Behind the Genes

Natasha Gordon-Douglas, Oleander Agbetu, Jayson Kupoluyi and Marie Nugent: How can organisations support those living with sickle cell?

For Sickle Cell Awareness Month, our sickle cell Patient Voice Group discuss their lived experiences with sickle cell, shedding light on how organisations need to be considerate when engaging with patients. They emphasise the need for genuine engagement and transparency from researchers, while highlighting the importance of building trust within communities that have historically been overlooked. The discussion looks to the future, advocating for more personalised support, better treatment options and a stronger focus on the diverse experiences of those affected by sickle cell.

Marie Nugent, Community Manager for the Genomics England Diverse Data Initiative co-hosts this episode with Natasha Gordon-Douglas, sickle cell patient advocate for the Genomics England Diverse Data Initiative and Lead Mentor at the Sickle Cell Society. They are joined by Oleander Agbetu, who cares for her son with sickle cell, and is also a member of the Solace sickle cell and thalassaemia support group board, and Jayson Kupoluyi, sickle cell advocate and volunteer for the Sickle Cell Society.

The episode also features insights from some of the other members of the Patient Voice Group; Hazel Attua, Samuel Chuku and Zainab Garba-Sani.

The Patient Voice Group are a group of people affected by sickle cell who share with Genomics England their expertise, based on their lived experience, to inform our sickle cell programme within the Diverse Data Initiative.

 

"If we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone’s care, that’s what I want to do. That’s why I’m here."

 

You can download the transcript or read it below.

Marie: Welcome to Behind the Genes. 

Natasha: I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient’s voice in order to make things better, and not just be in a room where you’ve got all board members that think, “Okay, this is what is good for the patient.” No, actually, they’ve got the patients there to help support that voice, and saying, “Well actually, this is the reality,” rather than what you think might be the reality. 

Marie: My name is Marie Nugent and I’m the community manager for diverse data at Genomics England. I’ll be co-hosting today’s special patient takeover episode of Behind the Genes with Natasha Gordon-Douglas, who is a member of our sickle cell patient voice group. On this episode, we’re going to be speaking to two people who are also part of our patient voice group, Oleander Agbetu and Jayson Kupoluyi. Today we’ll be discussing what it’s like to live with sickle cell, and how organisations who wish to engage with patients need to be considerate of what is going on in people’s lives, and what good advocacy and support for patients who want to be involved in research looks like. If you enjoy today’s episode, we would love your support. Please like and share, and rate us on wherever you listen to your podcasts. 

Welcome everyone, thank you very much for your time today to talk about the patient involvement and engagement work we’ve been doing as part of our sickle cell and genomics programme at Genomics England. My name’s Marie, I’m the community manager for the diverse data initiative, and I am really involved in doing the sickle cell engagement work. I’m going to pass straight to Natasha now, who’s going to be my lovely co-host for this podcast. So, over to you, Natasha. 

Natasha: Thank you, Marie. I’m Natasha. I would say my background is nothing to do with the medical side. My background is in marketing and the corporate world. That’s how actually I got introduced by John James, because I actually got him into our workplace to do a podcast about sickle cell. So, you know, just – I’m working in an environment, which obviously – it’s about people understanding about my illness, so I actually got him in speaking, and then he mentioned about a project, “Oh, you might be interested in this.” So, that was kind of the introduction I got from John James. But as I said, doing patient work and engagement stuff was completely new to me, so this is my – I’m a rookie, I should say. But I feel like now after the two years, I know now, I understand [laughter]. But yeah, that’s kind of a quick background. And how I got introduced to Marie is from John James at the Sickle Cell Society. 

Marie: Great, thank you, Natasha. So, coming straight to you now, Oleander, I think it’s a bit different for you. So, you joined this particular group not too long ago, but from what I know, you’ve been doing this kind of advocacy work and engagement work for quite a while. So, tell us a bit about yourself. 

Oleander: Well, I’m a parent/carer of a teenager, young man with sickle cell, and I think I’ve been part of the Solace sickle cell and thalassaemia support group board for more than ten years now. And what we do is we support patients through our WhatsApp group, as well as through inviting different people to come and talk. We’ve had doctors, nurses, etc. And I have supported people who have called me personally to ask me questions, from advice, for help. Also written a letter to the hospital, which we are now working on with the hospital itself, to try and get things moving and make improvements for the patients who are actually patients there at Homerton Hospital and Royal London Hospital. 

Marie: And then over to you, Jayson. So, similar to Oleander, you joined this group fairly recently actually, but just tell us a little bit about the kind of work that you’ve done before. 

Jayson: My name’s Jayson Kupoluyi. My background is totally different from the sickle cell background. Because of the plight that I have with my health, I now decided that I wanted to make a change, so I – unbeknown to me – I didn’t know what advocacy was. I just – when I meet people, I ask them questions, and, you know, thankfully enough, they really try and help and support in terms of advising me and those kind of things. So, I took that advice on board, and through the years I’ve met fantastic people, i.e. Oleander and her son. I met her son during a trip – we took the kids to a trip for a week for self-discovery, self-awareness, teaching them how to cope, and probably to see where – you know, try to make them open up. 

So, I now decided to volunteer for the Sickle Cell Society and give them seven years of my time, in which I’ve met fantastic kids and fantastic people. And through that, I’ve learnt to be able to teach people and the kids under 16 – well, I’m teaching from 26 year olds down to 13 year olds on how to advocate for themselves in hospital now. I teach the adults how to fill in application forms for PIP. I also write complaint letters and help them deal with complaints. And I also – sometimes I have the chance, from Royal London and Queen’s Hospital, to enter and view the situation, and ask information from the patients, from the nurses, carers and things like that, to be able to compile my own findings. And all in all, it’s been rewarding, because I just wanted to give back. 

Marie: That’s incredible, you know, because something that we’ve been talking about more recently as part of our sickle cell patient voice group is this idea of advocacy, and I’m just reminded that I’m with a great group of people to actually explore this because of the experience that you’ve got, so this is wonderful. Now, you’ve all just said you’ve got varying like degrees of previous experience of being part of advocacy work. Natasha, I’ll come straight to you, what were your initial expectations as to what it would mean or look like to be part of like a patient voice group?  

Natasha: To be honest, very sceptical [laughter]. I was like, “What are they really going to – are they really going to take our voice on board, and is it just another tick box that they could say, “Okay, we’ve funded a group for you to – with sickle cell,”” and I was very, yeah, sceptical. But actually I would now advocate for everybody to be part of a patient voice group. I think it’s so important. And the collaboration that happens with all these different organisations as well that you open up your mind to – ‘cos I didn’t know – you know, especially for this particular project that we’re working on, you’ve got the James Lind Alliance, never knew this organisation existed. I think the fact is that people do want to hear from patients, and they do understand that actually you need the patient’s voice in order to make things better, and not just be in a room where you’ve got all board members that think, “Okay, this is what is good for the patient.” No, actually they’ve got the patients there to help support that voice and saying, “Well actually, this is the reality, rather than what you think might be the reality.” 

So yeah, I would definitely champion anybody regardless, even – yeah, you’ve got sickle cell, of course, but any kind of illness, if there’s any kind of projects, trying to get involved, to really be able to try and shape what can happen. Because, you know, I guess what we’re working on at the moment, the opportunities for development within sickle cell are endless. And yeah, it’s just being part of that steering group, part of that voice to actually make change, especially with sickle cell. You know, it’s one of the ones that has never had anything – hasn’t had change for I don’t know how many years - I’m going to give away my age, for at least 40-odd years, I’ll say [laughter]. But yeah, so from what I can see, it’s slowly now changing and we’re in that wave, and I’m so excited to be part of that. 

I know Oleander, so you with your son, you’ve obviously seen the kind of – if there has been change for you. I guess for me as a patient, I might see it slightly differently, whereas you as a carer, a parent, you might see it completely differently. So I guess for you, what would you say for a person who might be considering joining a patient group or a parent/carer group? 

Oleander: I too was sceptical at first, but at the same time I can say that I’m really happy that I have been involved, because it means that all the information that I find out about that might be relevant to other parent/carers, I can pass that on, and vice versa. Any questions that they might have or issues that they might be going through, I can also get those considered. And I just think that it can be quite sad when a patient goes into hospital and they are on their own, they don’t have anyone with them. And so for me, for example, when my son was in paediatrics, and I’m sure the two of you would also know that, the treatment is just very different to when you become an adult. I could see from my son’s face, he just was not impressed with the adult care at all. And he more or less says, “Mummy, I’m not coming back to hospital unless it’s really like a dire situation. I just don’t want to go back.” And that’s quite sad because really we’re supposed to be able to support our loved ones in hospital. When they need the care, they absolutely need the care. 

I actually spoke to a parent today of a young man in hospital right now. His PCA was failing, which is, you know, the pump that gives the medication, right? And they actually asked her, “Is he still in pain?” If he’s been put on a PCA, how can you ask that question? So, you know, it’s so good that she was there to advocate on his behalf. He couldn’t even talk. And, you know, I know for my son also, when he’s in really, really deep pain, he stops talking, just doesn’t talk. And if he’s there by himself, it’s a real issue. And so, you know, I think from that point of view, all of these kinds of stories are really important to bring to forums like this, so that people can understand that of course, yes, it first affects the actual patient themselves, but it has a knock-on effect for the families, and the carers and the people that are involved with that person’s care. So, if we as parent/carers and advocates and all the rest of it can even make a little slight difference to someone’s care, that’s what I want to do. That’s why I’m here. 

Marie: Thank you so much, Oleander. I think that’s a really powerful story as well, and it just shows so – I couldn’t help but think, as you were talking there, about this idea of – we use the word community quite a lot in this kind of engagement space, but I must admit, you know, I’ve been working in public engagement with health and research for well over ten years, and I must say that I really felt the sense of community in this sickle cell space, particularly with patients and the wider sort of community, and that feels like it’s a really important part actually. And it kind of speaks to what Jayson mentioned about, you know, he’s now reached this point in his own life where he wants to be actively kind of contributing back to the community. So, I’ll come to you now, Jayson. Again, what was your expectations about joining a group like this, and what were you thinking when you joined? And how has that maybe transformed now? Or potentially not? How has your experience been so far? 

Jayson: It’s been great actually, pleasant people, likeminded people working towards a common goal. When I first heard about this group, I said to myself, “Do I have space for another WhatsApp group?” It’s not because I don’t have space on the phone. It’s because getting calls in the middle of the night at the same time – and you can’t turn it down sometimes, especially if it’s in the family, ‘cos I have these people – I have - you know, it’s in our family and it’s very, very rampant. And when you say community, you can have a mother of your nephew, your niece call you, knowing fully well that you’ve gone through that, this sort of thing, what’s going on, blah-blah-blah, “Okay, this is what you need to do. This is what you need to do.” Then getting to the hospital is another ballgame, do you understand? And you just have to say, “Okay, you know what, if I take a moment of my time and say, “I’ll see you in the morning…”” I’ve had two incidents that I didn’t make it, and it’s a guilt trip to me, because I was thinking, “Hold on, if I had gone…” And then I was okay – if I wasn’t feeling okay then, yeah, but I was okay. I was just tired.  

And when I started, I was a one-man band, and I realised the last 20 years that it’s definitely not going to work, hence the community comes in. And the time I tapped into this community, I met people – “Okay, so, you could help me out, you could help me out, you could help me out.” And the more I meet people, the more my voice goes bigger, louder and reaches more people that I want to reach. So, when I first met Hazel, she was in pain, so I called her and I was like, “Madam, you don’t know me, but I know that you’re in pain, are you okay?” And she goes, “No, I just wanted to sit down.” I just sat down beside her, didn’t speak to her, just sat down, and she didn’t utter a word, but she came to a conference and I’m thinking, if you’re in pain, you know, okay, I’m the same – I just started explaining myself to her, “I have this, I’ve gone through this,” blah-blah-blah, and she was looking at me and she was like, “You don’t look like (inaudible 0:15:54).”  

So, meeting and coming to this group, my expectation was a bit elevated actually because, when I was speaking to Hazel, she said, “No, Jay, seriously, you need to be in this group because we need the other…” And I was like, “Not another one,” and blah-blah-blah. Hazel said to me, “Can you join the Solace group?” I was like, “Who’s in it?” She goes, “Oleander.” I was like, “Oleander’s good.” And everybody keeps on calling me, and I do appreciate that people want my advice sometimes, but this health is very precious to us. I am looking forward to greater things with this group. I am looking forward for us to reach some targets, some funding, some people out there, to be able to change so many things. And any time I see a sickle cell person in good health, no pain, no nothing, I give myself thumbs up. You don’t want to see anybody in that kind of pain, and people don’t recognise or have that empathy to share or say, “Just another sickler.” 

Sickler, that’s a word, hmm, I don’t like it. So, whenever I go to hospital, Queen’s or Royal London, they know, “Jayson, are you here to cause problem?” “As long as you answer the question, I will be fine. As long as we’re okay, I’ll be fine.” And, you know, we’re now friends. In the midst of adversity, we’re now friends.   

Marie: There is just so much I think in what you’ve just said, and I think that again something that I’m really struck by – so obviously, you know, I don’t come from any lived experience. I didn’t have people in my life that I knew that had sickle cell before starting to work on this as part of my job. And something that I’m really struck by is, first and foremost, from the No One’s Listening Report, the quite staggering evidence that, as a community of people, people living with and affected in some way by sickle cell are very neglected, and there’s all sorts of complex layers of like challenges and difficulties that people have to deal with, and it seems to come from all sorts of places and all sorts of kind of parts of life. 

I was just really struck by this really daunting situation actually to be put in. As someone who’s part of, you know, let’s be honest, quite a sort of – maybe quite far down the road in terms of direct benefits, like piece of work – so we’re here, I’m part of an organisation that is interested in supporting research and providing good quality research data, and research is a really important part of this whole system, but again it’s something that maybe will take five, ten-plus years before you’re seeing any direct benefit from in terms of the data that we’re creating.  

But something that I’m really struck by is this idea of, if we know that there’s going to be maybe a bit of a delay in the kind of benefits that we can bring to patients through the data that we’re generating, how can I try and build in as much benefit right now for the people that we’re engaging with and we can bring into this work right now? And that’s something that we’ve talked about and we’re about to initiate a bit of a project around exploring a bit further, but I just wonder if I can now come to you all and get your thoughts on what can organisations like Genomics England or other research based organisations – what in your view does being a good supporter or a good advocate for people living with sickle cell – what could that look like from a research organisation in your view? I’ll come to you first, Oleander. 

Oleander: I think a really massive thing is to support the removal of barriers. There’s so many people who would love to get involved with this, that and the other, but actually the barriers are there and the barriers are real. Even like from a personal point of view, the thing I was interested in attending, I can’t. It’s just not within my means. So, things like that are really important, because most people who are living with sickle cell, we are from marginalised groups. We’re from groups that are not known to be flushed, and we need the support from – you know, if you really want our help in terms of research and so on, we absolutely need your support and your help to provide you with that research and that help. So, it’s real. Giving someone a £20 voucher is nice and dandy, but actually if they’ve had to pay for whatever, accommodation or travel costs and all these things, they’re out of pocket before they even start. 

Marie: Yeah, this is something that we’ve been talking about recently, isn’t it? I know that organisations like ours do want to do better, but sometimes there’s just that not quite as good an understanding as to what these barriers really look like for people. Over to you, Natasha, what do you think about that? 

Natasha: There’s a couple of things I wanted to pick up on. One is definitely, yeah, the barriers. It’s funny, I was at a hospital this morning and I was talking to one of the consultants. He asked me the question, which I thought was quite weird, but he asked me, “Why do you think that sickle cell patients have to pay for prescriptions?” Like that alone, prescriptions, we’re on medication forever, you know, from the moment you’re diagnosed, which for me was at six months, so in my entire life, and you’re paying for prescription, that’s going to keep happening over and over, and you’re just – you know, there’s people, because of their sickle cell, they can’t work. There’s, you know, barriers of not being able to work. And then you’ve got potential – you apply and say your disability, and sometimes that’s not even taken on board either. So, you’ve just got these barriers in place that just make living day to day so exhausting, so tiring, and basically you’re fighting those barriers at every – you think you’ve passed one, you’ve come onto another. 

And I guess also the research side, which – it’s funny because I would say, when it comes to research, it’s fantastic, yes, that organisations like yourself are looking into it, but actually sometimes it’s not even – you can’t make the change where it’s going to matter immediately. It’s literally the frontline, you go into hospital and A&E, that’s your first barrier is trying to just get some pain relief or get any treatment. You’re sitting there for four hours. Four hours in pain for a person with sickle cell, that can really, you know, make things worse. And that’s the kind of – you kind of want the immediacy – like the frontline, those kind of things to change. And of course, yes, we do want more research and we do want people to take part, but it’s those things where you might not necessarily have the power to make those changes immediately that people will be willing to take part in research like this, because you can’t even just get the treatment that you need from the moment you step into a hospital. 

That’s kind of what I was thinking of as you are speaking about this. I’m like, you know, yes, this is great, but we just need sometimes just going into hospital to make it easier. Like what Oleander said, it’s unfortunate that the persons being asked about their PCA, if they’re in pain – well, what do you think? Like that’s just the basic [laughter], you know. It’s kind of like, how can you ask that question and you’re a healthcare professional being on the frontline? And that’s the worst. It’s the frontline staff sometimes which actually need the education. So, some of this research, it needs to go to education in these staff actually, you know. That’s maybe an area that needs to be sorted.  

Marie: For me, I completely have a whole new deeper appreciation for almost seeing people as the whole, how you work with the person. And it’s never been clearer to me - as I say, you know, in ten-plus years’ experience of doing this kind of work, it has never been clearer to me how important that is than now I work on sickle cell and how important that is. And I think that actually you’ve touched on a really important point there, which is that, you know, I know for sure that there’s incredible work going on through NHS England, through the inequalities workstream and in response to the No One’s Listening Report. There seems to be, you know, a huge increase in sort of focused action being taken to address a lot of these challenges that are being brought up in our conversation now.  

But actually, what you said, Natasha, did kind of really hit the nail on the head a little bit for me, which is that actually we kind of still look at this as kind of separate organisations, like, “Well, this is my bit and that’s your bit, so you stay over there.” And I think that something that we’re trying to start working towards through the Sickle Cell Society is actually how do we bring together a better sort of alliance of work and of people who are across research and healthcare, because these things feed into each other, right? So, how can we do better to sort of show that we are all aligned, that there isn’t just this one person or one group over here looking just at this little bit and then there’s a completely separate group, that we are all actually united in our, you know, intentions here to really improve the lives of people that are living with this condition. But of course, there’s just so much work to do, isn’t there? I think that’s another overwhelming thing, that everything needs to be better when it comes to sickle cell. 

Oleander: The thing I wanted to just add to this whole talk about what researchers can do in terms of supporting advocates, etc. Two things, understand that there is an issue for trust from our communities, because we’ve been burnt. And the second one is, we need transparency. So, be real when you talk to people about the information you’re gathering, what you’re going to do with it, how it’s going to impact the research, timetable of whatever’s happening, all of those things which will help people to gain more trust. 

Natasha: Yeah, Oleander, that’s so – yeah, I think definitely, that’s been echoed throughout this whole project, hasn’t it? It’s always about gaining that trust, because it is a case of, is this another where we’re going to have support and we’re going to be let down, or, you know, lied to, whatever you’re going to find out. And trust is a huge part of that, definitely, yeah. I think, yeah, definitely. Thanks Oleander for saying that, it is.  

Marie: Yeah, thank you all. So again just to say that I’m always blown away by just how generous you all are actually with what you say and with what you share, and with the messages that you’re ultimately trying to get across. And it’s very humbling, you know, to be able to work with you all, ‘cos you all are so incredibly passionate and driven, despite so many challenges, and it is nothing but inspiring. So, I can see absolutely why, you know, people living with sickle cell, for example, are called warriors, because you need to have that sort of fighting spirit to just keep going, and I have nothing but, you know, boundless like respect and admiration for people who are able to do that and contribute to the community in the ways that you all do.  

And I just think that again, you know, so talking now back to this idea of how research is set up, you know, I myself am part of an initiative that’s been, you know, initiated and only kind of guaranteed funding for this kind of iteration, for three years. It’s very difficult to sort of initiate and establish really good long-term relationships, and have like a longer term strategic sort of way in which you’re bringing in people and taking that long sort of like approach to building relationships, but it’s something that I’ve tried to be really mindful of actually, and to address a lot of the things that you just mentioned. 

You’ve heard us refer to other members of our patient voice group. Let’s now take a moment to hear from them. 

Samuel: Hello, my name is Samuel and I’m from Leicester. I have had the great privilege of working with some amazing people in Genomics England over the last few months, to hopefully one day be a part of something that takes down this condition that I struggle with known as sickle cell. Since John James of the Sickle Cell Society introduced me to Marie from Genomics England, there has been a door opened where the voice of a person dealing with the condition matters and holds weight, to help know what is required to further improve matters for people dealing with said condition. Hopefully, after reading the blog and hearing this podcast, you will know more about the work we’ve been doing, and feel as encouraged as we do. We don’t just want to stop here. There’s a long way to go, and we need all the help we can get to reach our goal together. 

Hazel: Hi everyone, I’m Hazel. I hope you enjoyed the podcast. Now we’re not done just yet. Keep your eyes out for our sickle cell and Genomics England patient takeover blog, where Natasha, Sam and I take you through what we’ve been up to and the future of genomics.  

Zainab: Hi, my name’s Zainab and I co-chair the Genomics England diverse data advisory board. I also have the pleasure of being part of the patient engagement group for this important piece of work. I’ve been a sickle cell advocate since before I even knew what advocacy was. As a child with sickle cell, I was exposed to different ways to help the community pretty early on, and have loved working with others to transform care for the better. Today, I hold a number of advocacy related leadership positions, including being a trustee of the Sickle Cell Society, chair for NHS England’s patient advisory group for sickle cell health inequalities improvement, and a member of faculty for Medscape’s committee on rare diseases. I also contribute to global sickle cell policy, practice and research. 

I’m super excited about the work we do with Genomics England because I think they’re a blueprint for what good patient centred work really looks like. My background is in health policies specifically related to research and innovation, so to see sickle cell being prioritised in this space is really special to me. We have an incredible opportunity to advance equity through research and innovation, especially related to genomics, and I myself am lucky to experience the transformative power of regenerative medicine. I’m excited for this group to continue to advocate for and enable better access for such incredible science. 

Marie: We’re very lucky to have such a wonderful group of people who are part of our patient voice group, and I hope you enjoyed meeting them. Just going back now to sort of what can be achieved, and if we, say, come back together in a year’s time, knowing the kinds of things that we’ve just talked about briefly that we maybe want to look at – we’ve mentioned things like doing more family sessions, looking at how we can engage young men in particular, doing what is needed to kind of give that really strong message about how you support people to be part of these kind of patient advocacy roles. But what would you really like to see that we’ve achieved together by say this time next year? I’ll come to you first, Jayson, this time. 

Jayson: Thank you very much. Going straight to the point, I would like us to have more one to one with the patients and family in terms of – mainly I think to move towards the male, because, you know, I’m a living experience of some of the things that’s happening, and put the awareness out there, and let them know that – not to scare them, but to give them adequate information to be able to arm and tool themselves for a better life for themselves, a better respite for themselves, and a better understanding of the situation. I know if sickle cell patients have enough time at work, at uni, at school, during their exams, they will achieve great results, and I would want that to be one of the forefronts of this campaign, to make sure that, you know, the male side – I do know a bit of the female side but I’ll leave that to Oleander and Natasha, but the male side of what they should expect, and how to – if I could put this in (inaudible 0:33:59), I am making myself a role model for them, because I have leapt over barriers and over so many expectations, and if I could do it, with the science and the support we have now, they can double it, they can triple it, they can do more. My journey hasn’t ended yet, but before it does, I want to tap into every organisation to hear more voice, to just give me five minutes to hear my voice. 

Marie: Thank you so much, Jayson. I can’t think of a better role model for young men who are dealing with this than you, so it’s brilliant to see your dedication to that. Over to you, Oleander, what would you like to see – if we’re here together in a year’s time, looking back on what we’ve done over the last year and what’s been achieved, what would you really like to see? 

