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In this explainer episode, weāve asked Meriel McEntagart, Clinical Geneticist in the NHS and Clinical Lead for Rare Disease Technologies at Genomics England, to explain how genetic conditions can be inherited, and other ways they may arise.
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 youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
To learn more about X-linked inheritance, as mentioned in the episode, tune in to our explainer episode, how does X-linked inheritance work?
You can download the transcript or read it below.
Florence: Are genetic conditions always inherited from parents? I'm joined by Meriel McEntagart, clinical geneticist for the NHS to find out more. So, Meriel, first things first. How can a genetic change cause a condition?
Meriel: We have about 20,000 genes. That's the estimate and they are the code or blueprint for how to grow and develop a human being. And, if you think about a code, you can have a mistake in a code or a variant in a code. And if that happens, such as one genetic letter being changed for another, the result can be that the code doesn't give the correct instructions about how to grow and develop that human being. There are lots of different ways in which those changes can happen.
Florence: And how can we inherit conditions from our parents?
Meriel: Well, for the most part, like I mentioned, we've got 20,000 pairs of genes and we get one of each pair from our mother and our father. And so, for lots of genetic conditions, they follow a pattern of inheritance where one copy of that pair of genes has got the variant or spelling mistake in it, which causes the condition.
So just having a single mistake in that pair of genes is enough to cause you to develop the symptoms of the condition. Other conditions show where you only develop the condition if both copies of the pair, the one you get from your mother and the one you get from your father have got a variant or a spelling mistake in the gene.
So, you actually don't have a working copy of that gene. There are other patterns of inheritance as well. And so, we talk about X-linked inheritance. That can arise because women have what we call two X chromosomes; men only have one X chromosome.
Florence: If you want to learn more about X-linked Inheritance, you can check out our previous podcast. How does X-linked inheritance work? So then do parents who have a condition always pass it on to their children?
Meriel: So, this is again, where we think about some of those patterns of inheritance that I've just mentioned. If somebody has a condition, for example, a dominant condition, they will have that variant or genetic change that's causing their condition in one of their pair of genes. So then it's 50:50 when they have a child, whether they pass on the gene that's carrying that variant or not, because the child will be getting the other copy of that pair from their partner.
If they do inherit that copy with the variant in it, then they will develop the symptoms of the condition in most cases. In some situations, however, a parent can have a genetic condition. So, they develop symptoms of the condition, and as I've mentioned, it's 50:50, whether it gets passed onto the child, so the child could actually inherit that genetic variant, but potentially not show signs of the condition. And this is what we call āreduced penetranceā. This means you can carry a genetic variant and probably some other event has to take place to cause you to develop symptoms.
So that might be that there's other genetic factors that you inherit that trigger you to develop symptoms or there might be an illness or something that you experience that brings out the expression of that gene. So that's quite an important, consideration when we're looking at genetic variants and whether somebody will develop symptoms.
Florence: And finally, how do we develop conditions that don't come from our parents?
Meriel: Well, I suppose the main explanation for that is what we call a de novo genetic event. So that can arise when we are conceived. So for example, genes get copied to be put into the sperm or our genes get copied to be put into the egg. And in that process of making the sperm and the egg, a spelling mistake or mutation can arise in the DNA and then that sperm or that egg, whichever one has it, takes that forward into making the baby. And then the baby from that point will have that genetic variant in every single cell in their body. So it hasnāt come from the parents, so itās not inherited but it still is a genetic condition.
This is something that now that we're able to do whole genome sequencing, we are finding is a more common explanation for developmental disorders or conditions in children than we previously appreciated. And quite a lot of conditions where the child has congenital abnormalities when they're born, like a congenital heart problem with some global development delay or difficulties or some other sort of problem, when we do their whole genome sequencing, we find that they have a de novo mutation in an important developmental gene.
There are also some more unusual ways in which a genetic condition can arise for the first time in the family. The first example I might give is, the condition, Huntington's disease. Huntington's disease is a neurodegenerative condition that causes a movement disorder, often starting in adult life. And sometimes people will know that it's in their family. However, sometimes it can arise in somebody and there's no history of it in the family at all. Huntington's disease is what we call a triplet repeat condition. This is where, in our DNA sometimes we have little strings of letters that are repeating after each other. So, usually we'd have 25 repeats or less. This can slip up on transmission from a parent to the child, so it can increase in size and if it slips up into the range of 40 repeats or more, then that person will develop symptoms of the condition.
Another example I thought that might be worth mentioning is what we call imprinting. When we inherit our genes from our parents, for some genes, it actually matters whether the gene copy has come from your mum or from your dad, and it will have an imprint or a mark on it that says, this is the maternal copy, this is the paternal copy.
The reason that imprint is there is that it may potentially switch off that gene and say, this shouldn't be expressed in the baby. And if this doesn't work properly, you can get some conditions like for example, Prader-Willi Syndrome. This is where a child has developmental delay and maybe a very increased appetite. And it's because the differential gene expression hasn't worked.
Florence: That was Meriel McEntagart, explaining whether genetic conditions are always inherited. If you would like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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In this episode, we explore findings from a groundbreaking study recently published in Nature which revealed potential targets for bowel cancer prevention and treatment. The study provides the most detailed understanding yet of bowel cancerās genetic makeup. The research, which used data from the 100,000 Genomes Project identified over 250 genes that play a crucial role in the condition, driver genes and potential drug targets. Our guests discuss the potential impact of these findings on patient outcomes, screening for bowel cancer, and future prevention strategies.
Helen White, Participant Panel Vice-Chair for Cancer at Genomics England is joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University.
"The people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldnāt benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what weāre seeking to realise now. But, you know, itās not a given when we treat people in the clinic so weāre very, very grateful to those individuals."
You can read more about the study in our colorectal cancer blog and our study findings news story.
You can download the transcript or read it below.
Helen: Welcome to Behind the Genes.
Ian: One of the great hopes is that some of these new genes that weāve found could be useful in preventing cancer and it doesnāt necessarily matter that theyāre rare, even if theyāre only 1% of cancers, by using those and changing those in the normal individual before they have had cancer then we may be able to reduce that risk. So, there are lots of potential new targets for prevention that are coming through.
My name is Helen White and Iām the Participant Panel Vice-Chair for Cancer at Genomics England. Today Iām delighted to be joined by Professor Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, Claire Coughlan, Clinical Lead for Bowel Cancer UK and consultant nurse in colorectal cancer, and Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology at Oxford University.
Today we will be discussing a pioneering colorectal cancer study which using data from the 100,000 Genomes Project has uncovered new insights that could transform diagnosis and treatment for patients with bowel cancer. If you enjoyed todayās episode we would love your support, please like, share and rate us on wherever you listen to your podcast.
Thank you for joining me today. Weāre going to be discussing the findings from a landmark study that has been published in nature. This study used data generously donated by people with bowel cancer who took part in the 100,000 Genomes Project giving us the most detailed look yet at the genetic makeup of colorectal cancer better known as bowel cancer. But before we get into that letās start by hearing from my guests. Could each of you please introduce yourselves.
Ian: Iām Ian Tomlinson, I work at the University of Oxford and most of my work is research into bowel cancer, itās genetic causes, the genes that are involved in actually causing the cancer to grow which may be different from genetic causes and also the use of that data to help patients whether guiding future treatments or potentially helping to prevent bowel cancer which would obviously be our optimum strategy to have the biggest impact on the disease and its incidents.
Claire: So, Iām Claire Coughlan, Iām the clinical lead for Bowel Cancer UK and my remit at the charity is to ensure that everything we do is clinically relevant and that weāre providing services that meet the needs of those affected by bowel cancer and the educational needs of those health professionals that work with people affected by bowel cancer. Iām also a nurse consultant in colorectal cancer at Lewisham and Greenwich NHS Trust and I lead an urgent referral service there and also work with patients with late effects of bowel cancer.
David: Iām David Church, Iām a medical oncologist and Cancer Research UK advanced clinician scientist at the University of Oxford. I treat bowel cancer clinically and do research on bowel cancer and womb cancer including a lot of research using samples and data from Genomics England data service weāre discussing today of course.
Helen: Great, thank you. Now letās turn to Claire to learn more about bowel cancer. Claire, can you share with us how common it is, how treatable it is and if there are any trends in terms of which groups of people are affected?
Claire: Of course, bowel cancer is a relatively common cancer, there are about 46,000 people each year in the UK diagnosed with bowel cancer so that is quite a large number. The thing that really drives us forward in bowel cancer is that the earlier stage youāre diagnosed at the greater chance of survival. So, the figures for that are quite stark, we stage bowel cancer through stage one to 4 with one being the earliest stage and 4 being the most advanced.
If you are diagnosed with bowel cancer at stage one you have a 9 in 10 chance of being alive and well 5 years after your diagnosis of bowel cancer. And if youāre diagnosed at the other end of the spectrum at stage 4 that drops to a 1 in 10 and should people survive after a diagnosis of stage 4, which more people than before do they will have had a lot of treatment for their bowel cancer so the burden of the treatment will also be with them after that. So, itās really important that we diagnose at the earliest possible stage which is why studies such as the one weāre going to talk about today are so important.
We have noticed that there has been a slight increase in being diagnosed at a younger age. That said the latest statistic is 2,600 people were diagnosed under the age 50 in the UK last year so itās still a disease of older people, you still have a greater chance of getting bowel cancer as you get older but itās really, really important that weāre aware that you can still get bowel cancer as a younger person.
Probably one of the most exciting things that has happened for bowel cancer of recent years is our bowel cancer screening programme and the age for that now has been brought down to 50, weāre not quite there all over the country, but in the UK that is the aim that everyone will be screened for bowel cancer at the age of 50. So, yes itās a common disease and staging an early detection is vital.
Helen: Thatās lovely Claire, thank you very much for that. David, turning to you could you please explain to us how bowel cancer typically develops?
David: Yes, so we know compared with many cancer types quite a lot about how bowel cancer develops because the bowel is accessible to collect samples by a technique called endoscopy which is putting a camera into the bowel from which you can sample tumours or lumps. And so from genetic research done in the last 10 years we know that, or weāve known for many years actually, for much longer, that cancer is a genetic disease, itās a disease caused by alterations in genes and particularly genes that control whether the cells in our bowel grow normally and die normally as they should do.
And collectively when there are alterations in genes that regulate those processes you can have a cell or collection of cells which are able to grow without restraint and donāt die when they should do which are some of the hallmarks of a cancer and they also require the ability to spread elsewhere in the body which is what kills people with cancer including bowel cancer. We know from research done in the last 10 to 15 years that some of the alterations in genes that can cause bowel cancer in combination occur very early in our life, even in the first and second decade of life, but donāt cause cancer.
The earliest detectable abnormality is typically a polyp which is a tumour, a lump within the bowel which is detectable and if removed is almost certainly cured by removal alone but if itās not detected then as that grows and acquires more alterations in genes then it can become a cancer and cancers develop the ability to invade the bowel wall, to spread to what we call lymph nodes or glands nearby and also to spread further afield, most commonly to the liver or to the lungs.
And for most people whom bowel cancer has spread to the liver or to the lungs or elsewhere unfortunately weāre not able to cure their disease which as Claire has said is why there is such an importance in detecting cancers and pre-cancers as we call them so that the tumours are not actually cancerous but come before bowel cancer as early as possible.
Helen: Thank you David. Moving on to the study, Ian perhaps you can take this, in the study that you carried out my understanding is that the whole genome sequencing was used to investigate the genetic changes that lead to the development and growth of bowel cancer. And for this participants with bowel cancer in the 100,000 Genomes Project donated both a blood sample and a tumour sample while those with rare conditions only provided a blood sample, can you explain why that is?
Ian: As you said the study really looked at 2 quite separate arms albeit with a little bit of overlap as weāll see. So, one very important aim was to look at individuals, both children and adults, who had medical problems or other conditions that were unexplained but which had some features that suggested that they werenāt necessarily inherited but there may be some variation in their genes that had caused them, and roughly half of the programme was dedicated to that.
Within that there was a small number of people who had a strong family history of bowel cancer or who had large numbers of polyps in the bowel and they were analysed in a separate part of the project from what weāre mostly discussing. Within the cancer arm there was a collection really throughout England of patients who had most of the common types of cancer and a few with less common cancers.
And because when weāre looking at genetic and related changes in cancers we need to make sure that those changes have actually occurred in the cancer as it started growing from its earliest stages with a small number of cells in the body that were slightly abnormal and then progressing. We need to look at what genetic variation the patient has in all the cells of their body. We donāt want to look at patients and say that looks an interesting change, we may be able to use that if itās present in all of the normal cells in that patientās system.
We want to make sure the change is specific to the cancer itself and therefore we have to sequence both a sample probably taken from blood and a sample taken from the actual cancer. And in a way we subtract out the changes in the blood to identify the changes that have actually occurred in the cancer itself.
Helen: Thatās a very helpful explanation. Does this research show that there is a role for whole genome sequencing in clinical care?
Ian: I think my own view is it is all a question of cost. I think the advantages it provides it can assess multiple types of genetic change at once. It is relatively consistent across each cancerās genome between cancers, even between centres mean that it is the method of choice. There are undoubtedly developments that will happen in the future, maybe being able to sequence longer stretches of DNA in one go that will help the analysis.
And some of the computational methods are likely to develop to identify some of the slightly difficult to identify genetic changes but it ought to be the standard of choice. There are issues and potential difficulties in collecting the high-quality samples that have been needed from pathology laboratory and that will be difficult going forward with current budges and there are lots of challenges but ultimately it in some form has to be the method of choice. What wasnāt done is to look at other molecule tests or essays, looking at RNA wasnāt really done on a big scale as well as DNA and other changes to DNA apart from the genetic changes were not looked at.
So, there are certainly ways it could be improved if you had limitless money but I think the project, 100,000 Genomes has shown the whole genomes are. They have a lot of advantages and ultimately probably will be adopted by the NHS and similar organisations.
Helen: David, could you now tell us about the findings of this pioneering study and what impact these findings might have on people with bowel cancer in the future?
David: So, this is the largest study to date to analyse the entire genome of bowel cancer by some margin and the fact that weāve done whole genome sequencing and in so many people it has really given us an unprecedented ability to identify the genetic alterations that drive bowel cancer. And within bowel cancer weāve known for some time it is not a homogeneous entity that bowel cancer is not all created equal, that there are sub-groups of bowel cancer and we have been able to refine those over previous efforts. And I guess if you were to ask what the biggest take home for me from the study is itās just the complexity of the disease.
So, as weāve mentioned we know that cancer is a genetic disease, that itās driven by genetic alterations, alterations in genes which regulate the growth of cells or the death of cells or the spread of cells. And weāve known for many years that there is a modest number of genes which are commonly malfunctioning in bowel cancer and they would be in the tens to dozens really. But with this work weāve hugely extended our understanding of the genes that drive bowel cancer and in fact weāve discovered nearly 250 genes which are altered in bowel cancer and appear to drive the growth of the cancer.
Now we know that not all of those will be validated and by that I mean that there are associations that we find at the moment, not all of which will be biologically relevant but interpreted in the data we know a large number that are previously undiscovered are or we can be fairly confident of that. And one of the take homes from that is that many of these are only altered in a small fraction of bowel cancers.
So, rather than being perhaps half of bowel cancers or a third of bowel cancers there are a good number of genes, a very substantial number of genes, which are altered in say 3 to even 1% of bowel cancers. And if we think about how we go about targeting those and perhaps weāll come onto treatment later that poses really challenges for how we work and we would think about treating patients with bowel cancer who have those particular alterations in their cancers.
Helen: Thank you David, yes weāll come onto treatment shortly, but I think Claire has a question for you.
Claire: Yes, thank you. For me as somebody who works in this every day this is such an exciting and interesting study, particularly in light of what we said earlier about early detection and how critically important that is for improving outcomes in people with bowel cancer. So, in your view do you think this research could help shape future screening programmes or prevention strategies?
David: Thatās a great question, I suppose in terms of screening at the moment the majority of screening is done in the UK at least by testing for blood in the stool which is relatively non-specific so Iām not sure that that would be directly impacted by this research. But one area of early cancer detection that is perhaps more relevant is quite a lot of work including from Oxford actually in recent years looking at blood tests. So, testing blood samples for early detection of cancer whereby you can test for genetic alterations, fragments of DNA that have alterations from the bowel cancer or any cancer that circulates in the blood and that tends to rely on a small number of common alterations.
And with this data I could see that we might be able to refine those tests and in so doing improve our early detection of cancer but that would need quite some work before we could actually say look that had real potential I think. And in terms of prevention there are, I think Ian may want to come in on this, one or 2 sub-groups which you might think that you could try to prevent but of course that needs a lot of extra work really.
But I think we have some clues of the biology of bowel cancer and particularly some of the sub-groups where you might think well this drug would work better in terms of preventing that sub-group or that sub-group but that will need to be the subject of future study.
Helen: Ian, did you want to come in on that at all?
Ian: So, at the moment prevention is a fairly new way of helping to reduce the number of people with bowel cancer at the level of the whole population which is what we have in the UK above a certain age group as we heard from Claire earlier. The methods used, again as we heard, are screening for occult blood in the stool and then colonoscopy to identify either hopefully early cancers or polyps and remove those. But when we think about the methods that we use for preventing other diseases then normally where theyāre successful using a more easily delivered and I have to say less expensive method.
So, high blood pressure is treated to reduce the risk of cardiovascular disease and there are other diseases where those what you might call molecularly-based prevented strategies are coming in. We really lack that for bowel cancer in particular, it does happen for some other cancers, but one of the great hopes is that some of these new genes that weāve found could be useful in preventing cancer. And it doesnāt necessarily matter that theyāre rare, even if there are only 1% of cancers, by using those and changing those in a normal individual before they have had cancer then we may be able to reduce that risk.
So, there are lots of potential new targets for prevention that are coming through and as David said it is going to take a lot of work to work out which of those are deliverable and who will benefit. But we have quite a lot of opportunities in that space and although that may not be us that takes that forward, it may be, but it may not be. We think it is a lot of material for those interested in chemo prevention using drugs of cancer that they can work on and with luck deliver some new ways of preventing cancer that may be simply popping a pill every morning to take your risk right down to as close as zero as we can.
Helen: Thank you Ian. David, I think you had something to add here.
David: Thanks Helen. One area of prevention that weāre really interested in Oxford and many others are is using the genetic alterations that we find in bowel cancers and other cancers as targets for vaccination. Now we know that gene alterations will cause abnormal proteins which while they might drive the cancer, make it grow or not die, can also be recognised by the immune system so the abnormal proteins can be recognised by the immune system as being foreign and as foreign they can be targeted by the immune system so the immune system will try and kill the cells carrying those alterations. And we know for some sub-sets of bowel cancers those alterations can be relatively predictable actually, they occur in quite a sizeable fraction of some sub-groups of bowel cancers.
And one area that weāre particularly interested in at the moment and actively pursuing is using those targets where you need some additional work to demonstrate when they are particularly recognisable by the immune system. But to use these genetic alterations is potential targets for vaccination with the intention ultimately of preventing bowel cancer in at risk individuals or ideally in the full-term time the whole population. And weāve received some funding from Cancer Research UK to pursue this line of research and we have a group working on this in Oxford and as I say many others do elsewhere.
Helen: Thank you David, yes I have a vested interest in this because my understanding is this work is aimed primarily at people with a genetic condition called lynch syndrome which predisposes the people who have inherited this gene change alteration to bowel cancer, womb cancer and other cancer. And I had womb cancer, as I think David you know, a few years back and discovered it was due to lynch syndrome and so itās really exciting that youāre now looking at vaccinating preventing because yes I take aspirin every day, I have my colonoscopy every 2 years which have some effect on preventing these cancers but itās not 100% guaranteed. And I donāt suppose it ever will be but having the vaccination in that armoury would be fantastic I think for future generations, itās very exciting and we look forward to hearing more about it.
Thank you Ian and David. I mean weāve heard a lot there about preventing bowel cancer but I think moving back now to potential treatments, you know, weāve heard from David how this study has shown a number of actionable findings but what are the next steps towards treatment? How can these findings be turned into real actions that will benefit those people diagnosed with bowel cancer in the future? Ian, perhaps you would like to pick up on this to start.
Ian: That step is one, you know, in which Iām not personally an expert but a lot of the newer treatments are based on the finding of so called driving mutations which are simply genetic changes that occur as the cancer grows and contribute to that growth and ultimately if itās not treated to the spread and dissemination of a cancer. And the fact that we have reported 250 which need validation but of which a large proportion are likely to be true drivers means that anyone of those can be a potential new target.
The criteria to be used for which of those mutations to pursue, which of those driver genes to chase up are quite complicated normally, depend on many things such as the interest of research groups and small and larger drug companies. And the similarity of those genes to other genes that have evolved and the processes that they make to go slightly wrong in the cancer.
So, there is also the issue that because these are uncommon, everybody talks a lot about personalised medicine or precision medicine, this would be truly precision or personalised medicine because a genetic change that was driving the cancer in only 1% of patients is obviously not a huge number of patients although bowel cancer is a common cancer so itās not a tiny number either. But it would mean investment at that level to benefit letās say 1 to 2% potentially of all patients with bowel cancer but I think thatās a nettle we have to grasp. And I think our results are showing that most of the really common drug changes either have not yet been successfully targeted in treatment or are too difficult to target.
