Behind the Genes

In this episode of Behind the Genes, we explore Black communities and health research. Our guests discuss why some people feel research is not intended for them, how historical mistrust affects participation, and what needs to change to make research more inclusive, transparent and beneficial for everyone. 

Our host, Sharon Jones, is joined by: 

Professor Segun Fatumo - Professor and Chair of Genomic Diversity at Queen Mary's Hospital

Christella Matoko - Project manager at Genomics England

Hazel Attua - member of the Participant Panel at Genomics England

We also hear from Mica and Mary, who took part in the Our health, our stories video on YouTube, who share their reflections on why taking part in research matters for Black communities. 

As mentioned in the episode, you can also listen to our latest Genomics 101 episode, What is equity in healthcare?, to learn more about what equity means and why it matters in health research and care. 

“Engaging in research is bigger than you. It shapes your community, and it shapes the lives of the children coming in the future.” 

You can read the transcript below.

Sharon Jones: [00:00:00] Hello, and welcome to Behind the Genes, the podcast that brings you the stories, research, and innovations shaping the future of genomic healthcare. Today, we're exploring Black communities and health research. Why do some Black people feel that research isn't intended for them? What role does trust play in participation?

Sharon Jones: And what needs to change to improve health outcomes now and in the future? I'm Sharon Jones, and joining me today are Christella Matoko from Genomics England, [00:00:30] Segun Fatumo, Professor and Chair of Genomic Diversity at Queen Mary's Hospital, London, whose work focuses on improving representation and equity in genomic research, and Hazel Attua, who's a member of the Participant Panel at Genomics England.

Sharon Jones: A warm welcome to everyone. So before we dive into these topics, let's start first to try and understand how people perceive research and how that can often influence whether they feel it's something for them. So Christella, I'd love to come to you [00:01:00] first. What comes to mind when you hear the words health research?

Christella: I think when I'm talking about health research, what comes to mind is the opportunities to understand certain health conditions in different communities, and it's about understanding that we can get better treatments, and these treatments can prevent health inequalities. Although I might look at it from this lens, the whole of the Black community might not.

Christella: I have the knowledge of medical care. I work in Genomics England, [00:01:30] so I understand the benefits of, um, health research and how it can improve outcomes within the healthcare. But when you speak about it in terms of the Black community, research doesn't necessarily sit naturally because of all of the historical mistrust that we've, you know, encountered.

Sharon Jones: Yeah.

Christella: So for me, good healthcare research should ultimately lead to better outcomes for everyone. And I think when I hear [00:02:00] health research, that's like what I like to think about.

Sharon Jones: Yeah. Thank you. Thank you for sharing that. And, and Hazel, like coming to you, does that reflect what you've seen or experienced?

Sharon Jones: You know, do you feel that research feels relevant to Black communities and why do you think some people may feel hesitant in, in taking part?

Hazel: Yeah, I mean, I completely agree with Christella. I think it's difficult for people in the Black community to sometimes trust when research comes out [00:02:30] because previously there's been a lot of mistrust around research because there hasn't always been a lot of research within the Black communities.

Hazel: Like when we talk about research, when we talk about, um, for example, with National Genomic Research Library, so when I used to do work with Genomics England-

Christella: Mm.

Hazel: I specifically was, um, working on the National Genomic Research Library within, um, diverse data. [00:03:00] And so our role was to get more diverse data into the National Genomic Research Library.

Hazel: And so for those that don't know what that is, it's like a biobank. And so a biobank is essentially, um, where you help collect samples. So if you've decided to get into research, it's collecting samples, processing samples. So when we decided to do the initiative or when Genomics England decided to do this initiative, I thought it was [00:03:30] amazing because essentially not that much research was done previously for the Black communities.

Hazel: And specifically for sickle cell. So to be able to do this, to be able to help understand the background for sickle cell for the Black communities, it's amazing. To be able to get more treatments and interventions, it's great. But like Christella is saying, like, it's interesting to see different people's [00:04:00] perspectives because, again, the trust and the misconceptions around research is different in everybody's eyes because of the, the lack of research that's been done before.

Hazel: And so the hesitation around it is like, "Why, why is it only coming about now?" Like, "Why are we doing it now?" But that's the thing about the UK, we're such a diverse population, and it's amazing. So research needs to reflect that. [00:04:30]And so I think hopefully going forward, it actually does do that because we do need treatments and interventions that actually reflect the community.

Hazel: Otherwise, we're not gonna get anywhere when it comes to medications, like, health data that actually reflects everyone.

Sharon Jones: So we're gonna hear from Mary now, who's a research nurse and midwife, who shares her thoughts on why people [00:05:00] may be hesitant in taking part in research.

Mary (Clip): Within the Black community, historically, the lack of participation in research stems from a lack of trust. Historically, I guess the best way to put it is why would I go to a party I've never been invited to? And it's trying to get people to understand that narrative has changed. The lack of trust should never be dismissed.

Mary (Clip): It's not a, a myth. It stems from [00:05:30] somewhere. However, there's been so, so, so much change, and I'm hoping that people can see that there are people that really want to make this change for you, for me, for us, for our community. It's so important that, yes, we still hold on to the history of where research is coming from, but we need to paint the picture of the future.

Sharon Jones: So Mary's analogy of being invited to a party you've never been to really gets to the heart of that question around trust. So [00:06:00] Segun, I'd love to bring you in at this point. From your experience working to improve representation in genomic research?

Sharon Jones: Can you explain to listeners why historically Black communities have felt disconnected to research, and what needs to change to make it feel like it's something for the community rather than something that's being done to the Black community?

Segun: So I think we need to get to a point where we acknowledge that there's mistrust.

Segun: So some Black community are fed the old, kind of research that is being done on them and not being done with them. You cannot just show up in a community and start asking for their blood sample or asking for their data, and you just do research on them without, uh, proper community [00:07:00] engagement, without getting them involved, without asking them what are the things that are really very, very important, uh, to them.

Segun: I think, uh, we researchers and also institution and as well as a nation, UK, where we are taking a lead in global genomics, needs to get to a point where we understand that the trust h-has gone, and, uh, we should not expect the Black community to [00:07:30] give us their trust.

Segun: We need to get to a point that where we earn that trust from them, and we're able to do our study on them. So currently in the UK, if you look at some of those, uh, very successful, uh, Black community is really underrepresented. And one of the reason why you hear that is they say that the Black community, they are very hard to reach.

Segun: So they're hard to reach because of the same issue. Community engagement has to [00:08:00] be done in a proper way. Yeah, you need to do research in a way that you go to those Black community and don't expect them to come to you.

Segun: And we see a lot of that during, uh, during COVID. You see that many, uh, Black community were very hesitant to participate in any vaccine. So we need to get to a point where Black community earn our trust.

Sharon Jones: Thank you. Christella, [00:08:30] what do you think about the role that trust plays in deciding whether to participate in research?

Sharon Jones: You, you know, given that you've worked on the Generation Study.

Christella: I think trust has to be earned, and I think Segun has said it perfectly here in terms of working with the community and coming into the community to understand how the community works. This mistrust that we're talking about is not something of today.

Christella: It's something which has been reported on. It's something which we have seen. It's something which has-- it's not a made-up thing. [00:09:00] So when, um, when organisations say Black communities are harder to reach, there is reason for it. That cannot be an excuse not to actually participate with those people in the community to show the difference in which we have made over the years, to understand that we are making changes with the transparency of what we do, you know, creating, um, work which you know where your data is going, because at the end of the day, I'm giving away my [00:09:30] sample.

Christella: I want to know who will have access to that sample, where that sample will go. And until we get to a point where we understand that trust has to be earned, it's always gonna be quite difficult if we think Black community are just gonna participate because there's a research available.

Sharon Jones: And that's a really fair point. And what do you think, given your sort of experience, what do you think helps build that trust in practice?

Christella: I think first of [00:10:00] all, um, not telling and actually going into communities and understanding. So when we talk about the Black community, it's not just a small group of people.

Christella: There are Black Caribbeans, there are Black Africans, there are people from different tribes within different countries. So it's not just a, a one-size-fits-all kind of thing here. Yeah. So it's understanding what you're actually trying to achieve, going into places where the Black community [00:10:30] actually congregate, so whether that is church, whether that's community events, whether that's, uh, Black-based events, actually going in and understanding what is it that you would like us to do to show that we are not the research of, you know, the, the early 19th century?

Christella: What have we done to show that we are progressing in terms of equality? What have we done in terms of how we're using your data? All those things there, it's not about [00:11:00] things being done to the Black community. It's the, it's the partnership, I think, that needs to be at the forefront of what we do now.

Sharon Jones: Yeah. Yeah, and Hazel, coming to you, what do you think enables that participation?

Hazel: Again, 100% agree with Chrisella and Segun that it's all about coming to the community and building that trust because it's, it's difficult, and it's about showing up and not just [00:11:30] showing up once.

Hazel: It's about consistently showing up and consistently building that trust because it's easy to do a workshop or do an engagement once and tell everyone this is what you're trying to achieve. But if you consistently show everyone who you are, what the research that you're trying to do is, it's not just about telling them about the research, it's understanding who they are before you actually trying to gauge them about the research because, like, [00:12:00] it's breaking down their walls and breaking down their barriers.

Hazel: As a Black community, we build up these walls, and I say it as we because we've been let down so many times and-

Hazel: like, I say this from my experience, from times where, from the sickle cell community, for example We had treatments that were brought in, so there was, for example, crizanlizumab and [00:12:30] voxelotor that were brought in, and they were approved in, uh, like, 2023, 2024.

Hazel: But then in 2024, they were then taken away. So early '24, crizanlizumab was then taken off the shelf.

Sharon Jones: Right.

Hazel: And then late September, October, voxelotor was then taken off the shelf, and that's very disheartening for patients with sickle cell. And in the Black community, you can see how also people have been let down [00:13:00] again and again

Sharon Jones: Yeah.

Hazel: in not just healthcare, but in general, like the stigma, the discrimination. And so to come in and just ask people to just get involved in research and then done and dusted-

Sharon Jones: Mm-hmm ...

Hazel: it's all about treating them as people before asking them to get involved in research. We have to be treated as people before we get involved in anything.

Hazel: So it's, I think that's how you get [00:13:30] people to be involved and enable them to get involved in research.

Sharon Jones: Yeah.

Hazel: It's just treating them as people before anything else.

Sharon Jones: And were there any factors for you that, you know, at first you might not have felt comfortable taking part, and what were sort of deciding factors that made you to get involved and participate?

Hazel: So for me, coming from, like, a personal point of view, 'cause I was on voxelotor, um, for me It, again, it was very disheartening- Mm-hmm ... um, when it was taken off the shelf, [00:14:00] and it was done very quickly overnight.

Sharon Jones: Right.

Hazel: And so for me, it's kind of one of those things where it's like, hmm, what do I do? Do I just not trust the system anymore?

Sharon Jones: Yeah.

Hazel: But then, like the flip side to that is, okay, we've had this drug, and it actually worked for me very well. And the look of that is, okay, so we've had this drug. It was amazing. The potential is we'll get more drugs that will be like this. And so [00:14:30] going into the Diverse Data program and thinking about how we approach people to say, "If you can get involved in this study, the likelihood is we actually might get more drugs, more treatments, more interventions that are going to be as amazing as Voxzelator was."

Hazel: Because the likelihood is we've had a drug that was great, and we could actually get more drugs that could be available.

Sharon Jones: Yeah.

Hazel: But we need research to do it because at the end of the [00:15:00] day, it's research. It's gonna take time, and the results are always gonna shift up and down. So yes, it can be disheartening, but at the end of the day, we've got to keep trying.

Hazel: Otherwise, if we don't keep trying, then we're not gonna get anywhere.

Sharon Jones: Yeah.

Hazel: So I had to ... You have to bite the bullet sometimes, and that's all you can do. So yeah, I think that was what shifted my mindset from not [00:15:30] -from being upset about it to then actually looking at the positives around it.

Sharon Jones: Yeah. Yeah. I mean, that is a difficult reframe when something that is working so effectively is suddenly kind of shelved, uh, very quickly like that.

Sharon Jones: So changing your mindset couldn't have been, couldn't have been easy. Christella?