Oleander: I’d like to see sickle cell actually being taken seriously, that people don’t make assumptions that, “Oh, it’s just a small, you know, blood thing, it’s nothing that deep, nothing that big,” whatever. Because the reality is, for a lot of indigenous people here, the majority ethnicity in this country, sickle cell is spreading because more people are mixing, more people have come over, refugees, economic migrants, etc, and mixing, and so they will find that actually it isn’t just a tiny minority of people. We’re told it’s 17,000 people in the UK, but actually that number’s going up. So, you know, it is a bit of a shame that it takes it to affect the ethnic majority in this country that anything would change, however this is the reality we live in. So for me, that’s what I would like to see, that sickle cell is taken seriously, that we’re not just stuck with one or two authorised drugs for people living with sickle cell, and actually one of them is not even a sickle cell specific drug. 

So yeah, we want sickle cell to be taken seriously, and so that people can actually trust the process and trust the people who are genuinely trying to research issues to do with sickle cell, so that we can make the difference that we need to make for people’s lives. 

Marie: Thank you, Oleander. That just reminds me that, you know, hopefully – so, one of the projects that you are also involved in that we’re doing is – and that’s been already mentioned, the James Lind Alliance and the Sickle Cell Society partnership that we’ve got, the priority setting partnership. Hopefully, one of the things that’s part of doing that is that we do create that sort of focused priority areas, and that’s really strongly centred on the voices of people living with the condition, supporting people with the condition, whether they’re parents, carers, healthcare professionals. So yeah, I completely agree, you know, really putting it on the map, taking it seriously, raising the understanding, raising it as a priority, I think that would be great to see in a year’s time for sure. So of course, last but not least, over to you, Natasha. 

Natasha: Well, Oleander has literally taken the words out of my mouth. That is exactly what I would want to see in the next year, and to me, it can be done. There should be no reason why it can’t be, with all the technology, with all the advancements that’s happening. There is no reason why sickle cell should not be leaps and bounds with the information, with the project, of getting this information from sickle cell patients. It should come to a point where actually no one has to suffer from sickle cell because, you know, the – what’s it called, the medication, that one that’s recently come out, that’s way overdue. I can’t even believe it’s taken this long to just come up with that one, you know. The stem cell treatments and what they give as an alternative, it’s not good enough basically. And, you know, we had this new one come out – I say new one, but this hydroxycarbamide, it’s like that wasn’t even for us. It was all by mistake that, “Oh actually, this might help sickle cell, let’s see.” And that’s what’s the afterthought, and we shouldn’t be an afterthought. It should be a priority.  

And yeah, having that priority setting that we’re doing with the James Lind Alliance – it’s funny, ‘cos I remember, we had a call in our patient voice – I think he mentioned – I think it was something about maybe the questionnaire that we were going to give people, or – I can’t remember the particular thing which I said to you, you’re having trouble – you know, we’re underrepresented, there’s no data on us for a reason, and you had a template, and it’s like this template’s not going to work, because you have to approach it differently. Like you have to literally rip it up and start from the very beginning, because what you’ve tried to do in the past hasn’t worked, or, you know, the majority of people, especially in the European world, it works for them, great, but you’re coming to an underrepresented community and you’re thinking, “Oh actually, we can just use that thumbprint and put it on this.” No, you’ve got to start again. 

And I think it brings the importance of actually taking part in things like this, is that without actually knowing this, you would have thought, “Oh actually, people just aren’t interested, you know. Patients don’t want to know. They don’t want to give any information over to us.” But it’s like, well no, it’s not that at all, it’s just that you need to approach us differently. You need to, you know, understand what actually we’re going through before you can then try and fix anything or provide information, or get, you know, medication advancements. Like these things need to be done and the groundwork first, and not thinking, “Oh okay, we can just put a little plaster and that’ll heal that.” 

So for me, definitely, more options when it comes to treatment. And, you know, that we’re not the minority when it comes to data. Because especially with sickle cell, it affects different people in so many different ways, and they’re just trying to understand, “Oh, why does it affect this person this way but it hasn’t done it in this person?” And it’s just like, great, you’re asking these questions, but now let’s move it forwards. Like let’s not keep talking and let’s start the action. And that’s probably one of the other things is, I want to see the action. It’s the action now. You know, of course, if you want us to talk, we’ll talk, you know. We won’t stop, and we can keep going. But ultimately let’s actually have some movement. Let’s have an action that you’re – I say you as in you as an organisation, but wider, everybody that’s part of the process comes and says, “Look, this is what we’ve been able to achieve.” And, you know, then you know you have been listened to. A bit like Jayson said, you know, still not listening. Actually, now you can say, “Yes, we’ve heard and now this is what’s come from it.” So yeah, that’s probably I think for me the biggest utopia is that actually sickle cell just won’t exist. It’s done. They’ve been able to sort it out [laughter], it’s no longer an issue at all. But yeah, we won’t get to that next year, but, you know, hopefully eventually down the line there is that cure or change that they can do. 

Marie: I think for me, it kind of just brings me back to this point that there needs to be a united front in terms of like dealing and addressing with this. And also importantly, it needs to come from the community itself in terms of setting the priorities of what is done now, what is immediately needed to be done now, what can be looked at maybe a little bit later down the line, as there’s maybe a bit more information, a bit more understanding, a bit more knowledge to kind of maybe base some things on. But yeah, every time I hear, you know, people speak about all the various challenges that, you know, of course, come from their own lived experience and having to see how this affects their community, and yes, there are steps being made in the right direction, but I think we all probably agree that we could all probably be doing more to just improve the way we’re uniting this work, and we’re doing it in a way that is really coming from the community themselves and saying, “We want this to happen now and in this way, and this is what we want you to look at addressing.” 

We’ll wrap up there. Thank you to my co-host Natasha Gordon-Douglas, and guests Oleander Agbetu and Jayson Kupoluyi for joining me today as we discussed engaging people with lived experience of sickle cell in research and advocacy. If you’d like to hear more about this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host, Marie Nugent. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand. 

Aman Ali, Anna Smith, Moestak Hussein and Naimah Callachand: How can we bridge the gap between diverse communities?

In this episode of Behind the Genes, we explore the challenges diverse communities face in accessing genomic medicine. The discussion focuses on issues including language barriers, cultural differences, and socioeconomic disparities that hinder marginalised communities from accessing and benefitting from genomic medicine.

Our guests delve into successful strategies for engaging these communities in healthcare research and decision-making, highlighting the importance of building trust with groups that have historically been underserved or mistreated. The episode also emphasises the need for culturally sensitive communication from healthcare professionals and how meaningful community engagement can foster collaboration and trust within genomic research.

Our host, Naimah Callachand is joined by Aman Ali, a Community Ambassador at Genomics England and Community Engagement Manager at Our Future Health, Anna Smith, Child and Adolescent Integrative Psychotherapist at Rareminds, and Moestak Hussein who works for Bristol City Council in Public Health & Communities, working directly to build and imbed cohesion, inclusion and social justice approaches in her role.

 

"If we talk about co-production, true co-production is really creating a power balance where there’s no hierarchy. It’s an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve."

 

You can download the transcript or read it below.

Naimah: Welcome to Behind the Genes. 

Aman: It’s really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with. 

Naimah: My name is Naimah Callachand and I’m Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m going to be joined by Anna Smith, child and adolescent integrative psychotherapist for Rare Minds, Aman Ali, a community ambassador for Genomics England, and Moestak Hussein, community coordinator at Bristol City Council. Today, we’ll be discussing the disparities in access to genomic medicine amongst diverse communities. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts. 

Aman: Hi, my name’s Aman Ali, I am an ambassador at Genomics England, a person very passionate about health research and ensuring that diverse communities are involved in health research, and I work as a community engagement manager at Our Future Health. 

Anna: My name’s Anna Smith, I’m a psychotherapist. I work in private practice and also with Rare Minds, who are a company who provide therapy to people with rare and genetic conditions. 

Moestak: Hi, my name is Moestak Hussein and I have a background in community development, and I’m passionate about tackling health inequalities, and building social justice and inclusive approaches to address health inequalities. I work at Bristol City Council in the public health team, and I’ve participated in the Bristol workshops around equity in research in genomics. 

Naimah: So, let’s jump in and first of all I want to talk about barriers to access for diverse communities. I want to talk about how there are language barriers, cultural differences and socioeconomic factors that impact access to genomic medicine for marginalised communities. Anna, I wonder if you maybe could talk to me a bit about this. 

Anna: Yeah. So, I’m talking about the traveller community, and we refer to this community as a GRT community, which is Gypsy, Romany and Traveller, so it encompasses people in the UK, people living in Ireland as well. And some of the barriers to accessing healthcare are a lack of understanding of culture. There’s been studies done where it says that people from GRT communities show up lower on all markers for poor healthcare and poor mental healthcare, and part of the reason for that is things like illiteracy. You know, you’re dealing with people who can’t read or write. They can’t read appointment times. They don’t have access to public transport. A lot of women don’t drive in this community, and also women are not very well supported within the community by the people who can drive and who can get them places, because it’s not seen as something that they need access to. Because the community is so closed, everything sort of takes place within the community.  

In terms of genomic healthcare, access right from the start of life, if people are not accessing healthcare right from birth, they’re not getting the genetic testing that’s needed, so then a lot of these things don’t even show up until the illness presents itself, and then accessing healthcare from there is really difficult. You know, it’s something that – it doesn’t happen a lot. Only 67 percent of people from the GRT community were able to get a doctor’s appointment when they needed it, compared to nearly 90 percent from other communities, and that’s through things like not having a fixed address. Lots of GPs don’t offer temporary registration, which means that if you are travelling, you do not have access to a GP, which is your first port of call if you need any access to healthcare. So, many people from the GRT communities are using A&E services in order to get healthcare, which – you know, they are not set up for dealing with long-term life changing conditions. They’re there to deal with what’s right in front of them and then they move on. There’s no sort of continuity of care. 

Naimah: Thanks Anna, that’s really highlighted a lot of barriers for the GRT community. And I wonder, Aman, if you want to come in now and maybe discuss some of the barriers that maybe the Muslim community might experience. 

Aman: Yeah, I think anyone involved in medicine or anyone who’s a doctor is really well respected in the Muslim community. That profession is something that every parent aspires for their children to get involved in. They at least want one of their children to be a doctor. Having said that, there’s this willingness to engage with the space, but there’s a lack of knowledge, which is a huge issue here. People don’t know what the word genomics means or genes, or understand DNA. Some of this language is a huge barrier to understanding and then eventually accessing some of the services that could be available to people from Muslim communities. Because when we speak about Muslim communities, we’re talking about a huge, diverse group of people from South Asia, from North Africa, from the Middle East, and they all have their nuances and different cultural experiences as well. 

Just to kind of point out maybe one or two, most people in the UK have grown up in the UK, where access to healthcare is free, whereas this is quite a strange phenomenon for people who may have not been born in the UK and then access healthcare services in the UK. And the context being here is usually they pay for healthcare in other countries, and whenever any public or free healthcare is provided, it’s usually seen as kind of not very good or suboptimum, or yeah, it’s not going to be very helpful for us. So, when they see free healthcare in the UK, there’s that kind of apprehension, “Actually, is this going to be worthwhile? I’m not paying for this, so it’s not going to be very much good for me.” So, those are some of the cultural nuances that certain communities where healthcare is not for free in certain countries that poses a barrier. 

Language in terms of speaking and reading is an issue. So, a lot of people, they may speak a language, but they don’t know how to read a language. So, even when services are translated – I, for example, can speak Bangla, but I can’t read or write Bangla, and not a word of Bangla at all. So for my parents, who can speak Bangla very well, their reading level is actually quite good, but I know that many within the community, they didn’t get education back home, and therefore reading and writing is a challenge as well. And then you have the issue of dialects. There’s so many dialects within so many different communities, so when a language is spoken or written in a particular way, if that dialect isn’t your mother tongue or a dialect that you’re familiar with, then that causes challenges to access as well. 

Naimah: Moestak, how do cultural beliefs and values influence attitudes towards genomic medicine within each of these different cultural communities? 

Moestak: I think Aman and Anna touched on it a lot, and it’s about communities being able to coproduce that historically hasn’t been there. The supremacy of certain communities to have a voice and be able to express how they would like to shape their healthcare, but also access to healthcare barriers have been part of having a barrier in access. And I think Aman touched on like even the term genomics, I don’t think it exists in particularly my community. I come from the Somali community, and I’ve tried to look at historical kind of words and terms. I mean, our language only got developed in 1973, the written language, so you can imagine that there’s a lot of gaps or there’s other terminologies. 

So, the cultural beliefs and values is also communities’ recognition to be driving their own health needs and priorities is not valued within those sectors such as healthcare. I mean, we’re still talking about holistic medicine. People go to their faith leaders in the first instance to have support around prayer. That’s not necessarily recognised by mainstream health provision. And I think it’s about how do we build on those strengths and how do we recognise that that is a really great part of communities. And it’s also tradition and customs within childbirth, from birth, understanding what children and young people and families will need. I know there’s customs and traditions for women to stay at home, for example, for 40 days, and those are the kind of traditions that could be built on. And I think it’s about making sure that the child doesn’t pick up bacteria or things like that.  

So, there is an understanding and knowledge within communities of genomics. It’s the awareness and the training around patient centred approaches are still missing, in my opinion. And I think that influences how people view genomic medicine. It goes back to the lack of trust and historic past abuses and cases, that communities has resulted in lower participation and a reluctancy to be part of genomic testing, but also that lack of understanding. 

Naimah: Anna, did you have something you wanted to add in there? 

Anna: What you were just saying about keeping it within the community, that’s something that we see with the GRT community massively is everything is handled within the family, and I think that’s not necessarily valued outside of that community. If you arrange an appointment with someone and the whole family turns up, it’s like, “Woah, what’s going on here? You know, how is this managed?” And it becomes a safeguarding issue, when actually that is how it's managed, and very often you need to get the whole family on board before you can start working with an individual. Because within the GRT communities, individuals do not exist outside of their families. Even what we’re saying about language, a lot of the GRT community who live in England now speak English, but the words that they use for mental health are very different.  

You talk about mental ill health, that translates as psychosis in the GRT community, whereas if you’re talking about depression and anxiety, somebody might say that they’ve got bad nerves. So, if you come up and say, “We’re dealing with mental health now,” people would say, “Well, I don’t have psychosis, I don’t have that, this is not an issue for me.” And it’s like you’re speaking different languages even though you’re using the same words. 

Naimah: From what all of you have said as well, it does sound like there are a lot of similarities in the barriers in each of the different cultural communities. 

I wanted to move on to ask about what strategies have been effective at engaging these diverse communities in healthcare research and decision making processes. 

Aman: There are a number of ways I’ve seen best practice take place in regards to kind of community engagement. The approaches have been one of two approaches. One, either inviting the community to come to your spaces, i.e. organising events or having opportunities where people can engage with your service. Or the alternative approach, which I think is actually more effective, is actually going to the spaces where communities are most familiar with. So, whether that’s holding a focus group at a community centre, at a church or at a mosque, or engaging in coproduction with a community organisation, to come together, to come up with an idea of how to best engage communities. And I also feel like there’s a difference between PPI, patient and public involvement, versus community engagement.  

And those are the two major approaches that I’ve seen when it comes to community engagement, and I’m a big advocate of community engagement, because you’re going into spaces which are authentic to the very communities that we are hoping to engage, but you’re going into an unfamiliar environment as opposed to bringing that community into an unfamiliar environment, where they might be a bit guarded with what they want to share and how comfortable they feel. So, those are some reflections on good practices in community engagement. 

And I think one of the key things that we need to do is understand who are the key community leaders within that community, ‘cos it’s one thing being within that community, and being able to speak about that community are two different things altogether. So just to articulate what I mean by that, I live in Luton, but I’ve just moved to Luton two months ago, so if you ask me about what life is like in Luton, I’ll be able to speak about my experience, but if I was to live here for 20, 30 years then I’d be in a better position to speak about how people in Luton live and what their experiences are like, and that’s two different perspectives you’re going to get. So, it’s really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with. 

 

Naimah: Thanks Aman. I think you made a couple of really good points there, and I think you kind of have this overarching feeling of building trust, which is what Moestak mentioned in the previous question as well. I thought maybe now would be a good time to discuss your first responders project, Aman, if you could tell us a bit about that. It’d be good to hear the kind of developments from that community work. 

Aman: Yeah, so one of the ideas that came about from engagement actually that we had with some community leaders within the Muslim community, primarily some imams, they heard about the work of Genomics England, they heard about the work of research in particular, and they were really keen to get involved even further, but they were honest in saying that, “I know very little about this space. And it’s one thing for me not to know much, but then if I don’t know anything then I’m not able to then advocate for this within the community. So, two things you need to help me with. One, help me understand this space, but also allow me to then be able to advocate for services or information that my community can benefit from.” 

So, that’s where the inception of this first responders idea came about. The idea being that community engagement happened with some imams from all across the country, where we trained them to understand a bit more about genomics, and genomic healthcare and medicine, but also to be able to navigate a number of scenarios that they may face in the community. For example, there’s a mother who has been recommended by their GP to go see a genetic counsellor, but they’re really worried about broaching that conversation with their husband or their family, because of the challenges that they may face. So, how would you support someone in the community when that scenario comes up? Or for example, someone like Genomics England or Our Future Health or another organisation has approached you about a research study, and they want to engage your community, how would you have that conversation with that particular organisation, advocate for those health programmes within your community? 

So, we just presented a number of scenarios. But I think the main thing that we ended with was giving the imams in this particular incident the ability to signpost to services, be it helplines that are available for communities to access more information, or websites that people can access in order to understand more information about different issues to do with health conditions, or whether it be better understanding issues like cousin marriages or kind of accessing genetic testing. 

Naimah: That sounds like you’re empowering the leaders to advocate for healthcare and share this with their communities through this work. I wonder, Anna, is that something that you could do in the GRT community as well, like empower the leaders of the family to disseminate these healthcare messages, and how would we do that? 

Anna: Yeah, I think so. I think a lot of it would need to be outreach, and there are people out there who can help bridge that gap. For example, there’s a great team called Family Friends & Travellers, and if you get in contact with them and let them know which community you’d like to go into, they can help arrange, or they will come with you to go into that community. Because the GRT community, you know, is very mistrustful of anyone coming in, and rightly so. It was only in 2011 that they were included on the national census as an option to say you’re from that community, so I think there’s massive mistrust there of anyone coming into the community. 

So, if you want to engage the leaders of the families or of the communities, you’re going into a settled traveller site, there will usually be somebody who is in charge of that site, not officially, but maybe their family might be the biggest family or they might be the most important family. And there are people out there who will allow you to start to engage with that person, who can then disseminate the information. But it needs to be outreach care, and the information that you disseminate, it needs to be tailored to people who have left school at primary age, who don’t have the skills to read or write, or to manage appointments or read prescriptions, or have access to that type of healthcare. That’s where it really needs to be tailored. 

And I think confidentiality as well needs to be tailored a lot, because gossip and reputation and shame is huge in the GRT community, and if you are seen to be engaging with someone outside of the community, that is something that can bring a lot of shame to you and your family, so it needs to be handled really, really carefully. 

Naimah: Just to kind of go along with this theme of trust that you’ve all now mentioned, Moestak, I wonder if you could maybe comment on what strategies can healthcare organisations and researchers employ to build trust with these communities who have historically been underserved or mistreated? 

Moestak: Yeah, I think I mentioned earlier about the hierarchy of power around superiority and also mistrust of medical professional generally, and I touched there on how safeguarding concerns are triggered on not understanding cultural norms and practices within communities, and misconstruing that with safeguarding. There is generally that mistrust is there. And I think what Aman touched on there is really the importance of asset based approaches, and really building on transparent and really embedding transparent and inclusive practices from the onset. I mean, if we talk about coproduction, true coproduction is really creating a power balance where there’s no hierarchy. It’s an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve. 

And I think it’s important to embed those kind of approaches, and it’s Covid-19 – I mean, we took part in Bristol in King’s Fund research around the community champions model. It’s exactly that, about engagement, about community driving their own solutions, and being able to collectively collaborate, drive their health piece forward, but also increase the capacity of communities. We worked with clinicians who come from those communities, and it’s no surprise that the uptake of covid-19 vaccine increased as a result of working with those trusted voices.  

Quite often, those really effective programmes and engagement often are not funded adequately. They’re not sustained. And what happens is that we constantly are having to rebuild and restart, and that really does affect trust as well with communities. And when something works, why not build on it? And even now with that Covid-19 learning from the community champion model, the resource is not there anymore. It’s not valued anymore, sadly. That in itself is a risk, I think, in building the trust, but also the strength to continue that work and adapt in other ways around genomic medicine, and even increasing and diversifying the genomics data pool, helping communities understand and drive that. And that first responders project, communities being trained to capacity build and then being able to drive that within their communities, that’s the only way that we’re going to have effective strategies. 

Aman: I think adding onto what’s been mentioned, with regards to building trust, it’s really important to understand the motivations of communities, and to understand what messaging is going to resonate with different communities, and it’s going to be a different message for each community. You can’t have the same approach for all communities. A recurrent theme that I’ve come across when engaging different communities is this difference between messaging which is individualistic and then messaging which is about the community and more the collective message, and how that resonates a lot more with certain communities that I’ve engaged with, particularly within Muslim communities. And that’s something that I think is a bit untapped in regards to kind of any materials that are created, be it posters or videos or any content looking to reach out to communities. 

When we did some focus groups with some communities in Watford, who are primarily from the Pakistani community but also other parts of Asia in that region, the biggest response or biggest positive response that we got was when we posed the question, “If you were to know that people who look like you, from wherever your parents are, family may be from, would you be motivated to take part in that research?” And the biggest yes came on the back of that question. And that speaks to the fact that, “If I know that my family or my community, not just in the UK but abroad can benefit, then that would really motivate me and build trust that actually you’re not just here to benefit me as an individual, but you’re here to benefit my community as a whole, and therefore, yes, I’m going to be more trusting of this programme and be more motivated to take part.” 

Naimah: I just wanted to go briefly back, Moestak, you mentioned cultural norms, and I wanted to talk about the cultural norm in societies where maybe people may marry someone from the same ancestor, and what the societal fallout from these practices might be. 

Moestak: The stigma and the stereotypes often for communities comes from those beliefs and messages that are often sometimes not even backed up with scientific evidence. It can be seen as Islamophobic sometimes of Muslim communities that practice that. But also I think what’s important to understand is that concept around hereditary conditions and how that can determine one’s health, and it’s not really fully appreciated or desired. And so as a result, for example, a lot of people refuse to even have those early onset maternal testing for the foetus. My personal experience, I have three children, teenagers now, and I refused those tests as well, because my belief and my religious beliefs would kind of not align with being able to terminate a foetus if there were some genetic conditions. And so I think that is often not understood and made very clear to communities, and build on their beliefs and attitudes and values. And so those are the kind of cultural norms that are not fully understood. 

But also the opposite side of that actually around being able to prevent a good life for somebody or a bad life for somebody, and being able to prevent genetic conditions is also part of the religion on the flipside, but again it’s not creating that link. That cultural beliefs is not understood. I think also the community implications around the stigma. I mean, autism’s a big issue in the Samali community, and I remember years ago when I was working in education, we had a big issue around even acknowledgement of diagnosis and referrals, and it’s because of the stigma. Those perceptions do exist within communities that if someone has a genetic condition or ill health or a disease, it’s almost like being a black sheep in the community. And so it’s being able to build on those desires of the community wanting to be healthy and well, I think is not often understood. 

Naimah: And do you think it’s partly as well education of healthcare professionals to communicate in a really culturally sensitive way? 

Moestak: Yes, exactly, that’s exactly what it is. It’s missed opportunities really that we can build on. In that particular example of autism within the community, I was able to do a really positive piece of work with the community, and building on their interest and their skills, but using my own lived experience and understanding and knowledge, and being able to inform that within education sector but also the health sector, and providing that training and upskilling. And there is unfortunately a lack of diversity within the workforce if you look at the NHS. The lower level kind of cleaning and porter staff are ethnic minorities. And so it is about using those clinicians, as I mentioned earlier, that are coming from those communities are the forefront. 

We’ve recently had a really positive piece of work in Bristol around let’s talk about MMR, and we had a cohort of unvaccinated community, a Somali community, young people between the age of 16 to 25, and we worked with a Somali clinician, who led on that piece of work, and it was absolutely amazing. The young people as a result trusted her information and took up – but again also another thing that’s important is that a lot of data in the medical system is missing. I for one migrated here from the Netherlands, where I came there as a refugee at the age of three years old. My medical history is completely missing in both the UK records but also in the Netherlands, so I didn’t know if I had MMR vaccine. So, it’s a lot of gaps in information that people have, newly arrived communities that still need to constantly be updated and informed and education awareness raised with those communities. 

