you tell us a bit about what’s going on? 

Rich: Yeah, it’s been a really busy year, and we’ll dive into a few bits of the components we’ve been working on really hard. One really big theme for us is it’s been really fantastic to see genomics at the heart of the government’s thinking. As we’ll hear later, genomics is at the centre of the new NHS 10-year health plan, and the government’s 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 it’s great to see us as a key part of that. 

It’s also been a really great year as we’ve been getting on with the various programmes that we’ve got, so our continued support of the NHS and our work with researchers accessing the National Genomic Research Library. It’s so wonderful to see the continued stream of diagnoses and actionable findings going back to the NHS. It’s 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 that’s ongoing in the research library, so now we’ve 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 it’s so vital.  

And then, with our programmes, it’s 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 we’re beginning to hear about their experiences, including some of the families who’ve received findings from the programme. It’s really nice to see and hear from Freddie’s 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 we’re doing this, to make a difference and improve health outcomes. 

Sharon: That’s an incredible 12 months. Diving into that Generation Study piece and for listeners who don’t know what that is, it’s 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. Let’s year from Rachel now. 

Rachel: From the parents’ 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 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 what’s evolving in that model? 

Rich: Yeah. It’s been for the whole study, really, starting out asking a really big question here, what we’re aiming to do is generate evidence on whether and if so, how whole genome sequencing should be offered routinely at birth, and that’s 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. There’s 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. We’re looking to understand whether we should offer this routinely. It’s 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 aren’t hurried and make this decision. What we’ve 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, it’s an important part of getting the study design right so that we run the study right. It’s also a really crucial element of the evidence that will generate from the study so that we can understand if this is something that’s adopted, how should we communicate about it to families. What would they want to know? What’s 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. There’s a lot that we’ve learnt along the way and there’s a lot that we’re still learning. And as I say, important things that we’ll present as evidence later on. 

Sharon: Thank you. It’s fascinating there are so many moving parts and a lot to consider when you’re 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. Let’s 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, let’s 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: It’s 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 we’re not just interested in DNA for DNA’s sake, this is about thinking about health and how we can improve health outcomes. So, it’s also thinking about the other sorts of information that needs to link to genomic data to make a difference. Whether that’s just to provide routine healthcare with today’s knowledge, or whether it’s about continuing to learn and discover. 

As I mentioned at the beginning, I think a really important part of this whole picture is we’ve learnt a lot in the last 20/30/40 plus years about genomics. It’s incredible how much progress has been made, and we’re really just scratching the surface. Take rare disease and the progress that’s been made there, it’s wonderful how many more families we’re able to help today. We know that many thousands of families we still can’t 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. It’s 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 we’re, as the whole of the society, we’re 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 that’s coming in from around the world. It’s got real potential there. 

I think the biggest bottom line here is that it’s got the potential to be a really important tool in terms of our ongoing learning and improvement. I’m a doctor by background, the human intelligence alone is fantastic, it’s 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 isn’t a panacea, it’s 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 we’re 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. That’s a really important part of what we’re 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 we’re doing it and what it’s bringing. 

Sharon: Thanks Rich. It’s definitely a fast-moving conversation of which we really want to be part of. One of the things that’s come up again and again this year is participation and co-production. Let’s hear quote that really captures that. 

Bobbie: In an earlier conversation with Paul, which you might find surprising that it’s stuck with me so much, he used the word ‘extractive’. He said that he’d 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: It’s a great question. It’s one of the areas where I think we’ve 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 that’s 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 that’s one of the key capabilities we have internally as an organisation, so we work with partners externally, but also it’s 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 it’s empowering to see their voices and experiences shaping future treatments. 

Lindsay: Historically, there’s been a significant absence of a patient voice in rare disease research and development. And knowing that that’s changing, I think that’s 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 England’s 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, we’ve had a participant panel from very early in our life as an organisation. That’s 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, what’s 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 they’re worried that they might ask the wrong questions in the wrong way, they just don’t 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 can’t possibly, if you’re 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 people’s lives that, again, without hearing from their voice you just wouldn’t 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: That’s 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 what’s 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 we’ve been thinking, looking forward with that 10-year lens on it, what we always like to do, and I think it’s a real privilege to be able to do, because we’re here in the UK, because we have a National Health Service, because there’s 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 that’s there in genomics more broadly. So we’ve, 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. 

There’s a double helix on the front cover and, in fact, on the watermark on almost every page. And, there’s 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 that’s a really ambitious challenge. We see a really important role for us, as Genomics England, in contributing to that, but it’s 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 that’s 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 it’s 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 won’t just bring the health benefits, it also will secure the country’s position as the best place in the world to discover, prove and where proven role out benefit from genomic innovations. And we think it’s so exciting to be part of that team effort. 

Sharon: So, Genomics England’s 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 years’ 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 it’s 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 don’t need to know that you’re seeing an expert in genomics to benefit from it, really make sure that those benefits can be felt as just part of routine care. It’s not something separate where we recognise that the best healthcare is healthcare that’s 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 people’s consent, with their understanding of how their data is being used, we know that if we don’t 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.  

I’m 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 I’ve had a number of families where I’ve been seeing the family for years, and a researcher accessing data in the National Genomic Research library has found an answer that we’ve not been able to find for maybe their child’s whole life, and then finally we’re 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: That’s 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 we’re talking about is using it in a much more preventative way. Traditionally where we’ve been using it is diagnostically where we know someone’s sick and they’ve got symptoms of rare condition, and we’re looking to see what they might have. What we’re actually talking about is screening babies from birth using their genome to see if they’re 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, what’s your biggest hope for where we’ll be this time next year? 

Rich: I think it’s a really exciting time. As you can tell from how we’ve been speaking, I’m 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 today’s 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 what’s adopted, I think we’re in a really exciting place. 

From a 2026 perspective, I think what we’re 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 it’s a really important part of that wider jigsaw to generate the evidence that can inform future policy on whether this is something that’s adopted and offered routinely to every child when they’re born. 

I think a really important time now that the government’s 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 we’re looking at what evidence it’s important that we can provide that’s complementary to different work around by others in the ecosystem that needs to be there if we’re going to think about that potential broader use of genomics. 

Sharon: That’s great. It sounds like another exciting year ahead. So, we’re 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 today’s episode, we’d love your support, so please subscribe, share, and rate us on wherever you listen to your podcasts. I’ve been your host, Sharon Jones. This podcast was produced by Deanna Barac and edited by Bill Griffin at Ventoux Digital. Thank you for listening. 

In this explainer episode, we’ve 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 you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

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] or wherever you get your podcasts. Thank you for listening. 

In this explainer episode, we’ve 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 you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

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.