S3.08 Nothing about me without me: involving patients in genomic research
Kat: Hello, and welcome to Genetics Unzipped - the Genetics Society podcast with me, Dr Kat Arney. Research into genetic conditions relies on information from patients and their families, whether that’s detailed health records or genomic data.
As the tools and techniques for DNA and data analysis become cheaper and more organisations get in on this fast-growing field, it’s vital to make sure that the most valuable research resource - human lives - doesn’t get overlooked in the rush.
In this episode, recorded at the recent Festival of Genomics in London, we find out why it’s so important to make sure that both academic and commercial research studies are done with rather than on participants.
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Back in January, what feels like approximately a million years ago, I went along to the Festival of Genomics in London, hosted by Frontline Genomics. It was a great opportunity to catch up on all the latest advances in the world of genes and genomes.
One particular theme that came through over the two days of the festival was making sure that patients and their families are properly involved in research, and the benefits that can bring for academic researchers and commercial companies looking to use genomic data.
(I’ll warn you now that all these interviews were captured live at the Festival, so apologies for any background noises and chatter. )
Fiona Copeland is the chair of a support group for families affected by primary ciliary dyskinesia, or PCD - a rare genetic condition that affects the lungs - and is the mother of two sons with the condition.
They’re both now adults, but it took a long time to get them diagnosed when they were young, meaning that they have lasting lung damage and their quality of life as kids wasn’t great.
An organised and dynamic project manager by nature, Fiona realised that she has the skills and tenacity that could help to change the outcome for other families affected by PCD - so she did…
Fiona: We became involved with the PCD Family Support Group which had been set up by somebody else, because we offered to help organise an event and they realised that actually, I was quite good at organising things and perhaps I'd like to go on the committee. Quite soon after I became the Chair.
The reason I did this was because I really thought that I'd be able to help other families affected by the condition. Particularly to get a really early diagnosis because the earlier the diagnosis, the better care you will get.
Then because I'd become involved with it, some of the clinicians decided it would be a good idea to get me involved representing the patients on some of their research committees.
I became involved at the Royal Brompton Hospital. One of the lead clinicians said, "Why don't you come here and help us improve our research."
Kat: So what does that look like? What does it look like to be a patient representative? What do you have to do? Do you turn up and go, "I don't like that, don't do that."? What does it involve?
Fiona: One of the main things that I've been asked to do, I go to meetings. I'll attend a meeting sometimes in person but quite often I'll do it by telephone because that’s easier for me. And they realised that I'm more likely to attend a meeting if it's by phone than if you want to take a whole day to go to an hour's meeting.
So I'll go to a meeting and they'll ask me to review research applications. So, have a look at the research application, have a look to see whether the lay summary is actually understandable by someone that doesn't understand science.
I can also give them some hints and tips on how to recruit patients, some of the things you can ask patients. For instance, I looked at one research paper and they suggested they were going to do muscle biopsies on small children.
As a parent, I said, "I don't think that many patients are going to say yes to that. Why do you need to do it?", and then once I'd done that questioning, they said, "Well, actually we just wanted to do it because it was a nice to have.”
Well, a nice to have for a small child -- you don't want to make a small child cry, because that's what would happen -- and their parents! So, is it appropriate for the patient?
I'm a mum, I've been at the other end of some of these procedures. If it's worth doing and we think there's a value to it, then we'll let you do it.
So that's what I do. Mostly, it's attending meetings, answering emails and reviewing documentations but they do ask me my opinion and they normally get it.
Kat: And do they take notice of it?
Fiona: Yes they do, yes. I think it's a relationship that has developed. I've got to know them as researchers and clinicians and I'll ask them to come to events for us, come and talk about their research.
They are genuinely interested in the patients and they are generally interested -- sometimes it's just having those off-chance conversations with someone where you can talk about something and they'll say, "I didn't realise that was how it affected you."
People don't understand that if you have a child with a long-term condition, how it affects the whole family and how it affects other things. We're not thinking about the medical side all the time, we're thinking about the other things, like how it affects your income and your sleep and your general wellbeing, being a parent of a child with a long-term condition.