Christella: When we're talking about what, what, um, Hazel has just said in terms of something was available to everyone and then it wasn't available, and then that goes again to what I say about [00:16:00] transparency. I think if there was more transparency about what was happening with this particular drug in the community, there would be that, that trust that would have, there would be more of an understanding, there would be more of a, like Hazel's taken the, the stance of, "Okay, I will still trust in the research because I believe something better will come along."

Christella: It's because of also her knowledge within the research. She's been around- she's been around Genomics England, she's been with people that research has really helped. But those in the [00:16:30] community who haven't, they feel disheartened about this, and this is why I say transpare- transparency about what is happening is so important with our community 'cause we-- so we don't feel like things are just being done to us, we actually understand the reasons behind it.

Christella: So for me, there's a few points. It's having people who represent the community actually being clinicians, um, being researchers, you know, leading in these community spaces, the transparency, the [00:17:00] long-term relationship that Hazel was talking about within the community. It's not you come in once and then, you know, you get what you want, and then you leave again.

Christella: It's also sharing the findings, and it's also having a trusted message constantly in order for the Black community to actually participate in these research.

Sharon Jones: Thank you, Christella. So we've got these themes of, like, consistency around trust, around communication, transparency. So Segun, I wanted to come to you now.

Sharon Jones: So why-- if people at [00:17:30] home are still trying to understand why this is important, can you explain to them why representation matters in research, and what happens when communities are not adequately represented in research? What is the impact, and how does that show up?

Segun: So representation matters in research because eventually a decision about our health will need to be made, uh, with this.

Segun: I give you an example of, uh, a, a drug that we have today, medication we have today that is helping to lower cholesterol. So that medication came to be because some African ancestry individuals were involved in a study. So in that study, they found that those African individual, they have, uh, some genetic variation that is helping them to naturally, uh, lower their cholesterol.

Segun: So because they included those African ancestry individuals, so we had, uh, PCSK9 inhibitor where the medication was derived. Now this medication is not only useful for, uh, people of, uh, Black community, but for everybody globally. So helping to lower cholesterol and prevent heart attack.

Segun: So we are doing ourself harm if we continue to exclude some people from, uh, from res- from research. Diagnosis is very important. So some tool for [00:19:00] diagnosis might not be appropriate for an ethnic group or, or ancestry or maybe, for example, in this case, a, a Black community.

Segun: In a research where we get the right diagnosis, uh, the right treatment, uh, for the right people, for the right community. So we cannot just do, uh, all the research on one particular community, and it posts the finding on another community. So representation is really, really very important, not only among, uh, people that participate in research and also in research leadership.

Segun: It is much more easier for Black community, uh, to show interest in research if they see somebody that look like them. So the, the representation has to be at every layer, both the [00:18:42] participant and also at the, at the leadership level.

Sharon Jones: Yeah.

Segun: I give an example for, for my study, uh, genetic risk score, in most of the study that we've done, we've seen that where you develop a genetic risk score from one population, and you try to, uh, transfer that, uh, genetic risk score to a Black community, they do very poorly.

Segun: So we need to include-- We need to be able to get to a point where we involve a Black community adequately in studies so that we can [00:20:30] be able to develop, uh, the right genetic risk score to every, every community.

Sharon Jones: Yeah.

Segun: So represent-representation is really, is really key. Uh, it's not just about fairness.

Segun: It's about the, you know, accuracy. It's about, uh, you know, precision. It's about better healthcare.

Sharon Jones: Yeah, and it's like you say, it's sort of holistically, it's from participants, but also for people who are working in research that also aids the sort of uptake in participation if you see people who look like you.

Sharon Jones: We're now gonna hear from Mica, who is a mum who took part in a Generation study, and she's gonna talk about why getting involved was so important.

Mica (Clip): I think as a Black woman, as a Black person, put yourself forward because the narrative at the moment is there's not enough research, and we're getting all these sort of doom and gloom headlines about, you know, Black maternal outcomes, Black men and prostate cancer, for example. And I feel like if we as a community don't put ourselves out there and make ourselves available for research, that narrative isn't gonna change.

Sharon Jones: So, Segun, I'd like to come back to you again. On the flip side of that, how can research organisations better involve Black communities? And are there concerns that we've talked [00:20:38] about today that have, uh, been acknowledged and addressed effectively?

Segun: So the first thing is that we need to acknowledge there's a problem.

Sharon Jones: Yeah.

Segun: And we see the Black people are not really, you know, participating in research because of trust. So how do we overcome that? One major thing is relationship or what I call, uh, community engagement. So community engagement is not community consultation. You know, you want to do research, you just [00:22:30] show up at that time you want to do research.

Segun: You know, take people's blood sample and go away. So community engagement starts much more years ahead before... So when you have the right relationship with the community, it's much more easier to be able to do research with them.

Segun: So we have to ensure that, uh, people that are doing the research are also well represented. So we have people that, that look similar, people that understand the community, uh, people that live among the community, so it's much more easier to help, help us to boost the trust. So the third one that people don't talk a lot about is benefit.

Segun: I've done a lot about recruiting people into research [00:21:43] in, in Africa, and there's a benefit sharing component. What we, what we have done in Uganda is that if you have high blood pressure, we have medication. We refer you to, uh, the clinic that is under our own control.

Segun: So we support you with your diabetes, support you with your high blood pressure or whatever thing that you have. If we cannot take care of you, that is where we now refer you to either to a doctor or a general, uh, general hospital. This is [00:25:00] really very important that there's a benefit. And also, uh, recently we've been working with, uh, some, uh, big pharmacy company, and we talk about benefit sharing.

Segun: Uh, for example, if we done some study, uh, we find some drug and med-medication, and the, the company had make millions of, of USD. So what come back to the community? So now we talk about, okay, can you now build an hospital here in this, uh, village? So we have to think about an appropriate benefit sharing also for the Black community in the UK.

Sharon Jones: Thank you. And I know, Christella, you touched upon some of those similar points that Segun made there. What does meaningful community engagement look like for you?

Christella: The benefit sharing is so important because we have to understand there is a problem, first and foremost, okay? And we have to understand the impact of that problem.

Christella: We have to bring solutions for that problem, but we also need to show those benefits in these communities that we're actually trying to engage with. And for me, when I'm talking about engagement, I'm really looking at co-designing, you know, not just consulting and telling them what to do, but the real difference is between being able to actually co-design the studies around Black people, so you can understand the nuances within the, the communities.

Christella: So understanding how to actually engage with these communities is, is really important And I think it's also being honest about the limitations that we have, that we've seen in the past.

Christella: You know? It's not about creating engagement which says you are the knight in shining armour and, and you're here to, you know, put a magic wand and [00:24:00] make everything okay. It's literally being honest about, you know, the preconceptions that people have. You know, what you're trying to achieve in the community, that you're actually trying to benefit the community.

Christella: It's important that those who are creating these studies don't go into a room and assume how these communities work. It's really about understanding the experience of Black people and letting them be experts of their own experience, using that to then find ways to better engage with, with communities.

Sharon Jones: Thank you. And Hazel, is there anything you would like to add?

Hazel: I think Cristella and Segun have hit the nail completely on the head. I think co-design is so important when it comes to engaging with the Black community. And I also think that [00:24:49] when it comes to research, it shouldn't just be about the research.

Hazel: It should be about, like, essentially giving back to the community as well. So e- exactly what Segun and Cristella were saying. So if we're talking about we need to do questionnaires or giving samples, the community, whoever is, whoever this research is for, should be able to [00:28:30] see results from this. It shouldn't just be a couple of years down the line they still don't know what is coming from this research.

Hazel: Because sometimes we do research and people don't understand what's happened to, to this research, and sometimes that is off-putting to people.

Sharon Jones: Thanks, Hazel, and we're gonna hear again from Mica, who captures that idea so powerfully

Mica (Clip): The research isn't for the NHS, it isn't for any medical institution, it's not for the government. It's for our community. We're at the heart of that research, and, like, we've got a chance to do something about it, and if you're not gonna put yourself out there, then who else is going to?

Sharon Jones: So, Segun, how can we ensure the future of healthcare innovations benefit everybody and they don't deepen health inequalities?

Segun: I would say that, so what is the benefit of, uh, innovation, if it does not benefit everyone, particularly people that need it the most? Uh, give an example, maybe Hazel will know a lot about this.

Segun: So now we have a sickle cell gene therapy. Of course, a few people have benefited, so this probably costs about, uh, millions of USD for one person. This is a great innovation, but who can benefit from it? It's too expensive. No-nobody's able to afford that. So we need to get a point where, so the so-called innovation can get to the right people, people that actually need it, and it's actually cost-effective.

Segun: In my own, uh, domain of work, we're trying to develop a new, uh, gene-genomic test or genetic risk score. So what we have seen from the data that is currently available is that, you know, when you develop this, the score from one particular population, it doesn't transfer to other population. So it-- the genetic testing, uh, is a great innovation, but it doesn't, it doesn't really do well in the, in the Black community.

Segun: So I think we should have to think much more at the beginning of innovation, uh, whether who is this innovation being prepared for? Who is going to benefit from this innovation? If innovation is not gonna, uh, benefit people that need it most, it doesn't really make any sense.

Sharon Jones: That's a good point. And Christella, you also had an example of what happens when communities are not adequately represented in research.

Christella: Yeah. So recently, um, in the NHS, they've started to, um, test for [00:27:45] a specific enzyme, which is, which is found in the Black community, um, for cancer patients going through chemotherapy. Originally, there were four enzyme that they tested for, um, in the genes, and they found that there's actually a fifth one which affects Black people within the community.

Christella: And it's so important that this happened because Black patients were having, you know, severe side effects to the chemotherapy, and some patients unfortunately passed away due to this particular enzyme. So understanding that our genes do have variants in it and some, as Segun said, some things which work in one community will not always work, um, in a different community.

Christella: So now before anyone undergoes a chemotherapy, the cancer patients across England undergo genetic testing, which can then lead into a change of treatment and reduce adverse, um, side effects for the chemo. Now that the NHS can test for this, it's gonna bring better outcomes to those in the Black community going through chemotherapy.

Christella: We all know chemotherapy is hard enough to go through, so making it a little bit better for those in our community that are going through it is so important, and that's why we need to be part of this research, 'cause without us, they won't know what's best for us.

Sharon Jones: Thank you for sharing that. And if you'd like to understand more about equity, please listen to our Explainer podcast, What Is Equity?

Sharon Jones: So let's hear from Mary with a message she'd like listeners to leave with today.

Mary (Clip): Thinking about my experiences, I would love listeners to take away the fact that engaging in research is bigger than you. It shapes your community, and it shapes the lives of the children coming in the future. Black communities, we need to know our baseline.

Mary (Clip): We need to know where we are starting. It's bigger than us. My engagement helps the granddaughter I don't have, and that's what I need people to know.

Sharon Jones: And given what Mary said, I'd like to ask you all, what message would you [00:29:34] like to leave for listeners who are interested in learning about research? I'll come to Christella first .

Christella: I think first of all, we have to acknowledge that the questions and the hesitations within the community are very valid, and we have to understand that this makes sense given the history of research.

Christella: But I would love listeners to be left with the knowledge that history shouldn't be the final word of our relationship with research. We ask the hard questions that we need to ask and invite those who need to also benefit from this research. And like Mary said, "I'm helping my grandchild that I don't even have yet."

Christella: And I think that's how we need to look at it. It's not so much just about us, but it's the future generation. It's about having better outcomes for each and every one of us, and that includes the Black community. So help shape further research, and medicine will actually benefit us in the future.

Sharon Jones: Hazel, what message would you like to leave listeners today?

Hazel: I think going into research can sometimes be hard. However, I do think research is incredibly important, [00:31:14] especially for the younger generation.

Hazel: So I do think that we should get involved.

Sharon Jones: Thank you. And Segun?

Segun: Yeah, I would like to, uh, recall what, uh, Christella was saying, uh, particularly saying that for everybody, uh, listening to me right now, if you are invited to participate in the research, please participate, you know.

Segun: Ask the right question, "What is the research for?" And, uh, how does it benefit you? Maybe not you directly, maybe your children or maybe your grandchildren. Everyone should remember that, uh, so research is ultimately for the people, for better healthcare.