So, weāre going to have to start looking at these less common genetic drivers and design strategies, inhibitors, you know, again that can be delivered to patients relatively straightforwardly in order to see whether they benefit the patients concerned. But there is this problem of getting enough patients enrolled in clinical trials where a change is only present in a relatively small proportion of all the patients with that cancer type.
Helen: Thank you Ian. Presumably if there is a relatively small number of patients the people who are looking at running these trials might be looking at perhaps international trials, would that be one way to go?
Ian: So, I think David can speak with more personal knowledge but there are international trial networks and there are collaborations along these lines already under way. I would hope that those could be made use of even more than they are already. There is, you know, a financial consideration for those developing new anticancer treatments which are, you know, high risk work and also the costs of setting up trials and enrolling people is not a trivial thing. So, I think those are hurdles that can be overcome but it would need a concerted effort to do that. Patients will play a major role in that and patient organisations as well as 100,00 Genomes and other similar projects.
Helen: Yes, thank you, David I donāt know if you want to come in on that.
David: Yes, the challenge of testing therapies in small groups is a very real one and there is lots of interest at the moment in exploring alternatives to conventional clinical trials. And as we use more electronic patient records and we have pharmacy records so there is the potential to get those data from routine clinical practice and there is lots of investments and attention on that at the moment so called real world data which is always an interesting term as if patients in clinical trials arenāt in the real world which of course they are.
But itās perhaps a little more cost effective sometimes in clinical trials, of course it does pose its own challenges in how you disentangle true treatment effect from other factors because there are many factors impacting on how long people with cancer live. But there is a lot of investment and effort going into that at the moment and it will be interesting to see how that develops over the coming years.
Helen: Turning to you Claire based on your experience how well do you think people with bowel cancer understand how genomes can help with their care and what support is currently available to them in this area?
Claire: I think the answer, as it is so often is, itās dependent on individuals and not just one individual. So, I think some patients are very motivated to know as much about this as possible and to understand and to know what the next steps may be in their own treatment that may be helped by this. Others donāt want to have the same knowledge and want to be guided very much by their medical teams but I think oncologists obviously are at the forefront of this and we see at the charity ā¦ we have services at the charity that supports patients and we see lots of queries into our ask the nurse service where people have been given variable information about I suppose personalised medicine as Ian alluded to and how their very specific bowel cancer may be treated, so I think it varies from patient to patient.
There is support available so we have the ask the nurse service I alluded to. We have a brilliant patient forum actually and everybody in clinical practice will have seen this, patients often become more expert than anybody and they share advice and theyāre moderated forums that are a very safe place for people to ask questions where there is a moderator to ensure that it is made really clear that circumstances are individual.
And the same with the ask the nurse service because you donāt have all the clinical information so it is about empowering people, so there is support available. I think the other thing that is really important is equipping specialist nurses with the knowledge that they need to support their patients. This is a really exciting area of evolution for bowel cancer particularly I think in all cancers at the moment but for bowel cancer I think things have changed fairly rapidly in recent years and specialist nurses really need support in knowing that they have up-to-date information to give their patients.
So, thatās another challenge for us and any specialist nurses that might be listening to this podcast we have online education on genomics for specialist nurses. Just while weāre talking about that and you mentioned lynch syndrome earlier, so there has been a lynch syndrome project as Iām sure youāre aware where weāre trying to get testing for lynch syndrome brought into local hospitals.
So, there was some funding via NHS England so that the testing be done at time of diagnosis, so a pre-test and then a final test if thatās appropriate, for everybody diagnosed with bowel cancer to see if they have lynch syndrome. And in some trusts that has been done and in others it hasnāt yet and the funding hasnāt quite followed in the way that we need it to enable that to happen. Itās vitally important, we think there are about 175,000 people in the UK with lynch syndrome and we only know about 5% of them. And this is a gene change that is an inherited gene change so we can do what we call cascade testing where we test family members and we can then employ preventative strategies to prevent people from developing bowel cancer.
So, itās a really important project, so I think as well as supporting patients with the information around the changes that are happening in this area we also need to ensure that we support the workforce and have investment there to enable the support of all the changes and the genomic landscape.
Helen: Absolutely Claire and so much resonates there with what youāve said. Having myself had cancer discovered that was due to lynch syndrome, cascade testing offered to my family members so valuable. It turns out I inherited my change from my mum who is 83, has never had cancer, so I think thatās a very good example of, you know, it doesnāt necessarily mean that you will get cancer but actually on that point that you made about empowering patients I always have a right smile because there is my mum going off to all her other medical appointments because at 83 she sees quite a few people and she is always the one telling them about lynch syndrome and educating them because most of them havenāt heard of it, so yes itās really, really important.
And that patient forum, youāre probably aware of Lynch Syndrome UK, I donāt have any involvement in that other than being a member but that is so valuable for people with a particular condition to go somewhere where they can talk to or listen to other people with a similar condition, really, really valuable.
Right, well I think circling back really to the 100,000 Genomes Project I think you touched on this earlier David but reflecting on what you and Ian have told us about your study what is it about the 100,000 Genomes Project bowel cancer dataset that made this work possible?
David: There are a few things, one of which and not least of which is the sheer size of the effort. So, to have whole genome sequencing for more than 2,000 individuals is previously unprecedented and weāll be seeing more of this now as we scale up our research efforts but at the inception of the project it was very, very ambitious and to be able to deliver that is a huge achievement. And the quality and breadth of the analysis is very strong as well.
And ultimately, you know, the former gives thanks to the people that were kind enough to donate samples to the 100,000 Genomes Project, they did so knowing that they almost certainly wouldnāt benefit personally from their donation from their gift and that any benefits would be some way down the line and hopefully benefit others which is what weāre seeking to realise now. But, you know, itās not a given when we treat people in the clinic so weāre very, very grateful to those individuals.
And I think also to the scientists who worked incredibly hard over the last 5 years to deliver this work actually. So, having been part of the team and being lucky enough to be part of the team along with Ian weāve had hugely motivated individuals that really have dedicated a large fraction of their working lives to delivering this project which I think is a fantastic achievement as well.
Helen: Thank you, thank you to all those participants who at a time when their lives probably were turned completely upside down by a cancer diagnosis were offered the chance to join the 100,000 Genomes Project and said yes. As you say most of them will have known that it wonāt have helped them but by donating their data, you know, it has allowed this work to happen and potentially it could change lots of peopleās lives in the future, so thank you to them.
Ian: Could I also just emphasise and agree with what David has said, I wonāt go through all the individuals by name, but if anybody wants to read the published report of the work there are several people on there, Alex Cornish is the first author, but many colleagues from an institute of Cancer Research, The University of Manchester, Birmingham, Leeds, other universities in London that all contributed, but also colleagues in the NHS and/or universities who recruited patients, collected samples, processed them etc and of course the people who did the preparation of the samples in genetics laboratories and actually did the sequencing and basic analysis too.
So, it is a truly huge effort across particularly all the cancer types which is particularly a complex collection given the fact the tumour is needed and a blood sample. Itās quite difficult in a way to find a formal way of thanking them for all of this but without them it wouldnāt have happened.
Helen: On that note I think weāll wrap up there. A huge thank you to our guests, Professor Ian Tomlinson, Clare Coughlan and Dr David Church for an enlightening discussion on the groundbreaking study published in nature. This research is set to reshape our understanding of colorectal cancer and pave the way for new possibilities in treatment and patient care.
If you would like to hear more like this please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. I have been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital and produced by Naimah Callachand.
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In this explainer episode, weāve asked Adrianto Wirawan, Director of Bioinformatics Engineering at Genomics England, to explain what the term 'no primary findings' means.
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 youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Florence: What does āno primary findingsā mean? I'm joined by Adrianto Wirawan, Director of Bioinformatics Engineering for Genomics England, to find out more. So firstly, Adrianto, when we speak about findings from genomic tests, what does this mean? What are we looking for when we do a genomic test?
Adrianto: Our DNA is made up of a long sequence of letters that act like instructions for your body.
Genomic testing analyses these letters to see if there are any unusual patterns or changes that might change your health. You can imagine your DNA as a book full of recipes for your body. Every recipe tells your body how to make proteins that keep you healthy, and sometimes there might be a typo in the recipe, like missing an ingredient or mixing up the steps. This could result in a health problem, just like how a changed recipe can lead to a bad dish.
On average, we would expect about 5 million out of our 3 billion DNA letters to be different. And each of these, we call them a genetic variant. Genomic testing is designed to examine some of these variants to help inform our healthcare. So, for example, in understanding why certain health problems happen and in choosing the best treatment based on our unique genetic makeup.
Florence: And what do we mean by primary findings?
Adrianto: Primary findings mean that in a patient's genomic testing, we identified a set of variants that is linked to the patient's condition. The variants that we have makes us who we are. However, not all of them cause a disease or contribute to a health problem. our bioinformatics pipelines will automatically prioritise variants of potential relevance to the patient's conditions. Using this data, the NHS clinical scientists will then determine whether any of these prioritised variants are linked to the patient's condition and whether a genetic diagnosis has been identified, which would explain why certain health problems happen.
Florence: So, then what happens when there are no primary findings?
Adrianto: When no primary findings are found, that means that no genetic diagnosis has been identified. As developments are made and our knowledge of the variance improves over time, additional findings might be identified in the future.
The clinical team responsible for a patient's care may request reanalysis of data according to the national guidance, following a change in the patient's clinical status to inform reproductive decisions, or after significant new disease gene associations have emerged.
In addition, Genomics England also provides the diagnostic discovery pathway where we focus on uncovering new diagnosis, where the participants of the 100,000 Genomes Project, as well as the patient's sequenced through the NHS Genomic Medicine Service
This is meant to be more equitable as we don't rely on the clinical teams to raise individual separate requests.
Florence: And finally, what do we mean by secondary findings?
Adrianto: Secondary findings are additional findings not related to the conditions in which the patient was recruited for. For example, if a patient was recruited for one type of cancer, but perhaps we found variants linked to a different condition. We explored secondary findings for the 100,000 Genomes Project but we do not do secondary findings for the Genomic Medicine Service.
Florence: That was Adrianto Wirawan explaining what we mean by āno primary findingsā. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk.
Thank you for listening.
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In this explainer episode, weāve asked Mathilde Leblond, Senior Design Researcher for the Generation Study at Genomics England, to answer some frequently asked questions that we received from parents who we engaged with for the design of the study.
You can hear more information about Generation Study via the study's official website and in our previous podcast episodes:
How has design research shaped the Generation Study?Which conditions will we look for initially in the Generation Study?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 youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Naimah: You may have heard about the Generation Study. This research study led by Genomics England in partnership with NHS England will sequence the whole genomes of a hundred thousand newborn babies and will look for more than 200 rare conditions that could be treated in the NHS in early childhood.
The study seeks to improve how we diagnose and treat rare genetic conditions to enable babies and families to have better outcomes. Today I'm joined by Mathilde Leblond, who leads design research for the Generation Study, and will be answering some of the frequently asked questions that we receive from parents who we engaged with for the design of the study ā the same questions that expectant parents at participating hospitals might have before deciding if they want to take part.
So first of all, Mathilde, can you tell me a little bit more about your role?
Mathilde: Hello. So, I'm a design researcher. My role is to support my colleagues, understand our users deeply so that we can create experiences that are as positive and seamless as possible.
So today we'll talk about the parents who are the ones invited to take part in the Generation Study, but our users also include the midwives who are approaching them and taking blood samples. The clinical scientists who are interpreting the results and the specialist paediatricians will be contacting the parents if a condition is suspected, and even many more users actually.
So, we did a lot of research prior to launching to shape the Generation Study, and now that we're live, we continue doing more to keep improving the experience.
Naimah: Okay, so can you give us a bit of background? How did you engage with parents in this study?
Mathilde: Yeah, so today we've involved over 150 pregnant and recent parents in our co-design sessions.
And these sessions were slightly different each time with different topics and exercises, but generally we spend around 90 minutes with one parent. And we asked them to bring someone who helped them make decisions about their baby during their pregnancy. So that meant that we had their mums, their sisters, their husbands, their wives and friends as well, taking part and discussing the Generation Study with us.
During that time with them, we would test our materials. We listened out to what's important to them and what they asked about, and we got them to show us what would work better for them so that we could then shape the materials around that.
Naimah: So you can find out a bit more about why it's important to involve users in co-design in our podcast āHow has design research helped shape the Generation Study?ā, which is available on our website.
So, we have a list of frequently asked questions from some of the parents, and I wanted to post some of them to you today, Mathilde. So first of all, one of the questions was, why should my baby take part in this study?
Mathilde: Yeah, I mean, that's really the key questions that all parents are asking themselves before they even spend any time finding out more about the Generation Study. And our materials do reflect that. So what tends to matter most to the parents we spoke to, is that there's a small chance that their baby may benefit directly from taking part because if a condition is suspected, they'll be invited for further specialised tests within the NHS, and they could receive treatment much sooner than if we had waited for the symptoms to develop and for a diagnosis to come, which can sometimes take years for some rare conditions. But for a large majority of the babies, 99%, they will have no condition suspected and so their involvement really is more altruistic. Taking part means that their parents agree to share the baby's healthcare records on an ongoing basis and their genome with researchers who can then look at this together with information from thousands of other babies and patients to help improve our understanding of genes and health.
So taking part in the Generation Study also means that you might help uncover some life-changing early treatments for babies in the future. And finally, something that's super important to us is that people from Black, Asian and other minority ethnic communities have historically been underrepresented in this type of research. So, we're working hard to make the Generation Study as inclusive as possible to help genetic testing and treatments be improved for everybody in the future. So, there's many reasons to take part in the Generation Study.
Naimah: You mentioned the word altruistic there. Can you tell me what that means?
Mathilde: Yeah, so that's really to help society. They may not get benefits within their own lives or within their own family, but somebody somewhere will benefit from it in the future. And that's what altruistic means.
Naimah: Thank you. So, some parents might also ask, will this test tell me every illness that my baby might have now and in the future?
Mathilde: No. So first of all, we're still learning a lot about how genes work, how the environment affects them, and there's also many conditions that we still don't understand very well. So those are not in. Of the conditions that we do understand quite well. We did a big piece of public engagement in 2022 to try and decide which ones to include as part of the screening.
And while some parents told us that they would want to know every single thing in advance, a lot of parents were worried about how much it would raise their anxiety to find out about a potentially incurable condition at such a fragile and beautiful moment when you have a new baby. So, for this reason and many other reasons, we've decided to proceed really cautiously so that the conditions that we'll be testing for have been chosen to reflect 4 key principles. And you can find them on the website. But the main gist is that we'll only be looking for conditions that normally start in childhood, first few years of life. So, nothing around Alzheimerās, nothing around breast cancer, for instance. And another principle is that there's has to be already existing pathways within the NHS so that the babies can be seen and treated quickly. So, we're only including those conditions that start in childhood, and something can be done about them early on.
Naimah: You can also listen to our podcast on our website 'Which conditions will we look for initially in the Generation study?ā to find out more about the list of 200 conditions, which we'll look for in the study and how this may change over the course of time as new evidence emerges.
So, another common theme with the parents was that they are aware that the NHS is already under a lot of pressure, and they asked if my baby is flagged for more testing, will I really be able to get the support I need from the NHS in time?
Mathilde: Yeah, that's a question that we've heard a lot actually, and it really makes sense considering the media coverage that's coming out daily, and that's been really in the papers for months now about how stretched the NHS is.
We've worked really closely with the NHS to ensure that all the babies that have a condition suspected as part of the Generation Study can be seen as soon as possible. So, our team has been in touch with specialists from across the country to understand how ready they are to take in those babies, to run confirmatory tests and potentially start treating them sooner.
So, it's been really key for us to make sure that we're not flagging up a baby for more testing and they just have to wait for months before they can get extra tests and attention. And that's so important for us to get right. In the long term, we hope that screening could actually relieve some pressure from the NHS if we can get babies to the correct doctor earlier on while their health is still good.
Naimah: Some parents might also ask, this research sounds very new. Is my baby going to be a Guinea pig?
Mathilde: Those two words, Guinea pig, came up again and again in almost every single session that I've had with parents, it was almost a freaky coincidence. I find that most parents use this wording to mean, will we inject anything into their baby or give them any medication that has not been tested and approved?
And the answer to this is no. What does happen is that when a baby's born after the birth, we need to take a few drops of blood so that we can create their genome, their DNA, and normally we'll take a bit from their umbilical cords, and that is happening in most of the birth at the moment of the participants.
But if for any reason we couldn't take that, maybe it was a complex labour, there was some emergency. The parents are asked a bit later if they would allow for a bit of blood to be collected using the heel prick methods. And that's a method that's been used in the babies in the UK within 5 days of birth for many, many years. And it looks for 9 conditions, as a current NHS test. So that's definitely safe. And usually when parents find out that that's all there is to it, they feel a lot more comfortable. A little disclaimer here because we mentioned the 5-day heel prick, while we use a similar method to get the blood, if we couldn't get blood from the umbilical cords, it's important to see that this is a different test, it's a proven test within the NHS which says many lives. So, parents who choose to take part in the Generation Study are very much encouraged to also agree to the day 5 newborn screen screening.
With all of that being said, this is a new research study and there are some uncertainties. Most of them revolve around how quickly we can process the results, how will parents and the NHS react to receiving these results so early, but also will this be inclusive for everybody? And might we inadvertently create more inequities? We're actively listening to sites now that we have opened and we have a survey that our participants can fill out, and we're working with UCL to help evaluate the impact of the Generation Study in an unbiased way.
Naimah: Okay. And another frequently asked question, if you have my baby's DNA, does that mean that you can clone them?
Mathilde: Cloning comes up regularly in our interviews with parents, though sometimes I found that people can feel a little bit silly asking about it, but actually it's a quite big topic that's top of mind when we talk about DNA and genomes.
Not least because of how much it comes up in sci-fi, it's just everywhere. So first of all, about cloning, it's important to remember that it's completely illegal, but it also has a whole host of other ethical concerns, which we don't take lightly at all here at Genomics England. So, the research that our study will support will be firmly within the bands of law and ethics and will only focus on discovering answers to questions that could help the health and wellbeing of babies, and really all of us in the future. No cloning involved.
Naimah: Okay. And then the final question, how can I take part in the study?
Mathilde: We've already opened in over 10 hospitals in England, which we are very excited about and we're actively working on opening more. You can visit our website, www.generationstudy.co.uk, to see an up-to-date list of hospitals which are currently taking part, and to read more about what taking part entails. Then you can contact your local research team to log your interest if you're planning on giving birth in one of our partner hospitals, and they'll be in touch to let you know about the next steps.
Naimah: That was Mathilde Leblond answering some of the frequently asked questions from parents that we have engaged with for this study. If you've got any questions or you'd like to hear more, please contact us at [email protected], or you could find out more on the Generation Study website www.generationstudy.co.uk.
Thank you for listening.
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In this explainer episode, weāve asked Callum Morris, Pharmaceutical Research and Development Insights Manager at Genomics England, to explain what happens in a clinical trial.
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 youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Florence: What happens in a clinical trial? I'm joined with Callum Morris, Pharmaceutical Research and Development Insights Manager for Genomics England, to find out more. So, Callum, first things first. What is a clinical trial?
Callum: So, a clinical trial is a study that looks to people to answer a specific medical research question.
So, this involves gathering a group of participants that are willing to participate in providing evidence on how to improve clinical care. And so, the main purpose for a clinical trial is to evaluate health related outcomes between different groups of participants. If it's an interventional clinical trial, you change clinical care for one group and not another.
And evaluate whether the change you made improved health outcomes for that group, or if it's an observational clinical trial, you might focus on different groups but not change anything about their clinical care and collect real world data to understand how outcomes differ across the groups.
Florence: Can you briefly explain what we mean by real world data?
Callum: Sure. So real world data relates to data collected routinely as part of standard clinical care. So, it could be collected from your electronic health records, data from product or disease registries, or data gathered from other sources such as digital health technologies.
And all of this can inform on particular groups from the population you're interested in.
Florence: And are there different types of clinical trials?
Callum: Yes. Clinical trials can take many forms depending on the medical research question you're trying to answer. They could be related to understanding the risk of disease. So, evaluating a potential risk factor that you may be concerned with. They might evaluate preventing disease. So, what different approaches can you take to people who have never had the disease, and does this prevent its occurrence? You can have a clinical trial that looks at screening for disease. For cancer, that's really important.
Does a new screening approach mean more people with cancer can be identified earlier? And importantly, does this lead to an improvement in survival? You can have clinical trials that evaluate the different approaches to diagnosing a disease and can you diagnose a patient earlier and better?
And then the classical clinical trial is revolving therapeutics or different treatments, and you can have treatments that are addressing the disease itself. Or you'd have treatments that are controlling the symptoms of side effects you might get from another treatment you might be taking.
So even within a specific medical research question, you can have different clinical trials depending on how much evidence you already have regarding that question. For clinical trials involving the assessment of new treatments and therapies, these are broken down into three stages and we call these phases.
So, you have phase one, phase 2, and phase 3.
Florence: Can you explain a bit more about these phases?
Callum: Sure. So, the overarching medical research question might be, what is the safety profile of this new therapy, and does it work improving on the current standard of care? So, you'll break this down depending on the phase, and with each phase you expand your clinical trial to a larger population.
Phase ones are typically on a small group of people around, let's say 20 to 50, and are designed to check the safety of a new drug that's being entered into humans for the first time. Sometimes, especially in early phase cancer trials, you're trying to find the right dose for your patients.