Naimah: Anna, I wonder if you wanted to add anything onto that point. 

Anna: It’s really difficult with that mistrust and sort of how closed the GRT community is to getting that information in, and I think to getting that information understood as well and to make it seem like it’s important. Because family is the most important thing, people are accepted the way that they are. You know, if we’re talking about autism, people are accepted the way that they are, and it is a bit like, you know, “There’s nothing wrong with my child, how dare you suggest that there is?” That testing isn’t done because the access to healthcare is so difficult, because people can’t register with GPs, because they can’t access maternity care, they can’t access postnatal care. Because they can’t register with the GP, they’re not on the system, and then the records don’t exist. Still now there’s birth records and death records that do not exist for these people within the communities, never mind medical history throughout their lives. 

Naimah: I think it really highlights a lot of gaps, doesn’t it? Aman, do you want to add anything to that question? 

Anna: Your opening remarks is that it’s a cultural norm in all societies, and we see even within the royal family in the UK, that it seems to be that any disparaging comments are targeted towards certain communities, and even then unfairly. I mean, often it’s associated with Muslim communities, but I would say the majority of Muslim communities don’t practice marrying someone from within the same ancestor. It’s certain cultural communities who do practice this. Having said that, even that practice shouldn’t be seen in a disparaging way, because it’s how those communities live their lives, and so we should be respectful of that and not speak in any way disparaging towards that community. And I think we have responsibility – ‘cos obviously nationally the conversation then moves onto increased risks of genetic disorders, and so we should be very matter of fact about what the percentage increase is when it comes to the likelihood of genetic disorders within families who marry with the same ancestor.  

Because what happens is, if we’re not very clear with what the actual facts are with regards to the increased risk of genetic order then even within the community which practices marrying someone from the same ancestor, that figure can be inflated, and so this perpetuates fear and perpetuates the stigma even more. Whereas if we are just matter of fact, “This is the increased risk of genetic disorders,” and leave it there, then the communities can decide and they’ll have a more informed position. I think the figures are an increase from two to six percent increase, but if you were to ask people within the community, “What’s the increase of genetic disorders if you’re marrying someone from the same ancestor?” they might think it’s 40 percent or 50 percent or a really high figure. So, that’s something that we need to work towards better understanding, which will lead to removal of that stigma as well. 

Anna: Again, that’s something that we see in the GRT community as well, there’s been research done by a woman called Sally Anne Lynch into cousin marriage within the Irish travelling community, and when they tested people, they found more than 90 genetic conditions that are present within people’s DNA within that community that just aren’t tested at birth. And I think, you know, you’re right, it’s something that is not talked about, because outside of these communities it’s seen as wrong and it’s not seen as something that’s normal. It’s seen as abnormal. But within this community, it is very normal and it’s very accepted. But then the testing isn’t done because of the access to healthcare. 

Naimah: I think it just seems like it does kind of boil down to education and educating healthcare professionals that it is kind of normal practices. Aman, did you want to add something else? 

Aman: Yeah, Anna made a really good point about testing. I think there’s something that is a gap in the service that we probably don’t provide more widely is that, when it comes to people who practice marriage within the same ancestor in other countries, testing is very normal. So, I know there’s many countries around the world where it’s very standard practice and even a requirement in certain countries that you must be tested before you get married, and so maybe that’s something that we can learn from in the UK. 

Moestak: I think it’s important to understand that some communities, decision making of consent is sometimes done by the head of the family, and I think that that is not fully understood as well, and often can be a barrier to participation. And I think that there’s an element of empowerness that is needed, particularly around women that need that empowerment model around consent of decision making around their testing and genetic testing, and just medical consent. 

Naimah: That’s an excellent point as well, thanks Moestak. 

So, I know we’ve touched on aspects of this already, but I wanted to finish on this question, how can meaningful community engagement foster trust and collaboration in genomic research and healthcare initiatives? 

Aman: I think one of the things that I would really improve is just awareness around genomic healthcare and genomics in general. It’s a learning curve that’s going to happen within communities at different rates, and we need to be mindful of this because that rate will determine also health inequities that are experienced by those communities as well. So, we need to make sure that we are adequately approaching all communities to the best of our abilities. Having said that, target maybe more resourcing and educational opportunities for communities which have been underrepresented in health research and in genomic health research as well primarily, so we need to sort of prioritise certain communities in regards to our community outreach, because then we’ll dispel any myths that people might have and work towards chipping away at the mistrust that certain communities may feel towards just healthcare in general, but more particularly about genomic healthcare, ‘cos genomic healthcare brings up some unique challenges and some unique perspectives within communities. 

So, there’s a number of fears about the future, but also misgivings about healthcare in the past as well that we need to acknowledge. So, by having community engagement initiatives, which are prioritised from the beginning and not just an afterthought, we can go a long way towards getting over some of the challenges of the past, but also not making new challenges for us in the future.  

Anna: I think as a whole, the UK has got a long way to go with building trust with the GRT community. I think it’s going to take some time. They still are one of the most marginalised communities. For example, in the area that I live, there was a GRT funeral going on a few weeks ago, and all the pub shut because they didn’t want GRT communities in their establishments, and there is no other community or minority that that would happen with now. So, I think there is still quite a long way to go to gain the trust of the GRT community. And in terms of healthcare, I think we need to go right back to the start and learn about these communities, and understand their cultures and their practices, and how they work without that judgement. Living a nomadic lifestyle is still criminalised. There needs to be a decriminalisation around these communities before we can even start to begin to work out how to go there and allow them to access healthcare and knowledge and information around genetic conditions, and around health and mental health.  

It’s going to be a very long road from here, but I think what we can start doing is to start that destigmatisation. If you are a doctor and somebody turns up in your surgery identifying as someone from the GRT community, understanding the background they come from, and not having all those prejudices, you know, which is very difficult to do, to get rid of those thoughts that you already have about someone. I think we need to make a real effort to start, and I think there needs to be changes within the NHS in order for people to access healthcare better. I think the resources that are given and the information that goes out needs to be more specifically tailored to these communities if that’s who you’re trying to engage with, because there’s so much that goes on in the community that’s not known outside of the community, and it’s not spoken about, and within different GRT communities as well. You know, there are different GRT communities all around the UK, and what goes on in them is not known to other GRT communities either.  

So, it’s about being specific with the information that you’re getting out, with who you’re actually targeting. And I think a bit like we were saying earlier, it’s the women, you know. The women have childcare responsibilities almost all of the time, and they are the ones who bring up the children, but they’re not necessarily the ones that make the decisions about the children or the child healthcare. You know, women are expected to do jobs in the morning. Women are not available before 11 o’clock in the morning. So, think about when you’re making appointments for. Think about when you’re going. I think it is going to be a long, long road before we get there, you know, with building trust and getting the information out there, but I think we can make a start. 

Naimah: Yeah, it does seem like there is lots of ways we can start tackling it slowly. Moestak, I wonder if you had anything you wanted to add. 

Moestak: As a public health specialist, you know, we’ve not been taught genomic medicine or genomic health at all in terms of how that can benefit and radically change the NHS and improve determinants of health, so that’s a massive gap of knowledge within the healthcare sector and professionals. But I think in terms of addressing the historic mistrust, I think there needs to be an acknowledgement and a real openness around the historic, you know, abuse and unethical practices that have existed within health. There are other countries that are much more advanced in that and really embedding that within communities through pledges. That long-term kind of piece of work for me is missing. You know, it’s that wider education piece that’s missing that needs to be really embedded in the culture. 

But I think also investing in the infrastructure in the community. Like far too often, if the long-term vision is not there, communities are reluctant to get involved and have trust within that, so I think that’s an important part as well. And I think it’s also about demonstrating the benefits of genomic medicine. I think that needs to be done in a community level way, through storytelling. I know that there’s now a lot of development around cancer treatments around genomics, but I think it’s about having those people who have those lived experiences from different communities to be able to share the benefits and demonstrate that through their way, and being appropriately reimbursed as well. I think that’s really important. 

I think generally, I think there’s a long way we’ve got to go. I’ll never forget when I went to Vancouver on a conference around health, and there was a lot of reconciliation there, where there was really acknowledgement, and the indigenous communities there that have a lot of health disparities were able to kind of overcome some of that and start building as a community and addressing tackling health inequalities because that trust was built and that acknowledgement from high up, from government level, all the way trickled down to local. I think also patient centred approaches around – like we mentioned, we talked about linking the cultural norms and the values and the beliefs that people have, and the skills and the assets that they have to be able to lead on these solutions themselves, that really needs to be embedded to build trust.  

Aman touched on the perception around what could be done with genomic data. I don’t know if Aman wants to elaborate a bit on that, but that’s really important. It’s a big barrier. It’s how do we create transparent ways of storing data, but also use various ways of communication. It doesn’t have to be traditional reports. It could be through podcasts. It could be like community messaging.  

Naimah: Yeah, I think that’s a really important point. Aman, did you want to come in on that? 

Aman: Yeah, I think sharing the stories of the past in an appropriate setting, in an appropriate manner as well – ‘cos it’s a bit of a double edged sword, ‘cos you don’t want to scare people who are unfamiliar with these stories, but at the same time there’s a moral responsibility for all of us involved in this space to speak about these issues, one from the perspective of acknowledging what’s happened in the past, so then people feel like, “Okay, you’re not trying to hide anything here,” but from the perspective of also that we need to make sure that we don’t repeat some of the mistakes in the future, and that as people involved in genomic healthcare and involved in this space, that we’re cognisant of these misgivings in the past, and we’re cognisant of our responsibility to safeguard communities in the future. 

Naimah: Okay, so we’re going to wrap up there. Thank you so much to our guests, Anna Smith, Aman Ali and Moestak Hussein for joining me today as we discussed the barriers to access to genomic medicine for diverse communities, and the impact it has on these communities. If you’d like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

Vivienne Parry, Professor Bill Newman, Anita Hanson and Professor Matt Brown: Can genomic testing prevent adverse drug reactions?

Pharmacogenomics plays a critical role in personalised medicine, as some adverse drug reactions are genetically determined. Adverse drugs reactions (ADRs) account for 6.5% of hospital admissions in the UK, and the application of pharmacogenomics to look at an individuals response to drugs can significantly enhance patient outcomes and safety.

In this episode, our guests discuss how genomic testing can identify patients who will respond to medications and those who may have adverse reactions. We hear more about Genomics England's collaboration with the Medicines and Healthcare products Regulatory Agency in the Yellow Card Biobank and our guests discuss the challenges of implementing pharmacogenomics into the healthcare system.

Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Anita Hanson, Research Matron and the Lead Research Nurse for clinical pharmacology at Liverpool University Hospitals NHS Foundation Trust, and Professor Bill Newman, Professor of translational genomic medicine at the Manchester Center for Genomic Medicine, and Professor Matt Brown, Chief Scientific Officer at Genomics England.

 

"I think we’re moving to a place where, rather than just doing that one test that might be relevant to one drug, we’d be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it’s required, so that they’re not waiting for the results of a genetic test, it’s immediately within their healthcare record."

 

You can watch this video learn more about Jane's lived experience with Stevens-Johnson syndrome, on The Academy of Medical Sciences' (AMS) YouTube channel. The story, co-produced by Areeba Hanif from AMS, provides an in-depth look at Jane's journey.

Want to learn more about personalised medicine? Listen to our Genomics 101 episode where Professor Matt Brown explains what it is in less than 5 minutes: Genomics 101: What is personalised medicine? 

You can download the transcript or read it below.

Vivienne: Hello and welcome to Behind the Genes. 

Bill: What we’ve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They’ve been easier to identify and there’s a clear relationship between some drugs and some genetic changes where that information is useful. So, a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you’re given that treatment, then you can end up on intensive care and die, so it’s a really significant side effect. But as you say, the most common side effects aren’t necessarily fatal, but they can have a huge impact upon people and on their wellbeing. 

Vivienne: My name’s Vivienne Parry and I’m head of public engagement at Genomics England, and today we’ll be discussing the critical role of pharmacogenomics in personalised medicine, highlighting its impact on how well medicines work, their safety, and on patient care. I’m joined today by Professor Bill Newman, professor of translational genomic medicine at the Manchester Centre for Genomic Medicine, Anita Hanson, research matron, a fabulous title, and lead research nurse for clinical pharmacology at the Liverpool University Hospital’s NHS Foundation Trust, and Professor Matt Brown, chief scientific officer for Genomics England. And just remember, if you enjoy today’s episode, we’d love your support, so please like, share and rate us on wherever you listen to your podcasts. 

So, first question to you, Bill, what is pharmacogenomics? 

Bill: Thanks Viv. I think there are lots of different definitions, but how I think of pharmacogenetics is by using genetic information to inform how we prescribe drugs, so that they can be safer and more effective. And we’re talking about genetic changes that are passed down through families, so these are changes that are found in lots of individuals. We all carry changes in our genes that are important in how we transform and metabolise medicines, and how our bodies respond to them. 

Vivienne: Now, you said pharmacogenetics. Is it one of those medicine things like tomato, tomato, or is there a real difference between pharmacogenetics and pharmacogenomics? 

Bill: So, people, as you can imagine, do get quite irate about this sort of thing, and there are lots of people that would contest that there is a really big important difference. I suppose that pharmacogenetics is more when you’re looking at single changes in a relatively small number of genes, whereas pharmacogenomics is a broader definition, which can involve looking at the whole genome, lots of genes, and also whether those genes are switched on or switched off, so the expression levels of those genes as well would encompass pharmacogenomics. But ultimately it’s using genetic information to make drug prescription safer and more effective. 

Vivienne: So, we’re going to call it pharmacogenomics and we’re talking about everything, that’s it, we’ll go for it. So Matt, just explain if you would the link between pharmacogenomics and personalised medicine. And I know that you’ve done a big Genomics 101 episode about personalised medicine, but just very briefly, what’s the link between the two? 

Matt: So, personalised medicine’s about using the right dose of the right drug for the right individual. And so pharmacogenomics helps you with not only ensuring that you give a medication which doesn’t cause problems for the person who receives it, so an adverse drug reaction, but also that they’re actually getting the right dose. Of course, people’s ability to metabolise, activate and respond to drugs genetically is often genetically determined, and so sometimes you need to adjust the dose up or down according to a person’s genetic background. 

Vivienne: Now, one of the things that we’ve become very aware of is adverse drug reactions, and I think they account for something like six and a half percent of all hospital admissions in the UK, so it’s absolutely huge. Is that genetically determined adverse drug reactions? 

Matt: So, the answer to that is we believe so. There’s quite a bit of data to show that you can reduce the risk of people needing a hospital admission by screening genetic markers, and a lot of the very severe reactions that lead to people being admitted to hospital are very strongly genetically determined. So for example, there are HLA types that affect the risk of adverse drug reactions to commonly used medications for gout, for epilepsy, some HIV medications and so on, where in many health services around the world, including in England, there are already tests available to help prevent those leading to severe reactions. It’s likely though that actually the tests we have available only represent a small fraction of the total preventable adverse drug reactions were we to have a formal pre-emptive pharmacogenomics screening programme. 

Vivienne: Now, I should say that not all adverse drug reactions are genetic in origin. I mean, I remember a rather nasty incident on the night when I got my exam results for my finals, and I’d actually had a big bee sting and I’d been prescribed antihistamines, and I went out and I drank rather a lot to celebrate, and oh my goodness me, I was rather ill [laughter]. So, you know, not all adverse drug reactions are genetic in origin. There are other things that interact as well, just to make that clear to people. 

Matt: Yes, I think that’s more an interaction than an adverse drug reaction. In fact frankly, the most common adverse drug reaction in hospitals is probably through excess amounts of water, and that’s not medically determined, that’s the prescription. 

Vivienne: Let me now come to Anita. So, you talk to patients all the time about pharmacogenomics in your role. You’ve been very much involved in patient and public involvement groups at the Wolfson Centre for Personalised Medicine in Liverpool. What do patients think about pharmacogenomics? Is it something they welcome? 

Anita: I think they do welcome pharmacogenomics, especially so with some of the patients who’ve experienced some of the more serious, life threatening reactions. And so one of our patients has been doing some work with the Academy of Medical Sciences, and she presented to the Sir Colin Dollery lecture in 2022, and she shared her story of having an adverse drug reaction and the importance of pharmacogenomics, and the impact that pharmacogenomics can have on patient care. 

Vivienne: Now, I think that was Stevens-Johnson syndrome. We’re going to hear in a moment from somebody who did experience Stevens-Johnson’s, but just tell us briefly what that is. 

Anita: Stevens-Johnson syndrome is a potentially life threatening reaction that can be caused by a viral infection, but is more commonly caused by a medicine. There are certain groups of medicines that can cause this reaction, such as antibiotics or anticonvulsants, nonsteroidal anti-inflammatories, and also a drug called allopurinol, which is used to treat gout. Patients have really serious side effects to this condition, and they’re often left with long-term health complications. The morbidity and mortality is considerable as well, and patients often spend a lot of time in hospital and take a long time to recover.  

Vivienne: And let’s now hear from Jane Burns for someone with lived experience of that Stevens-Johnson syndrome. When Jane Burns was 19, the medicine she took for her epilepsy was changed. 

Jane: I remember waking up and feeling really hot, and I was hallucinating, so I was taken to the Royal Liverpool Hospital emergency department by my parents. When I reached A&E, I had a temperature of 40 degrees Celsius. I was given Piriton and paracetamol, and the dermatologist was contacted. My mum had taken my medication to hospital and explained the changeover process with my epilepsy medication. A decision was made to discontinue the Tegretol and I was kept in for observation. Quite rapidly, the rash was changing. Blisters were forming all over my body, my mouth was sore and my jaw ached. My temperature remained very high. It was at this point that Stevens-Johnson syndrome, or SJS, was diagnosed. 

Over the next few days, my condition deteriorated rapidly. The rash became deeper in colour. Some of the blisters had burst, but some got larger. I developed ulcers on my mouth and it was extremely painful. I started to lose my hair and my fingernails. As I had now lost 65 percent of my skin, a diagnosis of toxic epidermal necrolysis, or TEN, was made. Survivors of SJS TEN often suffer with long-term visible physical complications, but it is important to also be aware of the psychological effects, with some patients experiencing post-traumatic stress disorder. It’s only as I get older that I realise how extremely lucky I am to have survived. Due to medical and nursing expertise, and the research being conducted at the time, my SJS was diagnosed quickly and the medication stopped. This undoubtedly saved my life. 

Vivienne: Now, you’ve been looking at the development of a passport in collaborating with the AMS and the MHRA. Tell me a bit more about that. 

Anita: Yes, we set up a patient group at the Wolfson Centre for Personalised Medicine approximately 12 years ago, and Professor Sir Munir Pirmohamed and I, we wanted to explore a little bit more about what was important to patients, really to complement all the scientific and clinical research activity within pharmacogenomics. And patients recognised that, alongside the pharmacogenomic testing, they recognised healthcare professionals didn’t really have an awareness of such serious reactions like Stevens-Johnson syndrome, and so they said they would benefit from having a My SJS Passport, which is a booklet that can summarise all of the important information about their care post-discharge, and this can then be used to coordinate and manage their long-term healthcare problems post-discharge and beyond. And so this was designed by survivors for survivors, and it was then evaluated as part of my PhD, and the findings from the work suggest that the passport is like the patient’s voice, and it really does kind of validate their diagnosis and raises awareness of SJS amongst healthcare professionals. So, really excellent findings from the research, and the patients think it's a wonderful benefit to them. 

Vivienne: So, it’s a bit like a kind of paper version of the bracelet that you sometimes see people wearing that are on steroids, for instance. 

Anita: It is like that, and it’s wonderful because it’s a handheld source of valuable information that they can share with healthcare professionals. And this is particularly important if they’re admitted in an emergency and they can’t speak for themselves. And so the passport has all that valuable information, so that patients aren’t prescribed that drug again, so it prevents them experiencing a serious adverse drug reaction again.  

Vivienne: So, Stevens-Johnson, Bill, is a really scary side effect, but what about the day to day benefits of pharmacogenomics for patients? 

Bill: So, what we’ve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. They’ve been easier to identify and there’s a clear relationship between some drugs and some genetic changes where that information is useful. So a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if you’re given that treatment, then you can end up on intensive care and die, so it’s a really significant side effect. But as you say, the most common side effects aren’t necessarily fatal, but they can have a huge impact upon people and on their wellbeing.  

And it’s not just in terms of side effects. It’s in terms of the effectiveness of the medicine. Because if a person is prescribed a medicine that doesn’t or isn’t going to work for them then it can take them longer to recover, to get onto the right medicine. That can have all sorts of detrimental effects. And so when we’re thinking about introducing pharmacogenetics more broadly rather than just on a single drug or a single gene basis, we’re thinking about that for common drugs like antidepressants, painkillers, statins, the drugs that GPs are often prescribing on a regular basis to a whole range of patients. 

Vivienne: So, to go back to you, Anita, we’re really talking about dose here, aren’t we, whether you need twice the dose or half the dose depending on how quickly your body metabolises that particular medicine. How do patients view that? 

Anita: Well, the patient in question who presented for the Academy of Medical Sciences, I mean, her take on this was, she thinks pharmacogenetics is wonderful because it will allow doctors and nurses to then prescribe the right drug, but also to adapt the dose accordingly to make sure that they get the best outcome, which provides the maximum benefit while also minimising any potential harm. And so from her perspective, that was one of the real benefits of pharmacogenomics. But she also highlighted about the benefits for future generations, the fear of her son taking the same medicine and experiencing the same reaction. And so I think her concerns were, if we have pharmacogenetic testing for a panel of medicines, as Bill mentioned then, then perhaps this would be fantastic for our children as they grow up, and we can identify and predict and prevent these type of reactions happening to future generations. 

Vivienne: And some of these drugs, Bill, are really very common indeed, something like codeine. Just tell us about codeine, ‘cos it’s something – whenever I tell this to friends [laughter], they’re always completely entranced by the idea that some people don’t need nearly as much codeine as others. 

Bill: Yeah, so codeine is a drug that’s very commonly used as a painkiller. To have its real effect, it needs to be converted in the body to a different drug called morphine, and that is done by an enzyme which is made by a gene called CYP2D6. And we all carry changes in CYP2D6, and the frequency of those variants, whether they make the gene work too much or whether they make it work too little, they vary enormously across the world, so that if you go to parts of Africa, about 30 percent of the population will make more of the CYP2D6, and so they will convert the codeine much more quickly, whereas if you go to the UK, maybe up to ten percent of the white population in the UK just won’t be converting codeine to morphine at all, so they won’t get any benefit from the drug. So at both ends, you have some people that don’t respond and some people that respond a little bit too much so that they need either an alternative drug or they need a different dose. 

Vivienne: So, all those people who say, you know, “My headache hasn’t been touched by this painkiller,” and we say, “What a wimp you’re being,” actually, it’s to do with genetics. 

Bill: Yeah, absolutely. There’s a biological reason why people don’t – not for everybody, but for a significant number of people, that’s absolutely right, and we can be far more tailored in how we prescribe medication, and get people onto painkillers that work for them much more quickly. 

Vivienne: And that’s so interesting that it varies by where you come from in the world, because that means we need to give particular attention – and I’m thinking, Anita, to working with patients from different community groups, to make sure that they understand the need for pharmacogenomics. 

Anita: I think that’s really important, Vivienne, and I think we are now having discussions with the likes of Canada SJS awareness group, and also people have been in touch with me from South Africa because people have requested the passport now to be used in different countries, because they think it’s a wonderful tool, and it’s about raising awareness of pharmacogenomics and the potential benefits of that, and being able to share the tools that we’ve got to help patients once they’ve experienced a serious reaction. 

Vivienne: So, pharmacogenomics clearly is important in the prevention of adverse drug reactions, better and more accurate prescribing, reduced medicines wastage. Does this mean that it’s also going to save money, Bill, for the NHS? 

Bill: Potentially. It should do if it’s applied properly, but there’s lots of work to make sure that not only are we using the right evidence and using the right types of tests in the laboratory, but we’re getting the information to prescribers, so to GPs, to pharmacists, to hospital doctors, in a way that is understandable and meaningful, such that they can then act upon that information. So, the money will only be saved and then can be reused for healthcare if the whole process and the whole pathway works, and that information is used effectively. 