Segun: So our contribution really matter. So you're contributing your sample really matter and can change, uh, somebody's life, can change generation. Every participant has something valuable, which is really key. So I would encourage all the listener to participate in research if you are invited.

Segun: Thank you.

Sharon Jones: I think that's a very salient point. We'll wrap up there. We've covered a lot today, from trust to participation and what is needed to change to ensure that healthcare is for everyone. A huge thank you to our guests, Christella, Segun, and Hazel, for joining me today as we discussed how Black communities are being served in health research.

Sharon Jones: If you enjoyed this episode and you'd like to hear more, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I've been your host, Sharon Jones, and Behind the Jeans is produced by Deanna Barac, Sophie McLachlan, Katie Revell, Adam Wavy, and Patrick Wallace at Bespoken Media.

Sharon Jones: Thank you for listening.

In this explainer episode, we’ve asked Sasha Henriques, Director of Equity Assurance at Genomics England, to explain what we mean by the word equity in healthcare and 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, let us know on podcast@genomicsengland.co.uk.

You can download the transcript or read it below.

Florence: What do we mean by the word equity? My name is Florence Cornish, and today I'm joined by Sasha Henriques, who is Director of Aquity assurance here at Genomics England, and also has a PhD specifically looking at social justice in genomics. And Sasha is here with us today to tell us much more about the topic. 

So Sasha, I think with this topic, when it comes to discussing equity in healthcare, a good place to start might be by acknowledging that not everyone has the same experience with accessing healthcare or the same outcomes even when they do access it.  

Could you maybe tell us a bit more about why that is and what factors are at play there? 

Sasha: Hi, Florence. Thanks. It's a really interesting question because it's a really big problem. So, the reasons that we don't have access to the same things can have multiple different ways that we're affected, from where we're born, to the schools that we go to, to the education that we have access to. Lots of those things are outside of our control, and they're determined by the political landscape that we're born into, whether we're born in a rich country or a poor country, or a rich part of the country or a poorer part of the country. 

So those are kind of the structural things that might make things different. So, when we come to access healthcare, there might be different healthcare that's available to us. We might be able to negotiate the system differently because of what we understand about how healthcare works and what's available to us. 

And then there might be personal things about us that make those things more challenging, so the abilities that we have or don't have, both kind of the ways that we learn, the ways that we hear, the ways that we see. All of those things kind of change our access, so the way the system treats us, but also how we show up in the system are all things that can affect us when we come to engage with healthcare. 

Florence: And obviously, the topic of this podcast is equity, and  we hear this word equity a lot, especially in conversations around healthcare and genomics. But could you explain for any listeners who maybe aren't quite sure what exactly equity actually means?  

Sasha: Yeah. So I think lots of times people hear equity, and they think it's just about fairness, and it's just about treating everybody the same way. 

But what equity does is that conversation, that question that you asked me about, like, why do people experience healthcare different, there are all sorts of places in our lives where we will have different access, different benefits, different ways that we can participate.  

And what equity says is that because we're all different in those different ways and we have different needs, different ways that we're discriminated against, and different ways that we're privileged, what equity means is how do we design a system, how do we offer something or do something that enables everyone to have the same outcome of that benefit? 

So for example, you could make a research leaflet really easy for everybody to access. And what that would mean is that everybody gains more access to that information. But if you are discriminated against because of the way that you read information or the way that you access information, that's not really helped you. 

So it's helped everybody, so we can move everybody along, and that's kind of what we would call equality. But actually, you don't all get the same outcome at the end. And what equity means is that we understand the different needs that people have so that when we look at where everybody arrives to at the end, that's where we see the benefit, rather than just making a change that's the same for everybody.  

Florence: Can we dive a little bit deeper into that? That difference between equity and equality. Could you maybe explain a little bit more about that specifically?  

Sasha: Yeah. I guess there are different ways that people illustrate the difference between equality and equity. 

And so equality could mean, for instance that everybody needs to get to a certain position, like from position A to position B, and everybody needs a particular bike to get from position A to position B. And so equality would be that we give everybody the same bike. So we make sure that your bikes have the same speed, your bikes are the same make, that your bikes are as new as each other, so nobody is given a worse bike than the other to get from position A to position B. 

But it might be actually that you've given this bike to somebody who isn't able to ride a bike because they have a problem with their legs, or it might be that you've given a bike of everybody's bike is the same size, but some people are shorter than other people.  

And so while equality means kind of treating everybody the same, equity actually means that we take consideration of the fact that we may need to treat people differently, so that they can get the outcome. 

So everybody can make the journey, but not everybody's going to make the journey in the same way. And equity is about what do we do so that people can all experience things and benefits in the same way, rather than treating everybody the same way.  

Florence: Mm-hmm. And do you think there are any challenges in equity specifically to the field of genomics? 

Sasha: Yeah. So I think that's a really simple explanation that I gave between the difference of equality and equity, and genomics is a really interesting point to show why that's a really simplified version of thinking actually what equity means.

So when we think about genomics, there are a number of particular things about genomics and the history of genetics that make that equity conversation and the way that people's benefits and outcomes may be shaped really critical when we think about genetics. 

So one is, I spoke before about, you know, where you're born in the world can have a really big impact on what you're able to access and what you're not. And genetics is one of those things that kind of really changed the world but hasn't changed the world for everybody. And so the people who were studied, the people whose DNA was looked at, all of the things that give us the knowledge about how genetics should work, was largely done in only particular places in the world, so particular northern European countries, parts of the US, some of those studies have been done in Japan. 

So lots of the knowledge that we have around what genetics means for different groups and different people doesn't actually think about all of the people in the world. So when it comes to genetics, we're kind of using references and data that actually are already not equal with the people that we want to serve. 

So there's something like really embedded in the way that genetics works, that we're kind of already starting from an uneven landscape.  

And then genetics sits within healthcare, it sits within research, it sits within all these other places, which again, are affected by things like money and things like politics, political stability, geography, whether your country has legislation or policies for those things. So, I guess those are the kind of structural things that make genetics kind of different and more challenging when we think of those inequities that already exist. 

Florence: Yeah.  

Sasha: But then genetics itself is about finding information that, yes, is about you, but might also be information that we share with lots of other people, so people within our families, people within our populations. And so actually thinking about who has the rights over genetic information, how genetic information is shared, how the genetic information benefits everybody that it should, are other, like, really particular questions that come with genetics. 

So, there are all these different ways that the structure can build inequity into what we're thinking about genetics because of the history of where genetics has come from, but also the ways that the system kind of uses genetics, and the ways that genetics can be used against us. So I think it's really important, that conversation about equity in genetics, that it's not just about getting from place A to place B, it's about what is the road like? And what experience will you have? And when you get to the end of the road, what are people going to do with the information?  

Yeah. So actually, that really simple explanation that I gave can become really quite complicated when you think about something like genetics.  

Florence: And so you took on the role of director of equity assurance at Genomics England. Tell me a little bit more about that. What’s the purpose of this role? Do you have anything specific that you'd like to work towards or achieve?  

Sasha: So the reason that that role came about is because of some of those problems that I've mentioned, that you want organisations like Genomics England, research organisations, healthcare organisations, we often have missions and strategies that are about the benefit for society, that we do this work for the benefit of all, for the benefit of society. We want a world where everyone can benefit from genomic healthcare, for instance.  

These are really common kind of strategies, motivations, and intentions that organisations have, but they're so top level that actually what does that mean on a practical day-to-day?  

So my role really came about from Genomics England being really committed to the idea of equity and wanting to achieve it. But actually, in reality, how you make that happen in the different functions of an organisation can be really quite tricky. 

So how do we think about equity when we think about the science, when we think about the research, when we think about the data, when we think about recruitment, when we think about someone's experience of being part of research? There are equity questions in all of those places.  

Florence: Mm-hmm  

Sasha: Importantly, the thing that I want to achieve is to really appreciate the fact that everyone thinks that this is important, and give them some of the skills so they can think about what kind of dealing with inequity in their area kind of means.

But also kind of importantly, what the role also means is, like, there's equity and also there's assurance. So one of the things that doesn't quite always get attached to sometimes these conversations about equity, is that actually you can measure those things.  

So you can measure patients' experience. You can measure whether there was a benefit. You can measure whether there was a change in clinical outcome. 

So again, kind of using that example of the people on the bike, we can change things to meet people's needs, but actually we need to then kind of measure the times at the end of the race to see whether actually we improved the times for people now that we've made those adjustments. So that's what the equity and the assurance means, right? 

So the equity is kind of putting things in the system or in the design that we want to have the impact of fairness, but the assurance is, and how am I monitoring and measuring that so that I can say, "Well, actually, that was a successful change. I would do that again, or I wouldn't do that again." 

Florence: Well, I think we'll finish there, but that was such an interesting conversation, Sasha, thank you so much for coming on and, and taking the time to talk to us.  

Sasha: No problem. Thank you.  

Florence: If you want to hear more Explain episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. 

Thank you for listening.

In this episode of Behind the Genes, we explore how personalised cancer vaccines are being developed, and how genomics and AI could help make these treatments more precise. 

Our host, Florence Cornish is joined by: 

Dr Victoria Goss, Associate Professor of Early Diagnosis and Translational Research at Southampton Clinical Trials Unit and head of the Southampton Clinical Trials Unit Cancer Vaccine Launchpad team 

Professor Lennard Lee, Associate professor at the University of Oxford, Consultant Medical Oncologist, NHS 

Ali Richards, a participant who took part in a cancer vaccine clinical trial 

Together they discuss how cancer vaccines train the immune system to recognise cancer, how genomic information can help identify the unique features of an individual’s tumour, and how AI could help researchers analyse genomic data and accelerate the development of new cancer vaccines. 

 “The reason I said yes was because my treatment really was punishing. It was so many side effects to it. The cancer never made me feel sick, but the treatment made me really sick. So I said yes because I just wanted to help other people not have to go through what I went through.” 

 

Transcript

[00:00:00] Florence: What if a vaccine could help treat cancer? Hello and welcome to Behind the Genes, the podcast that brings you the stories, research, and innovations shaping the future of genomic healthcare. Today, we're going to be talking about cancer vaccines, how they're being developed with the help of AI, what role genomics has to play, and what it could mean for patients. 

[00:00:23] Florence: I'm Florence Cornish, and joining me today we have Dr Victoria Goss, who leads cancer vaccine research at Southampton Clinical Trials Unit; we have Professor Lennard Lee, who is a medical oncologist and Associate Professor at the University of Oxford; and Ali Richards, who took part in the Southampton Cancer Vaccine Programme. 

[00:00:45] Florence: I think before we get into cancer vaccines specifically, it might be good to start with the basics. So vaccines are something most of us have heard of and probably experienced as well, but we don't always necessarily understand how they work. So Lennard, can I come to you to explain what a vaccine actually is, how it works with our immune system, maybe at the most basic level for those who might not have a scientific background? 

[00:01:19] Lennard: Thanks, Florence. What's a vaccine? Very, very simply, something that protects your body from disease. We've had a few when we were younger, like which protects you against meningitis or hepatitis or different types of infections that can affect children. 

[00:01:36] Lennard: And it really does show that your immune system is really powerful. Every day, it looks around trying to work out what's there which shouldn't be there and takes care of it. And ideally, your immune system just works in the background without causing any problems. And so what a vaccine does is it really helps the body understand something that's abnormal. 

[00:01:55] Lennard: And the vision here is that you can use this technology to hopefully patrol against cancer, because half the people out there will never get cancer. They are the maybe the lucky ones or maybe the ones with a good immune response. And so a vaccine is basically giving your immune system a wanted poster: 

[00:02:11] Lennard: "This is what threat looks like. This is what you need to control".  

[00:02:16] Florence: And I think you mentioned some great examples there. There are lots of common examples of vaccines people might have heard of. I think maybe the flu vaccine is probably a common one that people are thinking about in the wintertime. I think another one is maybe the HPV vaccine. 

[00:02:29] Florence: Lennard, could you explain a bit more to our listeners about the HPV vaccine? What it is, how it works? I think people often think of it as a type of cancer vaccine, but actually it's targeting a virus. Is that right?  

[00:02:41] Lennard: Yeah, that's correct. So this is now a vaccine which has been rolled out across the NHS, and it's actually worked really well to get rid of a few cancer types, which is incredible. 