So, you might take a small group, test them on a low dose, and if there are no severe reactions to the new drug, you start incrementally increasing your dose a little bit more. And this gives you a really good idea of the safety profile of your drug as you try it for the first time in a human population.
Next, you'll move on to a phase 2. And these are typically larger than your phase one, around 50 to 200 people. And, usually you use the dose recommended by the phase one. So instead of slowly adjusting your dose and just focusing on the drug safety profile, the phase 2 will evaluate the safety of the medicine in a large population, but also have an additional focus on health-related outcomes.
Is the medicine causing the effect you want? Whether that's relief of symptoms or for cancer reduction in the size of your cancer. If the data is really promising from your phase two, it will move to a phase 3. And the idea is the same, increasing the size of the population. typically phase threes can be from 300 to 3000 participants.
And the key thing here is that you will evaluate the potential benefit of your new treatment against the current standard of care. Normally, meaning the treatments that are already available in the clinic. Health regulators will need to look at all the data collected from all the trials before they approve it for the general population.
And typically, they need a phase 3 to do this. They need a phase 3 to confirm that the benefit provided by the treatment outweighs the potential risks associated with it, across a fairly large cohort of participants. And this is to ensure the therapy is appropriate to be given to the general patient population.
But also, a phase 3 is needed to see that if the new treatment is moving clinical care forward in the right direction and in providing improvements for patients against what is already available in the clinic. And this is the process by which we call it evidence-based changes, to make improvements to clinical care.
Florence: So then how do people join clinical trials?
Callum: So firstly, it's about becoming aware of the clinical trial. You might be referred to a clinical trial by your doctor who's been aware of it and where it is. Or you might be able to find a clinical trial using clinical trial databases or finding about them through patient advocacy groups.
And they should be able to tell you which hospitals are taking part in the clinical trial. So, the next step might be your doctor can contact someone on the research team, and there is always a principal investigator per research site that is always a medical professional.
The study team at the site have all undergone training from the people organising the trial to run through the protocols necessary to keep the trial consistent in different sites.
Once they've been contacted, you'll undergo a screening process, and what they'll determine is your eligibility for the trial. They might assess medical history or your health status. And if you're eligible for the trial, the next step is to provide informed consent. The healthcare team should provide detailed information about the trial, its risks and benefits, the aim of the trial, and who's funding it.
And what are the treatment options for participating and not participating in the trial? How long is the follow-up in the clinical trial? And what will happen if you leave the clinical trial? And then also what are the safety concerns for the clinical trials and the possible side effects if it's something to do with a new treatment. Once you've been informed of all these details and you agree to be part of the clinical trial, you'll sign a consent form, and that means you're officially enrolled in the clinical trial.
Florence: And what happens once someone is enrolled in a clinical trial?
Callum: Once you are in the trial, you'll follow the procedures outlined in the trial protocol. This can take many forms, but normally it involves more regular follow-ups and check-ins with the clinical care team. And this is to establish safety concerns and to enable lots of data collection.
There also may be additional checks related to health outcomes during the trial, and so the study team may want to take additional samples to understand what is happening physiologically during the study. There also may be additional questionnaires for you to fill out, to capture patient reported health outcomes.
And this is to understand the patient's quality of life whilst they're on the trial. So, depending on the protocol, you may be followed up for a set period of time, and that may get less frequent as time goes on. And of course, you may pull out of the trial at any point after which the follow up will stop.
So, following data collection, there may be a while before you see anything, but results should be published following analysis of the data.
Florence: And finally, why might someone want to be involved in a clinical trial?
Callum: Clinical trials are all about providing evidence to improve clinical care. At any time we want to make a change to healthcare, we want it to be evidence-based. And so, this requires lots of people all contributing in a group effort to generate a data set large enough to determine how to change our approach to healthcare and move the field forward for improving people's lives.
Florence: That was Callum Morris explaining what happens in a clinical trial. If you'd like to hear more explainer episodes like this, you can find them on our website www.genomicsengland.co.uk. Thank you for listening.
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In this explainer episode, weāve asked Nicole Chai, Research and Development Bioinformatician at Genomics England, to explain what X-linked inheritance is.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Florence: How does X-linked inheritance work? I'm joined by Nicole Chai, Research and Development Bioinformatician for Genomics England, to find out more. So firstly, Nicole, can you explain a bit about the X and Y chromosomes?
Nicole: Sure. So, the X and Y chromosomes are what we call sex chromosomes. And chromosomes are packages of DNA in our cells that are inherited from our parents, and they contain information about our physical and biological traits.
Some examples of traits that are determined by our chromosomes include what colour our hair is and what colour our eyes are. And each of these individual traits are determined by smaller sections on the chromosome called genes. Genes can also determine what medical conditions we may inherit from our parents.
As humans, we all typically have 23 pairs of chromosomes in each of our cells. One of these pairs consists of the sex chromosomes, and as their name suggests, sex chromosomes determine sex of an individual. And typically, females will have two X chromosomes and males will have one X and one Y chromosome.
Florence: So then, what do we mean by the term X-linked condition?
Nicole: So, an X-linked condition means that the condition is associated with genetic changes on the X chromosome. And what we mean when we say genetic changes are changes to the normal sequence of DNA on the gene. And this can sometimes lead to medical disorders.
Florence: Do you have a specific example of an X-linked condition?
Nicole: Sure. So, an example of an X-linked condition is Duchenne muscular dystrophy.
And with this condition you get a progressive loss of muscle due to the lack of a protein known as dystrophin. Another example of an X-linked condition is red-green colour blindness. And this is where people affected with the condition can't see shades of red and green the way most people see them.
Florence: Could you explain how X-linked conditions are inherited?
Nicole: Sure. So, for many conditions, there are two ways they can be inherited, either dominantly or recessively. Dominant inheritance is usually when you just need one copy of the gene to be affected by the condition, whereas recessive inheritance is when you need two copies of the gene to be affected by the condition.
However, this works slightly differently with X-linked conditions, and most X-linked conditions are inherited recessively.
Florence: So why does inheritance work differently for X-linked conditions?
Nicole: So the reason that inheritance works differently for X-linked conditions is down to the differences between sex chromosomes, between females and males. As females have two X chromosomes and males have X and Y, this means that for recessive excellent conditions, males only need one altered gene to have the condition.
So, because males only have one X chromosome, if they inherit a faulty copy of a recessive gene, they don't have another healthy copy to compensate.
On the other hand, as females have two X chromosomes, if they inherit just one faulty copy, they do have a healthy one that can compensate for that one. So as a result, what we tend to see is that males are more commonly affected by X-linked recessive conditions.
Florence: That was Nicole Chai explaining the term X-linked inheritance. If you'd like to hear more explainer episodes like this, you can find them on our website www.genomicsengland.co.uk. Thank you for listening.
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In this explainer episode, weāve asked Arina Puzriakova, Scientific Curator at Genomics England, to explain what a polygenic disorder is.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Florence: What is a polygenic disorder? I'm joined by Arina Puzriakova, Scientific Curator for Genomics England to find out more. So, Arina, first things first. How can our genes affect our health?
Arina: So, genes are short sections of DNA that contain information that the cells in your body need in order to make proteins. Each gene carries the instructions for making a specific protein, and each protein performs a different task that allows the body to develop and function properly, depending on the genes that we inherit from our parents. Also determines our unique physical features such as our eye colour, hair colour, and height.
When a gene contains a change that disrupts the gene's instructions, also known as a gene variant, in some cases, this can lead to the production of a defective protein or prevents a protein from being made altogether. A missing protein or one that is not working properly can have a knock-on effect on how the body functions and this can result in health issues or the development of a genetic disorder.
Florence: So then how can a gene variant lead to a disorder?
Arina: So the genetics of each disorder are unique. In some cases, a change in a single gene is enough to cause a genetic disorder, and these are known as monogenic disorders. These conditions often occur in childhood and tend to cause severe illness. individually, they are more rare affecting a smaller number of people in the population, and usually they run in families as parents pass the damaging variance onto their children.
But these changes can also happen spontaneously without a known cause. An example of a monogenic disorder, which some may be familiar with, is cystic fibrosis. Cystic fibrosis affects one in every 2,500 babies born in the UK, meaning that there's about 11,000 people living with cystic fibrosis.
Florence: So, we've just talked through monogenic disorders. What do we mean by polygenic disorder?
Arina: So polygenic disorders are on the other end of the spectrum for disorders.
They are caused by the combined effects of multiple different genes. Individually, each gene has a very small effect on causing the disease, but many variations in different genes can act together to have a great impact on individual's susceptibility to that condition. Environmental and behavioural factors such as your lifestyle and diet also often have an effect.
Polygenic disorders are much more common, typically affecting millions of people in the population, and they're usually diagnosed in adulthood.
Florence: Could you give me an example of a polygenic disorder?
Arina: A common example of a polygenic disorder is type two diabetes. It affects almost 4 million people in the UK.
So this means that we know there are many genetic variants that could have made these individuals more susceptible to diabetes, but there are also other factors such as age or being overweight that could have increased their risk.
Florence: Are there specific challenges when it comes to diagnosing or treating polygenic disorders?
Arina: So, if I start with monogenic disorders, these are much easier to test for because we simply need to look for the presence or the absence of a faulty gene in order to determine whether someone is a carrier of a genetic disorder. On the other hand, testing for a polygenic disorder is a lot more complex as they are influenced by the combined effects of many genes.
Meaning there is no single genetic test or treatment that will work for all patients with the same condition. We need large and diverse groups of patients to study in order to accurately determine which genes are important and which ones are not.
And this can be challenging to obtain. Also accurately measuring and comparing lifetime environmental factors and exposures further complicates the assessment.
Another challenge with polygenic disorders is that even though they can cluster in families, the inheritance is not as clear cut or predictable as it is with monogenic disorders. Carrying a specific combination of genetic variants that are already known to be associated with polygenic disorder does not necessarily mean that you will definitely develop that disorder.
However, this information can be used to calculate something known as a polygenic risk score, and this provides an estimate for the risk of developing polygenic disease at some point in life based on individual's unique genetic profile.
Florence: And why can knowing apologetic risk score be helpful?
Arina: So, by being informed about the probability of developing a particular polygenic disease, an individual can make behaviour or lifestyles changes that could help reduce their risk. To go back to the previous example, somebody who is more likely to develop type two diabetes based on their genetic makeup can do things like maintain a healthy weight. And eat a healthy diet to help reduce their risk of developing type two diabetes in the future.
Florence: That was Arina Puzriakova explaining what we mean by polygenic disorder. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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The Generation Study is a research initiative aiming to explore the use of whole genome sequencing in newborns, to screen for more than 200 rare genetic conditions. This study will recruit 100,000 babies across England, and you can learn more about the Generation Study via the study's official website.
Design research has played a vital role in shaping the Generation Study. Parents, NHS staff, and the public have been involved from the start, providing input through public dialogues and usability testing to guide the development of the study.
In this episode, our guests discuss the use of design research in the Generation Study, and the importance of designing a robust and inclusive consent process, focusing on building trust and engaging diverse communities. They also discuss how the design of study materials such as posters, videos, and written content was shaped by community feedback.
Our host, Ćznur Ćzkurt, Director of design and research at Genomics England is joined by Mathilde Leblond, Senior Design Researcher at Genomics England, Rebecca Middleton, a rare condition patient, and Chair of the recruitment working group of the Generation Study and Sandra Igwe, CEO/founder of The Motherhood Group.
"Itās not enough to just ask people afterwards. Itās also not enough to engage just at the beginning and then stop listening once weāre live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadnāt considered before we launched, and just continue to learn."
You can hear more information about Generation Study in our previous podcast episodes too:
Genomics 101 with David Bick - What is the Generation Study?Which conditions will we look for initially in the Generation Study? With Vivienne Parry and David BickYou can download the transcript or read it below.
Ćznur: Welcome to Behind the Genes.
Sandra: Every communityās different and every patient is different as well, and so that may require different focuses or different formats, or different messages for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so itās really important to have representation because the lack of it in research can overlook communitiesā specific concerns and needs.
Ćznur: My nameās Ćznur Ćzkurt and Iām the director of design and research at Genomics England. On todayās episode, Iām joined by Mathilde Leblonde, senior design researcher at Genomics England, Rebecca Middleton, and Sandra Igwe, CEO and founder of the Motherhood Group. Today weāll be discussing how design research was used in the Generation Study by involving participant and usersā voices to address ethical considerations, implementation and consent. If you enjoy todayās episode, weād love your support. Please like, share and rate us on wherever you listen to your podcasts.
So, before we dive into our questions, would our guests like to briefly introduce yourselves to our listeners? Sandra, letās start with you.
Sandra: Hi everyone, Iām Sandra Igwe and Iām the founder and chief exec at the Motherhood Group. The Motherhood Group is a social enterprise that supports black mothers, birthing people in their pregnancy and beyond.
Ćznur: Great to have you on the podcast, Sandra. Rebecca?
Rebecca: Hi everyone, Iām Rebecca, Iām a rare condition patient, and I also have the pleasure of chairing the recruitment working group of the Generation Study.
Ćznur: Fantastic, thank you, Rebecca. And over to you, Mathilde.
Mathilde: Hi, Iām Mathilde. Iām leading design research on the Generation Study, and I have had the pleasure of working with Sandra and Rebecca and many others, trying to shape the processes and materials of recruitment and consent in the Generation Study.
Ćznur: Fantastic, thank you. Mathilde, letās start with our first question. What is the Generation Study?
Mathilde: Sure. So, whole genome sequencing is a technology thatās improving. Weāre finding new ways of using that, and thereās interest globally to explore the use of this technology to screen for rare genetic conditions in babies, so that we can treat them earlier on, so theyāre not having two different departments trying to figure out whatās wrong with them. And because we can look for hundreds of conditions with whole genome sequencing, itās really much more efficient, and weāre able to look at these rare conditions, so itās really exciting. Thereās still a lot of questions about implementing this operationally within the NHS, and so the Generation Study is aiming to explore this. Weāre going to be aiming to recruit 100,000 babies across England to take part in this, and they will be staying on the Generation Study for 16 years, or until they withdraw, so that we can see how their health develops, and really understand how genes affect their health.
Ćznur: Thanks Mathilde. And if youād like to learn more about the Generation Study, you can listen to our previous Genomics 101 podcast called What is the Generation Study, and Which Conditions Will We Look for Initially in the Generation Study.
Mathilde, can you briefly outline for us what we mean by design research?
Mathilde: So, design research is a design and research methodology, which involves users from scoping through iteration. So, even back when we didnāt know this would be called the Generation Study and we werenāt even sure of the boundaries of that, we were involving parents, NHS staff and other users of the service to try and understand what it might be. And later down the line it went all the way through to iterations once we started having materials and a better idea of what it could be like (inaudible 0:04:18) with users outside of the company to understand what their needs are, what would work well for them, and how we can shape the whole service to do things better.
Ćznur: And how have we implemented design research in the Generation Study?
Mathilde: Yep, so weāve also done a lot of engagement, which was bringing public views in the form of public dialogues, so understanding which conditions should be looked for, what principles should be guiding that work, but also weāve been involving users in regular rounds of codesign and usability testing to understand what works and what doesnāt work. Itās been around 105 people now that have taken part, and itās only going to be growing. Involving users has been shown to improve the implementation of interventions in the healthcare context, so we really hope that this will help the Generation Study when it launches. And regular rounds of codesign have had to be balanced with ethics, operations, feasibility, but Iām proud to say that user perspectives have been central to the decisions of the programme throughout.
Ćznur: Thatās fantastic to hear. Iām going to come to Rebecca and ask, why is it important for us to be guided by the patients and the participants?
Rebecca: Itās absolutely central, and the public dialogue that really underpinned this, which started in 2020, the messages from that have really come through to the whole codesign process of the project. The public consultation really told us that people were genuinely keen about the project, but wanted to ensure that they were part of the process, and that coproduction really began from day one. This is a new world leading project. This has not been done before, so we needed a whole new approach to how we produced and how we designed this with patients and with parents, and thatās exactly what weāve done. And why we have done it is because we know ultimately it leads to trust within the project, within the research study, which is essential, as I say, ācos this is a world first. But it also leads to better consent, a better pathway through the study, a better results pathway as well, and all the way through, ensuring that expectations are managed, that there is transparency, and people are fully informed and can make the right decision for themselves and for their baby.
Ćznur: Thank you. And would you like to add something, Sandra?
Sandra: Yeah, so I know from my community that we represent black mothers and black ethnic minority patients and participants, and we have very unique lived experiences that many research may not be privy to or just do not understand. And so engaging with patients from the community ensures that research is grounded in real authentic community needs and priorities. And also involving women like myself and those from my community, it can really help to identify and overcome barriers to inclusion or getting mums involved. I know I always hear, you know, āSandra, black mothers are so hard to reach, they donāt really get involved in research.ā Well, if you include those from the community to lead in the research or support in engagement, you will have a lot more uptake, and it leads to more accessible inclusive research, which of course everyone really, really desires to have more of.
And then also participants from the community can flag issues and suggest solutions that researchers may miss, because itās not knowledge, itās experience. Itās, you know, having someone go through the experiences without necessarily studying it, but again lived experience to me, itās more crucial than any other experience that you could possibly have.
Ćznur: 100 percent, lived experience is really, really crucial for us to make the services that weāre making really speak to the actual context of our users. Thank you for that. And Rebecca, how has this process been different to the 100,000 Genomes Project? What was your experience?
Rebecca: I was consented onto the 100,000 Genomes Project back in 2015, and I can remember that experience very vividly, on a cold, wet December afternoon, going off to meet my genetic counsellor, and receiving the consent form for the 100,000 Genomes Project, which was very much like War & Peace. Scratching my head at the time, going, āGosh, Iām going to have to (inaudible 0:08:54) to go through this.ā And then going home that evening and sitting on the sofa, and, you know, considering myself an educated woman, just realising I had so many questions. I really didnāt understand it, and I needed somebody to help me unpack this, and translate it. And Iām pleased to say that our consent process and our recruitment process is very different to this, which is a fantastic thing.
And whatās really key about the lessons that we have learnt from the 100,000 Genomes Project is that, to really build trust in a research programme and a new research programme, you need to manage expectations, and thatās wrapped up in building trust around the programme as well. And with the 100,000 Genomes Programme, there have been challenges and issues around that expectation management, and some expectations werenāt managed. And even now nearly ten years on, we are still feeling the effects of that, and patients and families are still feeling hurt because of that. So, we have learnt from that and therefore we have designed a process with patients and with parents. We know that no two experiences are the same, that we have to ensure that we remain flexible, and we have to ensure that we are addressing any misconceptions, any misunderstandings.
Perception and reality have to be treated the same. We have to understand how people are understanding genomics, because outside of pockets, genomics is not a standard NHS piece of healthcare. So, people come to this study with different assumptions, and we have to learn to go beyond them. We have to understand what their health literacy needs are, and how we can help manage that, how we can help translate, so that nobody is stuck at home on a cold, wet December evening, scratching their head, going, āWell, I donāt know what this actually means.ā We are ensuring that the NHS professionals and everybody involved in the pathway is fully aware of how to explain the project, explain the risks, explain the benefits, and be fully transparent. And we know what the risks and the benefits are that need to be addressed because weāve asked parents and patients as well.
So, we know the challenges and weāre trying to address them head on, and thatās essential. Itās essential in building trust, and thatās one of the key learnings from the 100,000 Genomes Project. And it has been brilliant to be involved in this project and really kind of learn from that past experience, but move forward in such a unique and fresh way that really will have benefit to those new parents.
Ćznur: Thank you, Rebecca.
And we have been talking about the consent process in the context of newborns, and we know that, while consent given for newborn screening is really high in the UK, parents often leave this conversation relatively uninformed. Sandra, can you tell us a little bit about what you think the risks of not designing this consent moment appropriately might be?
Sandra: I guess not designing appropriately can break down trust. So, I think engaging in a variety of parents in this research and design is crucial for trust. And thatās a topic thatās come up many times in our community is that they believe that there is a lack of trust between research practitioners and this wider system as a whole, and the community of marginalised patients, parents, mothers. So, I think itās really important that communities have this. But also researchers must make the effort to meet parents where they are at, not just physically but also conceptually, as well as emotionally. So, hosting conversations in familiar, comfortable community spaces is essential. We had our session in our hub, our community hub, and mothers were really familiar with the space and with each other as well. And so partnering with local grassroots organisations and leaders to create inroads is so beneficial, and I can hand on say that when you connect with the community, youāve already done the first step in building trust.
And consent conversations should be guided by what matters most to each parent within each community, ācos every communityās different and every patient is different as well, and so that may require different focuses or different formats, or different messengers for different groups. And so we like to have people with lived experience from the community representing that, and also driving the uptake of consent as well. But failing to engage diverse voices can lead to perpetuating inequalities in access and uptake, so itās really important to have representation because the lack of it in research can overlook communitiesā specific concerns and needs.
Ćznur: Absolutely, and that inclusion is really important for the study. Is there anything youād like to add, Mathilde?
Mathilde: Yes. When we talk about consent, oftentimes we think about that one moment, the moment of conversation with a clinician, and signing on the dotted line, and I think what we have done here in the Generation Study is to consider recruitment from the very first time that they hear about the Generation Study all the way down to that moment. And itās been really important because, yes, the moment of consent - you know, during pregnancy, youāve got a lot of information coming in, a lot of different priorities, so you may be a little bit all over the place and not understand specific things, or not have the time to really spend thinking and understanding jargon, etc. And that presents a big risk because, when you may receive results, there may be confusion. There may be a loss of trust if thereās media coverage that talks about the Generation Study in a way different from what you had understood it. So, these are some of the risks that weāre trying to avoid.