Vivienne: So, a lot of research to make sure that all of that is in place, and to demonstrate the potential cost savings. 

Bill: Yes. I mean, there are very nice studies that have been done already in parts of the world that have shown that the savings that could be accrued for applying pharmacogenetics across common conditions like depression, like in patients to prevent secondary types of strokes, are enormous. They run into hundreds of millions of pounds or dollars. But there is an initial investment that is required to make sure that we have the testing in place, that we have the digital pathways to move the information in place, and that there’s the education and training, so that health professionals know how to use the information. But the potential is absolutely enormous. 

Vivienne: Matt, can I turn now to the yellow card. So, people will be very familiar with the yellow card system. So, if you have an adverse reaction, you can send a yellow card in – I mean, literally, it is a yellow card [laughter]. It does exactly what it says on the tin. You send a yellow card to the MHRA, and they note if there’s been an adverse effect of a particular medicine. But Genomics England is teaming up with the MHRA to do something more with yellow cards, and we’re also doing this with the Yellow Card Biobank. Tell us a bit more. 

Matt: So, yellow card’s a great scheme that was set up decades ago, initially starting off, as you said, with literally yellow cards, but now actually most submissions actually come online. And it’s important to note that submissions can come not just from healthcare providers, but majority of submissions actually come from patients themselves, and that people should feel free, if they feel they’ve had an adverse drug reaction, to report that themselves rather than necessarily depending on a medical practitioner or the healthcare provider to create that report. So, Genomics England is partnering with the MHRA in building what’s called the Yellow Card Biobank, the goal of which is to identify genetic markers for adverse drug reactions earlier than has occurred in the past, so that we can then introduce genetic tests to prevent these adverse drug reactions much sooner than has occurred previously.  

So, what we’re doing is basically at the moment we’re doing a pilot, but the ultimate plan is that in future, patients who report a serious adverse drug reaction through the Yellow Card Biobank will be asked to provide a sample, a blood sample, that we then screen. We do a whole genome sequence on it, and then combine these with patients who’ve had like adverse drug reactions and identify genetic markers for that adverse drug reaction medication earlier, that can then be introduced into clinical practice earlier. And this should reduce by decades the amount of time between when adverse drug reactions first start occurring with medications and us then being able to translate that into a preventative mechanism. 

Vivienne: And will that scheme discover, do you think, new interactions that you didn’t know about before? Or do you expect it to turn up what you already know about? 

Matt: No, I really think there’s a lot of discovery that is yet to happen here. In particular, even for drugs that we know cause adverse drug reactions, mostly they’ve only been studied in people of European ancestry and often in East Asian ancestry, but in many other ancestries that are really important in the global population and in the UK population, like African ancestry and South Asian ancestries, we have very little data. And even within Africa, which is an area which is genetically diverse as the rest of the world put together, we really don’t know what different ethnicities within Africa, actually what their genetic background is with regard to adverse drug reactions. 

The other thing I’d say is that there are a lot of new medications which have simply not been studied well enough. And lastly, that at the moment people are focused on adverse drug reactions being due to single genetic variants, when we know from the model of most human diseases that most human diseases are actually caused by combinations of genetic variants interacting with one another, so-called common disease type genetics, and that probably is similarly important with regard to pharmacogenomics as it is to overall human diseases. That is, it’s far more common that these are actually due to common variants interacting with one another rather than the rare variants that we’ve been studying to date. 

Vivienne: So, it’s a kind of cocktail effect, if you like. You know, you need lots of genes working together and that will produce a reaction that you may not have expected if you’d looked at a single gene alone. 

Matt: That’s absolutely correct, and there’s an increasing amount of evidence to show that that is the case with medications, but it’s really very early days for research in that field. And the Yellow Card Biobank will be one of many approaches that will discover these genetic variants in years to come. 

Vivienne: Now, Matt’s a research scientist. Bill, you’re on the frontline in the NHS. How quickly can this sort of finding be translated into care for people in the NHS? 

Bill: So, really quickly is the simple answer to that, Viv. If we look at examples from a number of years ago, there’s a drug called azathioprine that Matt has used lots in some of his patients. In rheumatology, it’s used for patients with inflammatory bowel disease. And the first studies that showed that there was a gene that was relevant to having bad reactions to that drug came out in the 1980s, but it wasn’t until well into this century, so probably 30-plus years later that we were routinely using that test in clinical medicine. So, there was an enormous lot of hesitancy about adopting that type of testing, and a bit of uncertainty. If you move forward to work that our colleague Munir Pirmohamed in Liverpool has done with colleagues in Australia like Simon Mallal around HIV medicine, there was this discovery that a drug called abacavir, that if you carried a particular genetic change, that you had a much higher risk of having a really severe reaction to that. The adoption from the initial discovery to routine, worldwide testing happened within four years.  

So, already we’ve seen a significant change in the appetite to move quickly to adopt this type of testing, and I see certainly within the NHS and within other health systems around the world, a real desire to adopt pharmacogenetics into routine clinical practice quickly and at scale, but also as part of a broader package of care, which doesn’t just solely focus on genetics, but thinks about all the other parts that are important in how we respond to medication. So, making sure we’re not on unusual combinations of drugs, or that we’re taking our medicine at the right time and with food or not with food, and all of those other things that are really important. And if you link that to the pharmacogenetics, we’re going to have a much safer, more effective medicines world. 

Vivienne: I think one of the joys of working at Genomics England is that you see some of this work really going into clinical practice very fast indeed. And I should say actually that the Wolfson Centre for Personalised Medicine, the PPI group that Anita looks after so well, they’ve been very important in recruiting people to Yellow Card Biobank. And if anyone’s listening to this, Matt, and wants to be part of this, how do they get involved? Or is it simply through the yellow card? 

Matt: So at the moment, the Yellow Card Biobank is focusing on alopurinol.  

Vivienne: So, that’s a medicine you take for gout. 

Matt: Which I use a lot in my rheumatology clinical practice. And direct acting oral anticoagulants, DOACs, which are used for vascular disease therapies and haemorrhage as a result of that. So, the contact details are available through the MHRA website, but I think more importantly, it’s just that people be aware of the yellow card system itself, and that if they do experience adverse drug reactions, that they do actually complete a report form, ‘cos I think still actually a lot of adverse drug reactions go unreported. 

Vivienne: I’m forgetting of course that we see Matt all the time in the Genomics England office and we don’t think that he has any other home [laughter] than Genomics England, but of course he still sees some patients in rheumatology clinic. So, I want to now look to the future. I mean, I’m, as you both know, a huge enthusiast for pharmacogenomics, ‘cos it’s the thing that actually, when you talk to patients or just the general public, they just get it straight away. They can’t think why, if you knew about pharmacogenomics, why you wouldn’t want to do it. But it’s not necessarily an easy thing to do. How can we move in the future, Bill, to a more proactive approach for pharmacogenomics testing? Where would we start? 

Bill: Yes, so I think we’ve built up really good confidence that pharmacogenetics is a good thing to be doing. Currently, we’re doing that predominantly at the point when a patient needs a particular medicine. That’s the time that you would think about doing a genetic test. And previously, that genetic test would only be relevant for that specific drug. I think we’re moving to a place where, rather than just doing that one test that might be relevant to one drug, we’d be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when it’s required, so that they’re not waiting for the results of a genetic test, it’s immediately within their healthcare record. That’s what we’d call pre-emptive pharmacogenetic testing, and I think that’s the golden land that we want to reach. 

Vivienne: So for instance, I might have it on my NHS app, and when I go to a doctor and they prescribe something, I show my app to the GP, or something pops up on the GP’s screen, or maybe it’s something that pops up on the pharmacist’s screen. 

Bill: I think that’s right. I think that’s what we’re looking to get to that point. We know that colleagues in the Netherlands have made some great progress at developing pathways around that. There’s a lot of public support for that. And pharmacists are very engaged in that. In the UK, the pharmacists, over the last few years, have really taken a very active role to really push forward this area of medicine, and this should be seen as something that is relevant to all people, and all health professionals should be engaged with it. 

Vivienne: And on a scale of one to ten, how difficult is it going to be to implement in the NHS? 

Bill: So, that’s a difficult question. I think the first thing is identifying what the challenges are. So I have not given you a number, I’ve turned into a politician, not answered the question. So, I think what has happened over the last few years, and some of our work within the NHS Network of Excellence in pharmacogenetics and some of the other programmes of work that have been going on, is a really good, honest look at what it is we need to do to try to achieve pharmacogenetics implementation and routine use. I don’t think the challenge is going to be predominantly in the laboratory. I think we’ve got phenomenal laboratories. I think we’ve got great people doing great genetic testing. I think the biggest challenges are going to be about how you present the data, and that data is accessible. And then ensuring that health professionals really feel that this is information that isn’t getting in the way of their clinical practice, but really making a difference and enhancing it, and of benefit both to the healthcare system but more importantly to the patients. 

Vivienne: Now, when I hear you both talk, my mind turns to drug discovery and research, and Matt, I’m quite sure that that’s right at the top of your mind. Tell us how pharmacogenomics can help in drug discovery and research. 

Matt: So, pharmacogenomics, I think actually just genetic profiling of diseases in itself just to start off with is actually a really good way of identifying new potential therapeutic targets, and also from derisking drug development programmes by highlighting likely adverse drug reactions of medications that are being considered for therapeutic trials, or targets that are being considered for therapeutic development. Pharmacogenomics beyond that is actually largely about – well, it enables drug development programmes by enabling you to target people who are more likely to respond, and avoid people who are more likely to have adverse drug reactions. And so that therapeutic index of the balance between likely efficacy versus likely toxicity, genetics can really play into that and enable medications to be used where otherwise they might have failed. 

This is most apparent I think in the cancer world. A classic example there, for example, is the development of a class of medications called EGFR inhibitors, which were developed for lung cancer, and in the initial cancer trials, actually were demonstrated to be ineffective, until people trialled them in East Asia and found that they were effective, and that that turns out to be because the type of cancers that respond to them are those that have mutations in the EGFR gene, and that that’s common in East Asians. We now know that, wherever you are in the world, whether you’re East Asian or European or whatever, if you have a lung adenocarcinoma with an EGFR mutation, you’re very likely to respond to these medications. And so that pharmacogenomic discovery basically rescued a class of medication which is now probably the most widely used medication for lung adenocarcinomas, so a huge beneficial effect. And that example is repeated across multiple different cancer types, cancer medication types, and I’m sure in other fields we’ll see that with expansive new medications coming in for molecularly targeted therapies in particular. 

Vivienne: So, smaller and more effective trials rather than larger trials that perhaps seem not to work but actually haven’t been tailored enough to the patients that are most likely to benefit. 

Matt: Yeah, well, particularly now that drug development programmes tend to be very targeted at specific genetic targets, pharmacogenetics is much more likely to play a role in identifying patients who are going to respond to those medications. So, I think many people in the drug development world would like to see that, for any significant drug development programme, there’s a proper associated pharmacogenomic programme to come up with molecular markers predicting a response. 

Vivienne: We’re going to wrap up there. Thank you so much to our guests, Bill Newman, Anita Hanson, Matt Brown, and our patient Jane Burns. Thank you so much for joining us today to discuss pharmacogenomics in personalised medicine, and the benefits, the challenges and the future prospects for integrating pharmacogenomics into healthcare systems. And if you’d like to hear more podcasts like this, please subscribe to Behind the Genes. It’s on your favourite podcast app. Thank you so much for listening. I’ve been your host, Vivienne Parry. This podcast was edited by Bill Griffin at Ventoux Digital and produced by the wonderful Naimah. Bye for now. 

Sarah Wynn, Emma Baple, Lindsay Pearse and Naimah Callachand: How has a groundbreaking genomic discovery impacted thousands worldwide?

In this episode, we delve into the impact of the new groundbreaking research uncovering the RNU4-2 genetic variant linked to neurodevelopmental conditions. The discovery, made possible through whole genome sequencing, highlights a genetic change in the RNU4-2 gene that affects about 1 in 200 undiagnosed children with neurodevelopmental conditions, making it more prevalent than previously thought. This discovery represents one of the most common single-gene genetic causes of such conditions.

Our host, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Lindsay Pearse who shares her journey through the diagnosis of her son Lars. They are also joined by Sarah Wynn, CEO of Unique, and Emma Baple, Clinical Genetics Doctor and Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub.

We also hear from the 2 research groups who independently discovered the findings:

• Dr Andrew Mumford, Professor of Haematology at the University of Bristol
  • Link to the research paper: Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders 
• Assistant Professor Nicky Whiffin, Big Data Institute and Centre for Human Genetics at the University of Oxford
  • Link to the research paper: De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

To access resources mentioned in this podcast: 

• Unique provides support, information and networking to families affected by rare chromosome and gene disorders - for more information and support visit Unique's website.
• Connect with other parents of children carrying a variation in RNU4-2 on the RNU4-2 Facebook group.

 

"I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future."

 

You can download the transcript or read it below.

Naimah: Welcome to Behind the Genes.

Lindsay: So, this feeling that like we’ve been on this deserted island for eight years and now all of a sudden, you’re sort of looking around through the branches of the trees. It’s like, wait a minute, there are other people on this island and in this case actually there's a lot more people on this island. Yeah, it’s very exciting, it’s validating. It gives us a lot of hope and, you know, it has been quite emotional too and also a bit of an identity shift. Being undiagnosed had become quite a big part of our identity, and so now that’s kind of shifting a little bit that we have this new diagnosis and are part of a new community.

Naimah: My name is Naimah Callachand and I’m Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m joined by Lindsay Pearse whose son Lars recently received a genetic diagnosis, made possible by research using data from the National Genomic Research Library, Sarah Wynn CEO of Unique, and Emma Baple, a clinical genetics doctor. Today we’ll be discussing the impact of recent research findings which have found a genetic change in the non-coding RNU4-2 gene, to be linked to neurodevelopmental conditions. If you enjoy today’s episode, we’d love your support. Please like, share and rate us on wherever you listen to your podcasts.

Naimah: And first of all, I would like everyone to introduce themselves. So, Lindsay, maybe if we could come to you first.

Lindsay: Great, thank you. So, thank you for having me. I’m Lindsay Pearse, I live outside of Washington DC and I’m a mum to 3 boys. My oldest son Lars who is 8, he was recently diagnosed with the de novo variant in the RNU4-2 gene.

Naimah: Thank you. And Emma?

Emma: My name is Emma Baple. I’m a Clinical Genetics Doctor which means I look after children and adults with genetic conditions. I’m also a Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub.

Naimah: And Sarah?

Sarah: Hi, thank you for having me. I’m Sarah Wynn, I’m the CEO of a patient organisation called Unique, and we provide support and information to all those affected by rare genetic conditions.

Naimah: Great, thank you. It’s so great to have you all here today. So, first of all Lindsay, I wonder if we could come to you. So, you mentioned in your introduction your son Lars has recently been diagnosed with the de novo variant. I wondered if you could tell us a bit about your story, and what it’s been like up until the diagnosis.

Lindsay: Sure, yeah. So, Lars is, he’s a wonderful 8 year-old boy. With his condition, his main symptoms he experiences global developmental delays, he’s non-verbal. He’s had hypertonia pretty much since birth and wears AFO’s to support his walking. He has a feeding disorder and is fed by a G-Tube. Cortical vision impairments, a history of seizures and slow growth, amongst other things.

So, that's just a bit of a picture of what he deals with day to day. But he’s my oldest child, so first baby. When I was pregnant, we were given an IUGR diagnosis. He was breech, he had a hernia soon after birth, wouldn’t breastfeed. But all of these things aren’t terribly uncommon, you know. But once he was about 3 or 4 months old, we noticed that he wasn’t really able to push up like he should, and we were put in touch with early intervention services for an assessment. So, we went ahead and did that when he was about 4 or 5 months old. And as parents, we could just kind of tell that something was off from the assessors. And, you know, they were very gentle with us, but we could just get that sense that okay, something is off, and they’re worried here.

So, that kind of kickstarted me into making appointments left, right and centre with specialists. The first specialist that we saw was a neurologist. And yeah, again, that's another appointment that I’ll never forget. She referred us to genetics and to get an MRI and some lab work but at the end of the appointment, she said to us, ‘Just remember to love your child.’ And, you know, that was quite shocking to us at the time because it wasn’t something that had ever crossed our mind that we wouldn't do or felt like we needed to be told to do this. But on the other hand, it certainly set off a lot of worry and anxiety of okay, well, what exactly are we dealing with here?

So, fast forward, we saw genetics and that was about when Lars was about 8 months old. We went through a variety of genetic testing, a chromosomal micro-array, a single gene testing, then the whole exome testing. Everything came back negative, but it was explained to us that what was going on was likely an overarching genetic diagnosis that would explain his like, multi-system symptoms.

And so meanwhile as he was getting older his global delays were becoming more pronounced and we were also in and out of the hospital a lot at this time. At first, he was in day care and, you know, any sort of cold virus would always turn into like a pneumonia for him. So, we were just in and out of hospital seeing a myriad of specialists, trying to put together this puzzle of what's going on and it was really hard to accept that nobody could figure it out. That was just, you know, sort of mind-blowing to us I guess. So, we applied for and were accepted into the Undiagnosed Diseases Programme at the National Institute of Health over here. The NIH as it’s commonly referred to. So, we first went there when Lars was 2. He was one of their youngest patients at the time. But that was a really great experience for us because we felt like they were looking at him holistically and across a bunch of all of his systems, and not just seeing a specialist for sort of each system. So, we really appreciated that.

We also did the whole genome sequencing through this research study. Although that also came back negative and so at that point, we were told to kind of keep following up symptomatically. Keep seeing the specialists and eventually maybe one day we’ll find an overarching diagnosis, but that science just hadn’t quite caught up to Lars. It was hard for me again to believe that and to sort of wrap my head around that. But certainly, it was an education from all of the doctors and geneticists and everyone we saw at NIH, to realise like how far there still was to go in terms of genetic research. How it wasn’t also that uncommon to be undiagnosed in the rare disease community. I would say that being undiagnosed sort of became part of our identity. And it’s, you know, it was something that, you know, you had to explain to like insurance companies and to his school, and it became part of our advocacy around him. Because without being able to say oh, it’s this specific thing and if it was someone who hadn’t met Lars before, trying to explain to them that, you know, yeah, within the range of this community you can be undiagnosed, and they just haven’t found it yet, but I promise you there is something going on here.

And I’d say the other thing too without a diagnosis you have no prognosis, right? And so, trying to figure out what the future would look like. Also, family planning. We waited 5 and a half years before we had another child and, you know, it was certainly an anxiety ridden decision. Ultimately after seeing as many specialists as we possibly could, we still were left with the same answer of well, we just don’t really know if it will happen again. So, that was a big decision to make. But again, it just kind of became part of our identity and something that you did eventually accept. But I would say in my experience I feel like the acceptance part also of Lars’ disabilities perhaps took me a little bit longer. Because again, I didn’t have a prognosis, so I didn’t exactly know what we were dealing with. Only as he has become older and, you know, you’re sort of getting a better sense of what his abilities might be than being able to understand, okay, this is what I’m dealing with. I need to accept that and do what I can to care for him and our family in the best way that we can.

Naimah: Thanks so much for sharing that, Lindsay. I feel like you’ve touched on a lot of really, you know, a lot of complications and difficulties for your family. Especially, you know, with regards to keeping hopeful and things about the prognosis as well, I’m sure it was really difficult. You’ve mentioned that Lars was able to be diagnosed recently due to recent research efforts. So, Sarah, I wonder if you can tell us a bit more about these and what the findings have meant for patients with neurodevelopmental conditions.

Sarah: Yes. So, I think we know that there are lots of families that are in Lindsay and Lars’ position where they know that there is almost certainly an underlying genetic condition, and it just hasn’t been found yet. And so, I think we know that lots of researchers are working really hard to try and find those causes. I think over time we know that as time goes on and research goes on, we’ll find more of these new genetic causes for neurodevelopmental conditions. I think particularly as we start to look at regions of the genome that we haven’t looked at so much so far. But I think one of the things that's really extraordinary about this one is that actually it turns out to be much more common than we might have expected, for one of these new conditions that we haven’t found before. But I think it’s about one in 200 of those undiagnosed children with neurodevelopmental conditions, have this diagnosis so that's not a small number. That's not a rare finding at all actually, that's much more common than we could ever have anticipated.

But I think one of the things that we do know is that as we look further and deeper into that genomic sequence, so, we’ve started off looking at the bits of the sequence that are genes that code for proteins. This changes in a gene that actually doesn’t code for protein, so it’s less obvious that it would be important but clearly it is important in development because we know when it has a spelling mistake in it, it causes this neurodevelopmental condition. But there will be as researchers look more and more at these kinds of genes, and also the other part of the genome that is not genes at all, we’ll find out more and more the underlying genetic causes of these neurodevelopmental conditions.

I think it’s also really important to stress why this is so important to find these genetic changes and it’s because families really need a diagnosis. Lindsay talked quite eloquently and a lot about that knowing something was off and really wanting to know the reason why. Getting these diagnoses might change care management or treatment, but actually really importantly it just gives an answer to families who have often been looking for an answer for a really long time.

Naimah: I just wanted to go back to the point that Sarah made that actually this genetic change is relatively common. Emma, I wondered if you could tell us a bit more about maybe why it took us so long to discover it?

Emma: That's an interesting question actually. I suppose the sort of slightly simplified answer to that question is we haven’t been able to sequence the whole of a person’s genetic information for that long. And so, children like Lars would have had, as Lindsay described lots and lots of genetic tests up until they had a whole genome sequencing which is what Sarah was talking about. The types of tests that we had up until the whole genome sequencing wouldn't have allowed us to look at that bit of the genetic code where this RNU4-2 gene can be found. So, we can only really find that using whole genome sequencing. So, before that existed, we wouldn't have been able to find this cause of developmental condition.

Naimah: Okay, thanks Emma.

Naimah: Now we’re going to hear from one of the two research groups who are responsible for these research findings. First of all, let’s hear from Nicky Whiffin.

(Clip - Nicky Whiffin)

Naimah: How were the findings possible using the Genomics England dataset?

Nicky: So, most previous studies have only looked at genetic variants that, in genes that make proteins, but only a subset of our genes actually do makes proteins. The Genomics England dataset we have sequencing information on the entire genome, not just on these protein coding genes and that means we can also look at variants in other genes. So, those that make molecules other than proteins. And RNU4-2 for example, makes an RNA molecule.

Naimah: These findings translated to direct patient benefit for patients like Lars who were able to receive support from Unique. How does this demonstrate the value of the dataset?

Nicky: Yes. So, it was incredible that we could find so many patients with RNU4-2 variants so quickly. This was enabled by access to Genomics England data but also to other large sequencing datasets around the world. So, we worked with people in the US, in Australia and also in mainland Europe. These large datasets enabled us to spot consistent patterns in the data and by looking across multiple datasets we can also make sure that our findings are robust. When we realised how significant this was and how many families would be impacted, we very quickly contacted Sarah at Unique to see if we could direct patients to them for support.

(End of clip)

Emma: There's one thing I wanted to raise. It’s important to recognise the way that was discovered was through the National Genomic Research Library that Genomics England hosts. To highlight the value of that, and the value of having this centralised resource where families have been kind enough really to allow their data to be shared with some limited clinical information that allowed these researchers to be able to pull this out. And I think it highlights the power of the National Health Service in that we were able to create such a resource. It’s really quite astounding that we’ve found such a common cause of a rare genetic condition, and it wouldn't have happened in the same timescale or in this way without that resource. And then to just say that as Sarah talked about the fact that we’ve been able to get that information out there, also the researchers were able to get out there and contact the NIH and all of these other programmes worldwide. In Australia, America, everywhere in the world and quickly identify new patients who had this condition and get those diagnoses out really rapidly to people.

But all that came from that power of sharing data and being able to have that all in one place and making it accessible to very clever people who could do this work and find these answers. It’s so important for families like Lindsay’s, and all the families in England and around the world that have got these answers. So, I guess it’s a big plug for the value of data sharing and having a secure place where people feel that it’s trusted and safe, that enables these diagnoses to be made.

Lindsay: If I could just echo that, we’re so grateful that that exists in the UK. Just acknowledging like the privilege here that we have had to be able to, I mean for our family in the US, that we’ve been able to, you know, get ourselves into the NIH study and into the study at Children’s National. That takes a lot of work. I feel like not everybody has that opportunity to be able to spend the time to do these applications and to go to all the appointments and get the testing done and have the insurance to cover it. So, very grateful that the system exists in a way in the UK that made this sort of research possible. I just hope that that can be replicated in other places, and also to what Emma was saying earlier, come up with a lower cost test as well for this to further the growth of the community and of course then the corresponding research.