Kat: You mentioned that you spend a lot of time looking at grants and documents and scientific information. You've basically had to, I guess, learn a lot of the science behind it. How's that been? Where have you found resources to help you and what does help out with that?
Fiona: Yes, so when you first get involved with committees and things, they might give you a document that you really don’t understand any of the science behind it or anything. You begin to learn it. You become an expert user in your disease group. Some people give you training, some don't.
I personally have found my own training, so the National Institute of Health Research have a great online training thing for patients. You can go and do online training, it explains some of the wording, some of the understanding on what different types of research, translational research etcetera.
So there is some training available, but I think really it's just a question of turning up in meetings and actually, saying, "I don't understand that."
Quite often, I'll put my hand up like in school -- I don't really put my hand up, but you can actually say, "I'm really sorry, I don't understand that acronym, can you explain to me what that actually means?"
Normally, they are quite keen to do that. They just get institutionalised. That's how they talk all the time and they just assume that everybody understands them. So you have to say, "Sorry, I don't understand that."
Kat: What would be your advice to someone listening to this who is thinking, "That's something I'd like to do."? What are the first steps?
Fiona: Well, I would talk to your clinicians. If you want to become a patient rep then talk to your clinicians next time you take your child or you go with your family member to a thing. Say, "Are you involved in any research and can I help you in any way? Can I share my experiences with you, can I learn more about your research?", and I'm sure they will bite your hand off.
Kat: As well as academic researchers, we are also starting to see more companies getting involved, particularly in genomics, rare diseases and drug discovery and all of these kinds of things. How many of them are getting involved with having patients feeding into their research? What would be your advice for people setting up the companies that are focusing in these kinds of diseases?
Fiona: I would recommend that you get close -- if there is a family support group or equivalent organisation, get close to them. Reach out to them, offer to go and talk about your work at one of their family days or write a research piece or a piece for their newsletters.
Then go to those events and find someone like myself who is quite eloquent - sometimes, not today. But invite them to your offices, show them around, get to know them. Get to know what motivates them, what their interested in.
Most people, particularly with a rare disease, would like to help you. Because they want to see things developing and they want research into their rare diseases. So I think you should approach these people but be open and honest about what your motivations are and how you can help them.
Kat: And leading on from that, what are the benefits of really getting an integrated system going of research, academic research, commercial research and patient groups all feeding in together?
Fiona: I think the benefits of everybody collaborating is that sometimes you will have that little golden nugget. Someone will say something to you that you haven't really thought about, and quite often the patients will help you prioritise your research.
You might think that this is the most important thing to the patient, but actually what is more important is something that can help them on a day to day basis. Or it might be that there is some particular problem that they've got that you don't know about.
By having these conversations with patients you might suddenly get some really useful piece of information that you didn't know about - I think we're a valuable resource that isn't being used properly.
Kat: Fiona Copeland, chair of the PCD Family Support Group. She tweets as @PCDmum
As Fiona alluded to, while there are plenty of academic researchers who are interested in working together with patients and families affected by genetic conditions, there are lots of companies out there who are keen to get their hands on this kind of data.
This isn’t a bad thing: biotech, health tech and pharmaceutical companies have the investment, infrastructure and skills that are needed to take insights from research and turn them into tests, treatments and other interventions that can make a big different to people’s lives.
Many patients and families really do want to get involved in research that could help them or others in their communities. But it needs to be done in a way that is supportive and inclusive, not exploitative and intrusive.
One of the people trying to make this happen is Patrick Short. He’s the CEO of Sano Genetics - a Cambridge-based startup that aims to connect researchers with patients who want to take part in genomic research.
Patrick: So when we started the company we felt that there was a real opportunity to better connect patients to research and also researchers to patients. If we think about something like a clinical trial, it's pretty simple on the face of it.
Patients want medicines that might better treat their symptoms and researchers want patients to join the trials to see if they can prove that the medicines work well. But in practise, it's incredibly challenging to actually fit these two pieces together.
That's a specific example, in research more generally, finding the right patients and the right data to power studies and also asking the right questions in those studies, is often more challenging that meets the eye.