But the big risk is also, as Sandra has said, the risk of not engaging a wide variety of parents, not just in the moment of consent but the whole process. So, if weāre thinking about where weāre using the word genomic and how are we using that, this is a word thatās actually really scary for a lot of people. And we might be very proud of the cutting edge technology that weāre using, but actually it can sound very science-y and almost sci-fi to people. So to us, the moment of consent is really from the first time that you hear about the Generation Study, you start creating a mental model about what that means, all the way down to the consent moment, when the samples are taken, the results and beyond. Itās really been looking at this whole journey holistically.
Ćznur: And that language point is a really interesting one. I know that the study is obviously being communicated to the public through posters, leaflets, websites, which speak to how the study works, you know, the conditions we test for, and the benefits and risks of joining. Thereās a lot of language. Thereās written words in there, thereās audiovisual content, videos, images. How did we inform what type of content is needed to communicate the depth of the study?
Mathilde: I think the example of the introduction video is a really good one, and I want to discuss this a bit with Sandra, because actually it was quite a crucial turning point. We tested the video several times in user research before and after the Motherhood Group workshop, but the thoughts that her community gave us really helped change the tone of this video from something very professional to a conversation between parents raising questions. I wonder, Sandra, if you remember what your communityās feedback had been, and if you can talk a little bit about that.
Sandra: Yes. So, the mothers from our community at the Motherhood Group definitely gave lots and lots of feedback that the initial posters didnāt really resonate with mothers from our community. They said that the visuals and the language felt a little bit generic and also too clinical, and it didnāt speak directly to our community. They also expressed that seeing more black parents and more black families represented signals for us too as well ā so, seeing people like look like us in the posters and the media would have allowed a lot more uptake. So, narratives and videos featuring real people that looked like members of our community, they expressed that would go a lot further. And also it made them feel a lot more relevant, and again it goes back to the notion of having more trust and feeling less abstract, but more like an authentic way of engaging or directly communicating with our community.
They also appreciated the effort to be more upfront, but the risk and also the downside, not just selling only the positives. You know, members from our community were saying they wanted to know the real deal. And also our community have been misled in the past. You have to understand that. The history kind of shows that there has been a breakdown in trust, and so transparency, they shared, was really, really key to rebuilding that trust, as well as materials that are culturally tailored and designed for different formats for our community.
Mathilde: Itās really exciting how much this feedback has pushed all of us in the team and the designers ā pushed us to think about how to talk about the Generation Study, what narratives to use, what tone of voice, but also youāll see on the posters thereās space there to have photos of several different family types and people of different backgrounds. Itās not just one photo. And thereās also some very small tweaks, it seems like, but it actually has a very big impact, about what it is that youāre trying to say and what people understand in a split second when theyāre seeing that.
Ćznur: Absolutely, and that open dialogue is definitely key to keeping on bringing those perspectives in, and keeping updating and moving the language of the study as well. Obviously, the study will keep being shaped. Iām curious about how will design research continue to shape the Generation Study going forward.
Mathilde: Yep, so we will have an iterative process, where weāre still listening to the sides as theyāre launching to hear what are the questions that are being raised, what are some of the challenges that theyāre facing. At the same time, we have a survey that parents will be able to fill in, and we have an evaluation partner, UCL, who is doing an independent review of how well all of this is landing, and evaluating the work that weāve been doing to see is it really hitting all of these points, and what we may need to be iterating or changing as we learn.
Rebecca: I should also point out that the recruitment working group is very much in the background, but we are still very much alive, and we will come back to look at those first pieces of feedback and to look at what the experiences have been, and how we can learn and how we can help kind of shape what comes next. Because itās critically important that we have this always learning philosophy. Itās critically important that now, you know, the rocket has launched, how will it land, and we donāt know until weāve actually had that feedback. So, we can plan and absolutely plan to the nth degree, but actually how it exists out there in the real world, we wonāt know until the project goes live and that feedback comes through. And thatās what weāre also really excited about is to actually learn those first lessons and see how we can support going forward, and see what needs a tweak here, a change there. And again, itās that dialogue that started with the public dialogue back in 2020, and here we are in 2024 and that dialogue will still continue, and we are still listening and we are still learning.
Ćznur: Thanks Rebecca. Iād like us to reflect on the importance of continuous learning. Whatās the importance of continuous learning in this project? Iāll start with Sandra.
Sandra: Continuous learning to me and my community really means listening to the voices that are often seldom heard. It means trusting and placing trust in the community to be a part of or lead or be involved in research, changes that affect our community. It also means actively and proactively working to rebuild that trust, because thereās been a lack of trust from the community, and that means transparency. It also means honesty, and it also means continuous involvement as well. Thereās no point in involving us at the end of a study for our feedback, but at the very start to show that you are trying to be authentic.
Rebecca: Ultimately, genomics is the science of people. Genomics is people, so we have to keep talking to the very people that we are looking to try and support, help, care for, and ultimately impact them and their families as well. So, I completely agree with Sandra, continuous learning, itās a continuous dialogue, and understanding how our opinions differ, how our opinions may shape and grow as the general conversation about genomics continues as well in the public discourse. So, we have to understand and we have to stay sort of on our feet, that this is a dynamic conversation, therefore we need to change and we need to remain flexible as well. And if we keep our ears open and if we keep our minds open, then we will continue to build that trust, and we will continue to ensure that we have a robust study that will ultimately fulfil its research aims.
Ćznur: Thank you. And Mathilde?
Mathilde: I think thereās only so much that we could really cover in theory before we launched, and now, you know, itās going to go out into the world, and thereās many things that we couldnāt have predicted that will happen. We have that humility to understand that. And whatās super important going forward is that we have a team there to keep kind of staying on our toes, listening to whatās happening, to make sure that we respond to that, so that, as Sandra said, itās not enough to just ask people afterwards. Itās also not enough to engage just at the beginning and then stop listening once weāre live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadnāt considered before we launched, and just continue to learn.
Oznur: We will wrap up there. Thank you to our guests, Rebecca Middleton, Sandra Igwe and Mathilde Leblonde for joining me today as we discussed the use of design research in the Generation Study. If youād like to hear more episodes like this, please subscribe to Behind the Genes on your favourite podcast app. Iāve been your host, Ćznur Ćzkurt. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
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In this explainer episode, weāve asked Amanda Pichini, Clinical Director at Genomics England and Genetic Counsellor, to explain which healthcare professionals you may come into contact with in your genomic healthcare journey.
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 youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Florence: Which healthcare professionals are involved in my genomic healthcare journey? I'm joined with Amanda Pichini, Clinical Director for Genomics England, and genetic counsellor to find out more. So firstly, when someone has a genetic or genomic test, what kind of healthcare professionals might they come into contact with?
Amanda: Well, everyone has a different journey, and it can depend on the type of test you have and the reason for having it. Some tests might only look for a single gene. Some might look at many genes, and some look for a very specific gene change that's already known to be in someone's family. Some genomic tests are there to find the cause of a person's diagnosis, understand more about their cancer, or maybe to predict a future health problem that they may have or that's in their family.
So usually people start with their GP, who they go to with a question about their health or their child's health, and this could lead to them being referred to a clinical genetic service or perhaps another specialist team.āÆ
Florence: So, then what is the purpose of a clinical genetics team?
Amanda: Well, a clinical genetics team, in brief, aims to provide people that have a genetic condition or are at risk of one with health information, including information about prevention, counselling support, and genomic testing, and they focus on the whole family.
Adults and children can both be seen in a genetic service. Clinical genetics teams tend to focus on rare conditions and rare predispositions to certain types of cancers, so really anything that might have a strong genetic basis and could impact someone at any stage of their life. A clinical genetics team is made up of a range of roles, and that could include clinical genetics, doctors, genetic counsellors, clinical scientists, and administrative staff.
Florence: Could you tell me a little bit more about each of those roles?āÆ
Amanda: Sure. I am a genetic counsellor, so I'll start with that. Genetic counsellors are specially trained healthcare professionals that help patients and families understand information about their genomic health, as well as provide guidance and emotional support.
So, this could be about understanding their family history, making informed choices about having a genetic or genomic test, or helping them to come to terms with a result or a new diagnosis and the impact that could have on them or their family. Clinical geneticists are medically trained doctors that specialise in genetic conditions.
They understand the underlying ways that genetics can affect health, and they use that to help make diagnoses for patients. How about genomic scientists? These are often not seen directly by patients, but they're vital to someone's genomic healthcare journey. So clinical genomic scientists and genetic technologists work in labs, and they're involved in processing patient samples, working with those other healthcare professionals to select the most appropriate genomic tests to perform and interpreting those results based on the variance or genetic changes that are seen in patients, which are usually summarised in a lab report.
There's lots of other healthcare professionals that can also, um, be in a clinical genetics team. That could include administrative staff, family history coordinators, genomic practitioners or genomic associates. They might help arrange appointments, gather medical and family history details after a referral to help the clinical team know what might be done next.
Some genetic services also have psychologists, nurses, or other allied health professionals embedded in their team or in specialty clinics that they work with, and it's really important that everyone is working together as a multidisciplinary team to help those patients and families in their healthcare journey.
Florence: So, we know there are lots of different healthcare professionals within the clinical genetics team. Are there any other professionals involved in genomic healthcare as well?āÆ
Amanda: Absolutely. As genomics becomes part of routine healthcare, that means there's lots of other healthcare professionals involved in arranging genomic tests and giving back results, or at least having initial discussions about genomic tests before referring on to another specialist.
So, some examples might be midwives, arranging screening tests for women in pregnancy, a number of those screening tests have a genetic or genomic basis. They might also refer families with a history of a genetic condition whilst they're pregnant for more specialist genetic testing. Many paediatricians are ordering genomic tests for children that might be suspected to have a syndrome or an underlying cause for their health or developmental issues.
And many nurse specialists like those who work with people with cardiac conditions or neurological conditions. Might be involved in arranging or discussing genetic testing. Final example in the cancer world is oncologists who might often arrange genetic tests that will help give information about someone's cancer.
The last thing to call out isn't necessarily healthcare professionals, but patient charity organisations are super crucial to someone's genetic healthcare journey. It's really important for families when they've had a new diagnosis or when they're seeking information, and there are some charities that do have healthcare professionals that work for them, like a nurse or genetic counsellor or psychologist that may help to run a helpline, for example.
Florence: That was Amanda Pichini explaining which healthcare professionals are involved in a genomic healthcare journey. If you'd like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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Digital consent models, language barriers, and cultural differences are just a few factors that can exclude people from participating in genomic research. In this episode, our guests discuss these issues, and explore alternative methods such as in-person discussions and the use of trusted community figures to engage with their communities to increase awareness of genomic research. They also highlight the importance of communicating consent in ways that respect cultural dynamics, such as family involvement in decision-making.
Our host, Naimah Callachand is joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager at Southall Community Alliance and Trupti Patel, Policy Manager at Genomics England.
"I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community"
You can download the transcript or read it below.
Niharika: People are usually comfortable giving their data when they feel that there is transparency from the data collector, theyāre being completely transparent, they come with you with clear benefits, how itās going to benefit the community. And you are equally sort of agent of your own data and you feel involved in the research and you feel that you have power to give out your data and have control over the journey of that research.
Naimah: My name is Naimah Callachand, and Iām the Head of Product Engagement and Growth at Genomics England. On todayās episode, Iām joined by Maili Raven-Adams, researcher in bioethics and policy at Nuffield Council on Bioethics, Niharika Batra, Community Projects Manager for Southall Community Alliance, and Trupti Patel, Policy Manager at Genomics England. Today, weāre going to be discussing some of the ethical, legal and social implications of genomics research for diverse communities, and how we might overcome them to address the challenge of diverse communities health needs. If you enjoy todayās episode, weād love your support, please like, share and rate us on wherever you listen to your podcasts. First of all, Iām going to ask each of our guests to briefly introduce themselves.
Maili: Iām Maili Raven-Adams, I lead on work at the Nuffield Council on Bioethics to do with genomics. This has predominantly been looking at how to develop a best practice approach for genomics, and looking at the ethical implications of AI and genomics when theyāre used together in healthcare. Before here, I worked at the Global Alliance for Genomics and Health, where I developed policies related to diversity in datasets and genomic discrimination, so I have a particular interest in this area.
Naimah: Niharika, can we come to you?
Niharika: Hello, everyone, Iām Niharika Batra, Iām the Community Projects Manager at Southall Community Alliance. We are a charity based in Southall. Prior to joining the charity, I was working as a Youth Community Engagement Assistant in United Nations Development Programme in India, and I have a background in gender and development. I also bring with me lived experience of being a South Asian immigrant woman, and Iām really passionate about working with the immigrant communities in the UK.
Naimah: Itās lovely to have you. And Trupti, can we come to you?
Trupti: Hi, Iām Trupti Patel, Iām a Policy Manager at Genomics England. I work primarily within the diverse data initiative and I lead the equity in health research workstream. My background is in responsible research and innovation, as well as co-production, and more ethical ways in which members of the public can shape the direction of scientific advancements.
Naimah: So, first of all, Trupti, can we talk about the challenges around equity in data, and what this means for diverse groups in the context of genomics?
Trupti: Yes, as I mentioned, I lead the equity in health research workstream. Now we talk very specifically about equity in health data. As Genomics England, we are a biobank, and we hold health data on individuals who have consented to be a part of genomic research. When we talk about equity, primarily weāre talking about those of non-European ancestry, and there are very specific reasons as to why that is. So firstly, thereās a wider issue about representativeness within health datasets more widely. We know that across all health data sets that are located within Global North countries, the data held within them tends to not be representative of their populations. And what I mean by that is that they tend to overrepresent those of European ancestry, and underrepresent anyone who is not of European ancestry. The consequences of this is that healthcare innovation might stand to leave these population groups behind.
One of the other reasons that we talk about equity specifically, as opposed to things like equality, is that weāre also aware that if we look at research on a global level, the majority of research funding is given out through grant bodies located in Global North countries. So we already know that research portfolios can actually be quite skewed towards population groups who live in those countries themselves. We know that thereās a lack of financial investment as well within developing economies. So itās natural to assume that health innovation projects which address the needs of these communities are more likely to be conducted by researchers who are based in developing economies. However, their access to funding is very limited, and on top of that they tend to have much smaller life sciences sectors, so their access for private funding, as well as opportunities to collaborate with industry can actually be quite limited in itself as well.
Another reason that we care about equity is that we actually know that there are some sub-populations that are very diverse within themselves. So a good example is the genetic diversity of Africa as a whole is much larger than those who live outside of Africa itself. And for that reason there tends to be a focus on actually oversampling from people who are of these ancestries. And another example being South East Asians as well. The final challenge when it comes to equity is that we also know that there has to be a need for medical innovation for these population groups, and a desire for people to actually buy this type of innovation. So thereās a need for demand for these therapies and medications. Now if we already know that developing economies might be less likely to be able to afford these medications, then the demand will always be lower for these population groups. And therefore the demand for innovation might also be lower population groups. But as a country, because we would want to make sure that weāre able to provide medication to everyone equally, we need to take an equitable approach.
So one thing about the lack of diversity within datasets actually means that we canāt always accurately predict whether or not someone does or doesnāt have a condition. So weāre still at the stage where accuracy is not as good for these population groups as it is for others, and it leads to things that we call false positives and false negatives. So where we think that someone does or doesnāt have a condition, and in fact, they might or they might now. The incidence rates of that happening for anyone of non-European ancestry are higher. Thatās one of the tensions that weāre playing with at the moment, especially when it comes to providing genomic healthcare via a healthcare service. Understanding peopleās cultural background and nuances I think is really important. For example, a lot of those cultural practices can actually play into whether or not someone decides to receive or not receive a form of healthcare. And itās also important to understand things like timing, so the decision around whether or not someone decides whether or not theyāre going to take a preventative medication might be based upon cultural timings around things like giving birth or something.
Naimah: How can we ensure equitable access to genomic medicine for all of these communities?
Maili: So I think we need to understand that there are several understandable reasons that people might not have been involved in genomic research to date. Efforts have been made to engage with different communities, but this has sort of been piecemeal and we need to see how that engagement can feed into research practices. So that people feel as if their information that theyāve given has been taken on board, and that those research practices have been co-developed, and they feel more willing to engage so that that representation can increase. Thereās also been examples where research has been actively untrustworthy in the past. You know, thereās well known stories of Henrietta Lacks, whose cancer cells were taken without her consent, and then used to develop research. And thereās different examples across the globe that kind of mirror that sort of exploitation. So we kind of need to take note of these, and understand why people arenāt there, and then allow that to inform engagement practices. So that research practice can change over time and be more inclusive and encourage people to get involved and give good reason for them to get involved in that.
Niharika: Also, to add on to what Trupti and Maili mentioned. First of all, why this data gap exists, why is there inequity in genomic data? Itās because historically South Asian communities or the marginalised communities have been used to extract a lot of data, be it social research or medicine research. So when a researcher approached them or a data collector approaches them, they feel that theyāre just going to collect the data and there will be no feedback process, or it might not benefit the community. The communities do not understand what the clear benefits of these researches are. And in terms of genomics, when we talk about medicine research, historically these communities have been exploited. There has been information asymmetry, and we have observed a case in 1960s where in Coventry Punjabi women, or South Asian women, were given radioactive rotis, and they werenāt even aware what they were consuming. And it was in the name of research. So thereās always this hesitancy when it comes to medicine research.
One way to tackle the problem of the data gap in genomic research is by co-production . So when you're approaching the communities, it sort of helps who is collecting the data, there is no skewed power dynamic involved. People are usually comfortable giving their data when they feel that there is transparency from the data collector, they are being completely transparent, they come with you with clear benefits, how itās going to benefit the community. And you are equally sort of agent of your own data, and you feel involved in the research, and you feel that you have power to give out your data and have control over the journey of that research.
So it is also important how you frame the message when you're collecting the data. In our communities, the idea of sevÄ or Kismet is very embedded in the communities, which mean either giving out your services or your time for the benefit of the communities. So itās not just donation, but itās just spending more time or just working with the communities for a common or a collective benefit. So when the message is framed in such a manner that you are doing a sevÄ or you are helping your communities bridge the health inequalities and there might be a collective benefit for the communities, people are more motivated to give their data. But when the word donating data is used, then it puts a sort of emotional burden on the participant. So it all depends on the messaging, how you frame your messages when you're collecting the data, and itās important to be cognisant of the cultural sort of ideas. And this is something that can be used with South Asian communities, sevÄ and giving back to the communities.
Maili: I was just going to say, I completely agree with that, like 100%, itās really important as well that the global majority donāt feel pressurised into giving that data because of the language thatās being used. You know, the global majority are not represented in these datasets, so it could be that the language used might put pressure on people to donate that data to fill that gap, but thatās not the right language. I think it is about finding language to involve people, and figure out how the benefits of them donating data can relate to them and their community, so it just wanted to say that. And also, itās important when weāre using language like genetic ancestry that those arenāt conflated with things like race or ethnicity, which are social uses of that language. So I think this is just another area where it is really important to think about language and work with communities, to figure out what the right language to use it, and understand the benefits of using certain types of language.
Naimah: And it just kind of highlights how many different nuances there is, and areas that need to be considered.
Maili: Yes, I was just going to say, within that, we need to think about barriers to participation as well that might affect certain communities. You know, there might be some language barriers, to making sure that weāve got translators, or thereās investment in making sure that the resources are there to make the engagement and also the research accessible to people. Thereās things like people have lives, they have childcare, they have jobs, so making sure that they can donate data if they want to, at times that work for them and environments that work for them. And things like transport costs and that sort of thing might be covered by a research organisation, so that people are empowered to get involved, and thereās not too many barriers to become involved if they want to be. I think thatās really important to address as well.
Naimah: Trupti, did you have something to add?
Trupti: Yes, I was just going to say, I think it was really interesting that Niharika actually framed the benefit around community benefit. Because within the policy sphere, and actually even within wider conversations on data and health, people use frame benefit in terms of patient benefit specifically. And what we find is that when we engage with diverse communities, most of their concerns around harms are actually not harms necessarily to themselves specifically, but harms around their whole community. And I do wonder whether there needs to be a slight reframing in how we talk about benefit when it comes to genomics in particular. Because most people when they donate their data they know that it has consequences for those who are related to them.
Naimah: So I wanted to talk about research governance as well. And in the context of history of medical racism, with medical innovation now heading towards personalised healthcare, what are they key considerations we should have when it comes to rules around access to data?
Trupti: So, I mean, one of the rules that we have within our biobank, when it comes to access to data, is that we donāt want it to lead to any discrimination, and we won't allow access for things, for research projects, that do lead to discrimination. However, we already know that there are lots of unintended consequences when it comes to research in general. And when it comes to medical research in particular, and thinking about genomics in particular, lots of communities are aware that because in the past there has been a lot of research outputs have been used in ways that actually donāt benefit these communities, and actually have negative consequences for these community groups, it means that the barrier to encourage people to take part is actually quite high. When it comes to genomics in particular, obviously thereās been a history of eugenics, and at the moment, thatās quite a big area that lots of universities, especially in the UK, are going through eugenics inquiries. It has effects upon peopleās perceptions of genomics as an area, and whether or not people can be confident that those types of research won't be repeated, and the types of research that will happen will actually benefit them.