Sarah: I think firstly we have to sort of thank all of those families that took part and do share their data, because I think it’s not always clear why you might want to do that as a family. I think this is really a powerful example of the benefit of that. I also think the data sharing goes one stage further. So, it’s partly about getting the diagnosis, but the data sharing going forward about how this condition impacts families, both clinically and sort of day to day lived experience, is how we’ll be able to learn more about these conditions. And so, when families get this diagnosis next week or next year, not only will they get a diagnosis, but they’ll get a really good idea about what the condition is and how it might impact their child.

Naimah: And Lindsay, coming back to you. So, we’ve talked about, you know, what it meant for your family before the diagnosis, but what has it meant to have a diagnosis and how did you feel? And what happened whenever you received the diagnosis?

Lindsay: Sure. Lars was again part of the NIH Undiagnosed Diseases Research study. So, once you attend this programme and if you are not diagnosed like at the end of your stay, they keep your details on file and you’re part of this database at the NIH Undiagnosed Diseases Programme. So, if you’re undiagnosed after your sort of week-long work up, your samples stay within the research programme. We were also part of a research programme at Children's National Medical Centre, the Rare Disease Institute. So, our samples were sort of on file there in their database as well.

And so, at the end of March I was really quite shocked to receive a call from our long time and trusted geneticist at Children’s National that they had found a diagnosis. It was quite emotional. I really kind of didn’t believe it. I just kept asking, you know, ‘Are you sure? Is this it?’ you know, ‘How confident are we?’ Because I think in my head, I sort of always thought that we would eventually find a diagnosis, but I thought that Lars would be, you know, a 30- or 40-year-old adult. I thought it would be decades from now. Like I felt like for whatever reason we had to wait decades for the science to sort of catch up to him.

So, we were very, very grateful. It felt very validating, I guess. I had always kind of had this intuition feeling that we were sort of missing something and it’s more that the science just hadn’t quite caught up yet. But, you know, it was validating to know that okay, Lars is not the only person in the entire world with this, it is something that is relatively common in fact within the rare disease community. That is also very exciting to me personally because I’m hopeful that that will lead more researchers to be interesting in this, given how, quote on quote, common it is. I’ve sort of been describing it as like a mass diagnosis event but also more so this feeling that like we’ve been on this deserted island for eight years and now all of a sudden, you’re sort of like looking around through the branches of the trees. It’s like, wait a minute, there are other people on this island ad in this case, there's actually a lot more people on this island.

Yeah, it’s very exciting, it’s validating. It gives us a lot of hope. And, you know, it has been quite emotional too and also a bit of an identity shift. Because I spoke earlier about how like being undiagnosed had become quite a big part of our identity. So, now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. But yeah, we’re just very grateful that the research had continued. And, you know, I think sometimes you sort of have this feeling of okay, our files are up on a shelf somewhere, you know, collecting dust and are people really looking at them? And actually, it turns out that the research was ongoing and yeah, we’re just very grateful for that.

Naimah: Thanks so much for sharing, Lindsay. It sounds like it’s been a real rollercoaster of emotions for your family and I’m glad to hear that, you know, you’ve got some hope now that you’ve got a diagnosis as well. So, moving onto the next question. Emma, I wanted to ask you then, how will these findings improve clinical diagnostic services for those for neurodevelopmental conditions?

Emma: So, you asked me earlier about why it had taken so long to find this particular cause of neurodevelopmental condition, and I gave you a relatively simple answer. The reality is one of the other reasons is that almost eight out of ten children and adults who have RNU4-2 related neurodevelopmental condition have exactly the same single letter spelling change in that gene. So, actually that in itself means that when researchers are looking at that information, they might think that it’s actually a mistake. Because we know that when we sequence genetic information, we can see mistakes in that sequencing information that are just because the machine has, and the way that we process that data, it’s not perfect. So, sometimes we find these little mistakes and they’re not actually the cause of a person’s problems, they’re just what we call an artefact or an issue with the way that that happens.

So, that is part of the reason for why it was tricky for us to know whether this was, or rather the researchers to know whether this was or was not the cause of this particular condition. But that in itself is quite helpful when we think about how we might identify more people who have this going forwards. Because unlike in Lars’ case where we didn’t know what the cause was and so we were still searching, and we didn’t know where to look in the billions of letters that make up the genetic code to find that answer, we now know that this is really very common. It’s unbelievably common. I think we didn’t think we would be finding a cause of a rare genetic condition that was this commonly occurring at this stage. But the fact that it’s just a single, it’s commonly this one single change in the gene means that we can set up pretty cheap diagnostic testing. Which means that if you were somewhere where you wouldn't necessarily have access to whole genome sequencing, or a more comprehensive testing in that way, we could still be able to pick up this condition. And it’s common enough that even if you didn’t necessarily recognise that a person had it, you could still have this as part of your diagnostic tool kit for patients who have a neurodevelopmental condition. It’s common enough that just doing a very simple test that could be done in any diagnostic lab anywhere in the world, you would be able to identify the majority of people who have this.

Naimah: Now let’s hear from the other research group who are responsible for these findings. Here is Dr Andrew Mumford.

(Clip - Dr Andrew Mumford)

Naimah: Why are these research findings significant?

Andrew: It offers genetic diagnosis not just for a handful of families but potentially for many hundreds of families, who we all know have been searching often for many, many years for a genetic diagnosis. But actually, there are other gains from understanding how this gene causes neurodevelopmental disorder. We know that there's GRNU4-2 in codes, not a protein actually, but a small nuclear RNA which is unusual for rare, inherited disorders. It’s a component of a very complicated molecule called the spliceosome which in turn regulates how thousands of other genes are regulated, how they’re made into proteins. So, fundamentally this discovery tells us a lot about the biology of how the spliceosome works. We already know that some other components of the spliceosome can go wrong, and result in diseases like neurodevelopmental disorders. This gives us an extra insight and actually opens the door to, I hope, a whole load of more discoveries of genetic diagnosis possible from other components of this complicated molecule.

Naimah: Your research group used a mathematical modelling approach. Can you tell me a bit about this, and what this means for other rare conditions, Andrew?

Andrew: So, identifying relationships between changes in individual genes and different kinds of rare, inherited disease is notoriously difficult because of the volume of data that's involved and the need to be absolutely certain that observed genetic changes are actually the cause of different rare, inherited disease. So, applying statistics to that kind of problem isn’t new. But what my collaboration group have achieved here, is to develop, actually developed some years ago a completely new approach to applying statistics to genetic data. We call that BeviMed and we’ve been working for many years on the genes in code that make individual proteins. Most rare disorders are caused by genetic changes in genes that make proteins.

What this discovery comes from is actually we’ve applied the BeviMed statistical technique to genes that don’t make proteins, they’re non-coding genes. For example, genes that make small nuclear RNA, it’s just like RNU4-2. What's unusual about the BeviMed approach is that it’s very sensitive to detecting links between genetic changes and rare diseases, and it can detect statistical associations really driven by very, very small numbers of families.

So, we apply it to datasets like the 100,00 Genomes dataset and identify associations using statistics that have got a very high probability of association. Other members of the team then seek to corroborate that finding by looking at if we can see the association in other datasets, and we certainly achieve that with RNU4-2. But also, assessing biological plausibility by investigating what we understand already about in this case, a small nuclear RNA, and how it can possibly result in a disease. And we normally try and employ other independent evidence such as experimental investigation. Or going back to our families and asking for additional data to help really test this sort of theory that changes in this particular gene have resulted in a problem with neurodevelopment.

(End of clip)

Naimah: Emma, are there any other ways that we can identify these conditions based on their clinical presentation?

Emma: So, Lindsay and I were talking with you just yesterday, wasn’t it? And I asked Lindsay about what sorts of things Lars had in common with other children and adults who have been diagnosed with this condition? I actually think Lindsay probably gives a better summary than I would, so I might ask you to maybe repeat what you said to me yesterday. But the bit of it that really stood out to me was when you said to us that a lot of parents have said, ‘I'm not sure how we weren’t all put together in the first place because you notice so many things that were in common.’ So, maybe if you can give that summary and then I can translate that back into medical terms, if that’s okay Lindsay.

Lindsay: Sure, of course. Yeah, it been again, kind of mind blowing, some of the similarities. Especially as we’ve exchanged pictures and such, and baby pictures especially where some of the children like look like siblings. So, definitely some similarities in facial features, you know, everyone seems to experience some of the slow growth, so a short stature or quite skinny. There's feeding issues also that seem to be quite common. Also, you know, things like the global developmental delays, that's certainly across the board and histories of seizures, that's also quite common. Some people have experienced also some, like, bone density issues, that's not something that we’ve experienced so far, but that also seems to be quite common.

But then also, behaviourally, there's a lot of similarities which has been, I think, quite exciting to a lot of us because you’ve always thought okay, so this is just my child. And of course, some of that is true but it’s also interesting to find out some of these other things that are, you know, are quite similar. So, a lot of people have mentioned their child having, like, an interesting sense of humour. Kind of like a very slapstick sense of humour which is quite interesting. Or everyone seems to love water, everybody loves swimming pools and bathtime, and all of that. Lars loves a windy day. Something about the wind, he just loves it and plane noises and things like that have also come up with other people. So, yeah, it’s been really interesting and cool to see.

Emma: So, I guess Lindsay’s sort of very beautifully summed up what is written in the research publication. So, there's only two research publications so far on this condition, it’s all really new. And I am definitely not claim to be a clinical expert on this condition, and I don't think there are any yet. It will take people time to see lots of children and adults who have this particular condition. But ultimately what Lindsay summarised was the common clinical features that have been described by parents. In my job as a clinical genetics doctor, part of what we look at is a person’s appearance. So, Lindsay described the photographs of children particularly when they were little, looked very similar. In the photographs that I’ve seen, I would agree with that. And so obviously those children look like their mum and dad, but they have other features that are in common. They have a characteristic appearance and that helps doctors like me to have an idea as to whether a child or an adult might have a particular condition.

Then put together with the sorts of information that Lindsay gave us around the low tone, so being a little bit floppier particularly when they’re little. The slow growth and growth problems, problems with eating, also with seizures. Those are all common things that were pulled out of both of the two research publications on this condition and putting that all together into one picture helps doctors to have an idea whether somebody may have a particular condition. That would help us in this case to potentially request that simple test I was talking about, if maybe we were practicing in a part of the world where we wouldn't have the resources that we thankfully do have in the United Kingdom, and in the USA.

Naimah: So, Sarah, just coming to you next. How does this research spread awareness and help other patients with these conditions?

Sarah: So, I think one of the things that's been really great about research now is that we are able to, you know, social media and things like that mean that we can spread this information really quickly across the world basically. I think what that does is that as well as helping bring people together that they’ve got this diagnosis, what it does is I think it provides hope for all of those people that Lindsay was talking about at the beginning who don't have a diagnosis. So, that piece around people are still looking, the researchers are working hard and that even if you don't have a diagnosis today you might get one in the future. Lindsay talked about your sample being dusty and not being looked at. I think it gives lots of families, not just those that get this diagnosis but all of those that haven’t got a diagnosis, hope, that hopefully in the future they will get a diagnosis.

I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future. That prognosis information that Linsday said is really missing when you don't have a diagnosis. And I think the other thing that hopefully is the next stage in this journey with this discovery is that those two science publications that Emma talked about, what we will want to do here at Unique working with the researchers and those families that have got a diagnosis, is to produce a patient family friendly information leaflet about this condition.

One of the things we know is really important about those patient leaflets is including the photos. Because as both Emma and Lindsay have said that idea that they have facial features in common. And so, if you look at a leaflet and you can recognise your child in it, and you can see others that look like it, that can be a really sort of quite heartwarming experience in what often is a lonely experience with a rare condition.

Naimah: And I think kind of on that point about it being a lonely experience, I wondered Lindsay if you could talk a bit more if this research has allowed you to connect with other parents and families who have received a diagnosis, and what impact that's had on your family?

Lindsay: Yeah. I mean, and I think everything that Sarah has said was spot on. It’s wonderful to have resources like Unique to connect families and have those diagnoses on the platform, so other clinicians can look for it and sort of grow this group. I think that has definitely been the highlight of getting this diagnosis at this stage, right. Because there's not much more you can do with it, with someone so brand new so being able to connect with the other families has been wonderful. One amazing mum who with this diagnosis set up a Facebook group, RNU4-2 Family Connect. And, you know, it’s just been amazing to see people from all over the world joining this as they receive this diagnosis, you know, sharing their stories. We’ve spent countless hours on the weekends over the past couple of months on Zoom calls with total strangers, but just you find that you can just talk for hours and hours because you have so much in common.

It’s great to see what has worked well for other families and, you know, what has not worked. Sharing resources, just kind of all learning together. Also seeing the spectrum of this diagnosis, I think most genetic disorders have a spectrum and this seems to be the same here. So, that's been very interesting. And of course, our son is 8, Lars is 8. There's now a 33-year-old and a 29-year-old in the Facebook group. Speaking for me personally it’s just amazing to see them and like it’s very cool to see where they’re at. That sort of helps you answer some of those questions about that before were quite unknown when you were thinking about the future. Obviously, everybody’s development whether you have a genetic disorder or not, it is going to be what it’s going to be, and everybody is going to do their own thing. But being able to see what a path might look like is just so helpful. And, you know, we all want community and connection, and so this has been really, really great to have that now.

Sarah: I don't think there's much more that I can add because Lindsay articulated so well. But it’s really heartwarming for us to hear the benefits of those connections because that's really why Unique and other support groups exist. Is to provide, partly to provide information, but I think predominantly to put families in touch with other families so that they can find a new home and connect and share experiences. And, you know, stop feeling as alone as they might have done before.

Naimah: Okay, we’ll wrap up there. Thank you to our guests, Lindsay Pearce, Sarah Wynn and Emma Baple for joining me today as we discussed the research findings which found a genetic change in the RNU4-2 gene which has been linked to neurodevelopmental conditions. If you’d like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.

Dr Rich Scott and Helen White: How can we work in partnership towards a new era of genomic medicine and research?

Genomics has changed considerably over the past 10 years, and we are now exploring how to integrate it into routine healthcare. In this episode, our guests reflect on this evolution and discuss how the key learnings from the past 10 years can shape the genomics ecosystem of the future. They highlight the importance of partnership across teams, organisations and participants, emphasising the importance of keeping participant and patient benefit at the heart of research, whilst also addressing the ethical and safe storage of patient data.

In this episode, our host, Helen White, who is the Participant Panel Vice-Chair for cancer at Genomics England, speaks with Dr Rich Scott, CEO of Genomics England.

 

"There’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care."

 

You can download the transcript or read it below.

Helen: Welcome to Behind the Genes. 

Rich: There’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care. 

Helen: My name is Helen White and I am the Participant Panel Vice Chair for Cancer, at Genomics England. On today’s episode I’m joined by Dr Richard Scott, Chief Executive Officer for Genomics England. And today we’ll be discussing Richard’s recent appointment as CEO, lessons learnt from the last ten years in the evolution of genomics in healthcare, and how these learnings will be taken forward in the next ten years. And we’ll also visit the importance of keeping participant and patient benefit at the heart of research, as well as the ethical and safe storage of patient data. If you enjoy today’s episode we would love your support: please like, share and rate us on wherever you listen to your podcast.  

Before we dive into the interview with Rich, I wanted to take a moment to share my story and tell you a little bit about myself. I have been a member of the Participant Panel at Genomics England since 2018. It was the year before that when I was diagnosed with endometrial, or womb cancer, and was offered the chance to join the 100,000 Genomes Project, which felt like something positive at what was otherwise quite a scary time. It turns out that I have something called Lynch syndrome, that’s a genetic condition that increases my chance of developing certain cancers, particularly womb and bowel cancer, which is actually a really useful thing to know as there are things I can do to reduce my chance of getting cancer; things like having regular colonoscopies and taking daily aspirin. I have now been on the participant panel for six years and one year ago I was appointed as Vice Chair for cancer. This is a new and developing role and I am excited to have so far helped recruit more people with lived experience of cancer to the panel and to be assisting Genomics England with connecting to organisations that advocate for people whose lives have been touched by cancer.  

So that’s enough about me. I am delighted to be joined today by Richard Scott, and I am very much looking forward to our conversation. Welcome, Rich.  

Thank you. So Rich, you’ve recently been appointed CEO of Genomics England. Can you tell me a bit about your background and what brought you to this role?  

Rich: It’s a really good question and it’s one that doesn’t have a really very simple answer. I guess what it boils down to is I guess I’ve always had an interest, even as a child, for whatever reason, in genetics and genomics. I have also then always been drawn to things where I can have an impact and particularly the impact in healthcare and that’s what took me to being a medical student. And I guess it’s that combination of that particular interest in genetics and being able to see, even when I was at medical school I qualified in 2000 that this was an area of medicine that was going to be really important in the future. And then as I trained, as I did a PhD and as I saw the technology develop and change and then when I saw the UK government and the NHS investing in genomics in a really foresighted way, I found myself eight or nine years sitting at Great Ormond Street as a consultant in clinical genetics where I still practice, I still do one clinic a month there as a clinical genetics consultant seeing families with rare conditions.  

But I could see when Genomics England was established that this was something, as I said, really foresightful where we could really collectively across the country make more of a difference together in terms of patient and healthcare outcomes. So I joined GEL eight or nine years ago initially in a subject matter expert role, and really found myself the more time it passed, understanding how working in my role at GEL and helping GEL be a really productive part of what is a busy genomics healthcare ecosystem in the UK, we can make a big difference, and that’s the thing that just wakes me up in the morning, is realising how much there is left to do, being proud of the stuff we’ve done, the difference we’ve made to participants in our programmes already, but realising that many of those still need our support to do better and the big distance left to go before we really deliver on I think the long-term promise of genomics, and I feel my mixture of skills and experience make me really excited to be in the middle of that.  

Helen: Thank you. Yes, it sounds like you’ve brought many skills and experience, and interesting to hear that as a child you already had that interest in genetics and where that’s taken you. Can you tell me what being CEO Genomics England means for you? What are your aspirations for your first year in this position?  

Rich: Well, I guess, as you can tell, I’m really excited to take on this role. As I said, as a doctor I’m always focused on the impact for patients and our participants and ultimately it’s the broader health of the nation. And the role I see Genomics England playing and being able to play in the future, sort of building on that, the leadership position the UK’s always had in genomics – you know if you look back to the discovery of the structure of DNA, the invention of sequencing technologies and also the clinical implementation coming from that government investment and the NHS investment, what excites me most about GEL is that we can be there, playing a critical role alongside others in that ecosystem, whether that’s in the NHS, whether it’s our participants and the patients who we’re aiming to support academia and industry, to create a whole that’s greater than the sum of the parts, and I genuinely feel that the UK remains uniquely placed to live out that potential that genomics has, engaging in the questions, not just you know, the scientific questions of: what could genomics test for? Or, how could this be implemented and is it cost-effective? 

But also being able to have the nuanced conversation of what we all and our participants in the public and general, expect in terms of the care we receive or how our data is looked after, and getting that really balanced view on how we chart a path forwards where we can really see big differences being made in the future, and I think always being honest to ourselves about where we are today and that things don’t come in spotting some position a long time in the future that we want to navigate to, but also being really focused on the here and now and what is possible and what is evidenced, and what the next set of evidence or discussions or conversations in the public we need to have to help navigate ourselves there and that’s where at the moment our focus at Genomics England is both being very clear sighted on where Genomics could go, and also thinking very clearly about where we are today, and so very much at the moment for us it’s about focusing on the life service we offer to the NHS and we’re really proud to be part of a world-leading whole genome sequencing service, the first national health service in the world to be providing that in the context of cancer and rare disease, and so offering and providing our service that contributes to that.  

Supporting researchers so that we can keep the flow of discoveries coming and also for example, making sure that our participants in existing programmes continue to get new answers as the science evolves. So, the last year more than 2,000 families had new findings fed back because of new knowledge that’s accumulating, keeping that flow going. And then we’ve got three big research initiatives going on at the moment where we’re really focusing on delivering around them. We’ve got a diverse data initiative where we’re really focused on making sure the research library, the National Genomic Research Library, our participants are representative of the UK population, so the discoveries that we’re supporting are relevant to everyone; our cancer initiative which is exploring the use of new sequencing technology in the context of cancer, and also looking at the use of image data and other modalities of data, alongside generic data to drive new discoveries.  

And then the third initiative is our newborn genomes programme, where we’re asking a big question through a research study to generate evidence to ultimately answer the question: should every baby when they’re born be offered whole genome sequencing? Most pressingly to improve and broader the range of conditions that we can look for that are severe and treatable. So, this year we’re very much focused on delivering on those promises that we’ve made to our participants and our partners and through those programmes and very much with an eye to the future thinking about what we need to change in terms of the use of underpinning technology, so that we know that we’ve got the potential to scale, to think about the broader use of genomics in years to come as evidence evolves.  

Helen: So Rich, there have been many advances in genomics in the last ten years. What do you think are the big lessons from those last ten years, and what do you think the next ten years will look like for the genomics ecosystem, what impact will this all have on healthcare as we know it?  

Rich: So, genomics has changed extraordinarily in the last ten years thanks to shifts both in the technology, particularly the sequencing technology but also some of the computing technology that’s there to deal with the scale of data. Ten years ago we were talking about the 100,000 genomes project and beginning the project itself, but it was still very early in the use of whole genome sequencing, that’s gone from something where the big question around the 100,000 genomes project was: can this technology be used in routine care in cancer and for rare conditions, and if so, how do we do that?  

And we’ve learnt both I think about that specific question and as I mentioned, we’re enormously proud to be part of enabling the NHS whole genome sequencing clinical service, so that has entered routine care. I think along the way the biggest lesson for me is actually one about this being about partnership and about working as a team across many different organisations and with our participants, and recognising that this isn’t just about one set of questions, or it’s not just about clinical or scientific questions, it’s about joining everything up together back to that point around, so a discussion about what people expect – this is about doing stuff together and learning often quite complex lessons about practicalities is one things, for example, one of the really big lessons we learnt around the use of whole genome sequencing in cancer are just practical lessons about handling of tissue samples and the need to make sure the right fridges are available on the right corridor of a hospital, with plugs available to plug them into, through to questions around, as I say, people’s expectations around how their data is stored, which it’s used for, which again there’s really strong precedent for, and as we explored, different uses of genomic technology, we shouldn’t just take those previous answers for granted, we need to make sure we validate and check with people what their expectations are.  

So I think that’s the big one for me is sort of the number of different angles with which one explores questions and the fact that this is very much about doing it together. I think just one other piece which is so easy for us here to take for granted is that doing things at national scale with national scale investment from government, from other funders and from the NHS is absolutely critical and when you look across the world, we are in an extraordinarily privileged position here in this country because of that investment and because that investment recognises the need critically to join clinical care and research in a whole, where you recognise that you’re doing multiple things at once, but joining them up rather than them being two worlds, is really, really critical, and we’re really lucky to be able to do that at national scale.  

So then thinking about what the next ten years might look like for the genomics ecosystem, I think lots of those things continue, so I think national scale and the need for ongoing investment to keep up our position at the forefront in terms of answering these big questions about the use of genomics in healthcare, and to where the evidence supports their implementation to roll them out and keep that link there between healthcare and research, and so making sure the systems talk to each other and I mean that in a digital sense as well as a human sense is absolutely critical.  

And then, so in ten years’ time what are the areas of healthcare that will have been impacted, or could have been impacted by genomics, I’m really pleased that we’re doing a better job for families with rare conditions and people with cancer than we were ten years ago, I think there’s a long distance left to run even in those settings for us to do better and to continue to learn, so we expect our major focus to continue to be in those areas where we know they can have an impact and there’s more to do. We also then have the different areas where if the evidence pans out to support the use of genomics or if we can implement systems that can support it there can be a big sort of area of growth. For example, our newborn genomes programme is asking questions and developing evidence so that in the future policymakers can decide should that become part of routine care, and I think that’s something that could have become part of routine care in the next ten years if the evidence supports it and if that’s something that the public support.   