[00:02:51] Lennard: And why is that important? Well, cancer can be caused by many, many different things. Sometimes it's because you've done things like smoking or weight plays a role or just bad luck or the genes that you've inherited. But some cancer types are caused by viruses. And so many people nowadays are getting the HPV vaccine to stop cancer types like cervical cancer, hopefully head and neck cancer, and many of the rarer cancer types. 

[00:03:21] Lennard: And so again, what you're doing here is you're taking the immune response, telling it the body shouldn't get this virus and hopefully prevent some of the bad consequence of getting this viral infection, like cancers.  

[00:03:33] Florence: Thank you. That's really helpful to understand. So we've talked about how vaccines can be used to treat viruses, and I think most of us, when we hear the word ‘vaccine’, we probably do associate it with something that stops us from getting ill. 

[00:03:46] Florence: Victoria, could you tell us about how vaccines could be used to treat cancer?  

[00:03:50] Victoria: Yeah, absolutely, and it is great to be here today. Thank you. So Lennard's already sort of spoken about preventative vaccines, and when we think about cancer vaccines, we're thinking about therapeutic vaccines. So we're thinking about training the immune system to recognise the cancer as something that needs to be dealt with because cancer is really tricky because it's our own cells that have gone wrong, if you like. 

[00:04:16] Victoria: But that means it also is very good at evading those signals which tell the immune system that it needs to be cleared. So the analogy that Lennard has already given of a cancer vaccine sort of creating a wanted poster sort of builds on an analogy from one of your previous podcasts where they described the immune system as like the police almost trying to catch criminals, which are the cancer cells. 

[00:04:41] Victoria: And the cancer vaccine analogy builds on that. So you've created a wanted poster which is training and giving the police more information about what those cancer cells look like. And then when we think about building on that with sort of personalised cancer vaccines, which is an incredibly exciting step when we think about the development of how cancer vaccines can be used, sort of really individualised therapy going forward, that wanted poster gets even more specific. 

[00:05:07] Victoria: It's almost like giving a phone number or an address for that specific cancer type that is very specific to that patient. So the therapeutic vaccine is, is targeting the immune system. It's training our immune system to recognise the cancer as something that needs to be dealt with.  

[00:05:26] Florence: It's funny you mentioned that analogy because I was just about to point listeners to that episode. If anyone wants to learn more about cancer vaccines specifically, you can check out our previous Genomics 101 podcast episode called ‘What Are Cancer Vaccines?’ So Ali, I think I'd love to bring you in at this point because you have experienced this from the patient side of things. 

[00:05:49] Florence: Could you tell us a little bit about your journey, your cancer diagnosis and treatment, and maybe more about the clinical trial you were part of, if you feel comfortable sharing that?  

[00:05:57] Ali: Yeah, sure. Hi, Florence. It was Christmas 2015, and I felt a lump in my neck. And maybe because I'm a woman and we're always taught to treat lumps seriously, in the January I made an appointment with the GP, and she very quickly fast-tracked me through to the hospital. 

[00:06:19] Ali: And January 2016, I got a diagnosis. It was a tumour on the base of my tongue at the left, and I was told it was caused by a variation of the HPV virus. So yeah, that was all a bit of a shock. I was shocked and I was scared, but I was also really angry because I look after myself. I eat well, all those things. 

[00:06:45] Ali: It's just bad luck that it was a virus that my body couldn't deal with. I just, I felt guilty as well because of what I was gonna put the family through. So I had various scans and tests. I had an operation to remove my tonsils, although we soon discovered there weren't any left anyway. And they took a biopsy, which I didn't know at the time, but turned out to be important later on for the trial. 

[00:07:15] Ali: Then I had to have a whole load of prep beforehand because of the impact of the treatment. So I had to have restorative dentistry, audiology tests. I had a PEG fitted, that's a feeding tube, in my stomach, and I thought, "Surely it's not going to be this bad." But that PEG, that feeding tube was a blessing in the end. 

[00:07:40] Ali: And I had a mask made, and the mask fits you and basically pins you down to the radiotherapy table so you don't move when... because it's very precisely targeted at your tumour. So yeah, I went on to have five sessions of chemo, which felt quite easy. The radiotherapy was the really, really tough part. I had, uh, seven weeks of it, 35 sessions. 

[00:08:08] Ali: So that was, yeah, that was a challenge.  

[00:08:11] Florence: Thank you, Ali. Thank you for sharing that. I think it's always really valuable to get that patient perspective when we're talking about things like this. Lennard, I wanted to come back to you now to talk about the different types of vaccines that exist and which ones are being used specifically in the treatment of cancer. 

[00:08:30] Lennard: Um, thanks, Florence. And Ali, are you 10 years now down the line since your diagnosis?  

[00:08:34] Ali: Yeah, it feels good.  

[00:08:37] Lennard: Congratulations.  

[00:08:38] Ali: Yeah, yeah. It feels good. I really valued the follow-up checks that I had, both from my oncologist, but also I got some through the trial, and it really helped restore some confidence in myself and my body to deal with things and to be able to move on as well. 

[00:08:56] Lennard: Oh, well done. That's fantastic because you telling us that story just really brings it to life about how scary this can be and also the fact that you had to go through all those sessions, thirty-five sessions and, um, and now you're 10 years down the line and still talking and giving hope-  

[00:09:11] Ali: Yeah ...  

[00:09:11] Lennard: that new technology still comes, so thanks, Ali. 

[00:09:13] Ali: That's a pleasure.  

[00:09:14] Lennard: Um, yeah, so Frances, this is what's really exciting. What types of vaccines are there? Well, first thing to say is that we're really good in this country about vaccine research. If you look around the world, what are we good at? Well, everyone knows that we developed the pandemic vaccine, and actually that technology is something that we can control. 

[00:09:31] Lennard: We're world leaders at. It's quite cheap technology, and it's something that we are really good at bringing to patients. And Ali's our testament where she got on the trial, she helped test it and really pioneered new ways of research. So what types of vaccines are there? Well, I think we talked to the first bit where Victoria taught us that some of them can treat cancers and some of them can maybe prevent cancers. 

[00:09:53] Lennard: And the HPV's one which is maybe be able to do both one day, which is brilliant. What would like... what else do people know about? Well, people might know that there are different types of technologies. So if we think back a few years now, back to 2020, there are some which are viral-based, and some which are mRNA based. 

[00:10:12] Lennard: Both of these were new technologies which the whole population of the world came together to create and some of them are peptide-based. So there's probably three different types here. The protein ones or peptide one, which you always had, and then in the last five years, it's an incredible time to be alive, where new vaccine technology comes through, it's more effective and safer. 

[00:10:32] Lennard: These are the viral ones and mRNA ones, and everyone's now pursuing all of these to try and make sure that we can maybe treat cancer in future.  

[00:10:41] Florence: Can I possibly pick your brain a little bit more about the mRNA ones specifically? I think as you mentioned, lots of people might have heard of those during COVID. 

[00:10:50] Florence: Could you maybe explain a little bit more about those and how they work?  

[00:10:53] Lennard: Yeah. So this is going to take us all the way back to GCE biology now. If you remember - and we are Genomics England, so we, we got to work out why genomics is important, and we'll probably get to this. But remember, genes make RNA, which then makes protein. 

[00:11:11] Lennard: And so if you're trying to reprogramme the immune response, you could give your body a protein, the back end of it. You can maybe give it an RNA, which is a blueprint too. And so what an mRNA vaccine is, it's a way of giving the blueprint or the instructions to the body of what to recognise, what the cancer looks like, um, um, or what the virus looks like, and target it. 

[00:11:32] Lennard: If you want the analogy, well, for those people who had the pandemic vaccines, the ones which was mRNA based was, uh, the Pfizer one, and that worked really, really well. Cheap to make, easy to produce, and, uh, it's just a jab. And so people are now exploring that for cancer treatment now. Take new technology, which has only been developed five years ago, technology, which is just a blueprint, cheap to make, easy to update, and now we're targeting cancer. 

[00:11:59] Lennard: Um, so that's basically what an mRNA vaccine is, giving the body the blueprint or the instruction of what a cancer looks like and trying to target that cancer.  

[00:12:08] Florence: And you kind of alluded to it a little bit in your answer, but, um, it would be good to know more about where genomics comes into all of this. You know, why is it such an important part of developing vaccines? 

[00:12:18] Lennard: And that's a great question, and really comes back to our second strengths, which is that we're really good at vaccine research, and yet we are also world leaders at genomic research. It's a really exciting time because, um, when Victoria and me and Ally at school, we would-- we, we learnt about that race to sequence the first human genome. 

[00:12:38] Lennard: It was really exciting because for the first time, we can see every single genetic base in every human, and that used to cost billions of pounds to do that, and it would take many months or years to do that Fast-forward a few years, and then now Genomics England delivered the next success for humanity. 

[00:12:57] Lennard: I think it was about 2015 to 2017 where they, they did 100,000 Genome Project, where the UK led the world in sequencing 100,000 people, including people with cancer, to try and understand what caused their cancer, what the risk factors are. And why is that relevant now? Well, it's because if you know what a cancer looks like, then you know what the abnormality is, well, then you can vaccinate against it. 

[00:13:22] Lennard: So we've now gone from this amazing arc of discovery here, where when we were at school, we worked out what the human genome looks like. We can sequence it end to end and see in all its detail. Then a, an amazing organisation came out the ground called Genomic England, which shows that you can run it in the NHS. 

[00:13:39] Lennard: 100,000 people could do it. And now we're making the next big jump now, which is it's not just going to give you a diagnosis, but maybe becomes a drug and a vaccine in future. And actually, probably it already has because Ali's that example, a success example of it happening.  

[00:13:54] Florence: Yeah, I wanted to actually ask you about that, Ali. 

[00:13:56] Florence: So just as you were saying, Lennard, it kind of... The cancer vaccine sounds quite futuristic, but as you said, it's, it's sort of already happening. So Ali, do you remember kind of how you first heard about the cancer vaccine trial?  

[00:14:11] Ali: Yeah. I had a bit of an unfortunate time because after all that radio and chemo, my cancer still hadn't gone, and I had to have an operation to remove lymph nodes. 

[00:14:22] Ali: But my oncologist at Poole Hospital, who's a fantastic woman, she had been involved, unknown to me, in the some of the thinking behind the trial, and particularly that she could recruit people because they were sat in her office. So she asked me if I'd like to take part, and without knowing anything, I said yes. 

[00:14:49] Ali: And the reason I said yes was because my treatment really was punishing. It was so many side effects to it. The cancer never made me feel sick, but the treatment made me really sick. So I said yes because I just wanted to help other people not have to go through what I went through. I didn't really understand it, if I'm perfectly honest. 

[00:15:16] Ali: I didn't really know what was going on, but then I'm not, you know, a super brain like Lennard and Victoria. I knew that I just wanted to do something to help people going forward, not having to deal with the same. So yeah, I put my hand up and there I was on the trial.  

[00:15:37] Florence: So you mentioned there the, the really horrible side effects that you got from your original treatment. Did you have, um, what was your experience with side effects with the vaccine? Was it similar? Was it different?  

[00:15:47] Ali: Oh, no, the, the vaccine was like a holiday compared to the treatment. Absolutely. At, at worst, in the first few treatments, you felt a bit like you had a cold, bad cold coming on, maybe slightly flu-y, but you took, you were given Ibuprofen at the same time as you had the vaccine. 

[00:16:10] Ali: So no, it, the treatment with the vaccine was an absolute breeze. Which is kind of like, yes, this is what I want for people. You know, not, not the radiotherapy, not the chemo. So yeah, it was, it was really very easy by comparison.  

[00:16:29] Florence: Oh, I'm so glad to hear that that was your experience. I'm just curious now also, was there anything that surprised you about the trial? 

[00:16:35] Florence: You said there that you didn't really, like, have an understanding of cancer vaccines. You, you agreed to it straight away. Was there anything that maybe, like, you weren't expecting or surprised you?  

[00:16:45] Ali: I think it surprised me that it was really quite easy.  

[00:16:48] Florence: Yeah.  

[00:16:49] Ali: Uh, I was delighted to have the team I had looking after me because they were fantastic. It all felt very simple. 