I mean, thereās a good example that one of the community members gave, not directly to do with genomics, but actually they knew that if you're first name is Mohammed, your car insurance is actually much higher, your premiums are much higher. And so they were concerned that if you were grouping people within genomic ancestries, or genetic ancestries, what consequences that has for them can be quite nuanced in the first instance. But in the long-term it would actually mean that people might be grouped within these ancestries and policies and things that are created as a consequence were quite concerning for them.
Naimah: And Maili, I wonder if you could tell me how people might feel more comfortable in the ways in which their data is being used?
Maili: I guess if thereās transparent governance mechanisms in place and they can understand how their data is being protected, you know, that goes right through data access committees. Thereās one at Genomics England that as Trupti said reviews data. So if they can understand what sorts of considerations that committee are thinking about in respect to genetic discrimination, and they can understand that certain considerations have been taken into account when their data is being used, thatās one thing. Another could be through consent processes. So thereās different sorts of consent models that could be explored with communities to figure out which one theyād be more comfortable with. So broad consent I think is the one thatās used at Genomics England at the moment. So that means that people give their consent once, and then that data can kind of be used for a broad range of purposes. But itās not always clear to people what those purposes are, or where that might be used over time.
So thereās different sorts of mechanisms that could be explored, like dynamic consent, where people are updated over time about what their data is being used for, and they can either opt out or opt in to those research practices. Or forms like things like granular consent, where when people give their consent thereās different options of people that theyād be happy for their data to be shared with. So we know that people are less trusting of private companies, for example, so people might be able to say, āYes, my data can be shared with nonprofit organisations or research organisations affiliated with universities or the government, but I donāt want my data to be shared with private companies.ā And that might make people feel more comfortable in donating their data, because they might feel like they have some more control over where that is ending up. And I think transparency there is really important, so people can understand when they give their data or they donate their data, they can understand what benefit might be coming from that. And that might encourage people to get involved as well.
Trupti: I was just going to add to that comment about dynamic consent. So actually an interesting thing that Niharika mentioned earlier was this feeling that the people that we engage with actually really wanted a sense of control over their own data still. Obviously when you give broad consent, your giving your consent, as Maili said, to a wide range of research that will happen or can happen in the future. But interestingly, dynamic consent, I think culturally it is really valuable for some population groups, partly because it fits in very nicely with the idea that your biological data is actually a part of who you are. And that cultural philosophy can still exist within a lot of these communities that weāre engaging with and a lot of these communities that weāre trying to encourage to actually provide us with data. Do you ever think that there could be like a medium position, where it was actually dynamic withdrawal?
Maili: Yes, I guess that is something that could be explored, and I think thatās one of the models that sometimes is talked about in academia or in these sorts of forums. I think if people were dynamically kind of withdrawing, it might be interesting to understand why theyāre withdrawing and their reasons for that, so that research practice can change and take account of why people maybe no longer want to get involved in a certain type of research. And I know thatās something that youāve spoken about in your community engagement groups.
Naimah: Niharika, do you have something you want to add?
Niharika: Yes, so when we were engaging with our communities, we primarily engaged with Hindi speaking people from Indian origin, Punjabi speaking people from Indian origin, and Urdu speaking people from Indian origin, and we spoke to them about genomic research. We also spoke to them about the branches of genomic research and how their data could be used. So while their data could be used for innovation in pharmacogenomics, which seemed to be more palatable for the people as this is an extension for treatments theyāve already been using. For example, treatment for a chronic condition like hypertension or diabetes. Whereas they were quite reluctant when it came to their data being used for gene editing. So in Hindu religion, humans are considered the creation of Brahma, who is one of our main Gods. And similarly in Islam, humans are called (Islamic term), which means Godās greatest creation. So when it comes to gene editing, some people believe that it means you are playing God, it means that you're tampering with the DNA, you're tampering with Godās creation. So they were really reluctant in providing their data for an innovation that entails gene editing or genetic screening or gene therapy.
And when it comes to consent, I know Genomics England takes a broad consent, and thereās scope of dynamic consent. Where people are constantly engaged on where their data is being used, how their data is being used, which innovation their data is being used for, which research their data is being used for. And they have an opportunity to withdraw their data if theyāre uncomfortable with any aspect of research.
Maili: I was just going to say something else about consent models. When weāre thinking about different forms of consent, like dynamic consent, itās also important to consider the accessibility of those, lots of those models would rely on the internet and people having access to laptops or phones. And so when weāre exploring those models, we need to make sure that people have access, and if they donāt have access that thereās other ways that that sort of consent model might be able to be replicated, or there is an alternative way, so that people arenāt excluded through that.
Naimah: Is there a question around language barriers as well with the consent models?
Maili: Yes, when verbal consent is taking place, the same problems of language barriers are there within the online version. You know, how do you make sure that things that are translated, and translated well as well? Because genomics is a complicated area with lots of jargon and complex language. So how can we make sure that we translate that language in a way thatās done, where the meaning is kind of translated as well.
Trupti: The language thing was something that came up within some of our community workshops. And I think one of the things that really came out was that genomics research itself has so much technical language that often you simply cannot translate the word into other languages. And different ways in which you can convey information, so that you're still making sure that you're getting informed consent from participants I think is really important for these groups, beyond simply translating written material. Whether thatās through analogies or visuals that convey information, I think thatās quite an underexplored area actually, within research more generally, but as a starting point genomics.
Naimah: And did any of those community groups identify any preferences for what way they wanted to be communicated with, for consent and things like that?
Trupti: I mean, certainly having online consent was a huge barrier. So the idea that you log into a platform online in order to provide your consent to something wasnāt something that people were that comfortable with. Especially since these participants are often very reluctant to take part in the first place, so you're almost creating a barrier to them as well, itās an extra thing that they have to do. They did feel that consent should really be in person. They also preferred the idea of being able to discuss genomics widely within less formal settings, so outside of healthcare settings, or outside of research settings. Because it meant that they felt that they were primed for the questions that they might have.
One of the things that I was going to add is actually for genomics in particular, I mean, I mentioned before about when people decide whether or not they would like to consent to take part in genomic research.. They feel like theyāre not just consenting for themselves, theyāre also consenting for people within their network. And so these are people that they would consult probably as to whether or not they should or shouldnāt take part. And so when you are making that decision and you're having those consenting conversations, whether that be within a research setting or a healthcare setting, itās important I think for people to understand that those decisions have been taken not just by an individual, they are actually reaching out to a much wider range of people within their own communities.
Naimah: And is there something around that these decisions are often made with family members as well?
Trupti: Yes. So in situations where there are people from some cultures who are much more likely to take part in cousin marriages, these particular populations have scientifically been shown to have much higher likelihood to develop genetic conditions. Now if that is the case, that can lead to a lot of stigmatisation, and it can proliferate a lot of discrimination that these population groups might be facing already. So I think thatās something to be considerate of. And it might influence their decision making as to whether or not they or their family members should or shouldnāt take part.
Niharika: Yes, just to add onto what Trupti and Maili actually said, while language plays a very important role in terms of consent, how consent is being taken, it also depends on the setting. In our areas where we engage with communities, usually the consent, or consent regarding medical research or genomic research is taken via the GPs. And the GP services here in our areas are so overwhelmed at the moment, there are long waiting lists, like three months. And when people actually get through the waiting list and go to their GP, theyāre so done with the process of waiting that when their GPs ask them for consent, they just either feel that they need to succumb to the pressure of, okay, giving the consent. Because thereās this skewed power dynamic over them as their white man or white doctor asking for the consent. But also, they donāt know what exactly to do in that moment, theyāre very frustrating from the long waiting line. And they feel theyāre okay, they might need a little time to sort of cool down, go back home, look at the consent form, what is it about?
And in South Asian settings usually the decision making is done in family setting, where you consult your families. And when we spoke to older South Asian women and asked them how would they give their data and why would they give data, they mentioned that they would give data because their children or husbands have advised them to do so. So yes, itās important to see the setting of where the consent is being taken, who is taking the consent, and if they have enough time to think about it and go back and give their consent. Also, it came up during the workshops that it helps if the consent is being taken by someone the communities already trust. So having accredited community champions seek the consent. So once theyāre trained, once they have enough knowledge about genomic research and how it can benefit their communities, theyāre able to better bridge the gap between the researchers or the research organisations and the communities.
Maili: Yes, I completely agree. And I was just going to add that itās important that healthcare professionals are properly informed and open and aware of those different cultural or contextual dynamics within those consenting conversations. So that they can properly listen and understand where people are coming from and give that time. And I get that thatās difficult in pressurised situations, where healthcare professionals are under a lot of time pressure. But that needs to really be built into that healthcare professional training over time so that carries on and people can talk about genomics in a really accessible way. And that carries through as well to genetic counsellors who give results to families, they need to be able to do that in the right sort of way. And they need to ask the right questions and understand the patient that theyāre talking with so that that information can be translated or got across in the best possible way.
And thatās even more important I think where there is a lack of diverse data thatās informing research and informing healthcare outcomes. I think healthcare professionals should be transparent with patients about some of the accuracy of certain things or how different results might mean different things for different people. And itās really important that those conversations are had very openly and for that to happen, healthcare professionals also need to get the training to be able to do that.
Naimah: Okay. So weāre going to move on to talk a bit about developing countries. Niharika, I wanted to come to you for this question. Why would diverse communities benefit from research being more collaborative with developing countries?
Niharika: So in recent times, we have witnessed growing diaspora in the UK. And when it comes to collaboration with developing countries, thereās increased collaboration with these developing countries. It can be a win-win situation for both the countries, for example, there can be increased innovation for these developing countries in exchange of information. And at the same time, people in the developing countries, if they provide their data, they have the sense that they are helping their own communities who are living abroad.
Naimah: Youāve touched on a few points already, but, Trupti, I wonder if you could talk about the considerations we should have when considering international partnerships?
Trupti: Yes. So one of the things that Genomics England has tried to do in the past and is still trying to do is increase the number of international academics that can have access to our biobank. Now we already know that internationally, especially in developing economies, thereās often a lack of data purely because the resource to do things like whole genome sequencing is so expensive. The resource to even have or host a biobank itself is so costly that the barrier to even developing the infrastructure is so high. So one way that weāre looking to encourage innovation within those settings is actually to allow access through particular partnership agreements to academics who are based abroad. Now obviously that means that thereās a benefit for them in terms of being able to do the research in the first place. But one of the things is that as a biobank weāre also known for being a very highly secure biobank, compared to others. So thatās something that as a data store people actually highly respect, and in particular, a lot of the data regulation within the UK is highly respected by other countries.
One of the things that we have seen happening recently is that essentially some of our data security laws and data protection regulations are being reproduced in other countries as a way to ease working with research datasets across geographic political boundaries. When it came to engaging members of local primary communities they have three primary asks when it came to the international partnerships that we might be developing in the future. One of them was that at the very least there would be tiered pricing. If we ever came to a situation where we were charging for access to our data, that pricing should be tiered to address the fact that if you are someone based in a developing economy, your access to financial resource to do research is much lower.
The second ask was that thereād be some way for us to foster collaborations. Now, whether that be led by an academic who is based abroad or an academic based in the UK was up for debate. It was more that those collaborations have to continue and have to be enabled in some capacity. And then the third thing that was a big ask was actually around IP sharing. So what happens to the financial benefits of doing this type of research? And also, more equitable basically knowledge sharing across these regions was what was asked. So what weāre looking at in the near future is whether or not these principles could be used in order to guide some of our international partnershipsā work.
Naimah: And I think just on that point you raised about fostering collaborations, Maili, I wonder if you could comment on how we could foster collaborations between the researchers and the communities that they serve?
Maili: Yes. I think here is when engagement is really important, and we need to get researchers and communities speaking to each other, to have some sort of meaningful dialogue that doesnāt just happen once but is embedded into whole research practices. So thereās many different opportunities to feed in and that practice is shaped based on the feedback the researchers receive. I think engagement is a really amazing thing, but it does need to be done well, and there needs to be clear outcomes from that engagement. So people need to feel that the information that theyāre giving and the time that theyāre giving is respected, and that those practices do change as a result of that. So I think we really need to make sure that engagement and practices are done well. And I was just going to say something on collaboration between different researchers. When researches are happening across borders, itās really important that thatās done in a really equitable way, and that those conversations are had between different researchers to figure out whatās going to work well.
We need to avoid instances of things like helicopter science, and sometimes itās called other things. Where researchers for example from the UK would go into a developing country and undertake research and then leave, taking all the benefits with them and not sharing them. And thatās something that we really need to avoid, especially in the UK, we donāt want to exacerbate colonial pasts. And I think it's really important in this context that those benefits are shared with communities. And again, we can do that through engagement and understanding that relationship and making sure that collaboration really is collaboration, and that we can provide things that maybe others need or want in the right sort of way.
Niharika: Just to reiterate our communities are still haunted by the colonial pasts. Thereās always this constant fear that our data might be misused, there might be data breaches and we won't be protected. And your DNA data contains a lot of personal information, so thereās constant anxiety around your DNA or genetic data. So itās important that the researchers maintain utmost transparency. Thereās a constant focus on flattening the hierarchies, where you sort of bridge the power gap between the researchers and the communities. And it can be done through, again, as I mentioned before, having community champions on board who understand the communities better, who are constantly in touch with the communities. And they provide that sort of semi-formal settings, where they know that where theyāre in constant touch with the authorities or the GPs or NHS, but also at the same time have very good relationship with the communities. So this is something that should be taken into consideration. And then just be cognisant of the cultural values, and not have very imperial ideas when you sort of approach communities.
Maili: I think this becomes even more important as genomics continues to evolve and new genomic techniques are developing. For example, with things like polygenic scores, where we can look at peopleās genomic data and predict how susceptible someone might be to developing a certain disease or trait or outcome, in relation to the rest of the population. Those are developing, and people are interested in them, but the data that theyāre based off again is that European genetic ancestry data, and therefore is not accurate or applicable to lots of communities. And itās not just genes that we need to be aware of, itās peopleās environments, and that data is really important to integrate with things like polygenic scores. I think we need to really address these issues now and make sure that as genomics develops that these things arenāt perpetuated and existing health inequalities arenāt continued to be exacerbated.
Naimah: Okay, weāll wrap up there. Thank you to our guests, Maili Raven-Adams, Niharika Batra and Trupti Patel, for joining me today as we discussed the ethical, legal and social implications of genomics research for diverse communities. If youād like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iāve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.
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For Sickle Cell Awareness Month, our sickle cell Patient Voice Group discuss their lived experiences with sickle cell, shedding light on how organisations need to be considerate when engaging with patients. They emphasise the need for genuine engagement and transparency from researchers, while highlighting the importance of building trust within communities that have historically been overlooked. The discussion looks to the future, advocating for more personalised support, better treatment options and a stronger focus on the diverse experiences of those affected by sickle cell.
Marie Nugent, Community Manager for the Genomics England Diverse Data Initiative co-hosts this episode with Natasha Gordon-Douglas, sickle cell patient advocate for the Genomics England Diverse Data Initiative and Lead Mentor at the Sickle Cell Society. They are joined by Oleander Agbetu, who cares for her son with sickle cell, and is also a member of the Solace sickle cell and thalassaemia support group board, and Jayson Kupoluyi, sickle cell advocate and volunteer for the Sickle Cell Society.
The episode also features insights from some of the other members of the Patient Voice Group; Hazel Attua, Samuel Chuku and Zainab Garba-Sani.
The Patient Voice Group are a group of people affected by sickle cell who share with Genomics England their expertise, based on their lived experience, to inform our sickle cell programme within the Diverse Data Initiative.
"If we as parent/carers and advocates and all the rest of it can even make a little slight difference to someoneās care, thatās what I want to do. Thatās why Iām here."
You can download the transcript or read it below.
Marie: Welcome to Behind the Genes.
Natasha: I think the fact is that people do want to hear from patients, and they do understand that actually you need the patientās voice in order to make things better, and not just be in a room where youāve got all board members that think, āOkay, this is what is good for the patient.ā No, actually, theyāve got the patients there to help support that voice, and saying, āWell actually, this is the reality,ā rather than what you think might be the reality.
Marie: My name is Marie Nugent and Iām the community manager for diverse data at Genomics England. Iāll be co-hosting todayās special patient takeover episode of Behind the Genes with Natasha Gordon-Douglas, who is a member of our sickle cell patient voice group. On this episode, weāre going to be speaking to two people who are also part of our patient voice group, Oleander Agbetu and Jayson Kupoluyi. Today weāll be discussing what itās like to live with sickle cell, and how organisations who wish to engage with patients need to be considerate of what is going on in peopleās lives, and what good advocacy and support for patients who want to be involved in research looks like. If you enjoy todayās episode, we would love your support. Please like and share, and rate us on wherever you listen to your podcasts.
Welcome everyone, thank you very much for your time today to talk about the patient involvement and engagement work weāve been doing as part of our sickle cell and genomics programme at Genomics England. My nameās Marie, Iām the community manager for the diverse data initiative, and I am really involved in doing the sickle cell engagement work. Iām going to pass straight to Natasha now, whoās going to be my lovely co-host for this podcast. So, over to you, Natasha.
Natasha: Thank you, Marie. Iām Natasha. I would say my background is nothing to do with the medical side. My background is in marketing and the corporate world. Thatās how actually I got introduced by John James, because I actually got him into our workplace to do a podcast about sickle cell. So, you know, just ā Iām working in an environment, which obviously ā itās about people understanding about my illness, so I actually got him in speaking, and then he mentioned about a project, āOh, you might be interested in this.ā So, that was kind of the introduction I got from John James. But as I said, doing patient work and engagement stuff was completely new to me, so this is my ā Iām a rookie, I should say. But I feel like now after the two years, I know now, I understand [laughter]. But yeah, thatās kind of a quick background. And how I got introduced to Marie is from John James at the Sickle Cell Society.
Marie: Great, thank you, Natasha. So, coming straight to you now, Oleander, I think itās a bit different for you. So, you joined this particular group not too long ago, but from what I know, youāve been doing this kind of advocacy work and engagement work for quite a while. So, tell us a bit about yourself.
Oleander: Well, Iām a parent/carer of a teenager, young man with sickle cell, and I think Iāve been part of the Solace sickle cell and thalassaemia support group board for more than ten years now. And what we do is we support patients through our WhatsApp group, as well as through inviting different people to come and talk. Weāve had doctors, nurses, etc. And I have supported people who have called me personally to ask me questions, from advice, for help. Also written a letter to the hospital, which we are now working on with the hospital itself, to try and get things moving and make improvements for the patients who are actually patients there at Homerton Hospital and Royal London Hospital.
Marie: And then over to you, Jayson. So, similar to Oleander, you joined this group fairly recently actually, but just tell us a little bit about the kind of work that youāve done before.
Jayson: My nameās Jayson Kupoluyi. My background is totally different from the sickle cell background. Because of the plight that I have with my health, I now decided that I wanted to make a change, so I ā unbeknown to me ā I didnāt know what advocacy was. I just ā when I meet people, I ask them questions, and, you know, thankfully enough, they really try and help and support in terms of advising me and those kind of things. So, I took that advice on board, and through the years Iāve met fantastic people, i.e. Oleander and her son. I met her son during a trip ā we took the kids to a trip for a week for self-discovery, self-awareness, teaching them how to cope, and probably to see where ā you know, try to make them open up.
So, I now decided to volunteer for the Sickle Cell Society and give them seven years of my time, in which Iāve met fantastic kids and fantastic people. And through that, Iāve learnt to be able to teach people and the kids under 16 ā well, Iām teaching from 26 year olds down to 13 year olds on how to advocate for themselves in hospital now. I teach the adults how to fill in application forms for PIP. I also write complaint letters and help them deal with complaints. And I also ā sometimes I have the chance, from Royal London and Queenās Hospital, to enter and view the situation, and ask information from the patients, from the nurses, carers and things like that, to be able to compile my own findings. And all in all, itās been rewarding, because I just wanted to give back.
Marie: Thatās incredible, you know, because something that weāve been talking about more recently as part of our sickle cell patient voice group is this idea of advocacy, and Iām just reminded that Iām with a great group of people to actually explore this because of the experience that youāve got, so this is wonderful. Now, youāve all just said youāve got varying like degrees of previous experience of being part of advocacy work. Natasha, Iāll come straight to you, what were your initial expectations as to what it would mean or look like to be part of like a patient voice group?
Natasha: To be honest, very sceptical [laughter]. I was like, āWhat are they really going to ā are they really going to take our voice on board, and is it just another tick box that they could say, āOkay, weāve funded a group for you to ā with sickle cell,āā and I was very, yeah, sceptical. But actually I would now advocate for everybody to be part of a patient voice group. I think itās so important. And the collaboration that happens with all these different organisations as well that you open up your mind to ā ācos I didnāt know ā you know, especially for this particular project that weāre working on, youāve got the James Lind Alliance, never knew this organisation existed. I think the fact is that people do want to hear from patients, and they do understand that actually you need the patientās voice in order to make things better, and not just be in a room where youāve got all board members that think, āOkay, this is what is good for the patient.ā No, actually theyāve got the patients there to help support that voice and saying, āWell actually, this is the reality, rather than what you think might be the reality.ā
So yeah, I would definitely champion anybody regardless, even ā yeah, youāve got sickle cell, of course, but any kind of illness, if thereās any kind of projects, trying to get involved, to really be able to try and shape what can happen. Because, you know, I guess what weāre working on at the moment, the opportunities for development within sickle cell are endless. And yeah, itās just being part of that steering group, part of that voice to actually make change, especially with sickle cell. You know, itās one of the ones that has never had anything ā hasnāt had change for I donāt know how many years - Iām going to give away my age, for at least 40-odd years, Iāll say [laughter]. But yeah, so from what I can see, itās slowly now changing and weāre in that wave, and Iām so excited to be part of that.