We felt like there was ultimately a lot of time being wasted. It takes many years to go from a research question to collecting data, to ultimately solving the problem. Patients need to be involved across the whole period of time, especially in the beginning in setting those priorities.
So what we're doing is basically building software to allow large-scale genome sequencing projects and other medical research projects to more efficiently connect with the patients that are participating in that, and allow patients to add data to their profiles and set the priorities for research.
Kat: Presumably then, you are already working with some patients to work out how to do this. How are you working with those groups?
Patrick: Yes, that's right. We do a couple of different things. One thing that we're starting to do quite a bit more coming up, with a project that we are working on with Genomics England, is running code development workshops.
So, giving patients and people from our company, from Genomics England together to develop the patient platform. And just to simply ask people, "What have your experiences with research been like before? How can we make research a better experience?".
An example that you probably hear a lot is we have apps like Deliveroo or Uber Eats. We can order food to our homes and we can rate the driver, even afterwards. We have nothing like that for research. There's no consumer interface for interacting with research, medical trials or these sorts of things.
So we do a number of workshops, we're in quite close contact with many of the patients who are early adopters of our platforms. We ask them, "How can we improve? What brought you here in the first place?", and try to have a very rapid feedback cycle between what people say they want and what we can actually deliver through the platform.
Kat: You're a commercial company. Have you noticed any differences in the attitude of patient groups towards more commercial enterprises, say, compared with academic research?
Patrick: Yes. I actually started my genomics career in academic research. I am from the US originally but I moved over here to the UK to do my PhD at the Sanger Institute.
I worked on a couple of large-scale rare disease genome sequencing projects. What was quite amazing about those projects is, once or twice a year, the researchers would get together with the patient organisations. There were quite a few good events that brought people together.
As a scientist, that was one of my favourite times of year because it really puts the research in context. You're spending most of the day analysing data at the computer or for some people working in a lab, to then actually speak to the families whose child or they themselves are getting a diagnosis through a project like this is quite exciting.
There's the same challenges with businesses and commercial entities, that often there's a grand reason that you're doing the work, to try to get new medicines or better medicines to patients. But it can often be quite distant from the actual patients themselves.
I think some of the ways in which our companies are organised makes this very challenging. There's a section of the company that's dedicated towards patient engagement, but the whole rest of the company has to somehow, via osmosis, get that feeling from the patient engagement section of the company.
So I think there's a lot more that can be done around infusing that patient-centricity through the organisations more widely. Whether it's things like events that are held at the company, or through solutions like ours that use software to basically more closely connect the scientist to the patients in a very dynamic fashion.
Kat: Do you ever encounter suspicion? Because obviously, with some commercial enterprises, there have been maybe some not so cool things that have happened in the past or maybe corporate companies that are working with patients and data do have a bad rap.
Patrick: Yeah, it's actually a big reason why we decided to go into this business, that we were seeing a number of companies in the direct to consumer genetic testing space, for example, that wasn't very clear to the customers of those genetic reports that their data was actually being used for other purposes.
It was in the terms and conditions somewhere, but most people just fundamentally didn't realise it was happening. We all do that. No one reads the 150-page document.
We felt like that was a real missed opportunity, and not the right way to do it because when people ultimately do find out that it's happening, it leaves a bad taste in their mouths.
If you actually took the time up front to explain to people the impact that donating their data to research could have, or even to go a step further, which we like to do, and share revenue from that data being used to discover new drugs with the people that provided the data in the first place.
Then people are almost always happy to contribute, if they trust the organisation and they trust that they are in control of their data and can choose how it's used.
So the approach we've taken from the beginning is to build the platform in a way that our participants; users, patients, depending on where they are in life, have full control over their data, transparency of how it's used and opt in for it to be used for purposes, rather than that being sort of assumed through terms and conditions.
Kat: We're here at the Festival of Genomics and it's so exciting to see the growth in the sector; start-ups, established companies, academic researchers all really wanting to build the sector, bring benefits to patients.
What would be your watchword for the future for companies and organisations really wanting to get into this space and what they should be thinking about?
Patrick: Yes. I like coming to this conference every year because it does bring such a diverse group of people together. Patients, patient organisations, pharmaceutical companies, academic researchers. I think above all, we're seeing a shift where people are systematically thinking about who the end user or the customer really is.