[00:16:59] Ali: And how nice that was. You know, if I could've had that instead of all my previous treatments, um, it would've, it would've made everyone's life so much easier. And I guess, I don't know about the cost of drugs, but I guess the cost to the NHS would've been less because I wasn't in and out of hospital, I wasn't having to have all these extra things done, and all this extra support like dieticians and so on because I had to have my feed tube replaced. 

[00:17:35] Ali: So all of that is impacts on the NHS, whereas this was very simple.  

[00:17:40] Florence: I wanted to come to you now, Victoria, and ask you about the outcomes of this trial that Ali took part in or other trials like it, and whether we know yet what the broader implications of, of these advances might be.  

[00:17:55] Victoria: So I think what we need to think about when we're thinking about developing these treatments and sort of evaluating the treatments at each stage is that it goes through a very clear pathway of progression, and Ali was involved in one of the, the earliest stages of that progression. 

[00:18:09] Victoria: And it's, it's always amazing to me to hear your story, Ali, and to know that patients are willing to take part in the research and that's what allows us to develop these treatments. So the trial that Ali was part of has now gone on to develop into a, a larger scale study which will be evaluated again. 

[00:18:27] Victoria: And that all starts to form the evidence for how these treatments can be shown to be effective, and also how they can show... Also, you know, Ali's already touched on there about the cost implications, so how we can show that that can be beneficial as well. And then we can start to think about how they can be taken up and become part of routine standard of care for patients like Ali, as she was describing. 

[00:18:50] Victoria: And all of that evidence comes together, which then gets evaluated and then it, and then it moves forward through that progression. But it's-- we have very clear, um, you know, a, a route that each new, new treatment has to go through, um, to be able to, to become part of standard of care.  

[00:19:07] Florence: And Victoria, you also play a key role in the Cancer Vaccine Launchpad. 

[00:19:12] Florence: For any listeners who might not be familiar with the Cancer Vaccine Launchpad, could you maybe tell us a little bit more about it?  

[00:19:18] Victoria: Absolutely. So in its simplest terms, the Cancer Vaccine Launchpad is designed to help find patients who might be eligible to take part in trials like the one that Ali was part of. 

[00:19:30] Victoria: It's an incredible project. Cancer Vaccine Launchpad is quite long, so we tend to abbreviate it to the CVLP, which I'll do from now on, if that's okay. The CVLP to me really demonstrates the power of collaboration because it's brought together so many different teams that have been necessary to make sure that, that what we're trying to achieve, so finding as many patients as possible for these trials, is possible. 

[00:19:52] Victoria: We deliver this project on behalf of NHS England. I know that Lennard was involved right from the start as well. The reason that we need the CVLP is because one of the biggest challenges in research of these new treatments is finding the patients who might be eligible. So one of the reasons for that is because when we are running the trials to test these new treatments, there's a lot of different infrastructure that's needed to support the delivery of those trials. 

[00:20:19] Victoria: So you need special pharmacy services, special research nurses. All of that has to come together to be able to deliver trials of new treatments. And actually, that means that actually those studies can often only take part in a small number of hospitals. So historically, you only had the opportunity to take part in those trials if you lived near one of those hospitals, which is, you know, like Ali did. 

[00:20:42] Victoria: So what the CVLP is, what, what it has done, it has created a formalised network which enables referrals to happen from ... we're opening 83 hospitals now across England. We've just expanded out to the devolved nations as well, which is a really exciting development, and it creates that, that network which allows patients who might live further away from a hospital delivering one of those vaccine or immunology trials to be able to be referred in to see if they might be eligible. 

[00:21:09] Victoria: So essentially, it's a bit like creating a big funnel. So you're finding all of the potentially eligible people that could take part in that trial, and you're funnelling them into the trial site to find those patients who are eligible.  

[00:21:22] Florence: And what impact do you hope that this could have for the NHS and also for, like, individual patients as well? 

[00:21:29] Victoria: So we've seen such positive results from the CVLP so far. The first study that we worked with was for a colorectal cancer vaccine trial. Before the CVLP started working with this trial, only 17% of the eligible patient population in England had the opportunity to take part because they lived near one of those hospitals delivering the trial. 

[00:21:52] Victoria: After the CVLP started working with it, we had increased that to over 60% of the eligible patient population. So you could really see how it has expanded out access, and that's just a fantastic opportunity to be able to bring, to bring patients. We also were able to show that the UK was screening, so looking for patients at three times the global average. 

[00:22:14] Victoria: So we really were able to see how the CVLP is supporting and accelerating recruitment to those trials I think the key thing for me has been the patient enthusiasm that we have seen though. So when we open up to a new trial where, that the CVRP is working with, we are always inundated with people who contact us to find out how they can be part of this network because they want the opportunity to take part. 

[00:22:40] Victoria: We know that some patients have travelled for two hours to a trial site to find out if they could be eligible because actually they want the opportunity. So the CVRP has really sort of enabled that patient choice, which is a fantastic thing to be able to do. But it also builds on what Lennard was talking about earlier, which is the UK is really good at this research and actually what the CVRP is then doing is showing how we can really support recruitment to these trials to accelerate these trials and that only brings more trials to the UK which again creates more opportunities for patients which is exactly what we're trying to do. 

[00:23:14] Victoria: We're trying to create more and more opportunities for patients to take part in these studies if they want to.  

[00:23:20] Florence: Yeah. That's really incredible. Thank you for sharing that with us. I wanted to ask you a question now, Ali, because I think when we were talking about trials and projects like this, as Victoria said, we often think about kind of the high level impact, but also it's an opportunity to create connections as well between patients and families and, and I know that you, you had a patient's family reach out to you about advice as to-- about whether they should take part in a trial. Is that right?  

[00:23:47] Ali: Yeah. I think it was the wife of a guy up in Liverpool who had throat cancer, and, um, she must have done some really good research on the internet. I'd done various bits of publicity both for Southampton Uni and cancer research around the trial. So she obviously found me and then stalked me on Facebook , which was absolutely fine. 

[00:24:13] Ali: I didn't have a problem. So her husband was down to go on the trial, which is the next stage that Victoria had spoken about, and she just wanted to know, would I recommend it, would-- what was it like, that kind of thing. So I said to her, "I would absolutely recommend it, of course," and told her what my experience was. 

[00:24:35] Ali: I couldn't guarantee his would be the same, of course, because things might have moved on. But it was a really, it was a kind of a nice feeling that I could say to her, "Get him to have it done because it's got to be the best outcome." I think his stage was much further on than me. So yeah, it had to be the way as far as I could see for him. And as far as I know, he went on the trial. Which is great.  

[00:25:05] Florence: How, how did it feel to kind of make that human connection, maybe not something you were expecting to come out of a trial?  

[00:25:13] Ali: No, it was really, it was really nice. I am a bit of a, a fangirl for, for Lennard and Victoria and all the team at Southampton. 

[00:25:22] Ali: If anybody asks me about vaccines and cancer vaccines, I'm like, "Oh, yes." And you-- So yeah, I'm, I'm a bit of an evangelist. So to, to have somebody real-  

[00:25:33] Florence: Mm ...  

[00:25:34] Ali: ask me about that was great feeling.  

[00:25:37] Florence: I think that's a, a really great example of how research can have impact far beyond, uh, one individual. And I think another great example of this is also artificial intelligence or AI as a potentially transformative force in, in healthcare. 

[00:25:54] Florence: Lennard, when we come onto this topic, I wanted to hand over to you because I know that you've recently received funding for a project exploring AI, and how it could support cancer vaccine development in particular. Could you tell us a bit more about this project?  

[00:26:08] Lennard: Thanks very much, Florence. And I also want to add, I feel very proud about what Ali did just there, where she's able to bring through opportunity for other people, too, which is amazing. 

[00:26:19] Lennard: The NHS is there to not just do the technology of today, but also be one of the best healthcare systems in the world to bring through new technologies. And it's just really exciting about people wanting to help the NHS, advocating for new technologies to be tested, and actually that's what Genomics England i there to do, make sure the NHS gets new technology in there so that patients will get new treatments. 

[00:26:41] Lennard: I just wanna just reflect what Victoria noted In the NHS, in their Cancer Vaccine Launchpad, patients are getting in at three times the rate of other countries.  

[00:26:51] Ali: Mm-hmm.  

[00:26:52] Lennard: That's really special. And also she's increased coverage to, uh, did you say 60% of population? That's 42 million people have potential access to this. 

[00:27:01] Lennard: So that is huge, and I think it's really a passion project for so many people out there, PICT trials units, the research nurses and doctors, and also patients who make this all happen. So it is quite impressive. It is very impressive. Oh, yes, and AI. I probably should cover that too. Just beyond what's special about the NHS and Genomics England. 

[00:27:22] Lennard: Well, AI I think is changing everything. I went to a garden party, and actually everyone's talking about how they're using AI to make their lives simpler, make them do things that they've never been able to do before, get the information instantaneously there. And I think that there's technologies which come through every so often in our lifetimes, which changes how we think, how we communicate, and actually makes us better in many ways. 

[00:27:47] Lennard: And so the great opportunity here is what happens if we take that third strength now? So we've already said we're really good at vaccine research in the UK. The UK invented vaccines. We also are world leaders at genomics. We did the 100,000 Genome Project. What happens if we use this new technology now? 

[00:28:06] Lennard: And what's a problem that we can solve? Well, let's say we did a whole genome sequence on someone, which is what Genomics England does every day for the NHS. Well, that creates a lot of data. Um, I tried to do the calculations before we went online. It's about 100,000 photos. You know, when you take on your phone, that's a lot of data. 

[00:28:25] Florence: Wow. Yeah.  

[00:28:26] Lennard: And that's a miracle what's happening in the NHS and Genomic England, and we need to make a cancer vaccine out of that. And so you need to process that. So that's time-consuming. It could be automated. And so what AI could do now in future is that we could use the supercomputer we built in the UK. 

[00:28:43] Lennard: In fact, we are doing this already. We've built supercomputers in the UK, and we're going well beyond other tools out there and designing cancer vaccines. And the AI scientists which can do that can do it at weekends, at nights, and help design the drugs. And so what it does is it heralds a future where every patient can contribute into a model that's created in the UK, stored safely in our supercomputers. 

[00:29:07] Lennard: It can now be made into drugs, and the UK will start to make things again, which will hopefully change cancer care across the world. We can deliver that legacy whereby our three strongest strengths come together - vaccines, AI, and genomics. It then super powers the NHS and everything that Victoria's done in the Cancer Vaccine Launchpad, so many millions of people around the world can get access to trials. 

[00:29:31] Lennard: And people like Ali can also help hold up the NHS even further. So people once again look back to us and say, "If you want to get things done, come to the NHS because it provides world-class care for patients." And so that's a big initiative now. Use AI to make better drugs, safer drugs, more effective, more precise in the UK. And it's only possible because of everything that we've built here with our funders, ARIA, MRC, Cancer Research UK, people raising, raising money through cake bake sales to make this happen. 

[00:30:02] Lennard: So it's very exciting.  

[00:30:04] Florence: Yeah. I think AI can be a topic that people often have very strong opinions about. When it comes to AI in, in your line of work, are there any misconceptions you think people might have, or are there any benefits to using it that maybe people might not be aware of?  

[00:30:21] Lennard: Oh, that's a tricky question, isn't it? I think you're right. Any tool that comes through can be used for good things and, and things that people will question because maybe we don't want to cross those boundaries. And yet I think what we're doing here is really special because we want to - as long as your heart's in the right place - we want to give more people like Ali hope so that she knows that one day the drugs in the NHS will be much safer so you don't get all those side effects, much more effective, much more precise. 

[00:30:52] Lennard: And on top of that, people like Victoria will be able to bring even more trials in the UK which will change lives and change practices around the world through an amazing working launchpad. So I think that's the right use of AI, make people's lives better. I think there are other uses of AI which I probably scratch my head and say, "Well, should we be doing that?" 

[00:31:10] Lennard: And that's what I think it's really special that we do think about these and talk about these things here, and then bring the public with us because I know that people reach out, and Ali's been reached out in the past before, and I think we need to have this discussion here. Is AI right to develop cancer drugs using capabilities from Genomic England to go through the NHS Cancer Vaccine Launchpad? 