I know Oleander, so you with your son, youāve obviously seen the kind of ā if there has been change for you. I guess for me as a patient, I might see it slightly differently, whereas you as a carer, a parent, you might see it completely differently. So I guess for you, what would you say for a person who might be considering joining a patient group or a parent/carer group?
Oleander: I too was sceptical at first, but at the same time I can say that Iām really happy that I have been involved, because it means that all the information that I find out about that might be relevant to other parent/carers, I can pass that on, and vice versa. Any questions that they might have or issues that they might be going through, I can also get those considered. And I just think that it can be quite sad when a patient goes into hospital and they are on their own, they donāt have anyone with them. And so for me, for example, when my son was in paediatrics, and Iām sure the two of you would also know that, the treatment is just very different to when you become an adult. I could see from my sonās face, he just was not impressed with the adult care at all. And he more or less says, āMummy, Iām not coming back to hospital unless itās really like a dire situation. I just donāt want to go back.ā And thatās quite sad because really weāre supposed to be able to support our loved ones in hospital. When they need the care, they absolutely need the care.
I actually spoke to a parent today of a young man in hospital right now. His PCA was failing, which is, you know, the pump that gives the medication, right? And they actually asked her, āIs he still in pain?ā If heās been put on a PCA, how can you ask that question? So, you know, itās so good that she was there to advocate on his behalf. He couldnāt even talk. And, you know, I know for my son also, when heās in really, really deep pain, he stops talking, just doesnāt talk. And if heās there by himself, itās a real issue. And so, you know, I think from that point of view, all of these kinds of stories are really important to bring to forums like this, so that people can understand that of course, yes, it first affects the actual patient themselves, but it has a knock-on effect for the families, and the carers and the people that are involved with that personās care. So, if we as parent/carers and advocates and all the rest of it can even make a little slight difference to someoneās care, thatās what I want to do. Thatās why Iām here.
Marie: Thank you so much, Oleander. I think thatās a really powerful story as well, and it just shows so ā I couldnāt help but think, as you were talking there, about this idea of ā we use the word community quite a lot in this kind of engagement space, but I must admit, you know, Iāve been working in public engagement with health and research for well over ten years, and I must say that I really felt the sense of community in this sickle cell space, particularly with patients and the wider sort of community, and that feels like itās a really important part actually. And it kind of speaks to what Jayson mentioned about, you know, heās now reached this point in his own life where he wants to be actively kind of contributing back to the community. So, Iāll come to you now, Jayson. Again, what was your expectations about joining a group like this, and what were you thinking when you joined? And how has that maybe transformed now? Or potentially not? How has your experience been so far?
Jayson: Itās been great actually, pleasant people, likeminded people working towards a common goal. When I first heard about this group, I said to myself, āDo I have space for another WhatsApp group?ā Itās not because I donāt have space on the phone. Itās because getting calls in the middle of the night at the same time ā and you canāt turn it down sometimes, especially if itās in the family, ācos I have these people ā I have - you know, itās in our family and itās very, very rampant. And when you say community, you can have a mother of your nephew, your niece call you, knowing fully well that youāve gone through that, this sort of thing, whatās going on, blah-blah-blah, āOkay, this is what you need to do. This is what you need to do.ā Then getting to the hospital is another ballgame, do you understand? And you just have to say, āOkay, you know what, if I take a moment of my time and say, āIāll see you in the morningā¦āā Iāve had two incidents that I didnāt make it, and itās a guilt trip to me, because I was thinking, āHold on, if I had goneā¦ā And then I was okay ā if I wasnāt feeling okay then, yeah, but I was okay. I was just tired.
And when I started, I was a one-man band, and I realised the last 20 years that itās definitely not going to work, hence the community comes in. And the time I tapped into this community, I met people ā āOkay, so, you could help me out, you could help me out, you could help me out.ā And the more I meet people, the more my voice goes bigger, louder and reaches more people that I want to reach. So, when I first met Hazel, she was in pain, so I called her and I was like, āMadam, you donāt know me, but I know that youāre in pain, are you okay?ā And she goes, āNo, I just wanted to sit down.ā I just sat down beside her, didnāt speak to her, just sat down, and she didnāt utter a word, but she came to a conference and Iām thinking, if youāre in pain, you know, okay, Iām the same ā I just started explaining myself to her, āI have this, Iāve gone through this,ā blah-blah-blah, and she was looking at me and she was like, āYou donāt look like (inaudible 0:15:54).ā
So, meeting and coming to this group, my expectation was a bit elevated actually because, when I was speaking to Hazel, she said, āNo, Jay, seriously, you need to be in this group because we need the otherā¦ā And I was like, āNot another one,ā and blah-blah-blah. Hazel said to me, āCan you join the Solace group?ā I was like, āWhoās in it?ā She goes, āOleander.ā I was like, āOleanderās good.ā And everybody keeps on calling me, and I do appreciate that people want my advice sometimes, but this health is very precious to us. I am looking forward to greater things with this group. I am looking forward for us to reach some targets, some funding, some people out there, to be able to change so many things. And any time I see a sickle cell person in good health, no pain, no nothing, I give myself thumbs up. You donāt want to see anybody in that kind of pain, and people donāt recognise or have that empathy to share or say, āJust another sickler.ā
Sickler, thatās a word, hmm, I donāt like it. So, whenever I go to hospital, Queenās or Royal London, they know, āJayson, are you here to cause problem?ā āAs long as you answer the question, I will be fine. As long as weāre okay, Iāll be fine.ā And, you know, weāre now friends. In the midst of adversity, weāre now friends.
Marie: There is just so much I think in what youāve just said, and I think that again something that Iām really struck by ā so obviously, you know, I donāt come from any lived experience. I didnāt have people in my life that I knew that had sickle cell before starting to work on this as part of my job. And something that Iām really struck by is, first and foremost, from the No Oneās Listening Report, the quite staggering evidence that, as a community of people, people living with and affected in some way by sickle cell are very neglected, and thereās all sorts of complex layers of like challenges and difficulties that people have to deal with, and it seems to come from all sorts of places and all sorts of kind of parts of life.
I was just really struck by this really daunting situation actually to be put in. As someone whoās part of, you know, letās be honest, quite a sort of ā maybe quite far down the road in terms of direct benefits, like piece of work ā so weāre here, Iām part of an organisation that is interested in supporting research and providing good quality research data, and research is a really important part of this whole system, but again itās something that maybe will take five, ten-plus years before youāre seeing any direct benefit from in terms of the data that weāre creating.
But something that Iām really struck by is this idea of, if we know that thereās going to be maybe a bit of a delay in the kind of benefits that we can bring to patients through the data that weāre generating, how can I try and build in as much benefit right now for the people that weāre engaging with and we can bring into this work right now? And thatās something that weāve talked about and weāre about to initiate a bit of a project around exploring a bit further, but I just wonder if I can now come to you all and get your thoughts on what can organisations like Genomics England or other research based organisations ā what in your view does being a good supporter or a good advocate for people living with sickle cell ā what could that look like from a research organisation in your view? Iāll come to you first, Oleander.
Oleander: I think a really massive thing is to support the removal of barriers. Thereās so many people who would love to get involved with this, that and the other, but actually the barriers are there and the barriers are real. Even like from a personal point of view, the thing I was interested in attending, I canāt. Itās just not within my means. So, things like that are really important, because most people who are living with sickle cell, we are from marginalised groups. Weāre from groups that are not known to be flushed, and we need the support from ā you know, if you really want our help in terms of research and so on, we absolutely need your support and your help to provide you with that research and that help. So, itās real. Giving someone a Ā£20 voucher is nice and dandy, but actually if theyāve had to pay for whatever, accommodation or travel costs and all these things, theyāre out of pocket before they even start.
Marie: Yeah, this is something that weāve been talking about recently, isnāt it? I know that organisations like ours do want to do better, but sometimes thereās just that not quite as good an understanding as to what these barriers really look like for people. Over to you, Natasha, what do you think about that?
Natasha: Thereās a couple of things I wanted to pick up on. One is definitely, yeah, the barriers. Itās funny, I was at a hospital this morning and I was talking to one of the consultants. He asked me the question, which I thought was quite weird, but he asked me, āWhy do you think that sickle cell patients have to pay for prescriptions?ā Like that alone, prescriptions, weāre on medication forever, you know, from the moment youāre diagnosed, which for me was at six months, so in my entire life, and youāre paying for prescription, thatās going to keep happening over and over, and youāre just ā you know, thereās people, because of their sickle cell, they canāt work. Thereās, you know, barriers of not being able to work. And then youāve got potential ā you apply and say your disability, and sometimes thatās not even taken on board either. So, youāve just got these barriers in place that just make living day to day so exhausting, so tiring, and basically youāre fighting those barriers at every ā you think youāve passed one, youāve come onto another.
And I guess also the research side, which ā itās funny because I would say, when it comes to research, itās fantastic, yes, that organisations like yourself are looking into it, but actually sometimes itās not even ā you canāt make the change where itās going to matter immediately. Itās literally the frontline, you go into hospital and A&E, thatās your first barrier is trying to just get some pain relief or get any treatment. Youāre sitting there for four hours. Four hours in pain for a person with sickle cell, that can really, you know, make things worse. And thatās the kind of ā you kind of want the immediacy ā like the frontline, those kind of things to change. And of course, yes, we do want more research and we do want people to take part, but itās those things where you might not necessarily have the power to make those changes immediately that people will be willing to take part in research like this, because you canāt even just get the treatment that you need from the moment you step into a hospital.
Thatās kind of what I was thinking of as you are speaking about this. Iām like, you know, yes, this is great, but we just need sometimes just going into hospital to make it easier. Like what Oleander said, itās unfortunate that the persons being asked about their PCA, if theyāre in pain ā well, what do you think? Like thatās just the basic [laughter], you know. Itās kind of like, how can you ask that question and youāre a healthcare professional being on the frontline? And thatās the worst. Itās the frontline staff sometimes which actually need the education. So, some of this research, it needs to go to education in these staff actually, you know. Thatās maybe an area that needs to be sorted.
Marie: For me, I completely have a whole new deeper appreciation for almost seeing people as the whole, how you work with the person. And itās never been clearer to me - as I say, you know, in ten-plus yearsā experience of doing this kind of work, it has never been clearer to me how important that is than now I work on sickle cell and how important that is. And I think that actually youāve touched on a really important point there, which is that, you know, I know for sure that thereās incredible work going on through NHS England, through the inequalities workstream and in response to the No Oneās Listening Report. There seems to be, you know, a huge increase in sort of focused action being taken to address a lot of these challenges that are being brought up in our conversation now.
But actually, what you said, Natasha, did kind of really hit the nail on the head a little bit for me, which is that actually we kind of still look at this as kind of separate organisations, like, āWell, this is my bit and thatās your bit, so you stay over there.ā And I think that something that weāre trying to start working towards through the Sickle Cell Society is actually how do we bring together a better sort of alliance of work and of people who are across research and healthcare, because these things feed into each other, right? So, how can we do better to sort of show that we are all aligned, that there isnāt just this one person or one group over here looking just at this little bit and then thereās a completely separate group, that we are all actually united in our, you know, intentions here to really improve the lives of people that are living with this condition. But of course, thereās just so much work to do, isnāt there? I think thatās another overwhelming thing, that everything needs to be better when it comes to sickle cell.
Oleander: The thing I wanted to just add to this whole talk about what researchers can do in terms of supporting advocates, etc. Two things, understand that there is an issue for trust from our communities, because weāve been burnt. And the second one is, we need transparency. So, be real when you talk to people about the information youāre gathering, what youāre going to do with it, how itās going to impact the research, timetable of whateverās happening, all of those things which will help people to gain more trust.
Natasha: Yeah, Oleander, thatās so ā yeah, I think definitely, thatās been echoed throughout this whole project, hasnāt it? Itās always about gaining that trust, because it is a case of, is this another where weāre going to have support and weāre going to be let down, or, you know, lied to, whatever youāre going to find out. And trust is a huge part of that, definitely, yeah. I think, yeah, definitely. Thanks Oleander for saying that, it is.
Marie: Yeah, thank you all. So again just to say that Iām always blown away by just how generous you all are actually with what you say and with what you share, and with the messages that youāre ultimately trying to get across. And itās very humbling, you know, to be able to work with you all, ācos you all are so incredibly passionate and driven, despite so many challenges, and it is nothing but inspiring. So, I can see absolutely why, you know, people living with sickle cell, for example, are called warriors, because you need to have that sort of fighting spirit to just keep going, and I have nothing but, you know, boundless like respect and admiration for people who are able to do that and contribute to the community in the ways that you all do.
And I just think that again, you know, so talking now back to this idea of how research is set up, you know, I myself am part of an initiative thatās been, you know, initiated and only kind of guaranteed funding for this kind of iteration, for three years. Itās very difficult to sort of initiate and establish really good long-term relationships, and have like a longer term strategic sort of way in which youāre bringing in people and taking that long sort of like approach to building relationships, but itās something that Iāve tried to be really mindful of actually, and to address a lot of the things that you just mentioned.
Youāve heard us refer to other members of our patient voice group. Letās now take a moment to hear from them.
Samuel: Hello, my name is Samuel and Iām from Leicester. I have had the great privilege of working with some amazing people in Genomics England over the last few months, to hopefully one day be a part of something that takes down this condition that I struggle with known as sickle cell. Since John James of the Sickle Cell Society introduced me to Marie from Genomics England, there has been a door opened where the voice of a person dealing with the condition matters and holds weight, to help know what is required to further improve matters for people dealing with said condition. Hopefully, after reading the blog and hearing this podcast, you will know more about the work weāve been doing, and feel as encouraged as we do. We donāt just want to stop here. Thereās a long way to go, and we need all the help we can get to reach our goal together.
Hazel: Hi everyone, Iām Hazel. I hope you enjoyed the podcast. Now weāre not done just yet. Keep your eyes out for our sickle cell and Genomics England patient takeover blog, where Natasha, Sam and I take you through what weāve been up to and the future of genomics.
Zainab: Hi, my nameās Zainab and I co-chair the Genomics England diverse data advisory board. I also have the pleasure of being part of the patient engagement group for this important piece of work. Iāve been a sickle cell advocate since before I even knew what advocacy was. As a child with sickle cell, I was exposed to different ways to help the community pretty early on, and have loved working with others to transform care for the better. Today, I hold a number of advocacy related leadership positions, including being a trustee of the Sickle Cell Society, chair for NHS Englandās patient advisory group for sickle cell health inequalities improvement, and a member of faculty for Medscapeās committee on rare diseases. I also contribute to global sickle cell policy, practice and research.
Iām super excited about the work we do with Genomics England because I think theyāre a blueprint for what good patient centred work really looks like. My background is in health policies specifically related to research and innovation, so to see sickle cell being prioritised in this space is really special to me. We have an incredible opportunity to advance equity through research and innovation, especially related to genomics, and I myself am lucky to experience the transformative power of regenerative medicine. Iām excited for this group to continue to advocate for and enable better access for such incredible science.
Marie: Weāre very lucky to have such a wonderful group of people who are part of our patient voice group, and I hope you enjoyed meeting them. Just going back now to sort of what can be achieved, and if we, say, come back together in a yearās time, knowing the kinds of things that weāve just talked about briefly that we maybe want to look at ā weāve mentioned things like doing more family sessions, looking at how we can engage young men in particular, doing what is needed to kind of give that really strong message about how you support people to be part of these kind of patient advocacy roles. But what would you really like to see that weāve achieved together by say this time next year? Iāll come to you first, Jayson, this time.
Jayson: Thank you very much. Going straight to the point, I would like us to have more one to one with the patients and family in terms of ā mainly I think to move towards the male, because, you know, Iām a living experience of some of the things thatās happening, and put the awareness out there, and let them know that ā not to scare them, but to give them adequate information to be able to arm and tool themselves for a better life for themselves, a better respite for themselves, and a better understanding of the situation. I know if sickle cell patients have enough time at work, at uni, at school, during their exams, they will achieve great results, and I would want that to be one of the forefronts of this campaign, to make sure that, you know, the male side ā I do know a bit of the female side but Iāll leave that to Oleander and Natasha, but the male side of what they should expect, and how to ā if I could put this in (inaudible 0:33:59), I am making myself a role model for them, because I have leapt over barriers and over so many expectations, and if I could do it, with the science and the support we have now, they can double it, they can triple it, they can do more. My journey hasnāt ended yet, but before it does, I want to tap into every organisation to hear more voice, to just give me five minutes to hear my voice.
Marie: Thank you so much, Jayson. I canāt think of a better role model for young men who are dealing with this than you, so itās brilliant to see your dedication to that. Over to you, Oleander, what would you like to see ā if weāre here together in a yearās time, looking back on what weāve done over the last year and whatās been achieved, what would you really like to see?
Oleander: Iād like to see sickle cell actually being taken seriously, that people donāt make assumptions that, āOh, itās just a small, you know, blood thing, itās nothing that deep, nothing that big,ā whatever. Because the reality is, for a lot of indigenous people here, the majority ethnicity in this country, sickle cell is spreading because more people are mixing, more people have come over, refugees, economic migrants, etc, and mixing, and so they will find that actually it isnāt just a tiny minority of people. Weāre told itās 17,000 people in the UK, but actually that numberās going up. So, you know, it is a bit of a shame that it takes it to affect the ethnic majority in this country that anything would change, however this is the reality we live in. So for me, thatās what I would like to see, that sickle cell is taken seriously, that weāre not just stuck with one or two authorised drugs for people living with sickle cell, and actually one of them is not even a sickle cell specific drug.
So yeah, we want sickle cell to be taken seriously, and so that people can actually trust the process and trust the people who are genuinely trying to research issues to do with sickle cell, so that we can make the difference that we need to make for peopleās lives.
Marie: Thank you, Oleander. That just reminds me that, you know, hopefully ā so, one of the projects that you are also involved in that weāre doing is ā and thatās been already mentioned, the James Lind Alliance and the Sickle Cell Society partnership that weāve got, the priority setting partnership. Hopefully, one of the things thatās part of doing that is that we do create that sort of focused priority areas, and thatās really strongly centred on the voices of people living with the condition, supporting people with the condition, whether theyāre parents, carers, healthcare professionals. So yeah, I completely agree, you know, really putting it on the map, taking it seriously, raising the understanding, raising it as a priority, I think that would be great to see in a yearās time for sure. So of course, last but not least, over to you, Natasha.
Natasha: Well, Oleander has literally taken the words out of my mouth. That is exactly what I would want to see in the next year, and to me, it can be done. There should be no reason why it canāt be, with all the technology, with all the advancements thatās happening. There is no reason why sickle cell should not be leaps and bounds with the information, with the project, of getting this information from sickle cell patients. It should come to a point where actually no one has to suffer from sickle cell because, you know, the ā whatās it called, the medication, that one thatās recently come out, thatās way overdue. I canāt even believe itās taken this long to just come up with that one, you know. The stem cell treatments and what they give as an alternative, itās not good enough basically. And, you know, we had this new one come out ā I say new one, but this hydroxycarbamide, itās like that wasnāt even for us. It was all by mistake that, āOh actually, this might help sickle cell, letās see.ā And thatās whatās the afterthought, and we shouldnāt be an afterthought. It should be a priority.
And yeah, having that priority setting that weāre doing with the James Lind Alliance ā itās funny, ācos I remember, we had a call in our patient voice ā I think he mentioned ā I think it was something about maybe the questionnaire that we were going to give people, or ā I canāt remember the particular thing which I said to you, youāre having trouble ā you know, weāre underrepresented, thereās no data on us for a reason, and you had a template, and itās like this templateās not going to work, because you have to approach it differently. Like you have to literally rip it up and start from the very beginning, because what youāve tried to do in the past hasnāt worked, or, you know, the majority of people, especially in the European world, it works for them, great, but youāre coming to an underrepresented community and youāre thinking, āOh actually, we can just use that thumbprint and put it on this.ā No, youāve got to start again.
And I think it brings the importance of actually taking part in things like this, is that without actually knowing this, you would have thought, āOh actually, people just arenāt interested, you know. Patients donāt want to know. They donāt want to give any information over to us.ā But itās like, well no, itās not that at all, itās just that you need to approach us differently. You need to, you know, understand what actually weāre going through before you can then try and fix anything or provide information, or get, you know, medication advancements. Like these things need to be done and the groundwork first, and not thinking, āOh okay, we can just put a little plaster and thatāll heal that.ā
So for me, definitely, more options when it comes to treatment. And, you know, that weāre not the minority when it comes to data. Because especially with sickle cell, it affects different people in so many different ways, and theyāre just trying to understand, āOh, why does it affect this person this way but it hasnāt done it in this person?ā And itās just like, great, youāre asking these questions, but now letās move it forwards. Like letās not keep talking and letās start the action. And thatās probably one of the other things is, I want to see the action. Itās the action now. You know, of course, if you want us to talk, weāll talk, you know. We wonāt stop, and we can keep going. But ultimately letās actually have some movement. Letās have an action that youāre ā I say you as in you as an organisation, but wider, everybody thatās part of the process comes and says, āLook, this is what weāve been able to achieve.ā And, you know, then you know you have been listened to. A bit like Jayson said, you know, still not listening. Actually, now you can say, āYes, weāve heard and now this is whatās come from it.ā So yeah, thatās probably I think for me the biggest utopia is that actually sickle cell just wonāt exist. Itās done. Theyāve been able to sort it out [laughter], itās no longer an issue at all. But yeah, we wonāt get to that next year, but, you know, hopefully eventually down the line there is that cure or change that they can do.