If I were to pick one other area where there’s a real potential for growth in the coming handful of years it’s in something we refer to as pharmacogenomics. What that means is looking at your DNA code (genomics) to help make decisions about prescription of medicines and sometimes that’s about avoiding these medicines in people who are at a higher risk of having an adverse reaction, or it’s about tailoring the dose because of something about for example the way the person metabolises, chews up, the medicine and so can influence how much dose they need. That actually has an enormous potential; we all have variations in our DNA code that influence how we respond to or metabolise medicines. If you look across primary care, GPs and so forth, primary care physicians and in secondary care, hospital care, I think there’s good evidence that actually probably half of all appointments, interactions in those settings, if you were to have DNA data available that could influence how prescription choices are made; sometimes that’s about knowing that you’re doing the right thing, giving the normal prescription, but sometimes it's about modifying it, that’s an area where I think there’s a real potential for growth and that’s an area that the NHS also really recognise and we’re exploring ways in which we might look into that and think about how that might be implemented, because actually a lot of the questions there are about how you make sure the right data, the right information is available to clinical teams and patients at the time that prescriptions are being made.  

There’s also real potential more broadly in thinking about more common disease settings, there’s lots of work going on from various research studies looking at the value of what people sometimes refer to as polygenic risk scores or integrated risk scores, where we use genomics as an element of estimating risk for common diseases like heart disease or cancer, that’s something where the evidence is being worked on and is developing, I think we’ll see a lot of evidence come out in the coming years and I think that will then influence how we implement genomics to help as part of that risk estimation process, which is routine now in GP practices where you go for an NHS health-check they do it with lots of complicated stuff, at the moment not genomics, and we’ll see how that plays out in the years to come.  

So I think there’s enormous room for growth where genomics where at the moment it’s making an important difference to people with certain conditions that we can do better on. In the future I see it becoming very much more part of the routine day to day of healthcare. As we make that transition there’s lots to work through about the evidence, the order in which that’s done and the way in which we, for example, store data, and make people part of the choice about how their data is used and what I’m really excited about in Genomics England is the role we play in the middle of that, bringing our particular expertise around what we call bioinformatics, which is sort of managing genomic data at big scale, particularly national scale to support healthcare and research, generating evidence that can help inform policy, and also critically drawing things together into the conversation amongst different players in the ecosystem and participants in the public so that we can not just think about evidence in a sort of terribly scientific way but we think about it in the round.  

Helen: That’s really interesting to hear you speak a lot about getting that evidence because that’s critical, but that takes a long time doesn’t it, so for example with the generation study, the newborn study it’s really important to measure the benefits of that if you’re testing young babies, newborn babies for diseases that if you pick up a condition that condition can be treated and something can be done about it early rather than poor parents going through this diagnostic odyssey, but also it’s that balance isn’t it with not leading to any harm, so if a number of parents come out of that thinking their baby might get a condition and it never happens there’s potential there isn’t there. But I think in terms of the public understanding of how long it takes to get evidence and everything else that needs to go on in the background I don’t think it’s always particularly clear that that’s a massive process that has to be gone through and there’s a lot of work going on behind the scenes – you can’t just do these things.  

I think as patients/members of the public we’re eager to get on and for change to happen and things to be better but it’s a big, big process, but also good to hear that you talk about it being a collaborative approach, it’s not just Genomics England, it’s the NHS, it’s members of the public and patient voices, it’s other organisations working in partnership, it’s a big undertaking.  

Rich: No, it is and I think that one of the words you used there was impatience, and I think that’s healthy and important to recognise, it can be easy, particularly for example as a doctor, sat in a clinic room to accept the status quo, and at the same time, one needs to recognise the complexity of the questions, the balance, the need to generate high-quality evidence to inform those opinions and I think combining both that sort of impatience and dissatisfaction with the status quo, and that mind-set about thinking really thoroughly and collaboratively about the right evidence that is needed to change policy.  

Helen: Yes, really important that those patient voices are there from the beginning, from the planning of obtaining this evidence and that you’re measuring the things that matter most.  

Rich: One of the areas where I think we’ve seen that play out, another area where I really see the potential for growth in the future is much more genomics-enabled treatments. We and you and the participant panel have helped us think about there’s a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer and thinking as we do that about how we structure the system to generate evidence and to respond to it and have a conversation about what the right balance of evidence for patients to make a choice about their own care, but also policymakers to make choices about funding, decisions and safety decisions, is really important and we’ve been supporting to a wider work in cancer in the UK called the Cancer Vaccine Launchpad, and likewise we’re part of something we call the Rare Therapies Launchpad, where in those two areas we’re exploring that, and that’s another area I think of real potential in the coming years, and also real nuance as we construct a way of navigating that together and making the most of the potential, but not just sort of rushing in and pretending we know all of the answers at the outset.  

Helen: And those launchpads are of particular interest to participants in the wider patient population, there are a lot of people and children with rare, ultra-rare conditions who are desperate for treatments that just aren’t available right now, equally for cancer patients there’s a big need isn’t there for more effective treatments, fewer side effects, that target that person’s particular cancer, so it’s good news I think for the wider public.  

It does seem that innovation and partnerships are crucial to Genomics England’s activities so how does Genomics England ensure that participant and wider patient benefit are at the heart of these activities?  

Rich: I think one of the really important things is actually governance is sometimes a boring word, sounds like it, but I think thinking about how we’ve structured the organisation and placed you, as the participant panel, as part of our governance to make sure that when we’re thinking about for example access to data in the National Genomic Research Library, participants are sort of driving those decisions, it’s an independent committee that makes those decisions with representation from our panel. One of the things is thinking about the governance and making sure that you as our participant panel hold us to account for the decisions that we’re making, which I think is really critical. 

I think then also as we’ve learnt a lot over the years, not always getting it right, about how we make sure that participants, or potential participants in the public are involved from the outset in the design of programmes because it always helps. I think certainly before I joined Genomics England I think I would have been unsure about the best ways of going about that and that brings with it sometimes a nervousness. I think the main advice I would say to people listening is to have confidence that just getting stuck in and have conversations is the way to do it. There are then also all sorts of expertise that we’ve really benefited from being to bear in terms of ways of doing that engagement work and that will come; the first thing is to have the confidence and the desire to put that at the centre of how you decide where your focus should be and how you design programmes.  

Helen: I think Genomics England has been very successful with that by integrating that patient voice from the very early days and here we are what eight years on I think now, and yes, hopefully we’ll be there for some time to come yet, as long as Genomics England exists.

So Rich, with more and more health data being stored, how do we ensure that this sensitive personal data is stored and used safely and ethically across the genomics ecosystem. And actually while we’re on this question, can you just explain what genomics ecosystem means, because we use that term I think quite a lot, but I think it’s not necessarily understandable to the wider public?

Rich: What I mean when I talk about it is I mean the mixture of different people, whether that’s sometimes organisations, us, Genomics England, the NHS, the NIHR, National Institute for Health Research; industry partners whether they’re people who are from pharma companies or from biotech, academic researchers, participants in programmes – everyone who comes together to work on genomics in the UK and a bit like the word as it’s used in biology, it’s a sort of busy ecosystem with all sorts of people playing their own role and then working together, and so I think it’s a really important thing to recognise that we’re part of that and in fact it’s one of the things I love most about my role at Genomics England is thinking about all of the different partners that we need to work with and to those outside it I think it can also be a bit intimidating, because it’s hard to keep up with who on earth everyone is.

So then thinking about the question of how we make sure that data’s stored and looked after and used in the ways that people expect and safely and so forth, I think that’s absolutely at the heart of my role and our role. And I think one thing is actually always sort of starting at the: why are we doing this? What benefits are we seeking to bring to people? Is that what they expect? What have they signed up for if you like? But that’s in a research study or when they’ve decided to say yes to having a particular test, which is the same in any part of medicine. And if we use that to drive our decisions, that’s what’s so critical. And so that’s where thinking about programmes we run, and also the things that we think might be worth something that we should prioritise in the future is always first driven by the benefit that you might be bringing, weighing up the costs and the potential downsides and harm that might be caused by the use of genomic data in that way and that’s what should always drive things, and there isn’t a one-size-fits-all, you know, genomic data should be used and stored in this way and that’s one of the things that I think making sure that participants and the public are at the centre of the conversation is absolutely critical, it turns out that genomic data is very much like health data at large in many senses and it’s very precious for those reasons.

It is also special in a few ways. One of the ways that’s sort of peculiar if you like is that pretty much the DNA sequence, the genome, that you’re born with, is the same one that you hold throughout your life, that’s different from say if you do a blood count or something that varies for various reasons over your life and most things in medicine do change quite meaningfully over a much shorter time period. One of the things about the DNA code: A) it makes it more precious because it’s very much about you, your whole life; also it makes it more useful and reuseable in many ways, so one of the things that we think about a lot more in genomics is about the storage and reuse of data on an ongoing basis through the lifetime. And I do think that that model in certain settings and potentially more broadly as evidence accumulates, may well be the path that we take forward where you consider your genomic data part of your health record where it can be used and reused.

And what we need to do is explore why you would in the first case generate someone’s DNA sequence, and what sort of sequence, is it a whole genome or less than a whole genome? What would you use it for in the first place when you first generate it? And what other uses could there be to support the healthcare and have you involved them or the public more generally in decisions about how it’s used? Because we do, as I said, see the potential for genomics being just becoming part of the fabric if you like of healthcare, good healthcare, the best healthcare.  

Linked to that is the point on research as well, like where people are happy for it, holding their genomic data and understanding how that impacts on longer term health outcomes, something we’ll continue to learn about for years and years. So I think the first point is about focusing on the why and whose data it is, one’s own genome belongs to you, it doesn’t belong to anyone else, what people are happy with and consent to and expect and then always holding that in mind as one makes the choices is critical. I’ve talked about how we think the governance and the involvement of the participant panel is really critical for that as well. And then it also comes down to doing in various ways, the job that people would expect in terms of, for example, that safety piece, using the very latest tooling to make sure that it’s held in a secure way, that it’s backed up so that it won’t be lost etc. and bringing sort of the right, very good minds around some of those more technical questions, but always with the expectations of the people whose genomes they are in mind and to say are we living up to their expectations, are we doing what they would expect?  

So, Helen, I wondered if I could ask you a couple of questions. The first one I wanted to ask is what you’re hopeful for in the coming years as a participant panel member?  

Helen: Thank you. I’ve actually already posed these questions to some of the other panel members, so I’ll try and make sure I include their responses here as well as mine, but I think it’s important to hear from everybody, not just me, Rebecca Middleton and Emma Walters have recorded their responses as well. I think the four main things that panel members are hopeful for is the coming years, the first is equitable access to whole genome sequencing, basically everybody who needs whole genome sequencing should get access to it regardless of where they live, their income, ethnicity or disability, so that’s something that we’re hopeful will get better over the years.  

We know this is essential to improving healthcare, to improving outcomes for patients and generally for sort of greater inclusivity and in genomic research, we want as well as Genomics England, the data is the National Genomics Research Library to be representative of the population as a whole, not just the people who 1) are offered, and 2) agree to have their data in the library. And also, obviously the more data that is held in that library, the more opportunity there is for research across those rare and ultra rare conditions and rare and less common cancers, where it’s all about numbers, you need numbers of sets of data in order to draw things together and make conclusions to look for patterns. 

And the other thing which I guess comes more under the umbrella of the NHS is that the panel is quite keen, they want everybody who’s undergoing genomic testing to receive good support and after care, I think regardless of whether that testing is via the NHS or as part of a research study, sometimes it will be both, but that’s for the patients at the coal face that is obviously critically important. 

The second, I think broad theme, coming from the panel members’ responses is that I think you’ve mentioned this already, is increased understanding of genomics amongst the general public is really important – there’s a need to demystify genomics and to generally improve public awareness of its benefits and to get those conversations going around its regulation and its ethical use, but to do that you need to get meaningful engagement from a wide range of people, you know, that’s not always straightforward, there are lots of challenges there, it’s all about prioritising inclusivity, accessibility, to make sure you get diverse views and perspectives on genomics and on genomics research.  

The other thing that came out very strongly from the responses which we have talked quite a bit about already is about this individualised healthcare. I think we as a panel are very hopeful that there will be this shift towards treatment strategies that are tailored more to the individual and their specific health condition, rather than a one-size-fits-all approach, we want effective treatments that will minimise side effects but also through the use of pharmacogenomics, to make sure if there’s a risk of a severe, sometimes life-threatening side effect that that can be identified and that individual doesn’t have that treatment either at all or has a lower dose, so it’s not so toxic.  

And let’s hear from Emma who talks about this. 

Emma: My hope is that we move to a truly individualised healthcare system and I’m really excited to see how in particular pharmacogenomics changes the healthcare landscape. For a long time we’ve gone with a one-size-fits-all approach, and that’s easy to deliver on a large scale basis that the NHS works on, but we know fundamentally that’s not how patients work, so to be able to consider individualising medication and knowing which won’t work, interests and excites me.  

Helen: So the panel is also very hopeful about the development of those innovative therapies, and you talked about the rare therapies launchpad and the cancer vaccine launchpad, because those offer real hope for treating previously untreatable conditions and generally improving accessibility to treatments. And we’re also hopeful that there will be a much better understanding of diagnosis of cancer, through things like the multi-model programme, because although there’s lots and lots of research going on with cancer there’s still a long way to go to have more effective treatments and to improve diagnosis of cancer.  

And then just finally just in response to your question, patient and public involvement, this is what the participant panel is all about, we are a group of individuals whose lives have all been touched by either a rare condition or by cancer currently, either we’ve had that condition ourselves or it’s affected our loved one, and we do bring these diverse views and perspectives to Genomics England and I think we have a crucial role in influencing its decisions about what it does with participant data and who has access to that data. It’s critically important that Genomics England listens to what matters to the people whose data it holds and who do that, as Rebecca here explains. 

Rebecca: Genomics is a fast-moving science and it has the impact to change lives and healthcare for future generations, but genomics is a science of people and therefore the only way you can truly understand the limitations and opportunities of it is to talk eye to eye to the very people it will impact, and not everyone will agree on everything. But how we understand genomics and its power to transform healthcare, our own and that of our children and the ones we love, can only progress at the pace of the people that it will benefit. It’s a simple equation but it’s not maths and indeed not science: we are all different and unique, our emotions, experience and history will be wrapped up in our viewpoints and thoughts, and that’s where the panel comes in, representing and advocating for the very many different voices of genomic healthcare, ensures Genomics England is stronger, healthcare design is more meaningful and research is more impactful. 

I have no doubt that the panel of the future will continue to be heard and understood at Genomics England, and I hope it continues to grow to reflect more diverse voices and experiences and continues to be the people inside the science.  

Helen: Finally, the panel is also hopeful for increased public and patient involvement in genomics research, this is integral for shaping research both academic and commercial, it helps with identifying research priorities, developing new treatments, basically getting that voice of the patient in there to tell researchers what’s the most important and what matters to them. 

Rich: So another question Helen, how do the panel feel about the changing genomics landscape?

Helen: A good question and I think overall it’s a balance between excitement and hope on the one hand, and a bit of apprehension and caution on the other. So the panel is really excited about the advances going on in healthcare, we’re entering an age now where we’re promised a much more proactive, as opposed to reactive approach to healthcare. You were talking earlier Rich, about having your genome sequence, and this is something that you have for life, it’s like your passport, your fingerprint, so from infancy to old age you’ve got this data which is held somewhere which holds so much promise of predicting if you might develop a disease, whether you might react badly to a drug, so ultimately it offers great potential to improve outcomes for patients, their families and the NHS. Again, we spoke earlier about this holds so much promise for producing the diagnostic odyssey that so many parents go through when the children are born with a condition that doesn’t have a diagnosis, potential to diagnose things like cancer a lot earlier where it’s more treatable and to prevent disease as well, I know that’s something Genomics England isn’t specifically looking at, but through screening programmes, using things for example like circulating DNA which may be able to pick up that there are things going on and picking things up earlier means that those things can be dealt with earlier. 

I mean thinking of my own personal example, I know I have Lynch Syndrome, I know that I am at risk of developing bowel cancer now, but that means I can do something about it. So I have my colonoscopies every two years, I take aspirin every day because that reduces my chance of getting bowel cancers and I’m much more symptom-aware, so having that knowledge up front is very helpful in being able to move forward and reduce my chance of getting an advanced cancer. 

The panel is also very excited about the ongoing collaborations and the novel therapies that are being developed through the rare therapies launchpad, these offer a lot of hope for treating previously untreatable conditions, and improving accessibility to treatments, and obviously more targeted treatments for cancer, you know, we’d need more effective treatments for cancer but with reduced side effects, so that in a nutshell, those are the other positive sort of things that the panel feel excited about. Where they’re slightly more apprehensive or concerned, I mean they do acknowledge that there are challenges ahead and there are big concerns about the NHS’s ability to cope with increase in demand for genomic testing and particularly worries about education and training of healthcare professionals in genomics, how do they effectively communicate research findings or results to patients if they don’t have a broad understanding of genomics? 

And then finally, let’s hear from Emma. 

Emma: I think I’m excited but cautious. I think it’s really important to acknowledge that the research being undertaken is groundbreaking and the vast majority of clinicians have very little to know genomics education, and translating these findings into tangible benefits for participants is so very important, and something I think we’ve really got to make sure we don’t lose sight of.  

Helen: We talked earlier about awareness among the public about genomics and we do feel that there’s a need to drive education forwards, you know but this is challenging, given the rapid pace of developments that we’ve spoken about, I think even for the panel members who I would say are relative experts in genomics now it’s hard to keep up to date, so how do we do that moving forwards? We’ve talked about security of data, we understand there are moves to link more genomic data sets both nationally and internationally and that clearly has significant benefits because that brings bigger numbers of patients data together, but opens up potential risks in terms of security, so how do we make sure that the security of that data is as good as it is currently when it’s held in one pot in Genomics England Research Library.  

And just a couple of final concerns that were flagged by panel members, there is some apprehension regarding potential misuse with genomic data by insurance companies; we’re given a lot of reassurance about that but there are concerns that could potentially lead to the most vulnerable in society being unable to get affordable cover if they’re found to have genomic changes that mean they are at risk of conditions or have certain conditions and there are also concerns about the ethical implications of AI in diagnosis and clinical decision making, you know, AI is obviously a fantastic thing for looking at patterns amongst a big lot of data, but how accurate is it and where does the human come in, in terms of decision making?  

So those are, I think, the broad concerns from the panel. I don’t know if you have any thoughts on those, Rich?

Rich: I think the big thing to say is I think having the participant panel there, you said in the middle of that, become collectively quite expert and you recognise that. Having the ability to have these complex nuance conversations and have people share that and speak directly to us about it I think is the biggest thing – lots of those points there made by the panel, I think both things that we have very much in our mind about things that one needs to balance and focus on, and there are also things that we already talk about which is reassuring I think as well, we talk about with the panel. I think one of the things for us as well is sort of being clear on some of the things where there are really clearly well-established red lines, for example, that point on insurance, but that is very clear and part of our role is making sure that that is there and people can feel comfortable in that context to understand that. 

I think the main thing that I would say is thank you to you Helen, and to all of the panel and all of our participants because I said earlier, this is a team thing and you are all very much part of the team and we would not be able to do our jobs in any way, I wouldn’t even say effectively, I would say with the relevance, which is the thing that we drive for, the relevance to have impact for people’s lives whose data we hold and will hold in the future. And so thank you for being part of the team.

Helen: Thank you. And I think thank you to Genomics England for having the foresight to create the participant panel in the first instance, it was there from the get-go and I think a really great opportunity for all of us to be involved in this, to have our voices heard and listened to, so thank you. 

We’ll wrap up there. Thank you for joining me today and thank you for discussing your appointment as CEO for Genomic England, and your view on what the genomics ecosystem might look like over the next ten years. If you would like to hear more like this, please subscribe to the Behind the Genes, on your favourite podcast app. Thank you for listening. I’ve been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand. 

James Duboff: Genomics 101 - How do pharmaceutical companies use genomic data for drug discovery?

In this explainer episode, we’ve asked James Duboff, Strategic Partnerships Director at Genomics England, to explain how genomic data can be used in drug discovery.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.

You can download the transcript or read it below.

Naimah: How do pharmaceutical companies use genomic data for drug discovery? Today, I’m joined by James Duboff, a Strategic Partnerships Director here at Genomics England, to find out more. 

So James, first of all, what is genomic data, and how does this relate to our genes? 

James: Let’s start with a simple explanation of what we mean by genomic data and our genes. So, every cell in our body contains a complete copy of our genome. Now, genome is kind of a mini instruction manual that describes exactly how to make you. Now, those instructions are written in a language called DNA, which is over 99 percent identical in every single human on the planet, so you and I are actually genomically very, very similar. The differences, however, are called variants, and they’re what make us unique. Now, some of those variants can actually be very dangerous, and they can code for things like rare genetic diseases or even cancer. So, we need to read in detail exactly what’s going on in your DNA and in your genome to see where changes are and where those variants really are, and we do this by sequencing the genome. So, if you get a DNA sequence, that’s effectively an electronic readout of your genomic data, which is your genome in computational form.

Now, understanding that and working with that is still a relatively new field, so what we try and do is connect the genomic data, your genome, with health information, such as hospital records and what you’re presenting with in clinic, if you’re in a patient setting, and look at those together to give context to those variants in the genome. So, genomic research is actually where we look at how genes and physical outcomes could be linked. So thinking of, you know, biology and physiology term, what does a variant exactly do and how might it cause a disease. 

Naimah: You mentioned both the genome and whole genome sequencing, and if our listeners aren’t too sure exactly what they are, they can listen to some of our other explainer episodes with Greg Elgar, who explains these concepts. So James, next could you tell me why are pharma and biotech companies interested in genomic data? 

James: Ultimately, pharma and biotech companies are interested in genomic data because that really tells them what’s going on within the blueprint or that mini instruction manual of an individual. So, pharma and biotech have dedicated research teams that focus on genomic research, and they look through genetic databases across the world, such as Genomics England and others, to really understand the role of the genome in their target disease areas. By looking at those, that helps them develop new drugs and tools to specifically diagnose, treat and also even cure these diseases. 

Naimah: So, how exactly do they do that? Can you explain it in some simple steps? 

James: I think there are four key areas that they need to focus on. So, starting with the first, where, whereabouts on a genome should they focus? Now, the way that a pharma company would do this, or any researcher really, is by taking two populations of people. So, you’d take a population who have a known disease, and you’d compare that to people without. Now if you’re looking at the genomes of people with the disease and those without the disease, you can kind of play spot the difference between those two, and understand whereabouts on the genome variants appear for the disease population and not for the healthy or undiseased control group. Now, when you do that, you can kind of pinpoint exactly whereabouts you see variants only in that patient population. That helps you identify your target, and that’s known as target identification, which is essentially pinpointing that spot on the genome that’s linked only to the disease. Once you know that, you can use that as a potential target for a new drug. 

So, once you’ve found that variant, the next step was, what does that variant do? Is it potentially overproducing something? Is it activating a promoter and therefore making more and more and more of a gene product that, you know, might be toxic inside a person if you have too much? Even too much of a good thing could be a bad thing. So, is that the case? Or does that variant cause an underproduction or something to just be not actually made by your body at all? So, if that variant kind of interferes with a piece of genetic code, it could stop that gene from producing anything, and therefore you might be effectively detrimented and deprived of that particular gene product. And both of those, an overproduction or an underproduction, could lead to a disease. So, to understand that in more detail, you might need to look at gene products as well. 

The next step, once you know whereabouts in the genome you’re looking and what exactly a variant does, the next step really for a pharma company is how could you fix that. So, if you’re looking at too little of something – so, if a variant stops a gene from actually developing into a gene product then you might need a drug to boost or to compensate for that, so potentially a supplement or having some kind of drug that can get the body to make more of that product. If on the other hand your body is making too much of something in a way that could be toxic, you kind of want a drug to reduce those levels, so a drug that could potentially breakdown that gene product so that you don’t have too much of it, or stop it from working effectively, so that it doesn’t seem as if you have too much of it, or otherwise prevent it being made altogether. 

Now, one example of this prevention is actually a gene silencing drug, or an ASO, as they’re effectively known, which can be used as a genetic mask. So, that sits on top of a gene and hides it, so the body can’t actually make that dangerous varied gene product. Now, if you’re going to make something like that, you need to be absolutely sure that masking that entire gene and stopping even a varied form of it isn’t dangerous, so that last step really is making sure that your drug is safe and wouldn’t cause any other issues. So, traditionally, that would have been done using animal models as kind of a surrogate organism, but now using genomic databases, you can use human genomics as kind of real world examples of applying say a genetic mask and hiding an entire gene or genetic section, and you can look through genetic databases to have a look for individuals who are alive and hopefully healthy in the population, who don’t express a certain gene. So, if you can find people who are healthy, who don’t have that gene or have variants that stop that gene from being produced, you kind of can be confident that you can make a drug to cover that and it would be considered safe. 