Whether you're a researcher, whether you're a pharma company, ultimately we are all doing this for patients. While that's quite well-known and we do think about that, it's often not always reflected in the way the processes of a business are set up, or how we go about doing things.
So I think that thinking about very tangible ways that we can re-orient business practices, the way we design software or tools to keep that in the very forefront of our minds and not as an afterthought, that actually it's about bringing patients closer to research and researchers closer to patients, at the end of the day.
Kat: It's funny, the more I work with start-ups and companies, you hear this phrase, "value", and they're like, "The value is in the data", or, "Where's the value in this?" This is human life. We're talking about human lives and joy and suffering. To me it feels like that should be where the value is.
Patrick: Yes, I think you're exactly right. There's no doubt that hundreds of companies have been started on the premise that - just like Facebook and Google - that data has value. To some extent it does.
We know that our data can help pharmaceutical companies discover better drugs and help us to stratify patients more effectively. But I think you're absolutely right that realising the value of that data should not come as paramount. That there are other requisite items that sometimes have proven to take second fiddle, like consent and making sure it's what patients want.
So ultimately, I think it's just about shifting the priorities and saying that if we as a company - the way we think about it is that if we can deliver a great experience for patients to get into research - and we are very transparent about our business model and matching patients to research - that the value creation will follow.
We have to start by doing what's right for patients, first and foremost.
Kat: That’s Patrick Short from Sano Genetics, who’s also the host of The Genetics Podcast, where he chats to leaders working in the field of genetics, genomics and bioscience.
Find out more by following @sanogenetics on Twitter and listen out for a familiar voice appearing at some point soon.
When Shelley Simmonds realised that something didn’t seem right with her infant son Fraser, she started asking questions. He was initially given a diagnosis of Duchenne Muscular Dystrophy, but that didn’t seem to be the end of the story.
Shelley and her family got involved in Genomics England’s 100,000 Genomes Project in search of answers - but things turned out not to be quite so simple.
Shelley: So when my son was around six months old, I felt like he just wasn't very strong. He was just a very floppy baby.
Luckily I took him to the doctors, who took my concerns seriously and we were referred to a paediatrician. It was from that appointment where all of the tests began for him.
Kat: What was it like then, receiving that diagnosis, hearing these words that there is this condition?
Shelley: Well, we were telephoned in the first instance to tell us that one of his blood test results was abnormal. That followed with a trip to Great Ormond Street Hospital, where we were told that our son had Muscular Dystrophy.
Kat: What impact did that have then on your feelings and your thoughts about your son and the rest of your family?
Shelley: We were absolutely devastated. I mean, we have no family history of this condition in our family at all.
I've got a daughter and she was fine when she was a baby, so it was really quite unexpected and it's a big diagnosis as well, so it's a lot to get your head around.
Kat: So what were you told then about what the outlook might be for him?
Shelley: I remember when I was told that he had Muscular Dystrophy, he was eleven months old at the time, I was holding him in my arms.
The first question that I asked after I was told what was wrong with him, I said, "Will my son die before me?" And the answer was, "I don't have the answer for you."
Kat: So then in search of answers, what did you go on to do?
Shelley: His bloods had to be sent for lots of genetic testing but they were testing one gene at a time, which obviously took quite a long time. So for a good four months, we didn't have any answers. We desperately wanted an answer but there wasn't one. I think it was just living in limbo, not knowing what was wrong with him.
Every time we were told that they were checking for this gene or that gene, we would do what everybody does and go on to Doctor Google and have a look and it's the worst thing that you can do. We were trying to come up with answers ourselves and that's not the right thing to do.
Kat: What made you get involved with the 100,000 Genomes project?
Shelley: When my son received his diagnosis after a muscle biopsy, they told us he had Duchenne Muscular Dystrophy. After a few years, after two to three years, we realised he wasn't progressing with the condition in a textbook fashion.
His clinician said to us that he had never seen a boy with Duchenne like Fraser before. His colleague said the same thing, so we were in a bit of an unknown territory, really.