Marie: I think for me, it kind of just brings me back to this point that there needs to be a united front in terms of like dealing and addressing with this. And also importantly, it needs to come from the community itself in terms of setting the priorities of what is done now, what is immediately needed to be done now, what can be looked at maybe a little bit later down the line, as thereās maybe a bit more information, a bit more understanding, a bit more knowledge to kind of maybe base some things on. But yeah, every time I hear, you know, people speak about all the various challenges that, you know, of course, come from their own lived experience and having to see how this affects their community, and yes, there are steps being made in the right direction, but I think we all probably agree that we could all probably be doing more to just improve the way weāre uniting this work, and weāre doing it in a way that is really coming from the community themselves and saying, āWe want this to happen now and in this way, and this is what we want you to look at addressing.ā
Weāll wrap up there. Thank you to my co-host Natasha Gordon-Douglas, and guests Oleander Agbetu and Jayson Kupoluyi for joining me today as we discussed engaging people with lived experience of sickle cell in research and advocacy. If youād like to hear more about this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iāve been your host, Marie Nugent. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
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In this episode of Behind the Genes, we explore the challenges diverse communities face in accessing genomic medicine. The discussion focuses on issues including language barriers, cultural differences, and socioeconomic disparities that hinder marginalised communities from accessing and benefitting from genomic medicine.
Our guests delve into successful strategies for engaging these communities in healthcare research and decision-making, highlighting the importance of building trust with groups that have historically been underserved or mistreated. The episode also emphasises the need for culturally sensitive communication from healthcare professionals and how meaningful community engagement can foster collaboration and trust within genomic research.
Our host, Naimah Callachand is joined by Aman Ali, a Community Ambassador at Genomics England and Community Engagement Manager at Our Future Health, Anna Smith, Child and Adolescent Integrative Psychotherapist at Rareminds, and Moestak Hussein who works for Bristol City Council in Public Health & Communities, working directly to build and imbed cohesion, inclusion and social justice approaches in her role.
"If we talk about co-production, true co-production is really creating a power balance where thereās no hierarchy. Itās an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve."
You can download the transcript or read it below.
Naimah: Welcome to Behind the Genes.
Aman: Itās really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with.
Naimah: My name is Naimah Callachand and Iām Head of Product Engagement and Growth at Genomics England. On todayās episode, Iām going to be joined by Anna Smith, child and adolescent integrative psychotherapist for Rare Minds, Aman Ali, a community ambassador for Genomics England, and Moestak Hussein, community coordinator at Bristol City Council. Today, weāll be discussing the disparities in access to genomic medicine amongst diverse communities. If you enjoy todayās episode, weād love your support. Please like, share and rate us on wherever you listen to your podcasts.
Aman: Hi, my nameās Aman Ali, I am an ambassador at Genomics England, a person very passionate about health research and ensuring that diverse communities are involved in health research, and I work as a community engagement manager at Our Future Health.
Anna: My nameās Anna Smith, Iām a psychotherapist. I work in private practice and also with Rare Minds, who are a company who provide therapy to people with rare and genetic conditions.
Moestak: Hi, my name is Moestak Hussein and I have a background in community development, and Iām passionate about tackling health inequalities, and building social justice and inclusive approaches to address health inequalities. I work at Bristol City Council in the public health team, and Iāve participated in the Bristol workshops around equity in research in genomics.
Naimah: So, letās jump in and first of all I want to talk about barriers to access for diverse communities. I want to talk about how there are language barriers, cultural differences and socioeconomic factors that impact access to genomic medicine for marginalised communities. Anna, I wonder if you maybe could talk to me a bit about this.
Anna: Yeah. So, Iām talking about the traveller community, and we refer to this community as a GRT community, which is Gypsy, Romany and Traveller, so it encompasses people in the UK, people living in Ireland as well. And some of the barriers to accessing healthcare are a lack of understanding of culture. Thereās been studies done where it says that people from GRT communities show up lower on all markers for poor healthcare and poor mental healthcare, and part of the reason for that is things like illiteracy. You know, youāre dealing with people who canāt read or write. They canāt read appointment times. They donāt have access to public transport. A lot of women donāt drive in this community, and also women are not very well supported within the community by the people who can drive and who can get them places, because itās not seen as something that they need access to. Because the community is so closed, everything sort of takes place within the community.
In terms of genomic healthcare, access right from the start of life, if people are not accessing healthcare right from birth, theyāre not getting the genetic testing thatās needed, so then a lot of these things donāt even show up until the illness presents itself, and then accessing healthcare from there is really difficult. You know, itās something that ā it doesnāt happen a lot. Only 67 percent of people from the GRT community were able to get a doctorās appointment when they needed it, compared to nearly 90 percent from other communities, and thatās through things like not having a fixed address. Lots of GPs donāt offer temporary registration, which means that if you are travelling, you do not have access to a GP, which is your first port of call if you need any access to healthcare. So, many people from the GRT communities are using A&E services in order to get healthcare, which ā you know, they are not set up for dealing with long-term life changing conditions. Theyāre there to deal with whatās right in front of them and then they move on. Thereās no sort of continuity of care.
Naimah: Thanks Anna, thatās really highlighted a lot of barriers for the GRT community. And I wonder, Aman, if you want to come in now and maybe discuss some of the barriers that maybe the Muslim community might experience.
Aman: Yeah, I think anyone involved in medicine or anyone whoās a doctor is really well respected in the Muslim community. That profession is something that every parent aspires for their children to get involved in. They at least want one of their children to be a doctor. Having said that, thereās this willingness to engage with the space, but thereās a lack of knowledge, which is a huge issue here. People donāt know what the word genomics means or genes, or understand DNA. Some of this language is a huge barrier to understanding and then eventually accessing some of the services that could be available to people from Muslim communities. Because when we speak about Muslim communities, weāre talking about a huge, diverse group of people from South Asia, from North Africa, from the Middle East, and they all have their nuances and different cultural experiences as well.
Just to kind of point out maybe one or two, most people in the UK have grown up in the UK, where access to healthcare is free, whereas this is quite a strange phenomenon for people who may have not been born in the UK and then access healthcare services in the UK. And the context being here is usually they pay for healthcare in other countries, and whenever any public or free healthcare is provided, itās usually seen as kind of not very good or suboptimum, or yeah, itās not going to be very helpful for us. So, when they see free healthcare in the UK, thereās that kind of apprehension, āActually, is this going to be worthwhile? Iām not paying for this, so itās not going to be very much good for me.ā So, those are some of the cultural nuances that certain communities where healthcare is not for free in certain countries that poses a barrier.
Language in terms of speaking and reading is an issue. So, a lot of people, they may speak a language, but they donāt know how to read a language. So, even when services are translated ā I, for example, can speak Bangla, but I canāt read or write Bangla, and not a word of Bangla at all. So for my parents, who can speak Bangla very well, their reading level is actually quite good, but I know that many within the community, they didnāt get education back home, and therefore reading and writing is a challenge as well. And then you have the issue of dialects. Thereās so many dialects within so many different communities, so when a language is spoken or written in a particular way, if that dialect isnāt your mother tongue or a dialect that youāre familiar with, then that causes challenges to access as well.
Naimah: Moestak, how do cultural beliefs and values influence attitudes towards genomic medicine within each of these different cultural communities?
Moestak: I think Aman and Anna touched on it a lot, and itās about communities being able to coproduce that historically hasnāt been there. The supremacy of certain communities to have a voice and be able to express how they would like to shape their healthcare, but also access to healthcare barriers have been part of having a barrier in access. And I think Aman touched on like even the term genomics, I donāt think it exists in particularly my community. I come from the Somali community, and Iāve tried to look at historical kind of words and terms. I mean, our language only got developed in 1973, the written language, so you can imagine that thereās a lot of gaps or thereās other terminologies.
So, the cultural beliefs and values is also communitiesā recognition to be driving their own health needs and priorities is not valued within those sectors such as healthcare. I mean, weāre still talking about holistic medicine. People go to their faith leaders in the first instance to have support around prayer. Thatās not necessarily recognised by mainstream health provision. And I think itās about how do we build on those strengths and how do we recognise that that is a really great part of communities. And itās also tradition and customs within childbirth, from birth, understanding what children and young people and families will need. I know thereās customs and traditions for women to stay at home, for example, for 40 days, and those are the kind of traditions that could be built on. And I think itās about making sure that the child doesnāt pick up bacteria or things like that.
So, there is an understanding and knowledge within communities of genomics. Itās the awareness and the training around patient centred approaches are still missing, in my opinion. And I think that influences how people view genomic medicine. It goes back to the lack of trust and historic past abuses and cases, that communities has resulted in lower participation and a reluctancy to be part of genomic testing, but also that lack of understanding.
Naimah: Anna, did you have something you wanted to add in there?
Anna: What you were just saying about keeping it within the community, thatās something that we see with the GRT community massively is everything is handled within the family, and I think thatās not necessarily valued outside of that community. If you arrange an appointment with someone and the whole family turns up, itās like, āWoah, whatās going on here? You know, how is this managed?ā And it becomes a safeguarding issue, when actually that is how it's managed, and very often you need to get the whole family on board before you can start working with an individual. Because within the GRT communities, individuals do not exist outside of their families. Even what weāre saying about language, a lot of the GRT community who live in England now speak English, but the words that they use for mental health are very different.
You talk about mental ill health, that translates as psychosis in the GRT community, whereas if youāre talking about depression and anxiety, somebody might say that theyāve got bad nerves. So, if you come up and say, āWeāre dealing with mental health now,ā people would say, āWell, I donāt have psychosis, I donāt have that, this is not an issue for me.ā And itās like youāre speaking different languages even though youāre using the same words.
Naimah: From what all of you have said as well, it does sound like there are a lot of similarities in the barriers in each of the different cultural communities.
I wanted to move on to ask about what strategies have been effective at engaging these diverse communities in healthcare research and decision making processes.
Aman: There are a number of ways Iāve seen best practice take place in regards to kind of community engagement. The approaches have been one of two approaches. One, either inviting the community to come to your spaces, i.e. organising events or having opportunities where people can engage with your service. Or the alternative approach, which I think is actually more effective, is actually going to the spaces where communities are most familiar with. So, whether thatās holding a focus group at a community centre, at a church or at a mosque, or engaging in coproduction with a community organisation, to come together, to come up with an idea of how to best engage communities. And I also feel like thereās a difference between PPI, patient and public involvement, versus community engagement.
And those are the two major approaches that Iāve seen when it comes to community engagement, and Iām a big advocate of community engagement, because youāre going into spaces which are authentic to the very communities that we are hoping to engage, but youāre going into an unfamiliar environment as opposed to bringing that community into an unfamiliar environment, where they might be a bit guarded with what they want to share and how comfortable they feel. So, those are some reflections on good practices in community engagement.
And I think one of the key things that we need to do is understand who are the key community leaders within that community, ācos itās one thing being within that community, and being able to speak about that community are two different things altogether. So just to articulate what I mean by that, I live in Luton, but Iāve just moved to Luton two months ago, so if you ask me about what life is like in Luton, Iāll be able to speak about my experience, but if I was to live here for 20, 30 years then Iād be in a better position to speak about how people in Luton live and what their experiences are like, and thatās two different perspectives youāre going to get. So, itās really important to engage community leaders who are really well embedded within the communities, who are attached to organisations or institutions which are well trusted in the community as well, so that we can get a wider perspective of how communities feel about genomic medicine and accessing services that we want people to engage with.
Naimah: Thanks Aman. I think you made a couple of really good points there, and I think you kind of have this overarching feeling of building trust, which is what Moestak mentioned in the previous question as well. I thought maybe now would be a good time to discuss your first responders project, Aman, if you could tell us a bit about that. Itād be good to hear the kind of developments from that community work.
Aman: Yeah, so one of the ideas that came about from engagement actually that we had with some community leaders within the Muslim community, primarily some imams, they heard about the work of Genomics England, they heard about the work of research in particular, and they were really keen to get involved even further, but they were honest in saying that, āI know very little about this space. And itās one thing for me not to know much, but then if I donāt know anything then Iām not able to then advocate for this within the community. So, two things you need to help me with. One, help me understand this space, but also allow me to then be able to advocate for services or information that my community can benefit from.ā
So, thatās where the inception of this first responders idea came about. The idea being that community engagement happened with some imams from all across the country, where we trained them to understand a bit more about genomics, and genomic healthcare and medicine, but also to be able to navigate a number of scenarios that they may face in the community. For example, thereās a mother who has been recommended by their GP to go see a genetic counsellor, but theyāre really worried about broaching that conversation with their husband or their family, because of the challenges that they may face. So, how would you support someone in the community when that scenario comes up? Or for example, someone like Genomics England or Our Future Health or another organisation has approached you about a research study, and they want to engage your community, how would you have that conversation with that particular organisation, advocate for those health programmes within your community?
So, we just presented a number of scenarios. But I think the main thing that we ended with was giving the imams in this particular incident the ability to signpost to services, be it helplines that are available for communities to access more information, or websites that people can access in order to understand more information about different issues to do with health conditions, or whether it be better understanding issues like cousin marriages or kind of accessing genetic testing.
Naimah: That sounds like youāre empowering the leaders to advocate for healthcare and share this with their communities through this work. I wonder, Anna, is that something that you could do in the GRT community as well, like empower the leaders of the family to disseminate these healthcare messages, and how would we do that?
Anna: Yeah, I think so. I think a lot of it would need to be outreach, and there are people out there who can help bridge that gap. For example, thereās a great team called Family Friends & Travellers, and if you get in contact with them and let them know which community youād like to go into, they can help arrange, or they will come with you to go into that community. Because the GRT community, you know, is very mistrustful of anyone coming in, and rightly so. It was only in 2011 that they were included on the national census as an option to say youāre from that community, so I think thereās massive mistrust there of anyone coming into the community.
So, if you want to engage the leaders of the families or of the communities, youāre going into a settled traveller site, there will usually be somebody who is in charge of that site, not officially, but maybe their family might be the biggest family or they might be the most important family. And there are people out there who will allow you to start to engage with that person, who can then disseminate the information. But it needs to be outreach care, and the information that you disseminate, it needs to be tailored to people who have left school at primary age, who donāt have the skills to read or write, or to manage appointments or read prescriptions, or have access to that type of healthcare. Thatās where it really needs to be tailored.
And I think confidentiality as well needs to be tailored a lot, because gossip and reputation and shame is huge in the GRT community, and if you are seen to be engaging with someone outside of the community, that is something that can bring a lot of shame to you and your family, so it needs to be handled really, really carefully.
Naimah: Just to kind of go along with this theme of trust that youāve all now mentioned, Moestak, I wonder if you could maybe comment on what strategies can healthcare organisations and researchers employ to build trust with these communities who have historically been underserved or mistreated?
Moestak: Yeah, I think I mentioned earlier about the hierarchy of power around superiority and also mistrust of medical professional generally, and I touched there on how safeguarding concerns are triggered on not understanding cultural norms and practices within communities, and misconstruing that with safeguarding. There is generally that mistrust is there. And I think what Aman touched on there is really the importance of asset based approaches, and really building on transparent and really embedding transparent and inclusive practices from the onset. I mean, if we talk about coproduction, true coproduction is really creating a power balance where thereās no hierarchy. Itās an empowering model. It empowers both the researchers or the person that comes in, but also the communities that participate, and you all start on the same level, on the same outcomes and the same goals and aims that you want to achieve.
And I think itās important to embed those kind of approaches, and itās Covid-19 ā I mean, we took part in Bristol in Kingās Fund research around the community champions model. Itās exactly that, about engagement, about community driving their own solutions, and being able to collectively collaborate, drive their health piece forward, but also increase the capacity of communities. We worked with clinicians who come from those communities, and itās no surprise that the uptake of covid-19 vaccine increased as a result of working with those trusted voices.
Quite often, those really effective programmes and engagement often are not funded adequately. Theyāre not sustained. And what happens is that we constantly are having to rebuild and restart, and that really does affect trust as well with communities. And when something works, why not build on it? And even now with that Covid-19 learning from the community champion model, the resource is not there anymore. Itās not valued anymore, sadly. That in itself is a risk, I think, in building the trust, but also the strength to continue that work and adapt in other ways around genomic medicine, and even increasing and diversifying the genomics data pool, helping communities understand and drive that. And that first responders project, communities being trained to capacity build and then being able to drive that within their communities, thatās the only way that weāre going to have effective strategies.
Aman: I think adding onto whatās been mentioned, with regards to building trust, itās really important to understand the motivations of communities, and to understand what messaging is going to resonate with different communities, and itās going to be a different message for each community. You canāt have the same approach for all communities. A recurrent theme that Iāve come across when engaging different communities is this difference between messaging which is individualistic and then messaging which is about the community and more the collective message, and how that resonates a lot more with certain communities that Iāve engaged with, particularly within Muslim communities. And thatās something that I think is a bit untapped in regards to kind of any materials that are created, be it posters or videos or any content looking to reach out to communities.
When we did some focus groups with some communities in Watford, who are primarily from the Pakistani community but also other parts of Asia in that region, the biggest response or biggest positive response that we got was when we posed the question, āIf you were to know that people who look like you, from wherever your parents are, family may be from, would you be motivated to take part in that research?ā And the biggest yes came on the back of that question. And that speaks to the fact that, āIf I know that my family or my community, not just in the UK but abroad can benefit, then that would really motivate me and build trust that actually youāre not just here to benefit me as an individual, but youāre here to benefit my community as a whole, and therefore, yes, Iām going to be more trusting of this programme and be more motivated to take part.ā
Naimah: I just wanted to go briefly back, Moestak, you mentioned cultural norms, and I wanted to talk about the cultural norm in societies where maybe people may marry someone from the same ancestor, and what the societal fallout from these practices might be.
Moestak: The stigma and the stereotypes often for communities comes from those beliefs and messages that are often sometimes not even backed up with scientific evidence. It can be seen as Islamophobic sometimes of Muslim communities that practice that. But also I think whatās important to understand is that concept around hereditary conditions and how that can determine oneās health, and itās not really fully appreciated or desired. And so as a result, for example, a lot of people refuse to even have those early onset maternal testing for the foetus. My personal experience, I have three children, teenagers now, and I refused those tests as well, because my belief and my religious beliefs would kind of not align with being able to terminate a foetus if there were some genetic conditions. And so I think that is often not understood and made very clear to communities, and build on their beliefs and attitudes and values. And so those are the kind of cultural norms that are not fully understood.
But also the opposite side of that actually around being able to prevent a good life for somebody or a bad life for somebody, and being able to prevent genetic conditions is also part of the religion on the flipside, but again itās not creating that link. That cultural beliefs is not understood. I think also the community implications around the stigma. I mean, autismās a big issue in the Samali community, and I remember years ago when I was working in education, we had a big issue around even acknowledgement of diagnosis and referrals, and itās because of the stigma. Those perceptions do exist within communities that if someone has a genetic condition or ill health or a disease, itās almost like being a black sheep in the community. And so itās being able to build on those desires of the community wanting to be healthy and well, I think is not often understood.
Naimah: And do you think itās partly as well education of healthcare professionals to communicate in a really culturally sensitive way?
Moestak: Yes, exactly, thatās exactly what it is. Itās missed opportunities really that we can build on. In that particular example of autism within the community, I was able to do a really positive piece of work with the community, and building on their interest and their skills, but using my own lived experience and understanding and knowledge, and being able to inform that within education sector but also the health sector, and providing that training and upskilling. And there is unfortunately a lack of diversity within the workforce if you look at the NHS. The lower level kind of cleaning and porter staff are ethnic minorities. And so it is about using those clinicians, as I mentioned earlier, that are coming from those communities are the forefront.
Weāve recently had a really positive piece of work in Bristol around letās talk about MMR, and we had a cohort of unvaccinated community, a Somali community, young people between the age of 16 to 25, and we worked with a Somali clinician, who led on that piece of work, and it was absolutely amazing. The young people as a result trusted her information and took up ā but again also another thing thatās important is that a lot of data in the medical system is missing. I for one migrated here from the Netherlands, where I came there as a refugee at the age of three years old. My medical history is completely missing in both the UK records but also in the Netherlands, so I didnāt know if I had MMR vaccine. So, itās a lot of gaps in information that people have, newly arrived communities that still need to constantly be updated and informed and education awareness raised with those communities.
Naimah: Anna, I wonder if you wanted to add anything onto that point.
Anna: Itās really difficult with that mistrust and sort of how closed the GRT community is to getting that information in, and I think to getting that information understood as well and to make it seem like itās important. Because family is the most important thing, people are accepted the way that they are. You know, if weāre talking about autism, people are accepted the way that they are, and it is a bit like, you know, āThereās nothing wrong with my child, how dare you suggest that there is?ā That testing isnāt done because the access to healthcare is so difficult, because people canāt register with GPs, because they canāt access maternity care, they canāt access postnatal care. Because they canāt register with the GP, theyāre not on the system, and then the records donāt exist. Still now thereās birth records and death records that do not exist for these people within the communities, never mind medical history throughout their lives.
Naimah: I think it really highlights a lot of gaps, doesnāt it? Aman, do you want to add anything to that question?