Naimah: Okay, so that’s really interesting. So, what you’re saying is, by using human genomic data, we can test the impact and safety of gene targeting drugs directly in humans.

James: Yes, exactly. So, you can ask that question of would hiding that gene entirely cause any other health issues or any adverse effects really from a drug that hides it. And the really useful thing about that is that we’d know the impact of a gene targeting drug before you’d say start a clinical trial, so that really stacks the odds in your favour of the drug working safely, which is really powerful for a drug company that would otherwise invest a lot of money in a clinical trial that could be a risky endeavour for the company and also for participants. So, this is very useful for patients, and also fundamentally it’s a lot more useful for a company to be assessing safety using humans and human genomics directly as opposed to using a surrogate organism like a mouse, which many people would argue is not a good reflection of what would happen in humans.

Naimah: Can you tell me briefly if genomics can be applied to other stages of the drug delivery pipeline? 

James: Yes, in fact genomics can be applied all along the drug discovery and development R&D pipeline. So, as an example, biomarker identification. A biomarker is a biological product or a chemical signal that’s associated with a disease, that you can find and monitor inside the 

body. So, you can look at an increase in that biomarker or a decrease in that to monitor whether a drug is working as you’d expect. Is the drug increasing levels of something being produced, or is it decreasing that product being produced? And you can use that to understand whether it’s possible to potentially develop that treatment, would that treatment actually work. So, that’s really important in monitoring drug impact and also understanding clinical endpoints for a trial. 

You can also look at biomarker identification to look for genes and variants that are associated with a disease that could help you understand who best to enrol in a clinical trial. So, clinical trial recruitment is another key area, where if you involve the genome in your enrolment criteria, you can essentially just recruit the most suitable people where you know the drug will work best, and also you’re sure that the drug would be most safe and effective at treating their condition. And then actually to go a step further on the clinical trial point, clinical genomic datasets are actually really useful, if you think about it, in the opportunity to recontact participants too where they’ve consented. So, what I mean by that is, a pharma company could directly find and recruit optimal patients with either a rare disease or a cancer where their drug would help most, based solely on their genome, and that’s a really, really exciting point, because that offers the opportunity for pharma to both develop a drug based on that genomic dataset, but also then deliver the drugs to treat those same exact people. 

Naimah: So, how do pharmaceutical companies access this data? 

James: Well, there are different datasets, and each different dataset has a different population within those, and each of them have their own consent models and governance rules on how that data can be used and who can access it, and how they access it. So, some of these datasets just hold genomic data, while others would have additional biochemical data and also health information potentially on participants. So, depending on the different types of data, there’ll be different access limitations and restrictions. So, some entities and some datasets can be simply downloaded, and that could be very useful for pharma and biotech companies, because that means that they could use them inhouse. Other datasets and groupings of genomic data and libraries of sorts would operate a TRE or an SDE model, so that stands for a trusted research environment or a secure data environment, and these are essentially – you could consider them as libraries, like a reading library, where you can come in and read the books but not take out those books, or genomes in this case. 

Naimah: Can you tell me, what impact does the use of genomic data for drug discovery have on the public or patients? 

James: Oh, there’s huge impact on drug discovery, and ultimately genomic research really helps drug companies make better treatments for patients and the public. So, we’ve already seen the benefits of genomics used in drug discovery, and I think we will do more and more as DNA sequencing is used more in clinic, and also that’s going to keep happening the more cost keeps dropping, which is making genomic medicine really and genomic healthcare increasingly feasible at scale. So, 20 years ago, it cost over £100 million and it took years to sequence a genome, but today you can sequence a genome within a few hours for under £1,000. 

Naimah: What are the benefits of having your genomes sequenced in a healthcare setting? 

James: Ultimately, genomics enable a faster and more accurate diagnosis. That enables early intervention, which can really maximise the treatment impact and improve outcomes. So, what I mean by early intervention, if you can give a drug before someone shows symptoms then you could prevent them ever getting the disease, so that’s moving towards preventative medicine, which is really exciting and absolutely enabled through genomics. So, genomics really help pharma companies make also better drugs and target the underlying disease directly rather than just addressing symptoms, so this helps them make more effective and safe treatments to really improve overall outcomes for patients.  

Another thing to think about is that some drugs are already on the market but used for different reasons. Genomics can help pinpoint the root cause of that disease within a genomic setting, so that can highlight repurposing opportunities for existing drugs. Now, existing drugs are those that have already been proven safe in humans and approved for use, albeit potentially in a different setting. Now, if a drug could be shown by genomic research to be targeting the same root cause within the same biological pathway, they could very easily be repositioned and applied in an entirely new disease. 

So, I guess to finish, through genomics, drug development can help us move towards precision healthcare, and by that I mean making targeted treatments for specific patients. That will be far more effective and have significantly fewer side effects. In the case of participants in clinical genomics sequencing programmes open to researchers, that also means matchmaking opportunities for companies to diagnose and treat unique patients. In the case of ultra rare conditions, that means they can create a treatment specifically for that patient and then work with their doctors to deliver the brand new drug just to them, to ultimately save lives. 

Naimah: That was James Duboff explaining how pharmaceutical companies can use genomic data for drug discovery. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

Professor Sir Jonathan Montgomery, Dr Latha Chandramouli and Dr Natalie Banner: Why do we need to consider ethics in genomic healthcare and research?

Ethical considerations are essential in genomic medicine and clinical practice. In this episode, our guests dive into the details of ethical principles, highlighting how they can be brought into practice in the clinic, whilst considering the experiences and feelings of patients and participants.

Our host, Dr Natalie Banner, Director of Ethics at Genomics England, speaks to Professor Sir Jonathan Montgomery and Dr Latha Chandramouli. Jonathan is the Chair of the Genomics England Ethics Advisory Committee, and a Professor of Health Care Law at University College London. Latha is a member of the Ethics Advisory Committee and the Participant Panel at Genomics England, and is a Consultant Community Paediatrician working with children with complex needs.

 

"You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things."

 

You can download the transcript or read it below.

Natalie: Welcome to Behind the Genes.  

Jonathan: The first difference is that the model we’ve traditionally had around clinical ethics, which sort of assumes all focus is around the patient individually, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions. Families differ enormously, some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approaches to  genomic issues must respect everybody in that. 

Natalie: My name is Natalie Banner and I’m the Director of Ethics here at Genomics England. On today’s episode, I’m joined by Chair of our Ethics Advisory Committee, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli, member of the Ethics Advisory Committee and the Participant Panel, who’s also a community paediatrician working with children with complex needs. 

Today we’ll be discussing why ethical considerations are crucial in genomics research and clinical practice and what consent means in the context of genomics. If you enjoy today’s episode, we’d love your support. Please like, share and rate us wherever you listen to your podcasts. 

At Genomics England, we have an Ethics Advisory Committee, which exists to promote a strong ethical foundation for all of our programmes, our processes, and our partnerships. This can mean things like acting as a critical friend, an external group of experts to consult. It can mean ensuring Genomics England is being reflective and responsive to emerging ethical questions, especially those that arise as we work with this really complex technology of genomics that sits right at the intersection of clinical care and advancing research. And it can also ensure that we are bringing participant voices to the fore in all of the work that we’re doing.  

I’m really delighted today to welcome two of our esteemed members of the ethics advisory committee to the podcast. Professor Sir Jonathan Montgomery, our Chair, and Dr Latha Chandramouli, member of our Participant Panel. So, Jonathan, if I could start with you, could you tell us a little bit about your background and what you see as the role of the ethics advisory committee for us at Genomics England? 

Jonathan: Thanks very much, Natalie. My background professionally is I’m an academic, I’m a professor at University College London, and I profess healthcare law the subject that I’ve sort of had technical skills in. But I’ve also spent many years involved in the governance of the National Health Service, so I currently chair the board of the Oxford University Hospital’s NHS Foundation Trust.  

I’ve spent quite a lot of time on bodies trying to take sensible decisions on behalf of the public around difficult ethical issues. The most relevant one to Genomics England is I chaired the Human Genetics Commission for three years which was a really interesting group of people from many backgrounds. The commission itself primarily combined academics in ethics, law and in clinical areas, and there was a separate panel of citizens think grappling with things that are really important. Genomics England has a bit of that pattern, but it’s really important that the ethics advisory committee brings people together to do that.

You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You don’t want to have separate discussions of things. My aim as Chair of the advisory committee is essentially to try and reassure myself that we’ve heard all the things that we need to hear and we’ve had a chance to discuss with each other as equals what it is that that leads us to think, and then to think about how to advise within Genomics England or other people on what we’ve learnt from those processes. 

Natalie: Fantastic. Thank you, Jonathan. And as you mentioned, the necessity of multiple different perspectives, this brings me to Latha. You have lots of different hats that you bring to the Ethics Advisory Committee, could you tell us a little bit about those? 

Latha: Thank you, Natalie, for that introduction. I’m Latha Chandramouli, I’m a Consultant Community Paediatrician and I’m based in Bristol employed by Siron Care & Health. I’m a parent of twins and from my personal journey, which is how I got involved, my twins are now 21 so doing alright, we had a very, very stormy difficult time when they were growing up with our daughter having epilepsy, which just seemed to happen quite out of the blue sometimes. It started to increase in frequency the year of GCSE, to the point that she would just fall anywhere with no warnings and hurt herself. This was difficult for me because as a clinician, I was also treating patients with epilepsy. I also was looking at the journeys of other people and was able to resonate with the anxiety as a parent. Worry about sudden death in epilepsy, for example, at night, these were the kind of difficult conversations I was having with parents, and I was now on the other side of the consultation table. 

I was also doing neurology in those jobs in a unit where there was epilepsy surgery happening, so it was, in very simple terms, very close to home. It was quite hard to process, but equally my job I felt was I should not separate myself as a parent but also as a clinician because I had information, I had knowledge, and we had conversations with my daughter’s clinician.  

We were then recruited into the 100,000 Genomes Project which had just started, so we were just a year after it had started. That was an interesting experience. We were in a tertiary centre with a lovely clinical geneticist team, we had the metabolic team, we had loads of teams involved in our daughter’s care. We could understand as a clinician, but there was also my husband, although a clinician, not into paediatrics and was in a different field. It was important that it was the whole family getting recruited into the journey. My daughter also was quite young, so obviously we have parenting responsibility, but we were very keen to make sure they knew exactly what they were getting into in terms of the long-term issues. Despite being informed, at times there were things that we went in with without understanding the full implications because life happens in that odyssey.  

I think that was my biggest learning from those exercises when I began to question certain other things because I then had a breast cancer journey, but obviously I was not recruited as part of that process for the 100k. Those were kind of some of the questions coming in my head, how does the dynamic information sharing happen, and that’s how I got involved, found out a bit more about the participant panel, and that’s how I got involved from 2018 which has been an interesting experience.  

Firstly, I think with Genomics England they are probably one of the groups of organisations having a big panel of people, genuinely interested in wanting to make a difference and represent thousands of participants who have got their data saved in the research library, recruited under the two broad arms of cancer and rare disease. We were under the rare disease arm, although I could resonate with the cancer arm because of my own experience. 

At various times there were lots of opportunities to think about how data is accessed, are we getting more diverse access to data, all those different issues. At various points we have been involved in asking those questions. We all have different skillsets, you see, in our group. Some have got information governance hats; some have got data hats and PR hats. I’ve got a clinical hat and a clinical educator hat. I am a paediatrician, so I have recruited people for the same, for the DDD, for CGH etc, and I’ve always gone through the principles of consenting, confidentiality, the ethics. I also work in a field, Natalie, where there is a huge, as you are aware with the NHS resource issues, there’s huge gaps and waiting lists, so it’s trying to make sense of what is the best thing to do for that patient or that family at that point in life. Are we obsessed by a diagnostic label? Are we going down a needs-based approach? It’s having always those pragmatic decisions to be made. That’s one of my clinical hats. 

I also am an educator so I’m very keen that young medical students, be it nursing students, everybody understands genomics and they’re signing up to it so that we can mainstream genomics. Those are some of my alternative hats which kind of kick in a bit. 

Natalie: Fantastic, thank you, Latha. As you say, there are so many different perspectives there. You talk about kind of the role of the whole family as part of the journey. You talked about consent, confidentiality, data access issues, lots of questions of uncertainty. Perhaps, Jonathan, I can come to you first to talk a little bit about what is it about the ethical issues in genomics that may feel a little different. Are they unique or are they the same sorts of ethical issues that come across in other areas of clinical practice and research? Is there something particularly challenging in the area of genomics from an ethical perspective?

Jonathan: Thanks, Natalie. I think all interesting ethical issues are challenging, but they’re challenging in different ways. I’m always nervous about saying that it’s unique to genomics because there are overlaps with other areas. But I do think there are some distinctive features about the challenges in genomics and I suppose I would say they probably fall in three groups of things that we should think about. The first you’ve touched on which is that information about our genomics is important not just for the individual person where you generate that data but it’s important for their families as well. I think the first difference is that the model we’ve traditionally had around clinical ethics, which sort of assumes it all focuses around the patient individual, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions and families differ enormously. Some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approach is genomic issues must respect everybody in that, so I think that’s the first difference. 

I think the second difference is that the type of uncertainty involved in genomics extends much further than many other areas. We’re talking about the impact on people’s whole lives and it’s not like a decision about a particular medication for a problem we have now or an operation. We’re having to help people think about the impact it has on their sense of identity, on things that are going to happen sometime in the future.  

And then thirdly, I think the level of uncertainty is different in genomics from other areas of medicine, and the particular thing I think is different that we have to work out how to address is that we can’t really explain now all the things that are going to happen in the future, because we don’t know. But we do know that as we research the area, we’re going to find out more. So, what are our obligations to go back to people and say, “we worked with you before and you helped us out giving data into the studies. We couldn’t tell you anything then that would be useful to you, but actually we can now.”. Now, that’s different. That continuity sometimes talked about, you know, what are our obligations to recontact people after a study. You don’t usually have those in the ethical areas we’re familiar with; you’re usually able to deal with things in a much more focused way.  

I think those differences, that it’s not just the individual, it’s the family, that it’s not just about a specific intervention but it’s about an impact on people’s lives and that we will need to think about what we had to do in the future as well as what we do immediately. They make it different in genomics. Some areas of healthcare have those as well, but I’m not aware of anywhere that has all of that in the same position. 

Natalie: Latha, I’m wondering if that kind of resonates with your experience, particularly the navigating of uncertainty over time? 

Latha: Yes. I would say that’s exactly what you’ve said, Jonathan. I think it’s the whole process of consenting with the view that you do not know much more beyond what you know about the situation here and now. Part of that is like any other situation, that’s why we have evolved from I would say penicillin to the SMA gene therapy. If we did not do this, we wouldn’t reach frontiers of medicine and kind of that’s how I explained to families when I’m recruiting and I’m also very clear that it’s not all about research but it’s combination of the tool and focusing on your, but it’s also helpful for research even if you do not get answers. I think it’s very important at that stage, Natalie, that we have to be clear we may not get many answers at the very outset and also when do we really look at data, do we have that kind of realistic pragmatic resources to be able to relook every time? Is there a method of dynamically having that information from our NHS spine if somebody of the trio has contracted a condition, would that be fed in.  

Those are the kind of questions parents and families ask. I cannot honestly answer that, and I often say that is optimal plan. If things go to plan, that will be the area we’d be heading towards, but currently I can’t give you timelines. I think it’s important we are honest at the outset and manage expectations. That’s how you engage families and, in my case, it’s more these children and families, so engaging is crucial. As you mentioned, it’s also the question that gets asked is very simply in my mind, you know, sometimes there is that conflict because of my own personal recruitment to the 100k project, I have an interest in genomics and, therefore, I would be very keen to embark on that journey and I feel that is the way forward.  

I also understand as a member of my clinical team, for example, where I know there’s a huge waiting list, how am I best using the taxpayers’ money that’s been entrusted to us. If I think the waiting list is so high, can I see two further patients in that time that I’m using to consent which is not going to add much more to that child’s journey, for example, with autism or ADHD. It’s trying to be careful where is the ethics in doing an investigation, and that’s like in any situation as a clinician. I think that’s not much different, but it is kind of similar, but it opens up a huge area of uncertainty. As you would with any investigations, if you just went and did scans on everybody, you might pick things up which you don’t need to do anything about. It’s being sensible and being honest. 

Jonathan: And for me, Latha, that raises two areas which I think are really interesting about genomics. The first of those is the language we’ve tended to use about consent I don’t think captures all the ethical issues that we raise, because we’ve tended to think about consent of something that happens once and then gives people permission to do things. Whereas what you’ve described, and what we find ourselves often thinking about, is that we have to get a respectful relationship with people, so the consent is not to doing certain things, it’s to agree to part of what I think about as a common enterprise. So, patients and families are partners with the clinicians and the researchers, and it’s not that they sign a form and then the consent issue goes away, which is how lawyers tend to think about it, it’s that we’re starting something together and then we need to think about how do we keep the conversation going with mutual respect to make sure that everybody’s values are there.  

I think the second thing you picked up is a sense of the need for a better explanation of how research and care interact with each other. Because the care we get now is built on the evidence that people have contributed to in the past, so we’re benefitting from our predecessors, and we want to contribute to our successors and our family getting better care in the future. I think one of the things about genomics is that the gap between those two things is really non-existent in genomics, whereas if you take a medicine, the research that’s been done to make sure that medicine is safe and effective will have been done on a group of people some time in the past that I’ll never meet, whereas in genomics I’m part of the production of that. I may get some benefit now, my friends or family may get some benefit, but there isn’t this sort of separation between the care and the research bit that we’re used to being able to think about. This is a much more mutual exercise and the stakes that we all have in it are therefore intertwined much more closely than they are in some areas of medicine. 

Latha: I agree totally. In our case, for example, I went in in thinking we might get a targeted medication. I know there are certain levels of epilepsy medications anyway, so in principle it wouldn’t have mattered a lot. However, it was important to know what the outcome was going to be because we had various labels, potential mitochondrial disease, potentially some susceptibility disorder, so we were on a spectrum from something very minimal to the other end on neurodegenerative situation. We were left dangling and we thought it would be good to embark on this journey, at least there’ll be some outcome, some prognostic outcome, and more importantly we don’t have any answers, but we actually can be a hopeful story for someone else in that same position, and I think that’s how we’ve embarked on it. That’s kind of my personal experience.

But in just harking back to some of the ethical issues, it’s again very clear educating the clinicians, as you said, it’s that relationship; it’s not just a piece of paper, it’s that development of relationship with your families, some of whom have got very complex issues going on in their lives themselves. I work in a very, very deprived part of Bristol, which is the highest deprivation index, so they have got lots of intergenerational things going on, there is poverty, there is learning issues and crime, lots of things going on. You’ve got to time it right, what is important for this family here and now, and then work on it.

There’s also the other issue that we may not continue to remain their clinicians after recruiting. I think that’s so important to recognise because the results might come back but you kind of discharge them and it may take a few years by the time the results come. How do you then cross that bridge if some unexpected results come, which then means contacting various other extended family members. I think that’s the bit we all do because that’s part of the journey we’ve embarked on, but it’s also thinking is there someone else who’s probably better placed, like a GP or a primary care person who’s actually holding the entire family and not just one person, not just the adult who has been the index patient. It’s just trying to think the ethics of it because it’s all about engagement and being transparent with families. 

Jonathan: I think you’ve put your finger on another element that’s really important about the ethics. In the same way as in relation to the position of the individual patient, and we need to see them in families, which doesn’t fit very easily with lots of the clinical ethics that we’ve been used to. It’s also the case that a lot of the traditional clinical ethics has focused on the individual responsibilities of clinicians, whereas what you’ve just described is that we have to work out what the system’s responsibilities are, because it may not be the same clinician who is enabling good ethical practice to be pursued. These are both ways in which our paradigm of ethics has to be expanded from other areas of medicine. 

Latha: Yes, I agree. And the other bit I think we can probably reassure quite nicely is about the ethics about information governance and we as data custodians storing information, how do we give with great ethics and discussion the access to research and being mindful that it is again thinking along the same principles GMC kind of had about the good for the common good and using resources equitably, but again being sensible with equality issues that a single condition doesn’t get forgotten. It’s that right balance that whilst we are doing common good, we might have a condition which might have a treatable medication, but we have to focus on that as well as research. I think it’s interwoven, all these ethical questions. 

Jonathan: I completely agree, Latha. That interwoven bit is something where we need to be able to think through, “what is the role of Genomics England to improving that?”. I think we’ve got issues around the good stewardship of information which can’t be left with an individual clinician, they can only do that effectively if the system supports them and their colleagues in doing that. But we’ve also got to be proactive, we’ve got to recognise the limitations of the system, so one of the really important initiatives from Genomics England is the Diverse Data initiative because we know that without aiming to solve the problem, we will get a skewed dataset and clinicians can’t properly look after people. That tells us that the ethics in this area has to do more than avoid things going wrong, it also has to work out what it means to do things right, and what systems we have to put in place to do that. I think that’s a particular example of a shift we need to do across our ethics around healthcare.  

If speak to the sort of things that lawyers have got wrong around this in the past and some of our history, we focused a lot of our effort on stopping things going wrong. That has meant that we haven’t spent as much time as we need to on thinking about how to make things go right, because stopping things going wrong is almost always too late. What we have to do if we’re being proactive is work out how to set things up in a way that will make sure that the chances of it going wrong are quite small and the chances of doing good are much increased. I think that’s one of the key challenges that we have in Genomics England and as an Ethics Advisory Committee. The things we’ve inherited tell us quite a lot about things that have gone wrong, but actually what we’re trying to do is to get our heads around what could go right and how to make sure it does. 

Latha: Also, you mentioned about Diverse Data, I think that’s another important thing as we noticed in COVID as well. There were lots of disparities in the social model and the inequalities that have resulted in death, but also potentially HLA or epigenetic issues which could have contributed. We do have the COVID-19 genomic datasets, but it’s again important to make sure that we don’t perceive certain ethnic minority populations. Just not accessing or considering them to be hard to reach, I would say for them Genomics England is hard to reach. It’s looking at it slightly differently and thinking, “how can we reach them? how do we maybe use community workers and maybe even clinicians?”, I think they’ve got the best trusting relationships with their clinicians and using them to recruit. As you say, even before things get more complicated, you recruit them earlier so that you’d go down the prevention route rather than the gone wrong route and then look for answers later. 

Jonathan: Latha, I think you put your finger on something really challenging for a group like the Ethics Advisory Committee at Genomics England, which is that however hard we try to get a range of experiences and voices, that’s not a substitute for getting out and hearing from people in real world situations. I think one of the things I’ve learnt over the years from my national health service work is that you cannot expect people to come to you, you need to go to them. In COVID when we were trying to understand why some groups were more reluctant to take up vaccines than others, there was no point in doing that sitting in your own places, you had to listen to people’s concerns and understand why they were there. One of the things we’re going to have to be able to do as the Ethics Advisory Committee is work out when we need to hear more from people outside of the Genomics England system, and I’m a great believer that if it’s right that we need to go where people are, you have to try not to reinvent mechanisms to do that. You have to try and learn where are people already talking about it and go and listen to them there.

Latha: Absolutely, yeah. I think they listen because I do work as a paediatrician with a safeguarding hat, and I think the same principles resonate in child death work. For example, simple messages about cot deaths, you would think that if a professional tells the same message to a parent or a carer it’s better received if it’s another family, a younger person, another layperson giving the same message. It comes back to who’s more receptive. It could be a community worker.

As you mentioned about vaccination, during the vaccination initiative I decided early on that I’m probably not going to do a lot because I’m not an intensivist, how do I do my bit in the pandemic. I decided to become a vaccinator and I thought with my ethnic minority hat on, if I went out there to the mass centres and actually vaccinated there or in mosques or wherever else, without even saying a word I’m giving the message, aren’t I, that, look, I’m fearlessly coming and getting vaccinated and vaccinating others, so please come. I think that has helped to some extent, just trying to reach out. Other than saying these people are not reaching us, it’s got to be the other way around. 