Then the consultant said that it was likely that he had another genetic condition alongside having Duchenne. He suggested we enter the 100,000 Genomes project to look for an answer.
Kat: What was that process like? What happened? What did you do?
Shelley: We went along to the clinical research facility at Great Ormond Street and we had some bloods taken. That was myself, my husband and my son. So we were entered as a three. They took the bloods; we signed the consent forms and then went home and waited for two and a half years to have an answer.
Kat: Wow, two and a half years. That's a long time to be just waiting. How did that feel?
Shelley: It's something that you kind of have to put to the back of your mind. They did tell us when we enrolled in the project that it wouldn't be a quick answer. So we were aware of that.
The issue is that we did wait two and a half years for the answer and the answer is that there is no answer. So, of the panels tested, for my son, nothing else was found. So we are no further forward than we were four years ago.
Kat: So there's no specific alteration where you could say, "Yes, that's it, we can put our finger on that and say that's the cause."?
Shelley: Not at this moment in time, no.
Kat: Is there any hope that might come in the future?
Shelley: Yes. So with the project, your genome will be put back in the project, they will continue to sequence your genome because there will be new answers discovered all the time. It just may happen that we'll gain an answer from somebody else's genome but it is a waiting game.
Kat: We do sometimes get the impression that once you get your genome done, once you get the test, there will be the answer and then you'll be able to do something about it. Was that the impression that you had going into it? What's your feeling about that now?
Shelley: When I did enter the project, I think I did think that I would have an answer. I don't know if that was being naïve, or misunderstanding, but I did think we would have an answer.
As you learn more about the project and how it works, you understand that actually, lots of people won't get an answer because there's lots of genes that are undiscovered, haven't been investigated. And your body is just an incredible thing and nobody really knows how it works completely.
Kat: No. The genome is a big place, six billion letters or whatever.
Shelley: I know. And you can't expect anybody to know all of those six billion letters and what an error means. You just have to be realistic, I think, with what you expect to get out of a project of this magnitude.
Kat: What would an answer look like to you?
Shelley: I suppose an answer to tell us why our son is different. Why is he showing with his diagnosis that he has already, why has he progressed with that condition differently?
I think there's still a lot of work to be done because it maybe that he has a fault on another gene, which makes his other diagnosis present in a different way. Maybe the other children who have got Duchenne don't have that faulty gene and that's why they present in the way that they do.
I think we are quite a long way off understanding how our genes interlink with each other. That's still a way down the line, I think.
Kat: To you, how important was it to get involved in research like this?
Shelley: It's really important to me because I think this isn't just about my son. It's not just about my son, it's seeing the bigger picture of things. And if we can help another family who receive a diagnosis, if they can receive an answer faster than we can by us speaking out, sharing our story, joining something like the 100,000 Genomes project, then that's really important to help people in the future.
Kat: And for you now, moving forward, how are you coping with Fraser's diagnosis? What are you doing to find your own answers in the world?
Shelley: We've taken his diagnosis in the most positive way that we can. There was a period of time where obviously, we struggled to accept that our life was going to be different and that our son would be a wheelchair user and he may experience lots of different challenges in his life.
But for us, we think having a positive outlook on life, focusing on the things that he can do rather the things that he can't do, that just works for us.
For a long time we saw the wheelchair as a real negative thing, but actually, it's the most positive thing that's happened to him. When my son was two he got his first wheelchair. He just got in it and off he went.
It was such a magical moment because it was like he'd just got a pair of legs that worked. It was absolutely amazing to see. He has now got a powered wheelchair which he uses when he goes to school and when we go out for daytrips and things. It's absolutely changed his life.
Kat: You are part of the Patient Participation Panel for Genomics England 100,000 Genomes project. Is your story typical? The kind of issues that you've had, are they typical of the families that are involved?
Shelley: I already had a diagnosis when we were entered into the project, which is different from most people. Most people are looking for an answer from the project. Essentially I already had an answer.
I think for my family we were quite fearful of something else being discovered because we had already sat there in that room and been given a diagnosis for our son. The thought of going through that again was quite terrifying.
Kat: Yes, what else is in there.