[00:31:31] Lennard: I say cautiously, yes, and we should do more of this. And I think the most important thing is there's a lot of people starting to use AI for benefit, and you know my views, Ali, and I don't know if they're right. Um, I'll be a bit cautious, but I do want to ask you, Ali, is this the right use of AI? Should this be what we develop? 

[00:31:50] Lennard: I don't know what you're going to say.  

[00:31:52] Ali: For me, I think it is. I do think AI is a bit if you put rubbish in, you get rubbish out. But if you- If you ask the right questions, if you give it data analysis and experts like you have set up the protocol in the first place and it makes everything faster and reliable, then it's got to be the right thing. 

[00:32:16] Ali: It gets used and abused for things, that isn't what AI should be doing, in my opinion. It should be used to do-- to help us, to supplement the work that we're doing, uh, and make it even faster than you're already making it. 

[00:32:38] Florence: Well, we've covered so much today from how vaccines work to the role of genomics, NHS trials, and of course, what all of this could lead to. So before we wrap up, I have two final questions for each of you. What do you think is the most important thing for listeners to understand and take away from personalised cancer vaccines? 

[00:33:01] Florence: And what are your hopes for the future? I think we'll start with you, Victoria, if that's all right.  

[00:33:08] Victoria: Yeah, absolutely. It's been a great conversation. Uh, there's so much to think about. I think when I think about what I'd like listeners to take away, I think it's that cancer vaccines, and particularly personalised cancer vaccines, really support and represent this paradigm shift that we're seeing towards a much more personalised, uh, treatment pathway. 

[00:33:27] Victoria: You know, like we've described, generating a cancer vaccine that has come from the patient's tumour, so the, the, the vaccine is, is designed to recognise mutations that are specific to that patient. It is such an incredible thing to be sort of witnessing and to see how that's developing through into sort of really changing patient care, and that's, you know, we've spoken about this so much, but that's been due to such incredible collaboration across scientific disciplines, across the NHS, pathologists. 

[00:33:58] Victoria: Everyone has come together to make all of this possible, and that's, that's an amazing thing to be a part of. In terms of my hopes for the future, well, I would like the Cancer Vaccine Launchpad to be open in every hospital across the UK to really sort of underpin that acceleration and to provide that opportunity for patients. 

[00:34:17] Victoria: You know, I'd just like to give a, a final shout-out to everybody who has been part of the Cancer Vaccine Launchpad from its very start, who's enabled this to happen and, you know, it's just been fantastic to see how this has, you know, supported patient choice for trials. And I guess if there's one tiny other thing, perhaps we could see how this, you know, this, what we've put together could be applied to other disease areas as well. 

[00:34:39] Victoria: But yeah, that, that would be my hope for the future, is it's open everywhere one day.  

[00:34:43] Florence: And Ali, I'll come over to you next.  

[00:34:45] Ali: I think what I'd say to any patient that was asked to go on a trial is, is just go for it. 

[00:35:02] Ali: And you know, Victoria, Lennard, all the rest of the team, you know, you are not doing jobs. You're leaving a legacy in my view. That's such an important thing. So yeah, if you're offered a trial, get on it. And my hope for the future is that everybody can have kinder, gentler treatments. The radiologists and chemo nurses I came across were lovely, lovely people. 

[00:35:31] Ali: But yes, I'd like to see them out of work and doing other things within the NHS because they don't need to do that work anymore. That, that's my dream.  

[00:35:40] Florence: Mm. And Lennard, any, any final thoughts?  

[00:35:44] Lennard: Thanks, Ali. I mean, your words gave me goosebumps about the amazing stuff that the whole community's doing for cancer vaccines, AI and genomic research. 

[00:35:51] Lennard: It's so powerful. Um, okay. What's the final thing? I think it's hope. Look, the country's in a new place now. You've got brilliant scientists running clinical trials, like the Cancer Vaccine Launchpad, which is reaching out to every single hospital. You've got patients who are building up the NHS again to deliver future care, and scientists using AI and genomics to make cancer vaccines. 

[00:36:11] Lennard: That is a good reason to be hopeful. When lots of things are going in other places of the world, great things are happening in the UK.  

[00:36:20] Florence: This has been such a brilliant conversation. 

[00:36:25] Florence: A huge, huge thank you to our guests today, Dr. Victoria Goss, Professor Lennard Lee, and Ali Richards, for joining me in our brilliant discussion about cancer vaccines.  

[00:36:50] Victoria: Thank you so much for having me. 

[00:36:55] Ali: Thank you, as always. I've learnt a lot.  

[00:37:00] Lennard: Thank you very much, Florence, too, from me.  

[00:37:10] Florence: If listeners have enjoyed this episode and you'd like to hear more, please subscribe to Behind the Genes on your favourite podcast app. 

[00:37:16] Florence: I've been your host, Florence Cornish, and Behind the Genes is produced by Deanna Barac, Sharon Jones, Sophie McLachlan, and Patrick Wallace at Bespoken Media. Thank you for listening.

In this explainer episode, we’ve asked Dr Antonio D'Alessio, Medical Oncologist at Guys and St Thomas Foundation Trust, to explain cancer vaccines and how they work.

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

If you’ve got any questions, or have any other topics you’d like us to explain, let us know on podcast@genomicsengland.co.uk.

You can download the transcript or read it below.

Florence: What are cancer vaccines and how do they work? My name is Florence Cornish, and today I'm joined by Antonio D’Alessio, who is a medical oncologist ay Guy's and St Thomas' Foundation Trust and King's College. And he's going to be telling us much more about the topic.

So Antonio, before we get into cancer vaccines, I wanted to first ask you about cancer. I know it's a pretty broad term, and it refers to the uncontrolled growth of cells in the body, but maybe it would be helpful for you to explain a little bit more about what cancer actually is, like what that term means, especially for listeners out there who might not have that scientific background.

Antonio: Yeah, of course. And first of all, thanks for inviting me today. Well, that's a big question. The point is that we know that in our bodies there are billions of cells, and all of these cells, they divide, they do their job, and they know when to die on schedule. The point is that sometimes there are cells that ignore this instruction and just keep reproducing and growing, and this is when cancer grows.

Our bodies have systems, which is the immune system, to recognize when this happens so that the immune system can recognize the cancer cells that are growing too much. They attack them and destroy them. But unfortunately, sometimes cancer is quite clever, they manage to escape from the immune system and starts growing without control, and that's when cancer starts.

Florence: And so, what are the standard treatments that we use for cancer at the moment?

Antonio: Well, broadly speaking, I would say that we have three types of cancer treatments. One, it's surgery, where we just cut the cancer out. Then we have radiotherapy, where we basically induce targeted damage to the cancer. And then we have a very broad umbrella term that is systemic therapy.

Systemic therapies can be chemotherapy, can be targeted therapies, and that can be immunotherapy. In particular, immunotherapy is quite exciting because over the past 20 years, we have learned how to boost the immune system of patients, so that's the white blood cells, the immune system of patients that can recognize cancer cells and attack them.

Sort of imagine that cancers hide behind an invisibility cloak, and immunotherapy helps unveil the cancer so that the immune system can recognize the cancer again and attack it. And vaccines and cancer vaccines are part of this family of immunotherapy drugs.

Florence: Yeah so speaking about that, I think lots of listeners might have heard of the term cancer vaccine before, obviously, its the topic of this episode.

And I think the term cancer vaccine sounds very interesting and promising, but also maybe a little bit intimidating as well. So maybe you could tell me more about what a cancer vaccine is kind of at the most basic level.

Antonio: Well, cancer vaccine is a vaccine, and we have received so many vaccines in our lives that our body basically has learnt already how to process a vaccine.

Imagine a vaccine as a wanted poster. So, we give the body the instructions to recognise something that shouldn't be there, and the immune system knows how to do it. So, the job of the immune system is to recognize strangers in our bodies - that can be microbes, bacteria, viruses, and also cancers.

And sometimes with a vaccine, we sort of help the immune system to do its job a bit better. And with vaccines, we provide the instructions to recognize these strangers in our body and help the immune system to, to get rid of them. And in particular, for cancer vaccines, we have different types of cancer vaccines.

There's a family of cancer vaccines that are called preventative, where we can try to give a vaccine even before the cancer develops to reduce the risk that the cancer develops. And, this is more early in the development.

While we have, another family of cancer vaccine, which are mostly mRNA cancer vaccines that are called therapeutic. So these are cancer vaccines that are given to patients who already have cancer, maybe who had the surgery for their cancers, so that the aim of the cancer vaccine is to boost immune system and reduce the chances that the cancer comes back after surgery, or, help other types of immunotherapy work better together with vaccine against the cancer.

Florence: So, I think for me at Genomics England, the mRNA cancer vaccines are probably most relevant to the work that we do here as an organization. Could you explain a little bit more about how those ones work specifically?

Antonio: Yeah, that's an exciting field, right? The mRNA vaccine. So, let's split this into different words, mRNA and vaccine.

We have just covered what vaccine means. We just have to think mRNA as just instructions. So we give the body of the patients the instruction to recognize the cancer. And the mRNA is basically the instruction for the immune system to recognize some of the proteins that are expressed on the cancer cells, so that's the white blood cells, the own white blood cells of the patients that can be more alert and identify the cancer cells if they are around.

And in particular, imagine when we give the mRNA vaccine, it's like we are giving the picture of a suspect to the police, right? The police is the immune system of the patients, and the suspect is the cancer.

And so, the immune system, so the police of our body, can go around the body, can go around the bloodstream, can go around the organs, and if they see the suspect, they are, they are already alerted, and they can tackle it, attack it, and destroy it before it develops into, into a cancer that can be seen on the scans.  

Florence: And are these types or other types of cancer vaccines being used in the clinic at all in real medical settings already?

Antonio: Well, I wouldn't say that we are using that in clinical practice, but probably in the future we will, and we are working hard to make sure that we will be able to use cancer vaccine for our patients.

At this stage, we are using cancer vaccines as part of clinical trials, and these clinical trials cover different types of cancer types, different types of setting, together with other drugs or given alone after surgery, for instance. And the NHS England, Genomics England and NIHR, they launched this massive infrastructure that is called the Cancer Vaccine Launchpad.

And it is aimed specifically to match the NHS cancer patients with personalized mRNA vaccine trials, so that once we have the results of those trials and we are ready to deploy it in clinical practice, then we already have the infrastructure to do that promptly, hopefully in the next future.

Florence: Mm-hmm. Yeah, so do you see a future where cancer vaccines are used in routine care?

Antonio: Well, we are working towards that. And I, and I do see a future where we're going to use that. I don't know when. Probably it will take still a few years.

But the, for example, in the UK and in England in particular, we have a national cancer plan, and the national cancer plan for this year has identified cancer vaccine as a top priority for our health system.

And this is because this is a technology that can be scalable, that can be widely deployed once it's demonstrated to be working. And at this stage, there are still some open questions, like which cancer types in which setting, which patients would benefit from it.

But once we address these open questions in clinical trials, then I do believe that we'll be able to use that in the, in the future.

Florence: I think we'll finish there. Thank you so much, Antonio, for coming on and for taking the time to talk to us.

Antonio: Thank you Florence, and thank you for the invite.

Florence: If listeners want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.

Thank you for listening.

Two years after researchers identified ReNU syndrome, where are we now?  

In 2024, two independent research teams identified the genetic cause of ReNU syndrome, a rare neurodevelopmental condition affecting thousands of people worldwide. The discovery marked the beginning of a new chapter for families searching for answers and opened up exciting new avenues for research. 

In this episode, host Sharon Jones revisits the story to explore what has happened since that breakthrough. She is joined by:

Professor Nicky Whiffin, Associate Professor and Wellcome Career Development Fellow at Big Data Institute and Centre for Human Genetics, University of Oxford

Christina Cox, Co-founder of ReNU Syndrome UK and parent of a child with ReNU syndrome

Dr Ana Lisa Tavares, Clinical Lead for Rare Disease at Genomics England

Together, they discuss how researchers around the world have built on the original discovery to deepen our understanding of ReNU syndrome, why studying the non-coding regions of our DNA is revealing previously unknown rare conditions, and how collaboration between researchers, clinicians and families is accelerating progress. They also explore how the growing ReNU community is supporting newly diagnosed families and what the future could hold for new treatments. 