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Natalie: I’m really enjoying this conversation. In part because I think it highlights just how valuable it is to sort of think about ethics a little bit differently. Historically, and certainly I think within the research community, ethics can just be associated with consent. Consent is the ethics issue and if you solve for consent, then you don’t have any other issues to think through. I think what this conversation is really highlighting is just how much broader the ethical considerations are. Beyond that, it’s still very important that consent can be that sort of anchor point for communication and engagement, but it’s not simply a one-off. And to be able to think through ethics not just in terms of risk or moving forward when things have gone wrong in the past, there is actually a really positive aspect to it which I think is critically important.  

It’s great to hear your thoughts about that different approach to ethics that I think does embed it much more in community thinking, in questions of equity; it’s not just the individual. I want to follow-up by just asking where do you think the future lies in thinking about ethics both for Genomics England and the Ethics Advisory Committee, but in the space of genomic research and medicine more broadly, given that it sits in this kind of very interesting and quite complex space between research and care in the clinic. 

Jonathan: I mentioned earlier in the conversation I think about this as a common enterprise that we have shared stakes in. Academic researchers have a stake in trying to build a better more robust evidence base, clinicians have a stake in being able to offer something to the people that they’re looking after. Families have stakes not just in their own immediate care, but they worry about their siblings, they worry about their children, their grandchildren. There are also of course industrial players, so people trying to build a business out of making better medicines in the future. There are government players trying to use public resources more effectively. I think what we have to try to create is a mutual process where we recognise that everybody has overlapping but slightly different values that they’re pursuing and trying to get out of it, and how can we make sure that we govern our work in a way that reflects all of those stakeholders and recognises the respect that’s due to them. I think this is more like a sort of membership of a common project. And the problem with consent is it risks us saying you can be a member of this club but only if you accept the terms and conditions that the committee has decided is there. That’s not going to be adequate going forward.

I think we need to make sure that everybody feels that they are respected, that they feel they can place their trust in the system that we’re designing. As an Ethics Advisory Committee, we have to ask ourselves what justifies us suggesting to people that this is trustworthy. We need to make sure we have good information governance that people are not going to expose themselves to breaches of privacy if they take part in this. But we also need to make sure that we don’t waste people’s efforts. If people are prepared to be part of the research project, we shouldn’t have rules coming down on the data usage that say that we’re going to reduce the value of that contribution by saying it can only be used for one project and can’t be used for others, because actually that would not respect properly people’s contribution to the process.  

We need to ask ourselves not just about the protective element of trustworthiness but that element that says we will make sure that you get as much as we can design of the things that you think are important from this project. They won’t be identical for each group, and they won’t be identical within each group. Different family members of participants will have different balances, but they all have to believe that this is a good club to be part of and that they have been part of agreeing ways of working that they think will produce a better future that they want to be part of and that they want to be proud of saying we have helped create this future. 

Latha: I kind of agree with all that you’ve said. I think it’s most important not to forget because I’m also a participant, like my trio sample is there in the pipeline, and I know my data is sitting there. I also have trust that there is good information governance, the data is secure, so it’s reinforcing that, but it’s also being very honest that it’s obviously the data is there, but we can’t forget the person or the persons at the centre of it, so it’s not just alphabets or sequences of alphabets, but it is that whole person, and that person represents a group of individuals, family members, different generations, and they have embarked on it. Even if they know they may not get hope they might provide hope for others. It’s being therefore respectful.

I think that is the first thing I think is the principle of it and if you respect. If you think it could be the same principle that we use in clinical practice, the friends and family test, because I’ve been on both sides of the consultation table, I think I’ve become a better doctor because I’ve been an anxious mum, and my anxieties were dismissed as being an anxious mum and I don’t care. As far as my child is concerned, my anxiety was valid and so I would do everything to reach an outcome as to what’s best for that person. It’s made me a better doctor because I can see it from both the perspectives. Most of us are human beings, apart from AI technology looking at the dataset, so we all have conditions ourselves, we’ve got doctors with health conditions, we’ve got clinicians, academics, technicians, nurses everybody who’s got a friend or a family member or themselves having a health condition. I think its fundamental principle is that friends and family test. How would I like my data stored? How would I like my data analysed? Could it do this, could it give me some information on how I would get cured or treated or be managed? How would it affect my insurance, or will it find out data about who’s the father of this child, for example? It’s being honest and being honest about the uncertainties as well.  

When I’m recruiting, I’m very clear that these are what I know that I can tell you about the risks. But then there may be other risks that I do not know about. If you’re honest about it and acknowledge what is the limit of the knowledge of science at this point in time, because you said there are so many stakeholders, there are researchers and academics who’ve got interest in some areas, it could have developed because of a family member having that problem, but whatever it is that is a great interest because that intelligent mind is thinking ahead and we need to encourage that. It could be for writing up papers, it doesn’t matter. Whatever be the reason, if it’s for the common good, that’s fine. It’s also thinking how are we keeping our families in the loop, so you have newborns, you’ve got young people sometimes with significant disabilities so they are relying on a parent or a carer to consent for them, but some are not so disabled but they have needs, they’ve got rare conditions, but they can make their consenting issues known when they turn 16, for example. It’s the changing policies and they can withdraw at some point in life or there may be a member of the family who doesn’t want to be part of that journey anymore. It’s allowing that to happen.

Jonathan: I think that’s a really interesting example you’ve just touched on, Latha, where I may diverge a bit in terms of what I think is the key issue. The right to withdraw I think is a really interesting challenge for us going forward, because we developed the right to withdraw in the ethics of research studies that had physical interventions. It’s really clear that someone who is being put to discomfort and is having things done to her body, if she wants to stop that, we can’t justify continuing on the basis of it being a research project. But I’m less clear whether that applies to withdrawing data from data pools. I think there are a few dimensions to that which I hope as an Ethics Advisory Committee we’ll have a chance to think through a bit more. One is the mutual obligations that we owe to each other. I’m not in these particular studies but I do try and take part in research studies when I’m eligible and invited to because I think research is important. When I take part in things and when our participants have taken part, they’re doing something in which they rely on other people participating because the aggregation of the data is what makes it power.

One of the things we have to be honest about is what are our mutual expectations of each other, so I think we absolutely have to hold on to the fact that people should be able to withdraw from further interventions, but I’m not convinced that you should have the right to say the data I’ve previously contributed that other people have relied on can suddenly be sucked out and taken out of it, because I think it’s reasonable for us to say if this is a sort of part of an enterprise. While you’re part of it, you’ve made some commitments as well as, and that’s part of the mutuality of the respect. I think I personally would want to argue you can withdraw from new things, but provided that your privacy is not intruded on, so we’re talking about data health anonymously, you shouldn’t be able to say don’t process it anymore.

Latha: No, no, no. What I meant was from my perspective I would like to be constantly involved and get information through trickling. I don’t know what my daughter feels years down the line, she might say I’m happy for my data to be used for research, but I don’t want to know anymore. There are two aspects of that, and I think if we are clear with that and say continue with my data being used for research, but I don’t want to get anymore letters. I think those are the kind of questions I face when I tell them families that these are the uncertainties, you can have your blood stored, you may not be approached again for a resampling unless you have some other issues, but are we happy with this? I think that’s what I understand, and I try and recruit with that intention.

Jonathan: And that makes lots of sense to me. As you say, you probably can’t speak for your daughters now, and you certainly can’t speak for them when they become parents for themselves and those things, but we do need to create an ethical framework which recognises that people will change their mind on things and people will vary about what they want to do. But because we have mutual obligations, what that means and the control we can give, we have to be open and honest about what choices we can give people without undermining the enterprise and what choices we say, “you don’t have to do this, but if you want to be part of it, there are some common mutual obligations that are intrinsic”, and that’s true of researchers, it’s true of clinicians, it’s true of anyone who works in Genomics England or the NHS.  

But I don’t think we’ve been very good at explaining to people that there’s an element of this which is a package. A bit like when I bank, I allow the bank to track my transactions and to call me if they see something that looks out of the ordinary as a part of the protections from me. I can’t opt out of that bit. I can opt out of them sending me letters and just say do it by email or whatever and I have some choices, but there’s an infrastructure of the system which is helping it to function well and do the things it’s able to do. I don’t think we’ve been very good at explaining that to people, because we’ve tended to say, “as long as you’ve signed the consent form at the beginning of the process, it doesn’t really matter what happens after that, you’ve been told.”. That’s not enough I think for good ethics. 

Latha: And I think that comes back to the other issue about training those who are consenting. I speak from personal experience within my own teams I can see somebody might say, “I don’t do whole genomic sequencing consenting; I don’t have the time for it.”. I might even have my organisational lead saying when we had a letter come through to say now we’re no longer doing this, we’re going to be doing this test for everybody, there’s a whole gasp because it’s at least two hours’ worth of time and how are we going to generate that time with the best of intentions. I think that’s where I think the vision and the pragmatic, you know, the grounding, those two should somehow link with each other. The vision of Genomics England with working with NHS England and with the future, Health Education England arm that is not amalgamated with NHS England, is trying to see how do we train our future clinicians who will hopefully consider it as part of their embedded working thinking and analysis, but also, how do we change the here and the now?

The more senior conservative thinking people, who are worried about how do they have to generate time to manage, we’re probably already a bit burnt out or burning out, how do they generate time? If you then discover new conditions whether there is already bottleneck in various pathways, how are we ethically managing the new diagnosis and how will they fit in in the waiting list criteria of those people on the journey who are symptomatic. I find that bottleneck when I have conversations with colleagues is the anxiety, how is that going to be addressed. 

Jonathan: Latha, you’ve sort of taken us around in a circle. We started off thinking what was special about genomics, and we’ve reflected on ‘we have to solve the problems of the health service’. I think that there’s some wisdom in that, because we are learning how to do things that are not unique to genomics, but there’s an opportunity in genomics to do it better and an opportunity for us to help other areas of the health service do better, too. I think we’ve come around in full circle in a sense. 

Natalie: Which feels like a lovely way to wrap up our conversation. I feel like we’ve gone into some of the deep ethical principles but also really shown how they can be brought into the practice, into the clinic and brought to bear the thinking and the feelings, the hopes the anxieties of participants. There’s a very, very important range of different voices so a very rich discussion.  

I’d just like to thank you both very much for joining us on the podcast. Thank you to our guests, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli for joining me today as we discussed ethics in genomics research and practice. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I’ve been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.

Professor Matt Brown: Genomics 101 - What is personalised medicine?

In this explainer episode, we’ve asked Professor Matt Brown, Chief Scientific Officer at Genomics England, to explain what personalised medicine is and how it could change the way we treat genetic conditions and cancer.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.

You can download the transcript or read it below.

Naimah: What is personalised medicine? I’m joined by Matt Brown, chief scientific officer for Genomics England, to find out more. So, first of all, Matt, can you tell me, what is personalised medicine?  

Matt: So, personalised medicine is about giving the right dose of a medicine and the right medicine to the right person. So, it’s exactly the opposite of one size fits all. It’s what doctors have been trying to do ever since we had effective medicines, that is generally looking at the patient, what disease have they got, what factors are there about the patient that can help judge what dose they should give and for how long, of which medicine.  

Naimah: So, people often refer to this as precision medicine. Is this the same thing?  

Matt: Generally, the two terms are used interchangeably. I think precision medicine is more specifically about the dose perhaps, but effectively they both mean the right medicine at the right dose for the right person.  

Naimah: And how can we predict what treatment will suit each individual patient best?  

Matt: Well, to some extent, of course, this depends on the disease the patient actually has. We also know from a patient’s history how they’ve reacted to similar medications in the past. So for example, some patients have lots of problems with anti-inflammatories, other patients don’t, so if you give an anti-inflammatory to somebody who’s had problems with them before, you’re likely to cause the same problems all over again. So nowadays, we have much, much better ways, other than trial and error, to predict what treatment will suit a patient best, and in particular, development of genetic markers to look at how their condition is going to respond best, and how the patient is going to tolerate the medicine you give them, and what dose you should be giving them.  

Naimah: How could personalised medicine change the way we treat genetic conditions and cancer?  

Matt: So, I’ll talk about cancer first up. In the past, we used to treat cancers based on the organ from which the cancer actually arose, and the more we’ve learnt about what the genetic mutations are that cause cancers, the more cancer treatments are being decided based on the genetic mutation which is driving the cancer, and this has proven to be more effective than just looking at the organ from which the cancer arose. It turns out then that some medications which were only being used for specific cancers, are actually useful across multiple cancers that are driven by the same genetic mutations.  

In lots of other common diseases though, we now know a lot about genetic variants which predispose people to adverse drug reactions, and so we can use genetic tests to predict who’s going to get those adverse drug reactions and avoid them. And similarly, we also know about genetic determinants of how people metabolise and, in many cases, activate medications, and that helps us a lot learning about what dose to give people.  

Naimah: And how far away are we from seeing this routinely in clinical care?  

Matt: We are seeing it in routine clinical care in some pretty narrow settings. So, there are genetic tests available for enzymes which are involved in activation of particular chemotherapy 5 agents. So, DPYD testing, for example, is widely used to predict people’s likely response to a class of chemotherapy agent called fluoropyrimidines, or 5-Fluorouracil is a common one, and the genetic test basically picks out a group of people, a small number of people who are likely to have severe adverse drug reactions to that class of medication, and that’s been a really big success.  

We also use it for picking some other severe adverse drug reactions to medications like gout medications, HIV medications and so on, but generally it’s pretty narrow. What we want to get to the point is where we have people tested in advance of them needing medications, so that when they go to the doctor to be seen about a particular condition, the doctor already has the genetic test available to them, so the doctor can say if the medication is safe and what dose to use. This is what we call pre-emptive testing.  

Naimah: That was Matt Brown explaining what is personalised medicine. If you’d like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

Will Navaie: Genomics 101 - What is 'ethics'?

In this explainer episode, we’ve asked Will Navaie, Head of Ethics Operations at Genomics England, to explain what ethics is and why it's important, in the context of genomics.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.

Want to find out more? Check out the blog 'Genomics 101: What is ethics?'.

You can download the transcript or read it below.

Naimah: What is ethics? Today I’m joined by Will Navaie, who’s Head of Ethics Operations at Genomics England, to find out more. 

Will: Ethics is part of philosophy, and it’s part of philosophy that talks through a set of moral principles that govern our behaviour and our conduct. So, it might be thinking about whether something is good or bad. It might be thinking about whether something is good or better, or whether something is bad and worse. So, it’s about values and how we demonstrate those values kind of in a moral framework. So, I like to think of ethics as, just because you can do something, it doesn’t mean that you should do something. So, the law dictates to us what we can do, but ethics then talks about actually you need to look at the context around a law and to see whether something is reasonable, and so ethics to me is the should. So, should we do something? Just because we can do something, it doesn’t mean that we necessarily should do that thing. 

So, in medical ethics, we have four pillars or four areas that we concentrate on. One is justice, and that’s making sure that something is fair and equitable and inclusive. And equity being the key here, so equity recognises that individuals have different circumstances, and equity allocates opportunities based on the needs of the individual. So, it’s not about giving everybody the same, but it’s recognising that to get an equal outcome for something, that some people will require more of something because of their set of circumstances. We also have autonomy, and autonomy in medical ethics is a bit of a focus sometimes, and what that is, is giving choices and respecting people’s decisions around that choice. Consent, we talk about a lot in medical ethics, but it is not the be all and end all. It’s really important, but actually it’s one principle among many that kind of make up ethics. 

Another one of those four is beneficence, and that’s talking about everything we do must create benefit for people, and that benefit might be at an individual level, it might be at a societal level, so there’s lots of different ways of realising benefit. And the other, which is the flipside of that, is non-maleficence, and that’s making sure that everything we do doesn’t cause any harm to people. 

Naimah: Okay, and then so if we’re thinking about ethics in the context of genomics, what does that mean? 

Will: So, those four principles that we just talked about are applied to genomics as much as anything else, so there’s no exceptionalism to those, so we live by those four pillars, if you like. But what does make things complicated in genomics is that genomic data is not just about you. It’s not just about an individual. It’s about your family, it’s about your future family, and what that means is that we need to take those four pillars, those four areas, and look at them through a lens of a group rather than an individual. Where it becomes more complicated is the kind of interface between the law and ethics, and the way that the laws are written in this country and in healthcare are very much around individual rights, and that becomes really tricky when the decision making of an individual can affect other people in their family. And so, what we try to do is to think about how we can influence behaviour that we want to see. So, the law says an individual has to give their consent for a thing to happen. What we do is we take a step back and we say, “okay, but because there’s other people involved, we need to respect that.” 

And so, we’re constantly thinking about how can we influence the behaviour that we want to see. So, we might say, “when you are thinking about whether you want to take part in medical research, or genomic medical research, you might want to speak to your family about this. You might want to speak to your children about this, because it does have implications on them.” And so again we’re using the sort of vehicle of consent to try and nudge those behaviours that we want to see. So again, it’s this kind of ethics complementing the law. So, the law’s not really working – it’s working to protect an individual, but it’s not necessarily respecting everybody, and so we just try to kind of affect those behaviours as much as we can. 

Naimah: Okay, and then what’s the best way to demonstrate ethics? 

Will: I think that’s a really interesting question, and I think it’s really important because ethics being part of philosophy means that very clever people have lots of opinions, and write lots of things, and there’s lots of words around ethics, but actually the really important thing is demonstrating that. So, in order to kind of build trust in something, you need to be able to demonstrate your trustworthiness, and i think the best way to do that is really through public engagement. If you don’t understand what people expect of you, it is not your role to tell people what to expect. It’s your role to listen and see what people expect of you, and once you understand what people expect of you, you then know how to act, how to behave in line with what people want from you, rather than telling people what to expect. So, in medical ethics, we talk about – or in healthcare in general, we talk about doing things with people, not to people, and i think the best way to demonstrate that is to listen. It’s to engage. It’s to act upon what the public are telling you, and sometimes those aren’t the things that you want to hear. But that’s how we make improvements. That’s how we build trust. 

I think a really good example of this from Genomics England is the newborns programme. In ethics, we talk about the needs of science should never outweigh the needs of society, and scientists have said, “we think genomics can help with newborn screening and diagnosis of rare diseases.” So, what we’ve done is said, “okay, science has said this, we think that we can make improvements, but actually we now need to go and see what society thinks about this. Is it acceptable? If it is acceptable, what are people’s thresholds for what we can do? And so the whole programme and the generation study has all been driven by user involvement, public involvement, and we have learnt so much, and we’ve adapted our approach so much to that. And i think that it’s a really good way of us demonstrating that we have listened and that we have acted upon what we’ve heard. I’m really proud of the way that ethics has been actually genuinely embedded in the decision making around that. 

Naimah: That was Will Navaie, explaining what we mean by ethics. I’ve been your host, Naimah Callachand, and if you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening. 

Marie Nugent: Genomics 101 - Why is diversity important in genomics research?

In this explainer episode, we’ve asked Marie Nugent, Community Manager for the Diverse Data Initiative at Genomics England, to explain what diversity is and why it's important, in the context of genomics.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.

You can download the transcript or read it below.

Naimah: Why is diversity important in genomics? Today, I’m joined by Marie Nugent, who’s an engagement manager for the Diverse Data Initiative at Genomics England, and she’s going to explain more. So first of all, Marie, let’s start at the beginning. What is diversity? 

Marie: I think it’s sort of a fiendishly seeming simple question, isn’t it, what is diversity, and I think you’ll get just as broad a range of answers as the people you might ask that question to. But for me, you know, it’s really got to be about how we do things. So to me, diversity is about recognising that there’s maybe a limited way in which certain things work, or the way in which we might go about doing certain things, and it’s also limited in terms of who’s involved in that and who might benefit from that. So, in the broadest sense, I think diversity means recognising the limitations of maybe what you currently do, and really looking for how can we open that up a lot more to provide the space and opportunity for a broader range of people and voices and experiences to really be brought into that and shape it. 

Naimah: And can you tell me a bit more about what diversity means in the context of genomics? 

Marie: I find this absolutely fascinating in the context of genomics, because genomics is really about how do we understand, you know, how our DNA, as an entire piece of information, is building us and shaping us as people, and having an impact on our lives, and, you know, for us predominantly our health. And the way in which we currently think about grouping people in genomics is unfortunately still very, very heavily influenced by social understandings of how people group together, not necessarily anything that’s really about your genetic ancestry, for example, which is very different. So at the moment, you know, it’s an interesting thing to play with and think about because in genomics it’s absolutely crucial that we understand the broadest sense of human diversity in terms of genetics and genomics, and only by doing that can we start to really fully understand what it means to be distinct, and therefore how small changes in DNA can have a massive impact on people’s health.  

So, diversity in the context of genomics has to actually completely change the very fundamental ways in which we currently understand how people group together, so it’s really getting at the heart of that academic thinking about the topic. But it’s more than that, of course, as well, because as I’ve sort of already mentioned about what diversity means more broadly, it’s got to be about how we do things and who’s involved in that, and who benefits from it. So, in the context of genomics, it’s playing at the ideas of how we even understand how people relate to each other and how they’re different from each other, as well as how we do things. It’s a really complex but fascinating topic, to be honest, to be able to look at and study in some way. 

Naimah: How does the inclusion of diverse populations contribute to improving genomic research? 

Marie: Yeah, so following on from what I’ve just said, we fundamentally need to include everyone, you know. In order for us to really understand what genetic ancestry means and what difference looks like across different groups, and how that impacts health, we have to be able to capture, as best as we possibly can, you know, what true genetic diversity looks like in people. So, including as many people as possible who are different from what we currently understand is absolutely crucial. It’s the only way in which we can progress this area. And as I say, that’s in terms of how we think about it maybe academically and what we can do in terms of research, and what we understand, but it’s got to also be about the practice and how we do things. So, there’s involving people and having good representation of people in, say, data, but we have to think about how we’re involving people in how we do things and how we understand things, and how we make decisions about these things too. 

Naimah: So, for these large groups of people, what are the challenges and barriers for including everyone? 

Marie: So, I think there are a lot of challenges and barriers that hinder the inclusion of a broader range of groups of people in studies. I suppose the main one that I’m going to focus on is it’s actually the way in which we do research. It’s actually our culture, if you like, of work in this area. That’s one of the biggest barriers, and that’s because, you know, research is a very fast paced, very competitive environment and area of work to be in. Quite often, you know, things need to be done at pace, and things need results, and things need to be published and all that sort of thing, and I think there is sometimes this perception of not having enough time to slow down a little bit, think a bit more carefully and outside the box about how we might approach a piece of work, for example.

So for me, I think the biggest barriers actually exist within the existing organisations and people who do this work currently. We’re quite sort of blinkered, I think, still in terms of how we can even approach this work. And finding ways of approaching doing research in a way that’s kind of outside the traditional sort of ways of thinking is for me personally, in my experience of working in this area, one of the biggest challenges still.  

Naimah: And finally Marie, how can we address these challenges? 

Marie: I think it’s not easy for sure, because this isn’t a new thing that people have been trying to do, you know. There’s a big body of work, you know, in the context of the UK that’s been going on for a number of years, that’s been about sort of trying to open up and challenge, you know, existing research culture and things like that. But I think it has to be about our approach. So, for example, we have the power at Genomics England to think about how we approach the new initiatives, the new pieces of work that we would like to initiate. We talk about trust a lot in this space, but for me, it has to link back to how do we therefore change the way in which we do things so that it opens up a little bit more, people can see for themselves that we’re trustworthy and they can trust in this, rather than just saying, “Obviously, you can trust us because we’re doing research,” or, “We’re doing something that’s going to be brought into the NHS.” Unfortunately, that just doesn’t quite cut it for a lot of people for various fairly understandable reasons. 

And I think, you know, we can make decisions about how we go about doing that work, and I think it’s about your priorities and things like that. So for me, the most effective way of actually addressing some of these existing challenges and barriers is to almost be brave enough to do it differently, and take that sort of perceived risk of maybe not doing things as expected and slowing it down, and allowing that extra time and space for people to come in and shape it, and not actually feel like we have to know everything and we have to make all the decisions. Sometimes I think it’s about, we hold the space, we have the resources and we have the access to the expertise, but how can we create the space where actually other people shape it and we just simply facilitate it. That’s the kind of thing I’d like to see organisations like ours and other research institutions and things like that start moving towards as facilitators of shaping work that will bring some sort of public benefit. 

Naimah: That was Marie Nugent explaining diversity in genomics. I’ve been your host, Naimah Callachand, and if you want to hear more Explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.