Shelley: Absolutely, that's what it felt like. What else? What else can be wrong? As it happens, our answer from the project is that there isn't an answer. So we're currently still just a one-diagnosis family.
Maybe that will change in the future and maybe it won't, but we've learned to live each day as it comes, I think. Rather than waiting for a diagnosis, we just take each day with the lovely little boy that we've got.
Kat: That’s Shelley Simmonds, who’s on Twitter at @Shelley_Simmo
Twitching in Paradise
And finally, there’s just time for a clip from the latest podcast from Heredity, the journal of The Genetics Society. The islands of French Polynesia form a South Pacific paradise, and thanks to the actions of an eccentric aviculturist in the 1930s, they’re also host to an interesting evolutionary experiment.
James Burgon chats to Ashley Sendell-Price from the University of Oxford who has spent a few months twitching in paradise, studying the divergent evolution of charming little songbirds known as silvereyes.
Ashley: The silvereye, it's a kind of small, great-tit sized bird that originates from the Australian mainland. This is a very interesting case because unlike the other island colonisations by the species, the French Polynesian population is the product of a relatively recent human mediated introduction by a guy called Eastham Guild.
So Eastham Guild was somewhat of a prolific aviculturist. In his own words, he says that he liberated more than 7,000 in different fields of 59 different species to the island of Tahiti.
So, despite being a completely crazy man and such introductions and stuff are a bit of an ecological disaster, if you're interested in studying very early stages of divergence, this kind of foolishness is at least for me, very useful because there are now 13 non-native terrestrial bird species on Tahiti and these can be used to study the very early stages of divergence from a much clearer vantage point than what we have had before.
James: I guess to answer some of these questions you had to have some pretty epic fieldwork?
Ashley: Yes, there's definitely many worse places to spend two months of your life than French Polynesia.
James: I bet!
Ashley: I was really lucky that with the support of a heredity fieldwork grant from the Genetics Society, I could visit 5 of the 11 islands that have silvereye populations.
It's kind of interesting that Eastham Guild, in his writings about French Polynesia, describes it as being an exotic paradise, but he also goes on to say that for some reason, "There is perfectly no bird life." That was his justification for introducing non-native species to Tahiti.
Having visited French Polynesia I can say of course there is an abundance of bird life in French Polynesia. But there were some times when I found myself maybe agreeing with Guild a little bit, especially when I was on the island of Huahine.
Everybody I spoke to when I showed them pictures of silvereyes, they would be like, "No, we've never seen these at all." So, trying to get local knowledge about a bird that nobody knows exists was a big part of spending two months hopping around paradise.
Kat: You can find the full interview with Ash, as well as his reflections on LGBTQ+ communities in STEM in the latest Heredity podcast - just search for Heredity in your favourite podcast app, or follow this link. There’s also a link to his paper, and a couple of fascinating blog posts about Eastham Guild and his introduction of birds into Polynesia.
As Ash mentioned, his research was supported by a Genetics Society Heredity Fieldwork Grant - and if you’re a researchers looking for support for your next field project click here to read more about the scheme and apply.
Sendell-Price, A.T., Ruegg, K.C. & Clegg, S.M. Rapid morphological divergence following a human-mediated introduction: the role of drift and directional selection. Heredity 124, 535–549 (2020). https://doi.org/10.1038/s41437-020-0298-8
Zoology Jottings, Tahiti - Introduced Birds - more information
That’s all for now. Thanks to Frontline Genomics, the hosts of the Festival of Genomics. You can browse their website packed with articles about the cutting edge of genomics, and sign up for their weekly newsletter at frontlinegenomics.com
Next time we’ll be digging into the twists and turns in the true story of the discovery of the double helix. In the meantime, you can find us on Twitter @geneticsunzip and please do take a moment to rate and review us on Apple podcasts - it really makes a difference and helps more people discover the show.
Genetics Unzipped is presented by me, Kat Arney, and produced by First Create the Media for The Genetics Society - one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics.
You can find out more and apply to join at genetics.org.uk Our theme music was composed by Dan Pollard, and the logo was designed by James Mayall, transcription is by Viv Andrews and production was by Hannah Varrall. Thanks for listening, and until next time, goodbye.
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