Links: 

Previous episode detailing the discovery of ReNU Syndrome 

ReNU Syndrome UK's website 

Original research paper from Nicky's team in Oxford 

Original research paper from the team based in New York 

 “It's been only two years since our paper came out about this, and in that time, there are now patient family groups that have been set up all around the world. There is the one in the UK led by Christina and the others. There's the one in the US that's led by a group of four women, and there are ones in France, Spain, like, literally all around the world. And all of these groups are also somewhat coordinated. The leads of these groups meet with each other. They've organised meetups. I've been to ones in the US, the UK, and in France. So the fact that they can mobilise all of that and create such a community so quickly is absolutely incredible.” 

You can download the transcript, or read it below.

[00:00:00] Sharon: In 2024, two independent research teams identified a genetic cause of a rare neurodevelopmental condition affecting thousands of people around the world. Since then, that initial groundbreaking discovery has grown into something much bigger, bringing together families, researchers, and clinicians, and building a clearer picture of what we now know as ReNU syndrome. 

[00:00:26] Sharon: Welcome to Behind the Genes, the podcast that covers everything from cutting-edge research to real-life stories in genomic healthcare. I'm Sharon Jones, and in today's episode, we're looking at what's happened since that discovery, what researchers are continuing to learn, and what the future could hold for people living with  ReNU Syndrome and their families. 

[00:00:46] Sharon: To help us understand more, I'm joined by Professor Nicky Whiffin, Christina Cox, and Dr. Ana Lisa Tavares. So, two papers were published around the same time for this condition. To start us off, Nicky, you worked on one of these papers. Could you explain how this journey first began?  

[00:01:05] Nicky: Yeah, so this was two years ago now, back in early 2024, where two research teams, so us based in Oxford and a, a group based in New York, were both looking at the data within the National Genomics Research Library, and we both kind of somewhat simultaneously found that there was variance in this very, very small gene, it's called RNU4-2, were found in individuals with previously undiagnosed neurodevelopmental disorders. 

[00:01:39] Nicky: And this was very, very striking because we initially actually identified the same single DNA change or mutation in 40 or so different individuals within the National Genomics Research Library, and we normally expect to see a whole host of different variants. We don't expect to see the same one. 

[00:01:59] Nicky: So this was a really, really surprising finding. And it was through a collaboration, large scale collaboration across the world where we started contacting our other collaborators who have similar collections of patients who have been genome sequenced to ask if they had any individuals with DNA changes in this gene. 

[00:02:17] Nicky: And we found some in the US, some in, in Australia, some in France and Germany. So very, very quickly built up this, this complete picture of variants in this gene, causing this rare neurodevelopmental disorder  

[00:02:35] Sharon: of people finding it at the same time, what, what did that feel like? 

[00:02:39] Sharon: Like, give us a ense of, like, that compelling, "We think we found something." What was that like?  

[00:02:46] Nicky: I didn't believe it initially. You're always told when you're a scientist that if it looks too good to be true, it's, it's not true, and this basically lit up like a beacon. There's this particularly one DNA change that we found in, um, I think it was about 40 different individuals, and we don't really expect that to be the case. 

[00:03:04] Nicky: We normally expect these genetic variants to be somewhat randomly distributed across the genome. So to find 40 individuals with exactly the same DNA change was very, very surprising. So initially, I didn't believe it. The whole team, including folks at Genomics England, spent a lot of time trying to check that these variants were real and tried to disprove the result, tried to find any other way in which any other reason why we would be seeing this. 

[00:03:31] Nicky: And after a little while, we had to concede that we couldn't disprove it, so it must be true, and that, that was a very exciting moment.  

[00:03:38] Sharon Jones: Was it the case that over in the States, the exact same thing was happening?  

[00:03:42] Nicky: I think we found out when we were both speaking at the same conference, actually. So we didn't actually know that we, that we'd both come across the same result. 

[00:03:49] Sharon: If you want to check out our previous episode on this initial discovery, you'll find a link to it in the episode description. 

[00:04:00] Sharon: So Christina, tell us a bit about your situation, your family situation, and for our listeners, what ReNU is.  

[00:04:05] Christina: So ReNU is, to us, is a family. We got a family when we got diagnosed with  ReNU. Beau - Arabella - already had other diagnosises, but people had always said to us, "Oh, there's something else. There's something else. 

[00:04:20] Christina: We're not sure what it is, but there will be something." And then when we got  ReNU, it was like, "Oh, okay, amazing. What do we do? What is it?" Because there was only four lines on Wikipedia when we first got told about it, and there wasn't anything that, ourselves could find. So we kind of went onto Facebook and looked for groups and different people, and there wasn't really anything except for Jess in America. 

[00:04:46] Christina: And then it grew, and then it kind of, we ended up finding more people in the UK and, like, all over. But for us, it didn't really change how we perceived Beau. It just made life easier. Like, knowing there was other families out there that we could find advice from and support from, and that we kind of knew what we had and going forward then, like, finding researchers and connecting with everybody. 

[00:05:15] Sharon: Yeah. And for those who don't know, can you talk about what  ReNU is? Like, how does it affect Beau?  

[00:05:20] Christina: So with Beau and  ReNU , it affects her with developmental delay. She's non-verbal. She's incontinent. She suffers for walking, so she can do a little bit of walking, but she needs a wheelchair It affects her mood swings. 

[00:05:38] Christina: It just affects everything. Although she has it, she's still a happy, outgoing, very stubborn, just kind of "keep-going" child. But it affects her in everything, like eating, sleeping.  

[00:05:51] Sharon: It sounds like life is, you know, very challenging on a day-to-day basis, lots of considerations. How did you feel when you finally got this diagnosis after years of wondering and waiting, not knowing? 

[00:06:02] Christina: Finding out was, like, really emotional because it was like, "Oh, wow, so we have this diagnosis. Now what? What are we looking for? What's going to happen?" And then we were kind of like, "Oh, but there's not many people that had it." Because we found out in the August, so then it was trying to find people. But it has been life-changing to know that we're not on our own and that there is other people around. 

[00:06:28] Sharon: Yeah, tell us a bit more about that. How did it feel to get that diagnosis?  

[00:06:32] Christina: It was quite strange because our pediatrician rang us and said, "Oh, we've got a diagnosis. She's got RNU4-2." And we were like, "Okay, so what's that?" And she's like, "I don't really know. There's four lines on Wikipedia at the moment." 

[00:06:46] Christina: She goes, "I don't like Wikipedia," but we still kind of... That was it. So then we went on a mission to find and look for where we could find support and find other families.  

[00:06:58] Christina: At that point, I didn't know of anybody in the UK, and my husband found Jessica in America. What then, kind of, we had somebody to talk to, and then families in the UK kind of started appearing. 

[00:07:09] Christina: So we ended up getting a whole network of people to bounce ideas off and talk about how it affects their children and what's for the future and things like that. It was really nice.  

[00:07:22] Sharon: Yeah, yeah, I can imagine. So Ana Lisa, how do these findings contribute to a growing understanding of the condition? 

[00:07:29] Ana Lisa: So this was an amazing discovery. Although we're finding new rare conditions quite often, not on this sort of scale. It was also an amazing finding because a lot of the genes that we know are associated with rare conditions are genes that encode proteins, and in the 100,000 Genomes Project, we were doing whole genome sequencing, and Nicky and her team were looking in the parts of the genome that don't encode for proteins. 

[00:08:03] Ana Lisa: And so this was, uh, exciting from that point of view as well. So the vast majority of our genome, more than 98%, does not encode for proteins, but it's relatively unexplored. And if we think about our genome and the letter code that makes it up, which is the manual for how our bodies are built, and grow and function day-to-day. 

[00:08:30] Ana Lisa: Those 3 billion letters, if you, if you printed them out in a 12 font regular print, it would stretch so far you could fly, I think, from London to Paris several times, maybe three times or something. And so, this actual gene is a very, very small gene, less than 150 of those letters. So again, it was incredible to find that by comparing across many, many different genomes in the National Genomic Research Library. 

[00:09:00] Ana Lisa: Going back to your question about a growing understanding of a condition, it was a completely new condition, but it also opened up looking at other related genes and actually now more disorders that are being found, like RNU2-2 by colleagues in the US, and that might be one of the most common recessive genetic neurodevelopmental disorders. 

[00:09:27] Ana Lisa: So it's really, really opened up this understanding about these types of disorders and also those non-coding parts of our genome and the power of collaboration and being able to look across many different whole genomes at the same time.  

[00:09:44] Sharon: Yeah. And Nicky, you've been involved in much of this research journey. 

[00:09:50] Sharon: What have been some of the biggest advances or learnings for you so far?  

[00:09:55] Nicky: I think the biggest one is just how common, or how frequent, these disorders are. So what we discovered recently in terms of new genetic disorders were rarer and rarer conditions, and that's why we hadn't seen them before. But from going from looking at the protein coding genes to looking at these non-coding genes, we found something that was as frequent as disorders that were found in the early 2010s when we first had large-scale sequencing projects that looked at the protein coding genes. 

[00:10:26] Nicky: So that was really, really surprising. And we now know there's this whole class of disorders. So RN4-2, this gene encodes this -- Well, it produces this small RNA that works in this huge molecular machine that is called the Splicer Zone, that mediates the processing of most of the other genes across the genome. 

[00:10:50] Nicky: And there are lots of these little RNAs that work in this molecular machine that are called the small nuclear RNAs or the snRNAs And we now know that there are a whole multitude of different disorders associated with different ones of these spliceosomal small nuclear RNAs, and that's really incredible. 

[00:11:09] Nicky: And for RNU4-2 itself, we also now know that there are, there's not just RENE syndrome, uh, which is a dominant disorder caused by chance de novo variants that are newly arisen in a child, but also a recessive disorder where a child inherits one, uh, gene mutation from each parent. And also another finding that there is a region of the gene where we find DNA changes that cause retinitis pigmentosa, so a retinal phenotype. So we now know a huge amount more about this single gene, but also all of this different class of genes or RNAs that work in the same molecular machine, uh, which is, is really fascinating biologically  

[00:11:52] Ana Lisa: Vicky, while you were talking, I was thinking about the splicing and how a bit like this podcast recording, you're going to splice out the kind of extreme, the noise that wasn't supposed to be there. 

[00:12:03] Ana Lisa: And actually, you could make slightly different versions of this podcast, couldn't you? And that's, that's what, what's happening in our bodies for a lot of our genes that, that the kind of output can be varied slightly.  

[00:12:15] Sharon: So Christina, how has collaboration been involved across the community and with researchers? 

[00:12:21] Sharon: You know, what sort of things have you been doing?  

[00:12:23] Christina Cox: So it's amazing to have researchers that are so open and amazing to work with the families. So at the moment, we are just putting together like a panel to discuss questions from families, to then be able to answer families, to work very closely with the researchers for what things are happening and the progress within. 

[00:12:47] Christina: It's just amazing to be able to work with researchers. They're just fantastic.  

[00:12:52] Sharon: And from what I understand, like, you, you have a charity, don't you? Can you tell us a bit more about that and how that came about?  

[00:12:58] Christina: So we have ReNU Syndrome UK, and it came about as there was a group of us parents that were like, we wanted to be able to support other families, knowing what it was like for us when we first started. 

[00:13:12] Christina: It was very difficult. So we wanted to start a charity that can support families and signpost them, give them the opportunity to have family meetups once or twice a year, so we can work with scientists and specialists to keep everybody in the community, like the ReNU family, up to date. But being able to connect with so many families, because a lot of the doctors don't really know of ReNU Syndrome yet. 

[00:13:46] Christina: So if we have a problem or a question, we put it in the WhatsApp group, and then somebody can answer it because they've been through it, or they, they've just asked the question. So it's just an amazing resource for everybody  

[00:14:02] Sharon Jones: That sounds amazing, and it sounds like you've all obviously become experts by experience. 

[00:14:04] Sharon: So, like you say, you kind of know more, you know, as the science develops, but you're living it every single day  

[00:14:10] Christina: It's kind of, you go into the hospital and they're like, "Oh, what's ReNU Syndrome?" And then you're like, "Ugh." So, then you just have to say it all. But, and then it's kind of them bringing, teaching new people who don't know about it in the medical professional. 

[00:14:26] Christina: We always give them the website so that they can go and then find, but being able to put more medical stuff on the website, it just helps everybody, and it's just broadening it out to as many people as possible. Because there's still a lot of people undiagnosed with RNU syndrome. It's, now it's easier to be signposted, but it's just keeping that connection. 

[00:14:49] Sharon: Yeah. And, and from what I understand, it's got quite an interesting sort of origin of a name, RNU. Where did that... Do you know much more about where that came from?  

[00:14:57] Christina: So, Nicky is the amazing person who, um, sorted the name and um, the origin. So, I'll pass that over to Nicky to answer that question because she's just amazing  

[00:15:11] Nicky: Uh, so the name ReNU syndrome is an interesting story. 

[00:15:13] Nicky: So, a lot of disorders or diseases are named after people. So, we all know Alzheimer's, Parkinson's, etc. And they're often scientists or clinicians that have spent a lot of time working on them. I think that's a little bit odd. I don't think it's the first thing that somebody should know about a disorder, is the name of somebody who's, who's worked on it or studied it. 

[00:15:36] Nicky: But they're a very, it's very hard to find an alternative. When we were initially doing the press release around our paper, we had a quote from one of the mothers, Nicole Cedar, who has a, a wonderful daughter called Mia Joy, and she said that within their family, they like to refer to RNU, to RNU4-2 as ReNU, which is a really nice play on the RNU in the gene name. 

[00:16:00] Nicky: So then I had an idea, okay, let's just change the spelling to make the, the kind of big R, little E, large N-U, then it would link to the gene name, but also would be a name that speaks to hope and the renewed hope of being given a diagnosis.  

[00:16:13] Sharon: Yeah, absolutely, and that's a great, a great story and a great way of kind of making it feel like there is, there is always hope. 

[00:16:20] Sharon: So, you know, Nicky, you're now part of the patient community. In a way. You know, so how does it feel to be on that other side of it from that sort of research perspective and now kind of, you know, in that, in that community?  

[00:16:34] Nicky: It's amazing. I've got a new family as well. It's not, not just Christina and everybody. 

[00:16:39] Nicky: I kind of, I'm a, a basic scientist. I'm not a clinician. Up until this point, we've always been one or two steps removed from actually interacting with the families themselves. Um, so my life has changed an awful lot over the last couple of years, uh, where now, um, I kind of talk to Christina or the folks in the US, really regularly, kind of on a weekly basis. 

[00:17:02] Nicky: Um, so that's really different. And I just kind of want to highlight just what these families have achieved. So it's been only two years since our paper came out about this, and in that time, there are now patient family groups that have been set up all around the world. There is the one in the UK led by Christina and and the others. 

[00:17:26] Nicky: Um, there's the one in the US that's led by a group of four women, and there are ones in France, Spain, like, literally all around the world. And all of these groups are also somewhat coordinated. The leads of these groups meet with each other. They've organised meetups. I've been to ones in the US, the UK, and in France. 

[00:17:46] Nicky: So the fact that they can mobilise all of that and create such a community so quickly is absolutely incredible. And they've got families, they've got so many researchers that are interested in the cause. They're interacting with the pharma companies. They've upskilled themselves to learn so much about genetics. 

[00:18:04] Nicky: And it's just an absolutely incredible thing to watch. They're so, so inspiring.  

[00:18:09] Sharon: And from what I understand, Christina, you feel, you know, very passionate about Nicky in the same way, about your paths crossing in this way.  

[00:18:16] Christina: Oh, my, yes. Every time I see Nicky, I've met her a couple of times, like, in person now, I just cry. 

[00:18:22] Christina: I literally, we saw her at the UK meetup, and she walked in the door, and that was it. I was done. I was like, it's just meeting somebody who has changed so many lives and brought a community to other families. It's just amazing. And the support that Nicky's giving us weekly, daily, is just amazing. It is just life-changing for all of us. 

[00:18:49] Sharon Jones: It's such a powerful connection. So Ana Lisa, why is collaboration between researchers, clinicians, and families so valuable in the rare disease research space? You know, and what role do large scale research projects and data sharing play in discoveries like this?  

[00:19:06] Ana Lisa: Collaboration is completely incredibly valuable and for progress in the rare disease space where there's just so much still to learn. 

[00:19:16] Ana Lisa: So more than half of patients and families where, uh, they're seeking a potential diagnosis, we're not yet able to, to find one, and there's so much yet that we still need to learn, and collaboration in so many different spaces and directions and across different spheres enables this progress. So for example, the fact that we have a really connected, uh, National Health Service and really close working between the NHS and Genomics England so that we can, for those patients and families that, that consent to their de-identified data being shared in the National Genomic Research Library, be able to work with many, many different researchers, uh, whether they're academic, institutions, industry, and try and find all the patients that could benefit from a new diagnosis and, uh, potentially new therapies in future clinical trials. 

[00:20:21] Ana Lisa: And without that collaboration, it would be really, really hard to find all those people So because we sort of have a clinical research interface where we can go back to clinical teams and therefore to patients and families, even if there's a really, really ultra-rare condition with very few people known to have it that could be under different specialties in different regions, we would be able to contact their clinical team. 

[00:20:51] Ana Lisa: So I think that, that collaborative working with the NHS is really powerful across researchers worldwide. Like in this example where a group in Oxford and a group in US were able to make this finding and then all the other findings that are coming from it. And really, without being able to compare across thousands of genomes, one wouldn't have been able to see this, this particular signal and see that there were more than 100 patients, and that was really powerful. 

[00:21:20] Ana Lisa: If you just had one genome, you could never have made this novel discovery. I think the other thing is that, and Nicky will say that, you know, she, she then contacted her collaborators who also had access to, to, to data that had been shared by other families and could compare. And again, it's a whole sort of network across the globe. 

[00:21:41] Ana Lisa: And we know that there are going to be many more diagnoses to be found. But also, um, I think collaboration will allow us to find new, new treatments. So if we can start to design treatments that target the DNA and RNA at, at source, then actually you could collaborate and say, "Well, this type of genetic mechanism could be targeted in the same way, potentially across even more than one rare condition and reach even more patients." 

[00:22:13] Ana Lisa: And actually the power of collaboration across the ecosystem is that hopefully we'll end up with a pathway that can actually go from finding a new genetic finding, like Nicky and her team made, to helping all the people who could benefit from a diagnosis, having one, and then can one develop a treatment and get it to as many patients? 

[00:22:42] Ana Lisa: And, and I think that will really demonstrate the power of collaboration.  

[00:22:47] Sharon: Yeah. Absolutely, and it can only, you know, benefit those families who have to wait such a incredible amount of time.  

[00:22:55] Ana Lisa: There's been such a diagnostic odyssey, and as more diagnoses are made, it becomes obvious that there's, uh... 

[00:23:03] Ana Lisa: and it was, it's already well-described, the therapeutic odyssey. Um, but hopefully these sort of novel understanding of our genome and opening up new biological avenues to treat, um, hopefully will also enable many more new treatments to be developed.  

[00:23:21] Sharon: Absolutely, and that is the key word there is, is that hope. 

[00:23:24] Sharon: So, so looking ahead, Nicky, what developments are you most hopeful about over the next few years?  

[00:23:31] Nicky: That's a difficult question. There's so much, so much happening. One thing is that we are gearing up to do large scale studies across the world to understand more about the progression of ReNU. So you might call them large scale natural history studies or just large scale profiling studies where we can do a range of different tests on ReNU patients and, and monitor them over time. 

[00:24:02] Nicky: So do those at regular, regular intervals over time so we can see what the progression looks like. And that's really important for trying to think about whether we can treat RNeU syndrome. And on that note, I'm very also excited about the potential for therapeutics. There's lots of people all around the world, both, uh, in academic settings, but also in pharma companies trying to work out whether this is something that we can treat. 

[00:24:30] Nicky: There's some very promising early data to show that we can selectively remove the RNA containing the mutation from cells, uh, leaving the copy of the RNA that doesn't contain the mutation intact so that can do the correct function. And biologically, we think this should be an effective treatment. 

[00:24:54] Nicky: Um, so we can do that in cells in a dish. We don't yet know whether we can do that in a patient with ReNU. Uh, but that's really, really promising early data. Um, so I'm very hopeful about where that, those studies might lead.  

[00:25:08] Sharon: And Ana Lisa, what role will genomics continue to play in improving understanding and care for rare conditions like this? 

[00:25:15] Ana Lisa: So following on from what Nicky said, I think the really big hope is that we will be able to develop many, many new treatments collaboratively across the world. And whether these are individualised treatments made for one patient but then shared because we can find perhaps other patients who could benefit from the same treatment, whether we understand the genetics better so that we can design treatments from the start that will work for a lot of patients. 

[00:25:46] Ana Lisa: So I think there will be sort of fancier and fancier ways of targeting rare conditions. And right now we're in a phase where the ecosystem is trying to work out how could we make an end-to-end pathway with initiatives like the Rare Therapies Launchpad in the UK, and that's going to require truly collaborative working. 

[00:26:08] Ana Lisa: No single organisation can do that. And I think having these incredible use cases will be really powerful for turbocharging the development of these pathways. And the hope is that once you've worked out how to do this across a range of different rare conditions, that one might reach a stage where one could do that a lot faster for many other rare conditions. 

[00:26:35] Ana Lisa: Because at the moment they're so underserved in terms of treatments available and there's a huge gap between being able to make a genetic diagnosis and then having treatments. The big hope is that understanding the genetics better will help to open up new pathways to treatment. I do hope that we'll also understand other aspects. 

[00:27:02] Ana Lisa: So for example, it might be that understanding the genetics better also helps us to understand different ways a condition might manifest in somebody, why it may be different from one person to another, why somebody might be more mildly affected and somebody perhaps more severely. And that might, may also help us to understand ways to treat a condition by getting, gaining these insights which are, are useful in and of themselves and may also lead to new therapeutic, uh, possibilities. 

[00:27:36] Ana Lisa: I think that would be one of my hopes that a lot of these areas overlap and lead to real benefit for patients and families, that we can translate that hope into concrete improvements in treatment for rare conditions. 

[00:27:57] Sharon: Do you have a sense of time, how long you think this could all take, that amount of collaboration? 

[00:28:06] Ana Lisa: Yeah, and I think this is actually another reason why sometimes it's quite tricky to make progress in this area because being able to predict those timelines is notoriously difficult when you look back historically. I'd like to hope that we're on the cusp of having an explosion of novel treatments that can target DNA and RNA, for example, or treatments that target something in the underlying biology that we now understand that we didn't before. 

[00:28:34] Ana Lisa: And I do think that there is going to be a big shift. But I think that the sort of confidence intervals around how big that range of time might be is very hard to predict. And that's why I think Christina and Nicky being able to share these stories and about their collaborative working really shines a spotlight on, on what could be done and how progress can happen. 

[00:29:02] Ana Lisa: That's really exciting. The other day at a conference, someone from industry stood up and said, "Oh, actually, we set up a clinical trial in the UK because we knew there were patients who could benefit from our work in the National Genomic Research Library," and that was really exciting for us because that's what we want to do; move forwards the opportunities for treatment for patients. 

[00:29:28] Sharon: And so finally, Christina, as a parent and member of this community, what are your hopes for the future, and what would you say to families who may still be searching for answers today?  

[00:29:39] Christina: It is a long journey, but there is the support and the help out there. If you have any inclination that you think you might have ReNU, reach out to your paediatrician or your doctor to see if you can get your genetic testing done because it's fighting to get the test, to go to people and say, "I think this is what we may have. Can we look into getting it tested?" And reach out to other families and the website and things because it's all about community and supporting and helping people find that diagnosis.  

[00:30:16] Sharon: Thank you, Christina, and we'll put the website in the episode description. A huge thank you to Professor Nicky Whiffin, Christina Cox, and Dr. Ana Lisa Tavares for joining me today and sharing their insights and experiences. To learn more about ReNU Syndrome, visit renusyndromeuk.org. If you'd like to hear more stories about the people, research, and discoveries helping to shape the future of healthcare, subscribe to Behind the Genes on your favourite podcast app. 

[00:30:45] Sharon: Thank you for listening. I've been your host, Sharon Jones. Behind the Genes is produced by Deanna Barac, Florence Cornish, Sophie McLachlan, and Katie Revell at Bespoken Media.