Anna: Your opening remarks is that itās a cultural norm in all societies, and we see even within the royal family in the UK, that it seems to be that any disparaging comments are targeted towards certain communities, and even then unfairly. I mean, often itās associated with Muslim communities, but I would say the majority of Muslim communities donāt practice marrying someone from within the same ancestor. Itās certain cultural communities who do practice this. Having said that, even that practice shouldnāt be seen in a disparaging way, because itās how those communities live their lives, and so we should be respectful of that and not speak in any way disparaging towards that community. And I think we have responsibility ā ācos obviously nationally the conversation then moves onto increased risks of genetic disorders, and so we should be very matter of fact about what the percentage increase is when it comes to the likelihood of genetic disorders within families who marry with the same ancestor.
Because what happens is, if weāre not very clear with what the actual facts are with regards to the increased risk of genetic order then even within the community which practices marrying someone from the same ancestor, that figure can be inflated, and so this perpetuates fear and perpetuates the stigma even more. Whereas if we are just matter of fact, āThis is the increased risk of genetic disorders,ā and leave it there, then the communities can decide and theyāll have a more informed position. I think the figures are an increase from two to six percent increase, but if you were to ask people within the community, āWhatās the increase of genetic disorders if youāre marrying someone from the same ancestor?ā they might think itās 40 percent or 50 percent or a really high figure. So, thatās something that we need to work towards better understanding, which will lead to removal of that stigma as well.
Anna: Again, thatās something that we see in the GRT community as well, thereās been research done by a woman called Sally Anne Lynch into cousin marriage within the Irish travelling community, and when they tested people, they found more than 90 genetic conditions that are present within peopleās DNA within that community that just arenāt tested at birth. And I think, you know, youāre right, itās something that is not talked about, because outside of these communities itās seen as wrong and itās not seen as something thatās normal. Itās seen as abnormal. But within this community, it is very normal and itās very accepted. But then the testing isnāt done because of the access to healthcare.
Naimah: I think it just seems like it does kind of boil down to education and educating healthcare professionals that it is kind of normal practices. Aman, did you want to add something else?
Aman: Yeah, Anna made a really good point about testing. I think thereās something that is a gap in the service that we probably donāt provide more widely is that, when it comes to people who practice marriage within the same ancestor in other countries, testing is very normal. So, I know thereās many countries around the world where itās very standard practice and even a requirement in certain countries that you must be tested before you get married, and so maybe thatās something that we can learn from in the UK.
Moestak: I think itās important to understand that some communities, decision making of consent is sometimes done by the head of the family, and I think that that is not fully understood as well, and often can be a barrier to participation. And I think that thereās an element of empowerness that is needed, particularly around women that need that empowerment model around consent of decision making around their testing and genetic testing, and just medical consent.
Naimah: Thatās an excellent point as well, thanks Moestak.
So, I know weāve touched on aspects of this already, but I wanted to finish on this question, how can meaningful community engagement foster trust and collaboration in genomic research and healthcare initiatives?
Aman: I think one of the things that I would really improve is just awareness around genomic healthcare and genomics in general. Itās a learning curve thatās going to happen within communities at different rates, and we need to be mindful of this because that rate will determine also health inequities that are experienced by those communities as well. So, we need to make sure that we are adequately approaching all communities to the best of our abilities. Having said that, target maybe more resourcing and educational opportunities for communities which have been underrepresented in health research and in genomic health research as well primarily, so we need to sort of prioritise certain communities in regards to our community outreach, because then weāll dispel any myths that people might have and work towards chipping away at the mistrust that certain communities may feel towards just healthcare in general, but more particularly about genomic healthcare, ācos genomic healthcare brings up some unique challenges and some unique perspectives within communities.
So, thereās a number of fears about the future, but also misgivings about healthcare in the past as well that we need to acknowledge. So, by having community engagement initiatives, which are prioritised from the beginning and not just an afterthought, we can go a long way towards getting over some of the challenges of the past, but also not making new challenges for us in the future.
Anna: I think as a whole, the UK has got a long way to go with building trust with the GRT community. I think itās going to take some time. They still are one of the most marginalised communities. For example, in the area that I live, there was a GRT funeral going on a few weeks ago, and all the pub shut because they didnāt want GRT communities in their establishments, and there is no other community or minority that that would happen with now. So, I think there is still quite a long way to go to gain the trust of the GRT community. And in terms of healthcare, I think we need to go right back to the start and learn about these communities, and understand their cultures and their practices, and how they work without that judgement. Living a nomadic lifestyle is still criminalised. There needs to be a decriminalisation around these communities before we can even start to begin to work out how to go there and allow them to access healthcare and knowledge and information around genetic conditions, and around health and mental health.
Itās going to be a very long road from here, but I think what we can start doing is to start that destigmatisation. If you are a doctor and somebody turns up in your surgery identifying as someone from the GRT community, understanding the background they come from, and not having all those prejudices, you know, which is very difficult to do, to get rid of those thoughts that you already have about someone. I think we need to make a real effort to start, and I think there needs to be changes within the NHS in order for people to access healthcare better. I think the resources that are given and the information that goes out needs to be more specifically tailored to these communities if thatās who youāre trying to engage with, because thereās so much that goes on in the community thatās not known outside of the community, and itās not spoken about, and within different GRT communities as well. You know, there are different GRT communities all around the UK, and what goes on in them is not known to other GRT communities either.
So, itās about being specific with the information that youāre getting out, with who youāre actually targeting. And I think a bit like we were saying earlier, itās the women, you know. The women have childcare responsibilities almost all of the time, and they are the ones who bring up the children, but theyāre not necessarily the ones that make the decisions about the children or the child healthcare. You know, women are expected to do jobs in the morning. Women are not available before 11 oāclock in the morning. So, think about when youāre making appointments for. Think about when youāre going. I think it is going to be a long, long road before we get there, you know, with building trust and getting the information out there, but I think we can make a start.
Naimah: Yeah, it does seem like there is lots of ways we can start tackling it slowly. Moestak, I wonder if you had anything you wanted to add.
Moestak: As a public health specialist, you know, weāve not been taught genomic medicine or genomic health at all in terms of how that can benefit and radically change the NHS and improve determinants of health, so thatās a massive gap of knowledge within the healthcare sector and professionals. But I think in terms of addressing the historic mistrust, I think there needs to be an acknowledgement and a real openness around the historic, you know, abuse and unethical practices that have existed within health. There are other countries that are much more advanced in that and really embedding that within communities through pledges. That long-term kind of piece of work for me is missing. You know, itās that wider education piece thatās missing that needs to be really embedded in the culture.
But I think also investing in the infrastructure in the community. Like far too often, if the long-term vision is not there, communities are reluctant to get involved and have trust within that, so I think thatās an important part as well. And I think itās also about demonstrating the benefits of genomic medicine. I think that needs to be done in a community level way, through storytelling. I know that thereās now a lot of development around cancer treatments around genomics, but I think itās about having those people who have those lived experiences from different communities to be able to share the benefits and demonstrate that through their way, and being appropriately reimbursed as well. I think thatās really important.
I think generally, I think thereās a long way weāve got to go. Iāll never forget when I went to Vancouver on a conference around health, and there was a lot of reconciliation there, where there was really acknowledgement, and the indigenous communities there that have a lot of health disparities were able to kind of overcome some of that and start building as a community and addressing tackling health inequalities because that trust was built and that acknowledgement from high up, from government level, all the way trickled down to local. I think also patient centred approaches around ā like we mentioned, we talked about linking the cultural norms and the values and the beliefs that people have, and the skills and the assets that they have to be able to lead on these solutions themselves, that really needs to be embedded to build trust.
Aman touched on the perception around what could be done with genomic data. I donāt know if Aman wants to elaborate a bit on that, but thatās really important. Itās a big barrier. Itās how do we create transparent ways of storing data, but also use various ways of communication. It doesnāt have to be traditional reports. It could be through podcasts. It could be like community messaging.
Naimah: Yeah, I think thatās a really important point. Aman, did you want to come in on that?
Aman: Yeah, I think sharing the stories of the past in an appropriate setting, in an appropriate manner as well ā ācos itās a bit of a double edged sword, ācos you donāt want to scare people who are unfamiliar with these stories, but at the same time thereās a moral responsibility for all of us involved in this space to speak about these issues, one from the perspective of acknowledging whatās happened in the past, so then people feel like, āOkay, youāre not trying to hide anything here,ā but from the perspective of also that we need to make sure that we donāt repeat some of the mistakes in the future, and that as people involved in genomic healthcare and involved in this space, that weāre cognisant of these misgivings in the past, and weāre cognisant of our responsibility to safeguard communities in the future.
Naimah: Okay, so weāre going to wrap up there. Thank you so much to our guests, Anna Smith, Aman Ali and Moestak Hussein for joining me today as we discussed the barriers to access to genomic medicine for diverse communities, and the impact it has on these communities. If youād like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iāve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.
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Pharmacogenomics plays a critical role in personalised medicine, as some adverse drug reactions are genetically determined. Adverse drugs reactions (ADRs) account for 6.5% of hospital admissions in the UK, and the application of pharmacogenomics to look at an individuals response to drugs can significantly enhance patient outcomes and safety.
In this episode, our guests discuss how genomic testing can identify patients who will respond to medications and those who may have adverse reactions. We hear more about Genomics England's collaboration with the Medicines and Healthcare products Regulatory Agency in the Yellow Card Biobank and our guests discuss the challenges of implementing pharmacogenomics into the healthcare system.
Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Anita Hanson, Research Matron and the Lead Research Nurse for clinical pharmacology at Liverpool University Hospitals NHS Foundation Trust, and Professor Bill Newman, Professor of translational genomic medicine at the Manchester Center for Genomic Medicine, and Professor Matt Brown, Chief Scientific Officer at Genomics England.
"I think weāre moving to a place where, rather than just doing that one test that might be relevant to one drug, weād be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when itās required, so that theyāre not waiting for the results of a genetic test, itās immediately within their healthcare record."
You can watch this video learn more about Jane's lived experience with Stevens-Johnson syndrome, on The Academy of Medical Sciences' (AMS) YouTube channel. The story, co-produced by Areeba Hanif from AMS, provides an in-depth look at Jane's journey.
Want to learn more about personalised medicine? Listen to our Genomics 101 episode where Professor Matt Brown explains what it is in less than 5 minutes: Genomics 101: What is personalised medicine?
You can download the transcript or read it below.
Vivienne: Hello and welcome to Behind the Genes.
Bill: What weāve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. Theyāve been easier to identify and thereās a clear relationship between some drugs and some genetic changes where that information is useful. So, a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if youāre given that treatment, then you can end up on intensive care and die, so itās a really significant side effect. But as you say, the most common side effects arenāt necessarily fatal, but they can have a huge impact upon people and on their wellbeing.
Vivienne: My nameās Vivienne Parry and Iām head of public engagement at Genomics England, and today weāll be discussing the critical role of pharmacogenomics in personalised medicine, highlighting its impact on how well medicines work, their safety, and on patient care. Iām joined today by Professor Bill Newman, professor of translational genomic medicine at the Manchester Centre for Genomic Medicine, Anita Hanson, research matron, a fabulous title, and lead research nurse for clinical pharmacology at the Liverpool University Hospitalās NHS Foundation Trust, and Professor Matt Brown, chief scientific officer for Genomics England. And just remember, if you enjoy todayās episode, weād love your support, so please like, share and rate us on wherever you listen to your podcasts.
So, first question to you, Bill, what is pharmacogenomics?
Bill: Thanks Viv. I think there are lots of different definitions, but how I think of pharmacogenetics is by using genetic information to inform how we prescribe drugs, so that they can be safer and more effective. And weāre talking about genetic changes that are passed down through families, so these are changes that are found in lots of individuals. We all carry changes in our genes that are important in how we transform and metabolise medicines, and how our bodies respond to them.
Vivienne: Now, you said pharmacogenetics. Is it one of those medicine things like tomato, tomato, or is there a real difference between pharmacogenetics and pharmacogenomics?
Bill: So, people, as you can imagine, do get quite irate about this sort of thing, and there are lots of people that would contest that there is a really big important difference. I suppose that pharmacogenetics is more when youāre looking at single changes in a relatively small number of genes, whereas pharmacogenomics is a broader definition, which can involve looking at the whole genome, lots of genes, and also whether those genes are switched on or switched off, so the expression levels of those genes as well would encompass pharmacogenomics. But ultimately itās using genetic information to make drug prescription safer and more effective.
Vivienne: So, weāre going to call it pharmacogenomics and weāre talking about everything, thatās it, weāll go for it. So Matt, just explain if you would the link between pharmacogenomics and personalised medicine. And I know that youāve done a big Genomics 101 episode about personalised medicine, but just very briefly, whatās the link between the two?
Matt: So, personalised medicineās about using the right dose of the right drug for the right individual. And so pharmacogenomics helps you with not only ensuring that you give a medication which doesnāt cause problems for the person who receives it, so an adverse drug reaction, but also that theyāre actually getting the right dose. Of course, peopleās ability to metabolise, activate and respond to drugs genetically is often genetically determined, and so sometimes you need to adjust the dose up or down according to a personās genetic background.
Vivienne: Now, one of the things that weāve become very aware of is adverse drug reactions, and I think they account for something like six and a half percent of all hospital admissions in the UK, so itās absolutely huge. Is that genetically determined adverse drug reactions?
Matt: So, the answer to that is we believe so. Thereās quite a bit of data to show that you can reduce the risk of people needing a hospital admission by screening genetic markers, and a lot of the very severe reactions that lead to people being admitted to hospital are very strongly genetically determined. So for example, there are HLA types that affect the risk of adverse drug reactions to commonly used medications for gout, for epilepsy, some HIV medications and so on, where in many health services around the world, including in England, there are already tests available to help prevent those leading to severe reactions. Itās likely though that actually the tests we have available only represent a small fraction of the total preventable adverse drug reactions were we to have a formal pre-emptive pharmacogenomics screening programme.
Vivienne: Now, I should say that not all adverse drug reactions are genetic in origin. I mean, I remember a rather nasty incident on the night when I got my exam results for my finals, and Iād actually had a big bee sting and Iād been prescribed antihistamines, and I went out and I drank rather a lot to celebrate, and oh my goodness me, I was rather ill [laughter]. So, you know, not all adverse drug reactions are genetic in origin. There are other things that interact as well, just to make that clear to people.
Matt: Yes, I think thatās more an interaction than an adverse drug reaction. In fact frankly, the most common adverse drug reaction in hospitals is probably through excess amounts of water, and thatās not medically determined, thatās the prescription.
Vivienne: Let me now come to Anita. So, you talk to patients all the time about pharmacogenomics in your role. Youāve been very much involved in patient and public involvement groups at the Wolfson Centre for Personalised Medicine in Liverpool. What do patients think about pharmacogenomics? Is it something they welcome?
Anita: I think they do welcome pharmacogenomics, especially so with some of the patients whoāve experienced some of the more serious, life threatening reactions. And so one of our patients has been doing some work with the Academy of Medical Sciences, and she presented to the Sir Colin Dollery lecture in 2022, and she shared her story of having an adverse drug reaction and the importance of pharmacogenomics, and the impact that pharmacogenomics can have on patient care.
Vivienne: Now, I think that was Stevens-Johnson syndrome. Weāre going to hear in a moment from somebody who did experience Stevens-Johnsonās, but just tell us briefly what that is.
Anita: Stevens-Johnson syndrome is a potentially life threatening reaction that can be caused by a viral infection, but is more commonly caused by a medicine. There are certain groups of medicines that can cause this reaction, such as antibiotics or anticonvulsants, nonsteroidal anti-inflammatories, and also a drug called allopurinol, which is used to treat gout. Patients have really serious side effects to this condition, and theyāre often left with long-term health complications. The morbidity and mortality is considerable as well, and patients often spend a lot of time in hospital and take a long time to recover.
Vivienne: And letās now hear from Jane Burns for someone with lived experience of that Stevens-Johnson syndrome. When Jane Burns was 19, the medicine she took for her epilepsy was changed.
Jane: I remember waking up and feeling really hot, and I was hallucinating, so I was taken to the Royal Liverpool Hospital emergency department by my parents. When I reached A&E, I had a temperature of 40 degrees Celsius. I was given Piriton and paracetamol, and the dermatologist was contacted. My mum had taken my medication to hospital and explained the changeover process with my epilepsy medication. A decision was made to discontinue the Tegretol and I was kept in for observation. Quite rapidly, the rash was changing. Blisters were forming all over my body, my mouth was sore and my jaw ached. My temperature remained very high. It was at this point that Stevens-Johnson syndrome, or SJS, was diagnosed.
Over the next few days, my condition deteriorated rapidly. The rash became deeper in colour. Some of the blisters had burst, but some got larger. I developed ulcers on my mouth and it was extremely painful. I started to lose my hair and my fingernails. As I had now lost 65 percent of my skin, a diagnosis of toxic epidermal necrolysis, or TEN, was made. Survivors of SJS TEN often suffer with long-term visible physical complications, but it is important to also be aware of the psychological effects, with some patients experiencing post-traumatic stress disorder. Itās only as I get older that I realise how extremely lucky I am to have survived. Due to medical and nursing expertise, and the research being conducted at the time, my SJS was diagnosed quickly and the medication stopped. This undoubtedly saved my life.
Vivienne: Now, youāve been looking at the development of a passport in collaborating with the AMS and the MHRA. Tell me a bit more about that.
Anita: Yes, we set up a patient group at the Wolfson Centre for Personalised Medicine approximately 12 years ago, and Professor Sir Munir Pirmohamed and I, we wanted to explore a little bit more about what was important to patients, really to complement all the scientific and clinical research activity within pharmacogenomics. And patients recognised that, alongside the pharmacogenomic testing, they recognised healthcare professionals didnāt really have an awareness of such serious reactions like Stevens-Johnson syndrome, and so they said they would benefit from having a My SJS Passport, which is a booklet that can summarise all of the important information about their care post-discharge, and this can then be used to coordinate and manage their long-term healthcare problems post-discharge and beyond. And so this was designed by survivors for survivors, and it was then evaluated as part of my PhD, and the findings from the work suggest that the passport is like the patientās voice, and it really does kind of validate their diagnosis and raises awareness of SJS amongst healthcare professionals. So, really excellent findings from the research, and the patients think it's a wonderful benefit to them.
Vivienne: So, itās a bit like a kind of paper version of the bracelet that you sometimes see people wearing that are on steroids, for instance.
Anita: It is like that, and itās wonderful because itās a handheld source of valuable information that they can share with healthcare professionals. And this is particularly important if theyāre admitted in an emergency and they canāt speak for themselves. And so the passport has all that valuable information, so that patients arenāt prescribed that drug again, so it prevents them experiencing a serious adverse drug reaction again.
Vivienne: So, Stevens-Johnson, Bill, is a really scary side effect, but what about the day to day benefits of pharmacogenomics for patients?
Bill: So, what weāve seen is that the limited adoption so far in the UK and other countries has focused particularly on severe adverse drug reactions. Theyāve been easier to identify and thereās a clear relationship between some drugs and some genetic changes where that information is useful. So a good example has been the recent adoption of pharmacogenetic testing for a gene called DPYD for patients undergoing cancer treatment, particularly breast and bowel cancer. And if you have an absence of the enzyme that that gene makes, if youāre given that treatment, then you can end up on intensive care and die, so itās a really significant side effect. But as you say, the most common side effects arenāt necessarily fatal, but they can have a huge impact upon people and on their wellbeing.
And itās not just in terms of side effects. Itās in terms of the effectiveness of the medicine. Because if a person is prescribed a medicine that doesnāt or isnāt going to work for them then it can take them longer to recover, to get onto the right medicine. That can have all sorts of detrimental effects. And so when weāre thinking about introducing pharmacogenetics more broadly rather than just on a single drug or a single gene basis, weāre thinking about that for common drugs like antidepressants, painkillers, statins, the drugs that GPs are often prescribing on a regular basis to a whole range of patients.
Vivienne: So, to go back to you, Anita, weāre really talking about dose here, arenāt we, whether you need twice the dose or half the dose depending on how quickly your body metabolises that particular medicine. How do patients view that?
Anita: Well, the patient in question who presented for the Academy of Medical Sciences, I mean, her take on this was, she thinks pharmacogenetics is wonderful because it will allow doctors and nurses to then prescribe the right drug, but also to adapt the dose accordingly to make sure that they get the best outcome, which provides the maximum benefit while also minimising any potential harm. And so from her perspective, that was one of the real benefits of pharmacogenomics. But she also highlighted about the benefits for future generations, the fear of her son taking the same medicine and experiencing the same reaction. And so I think her concerns were, if we have pharmacogenetic testing for a panel of medicines, as Bill mentioned then, then perhaps this would be fantastic for our children as they grow up, and we can identify and predict and prevent these type of reactions happening to future generations.
Vivienne: And some of these drugs, Bill, are really very common indeed, something like codeine. Just tell us about codeine, ācos itās something ā whenever I tell this to friends [laughter], theyāre always completely entranced by the idea that some people donāt need nearly as much codeine as others.
Bill: Yeah, so codeine is a drug thatās very commonly used as a painkiller. To have its real effect, it needs to be converted in the body to a different drug called morphine, and that is done by an enzyme which is made by a gene called CYP2D6. And we all carry changes in CYP2D6, and the frequency of those variants, whether they make the gene work too much or whether they make it work too little, they vary enormously across the world, so that if you go to parts of Africa, about 30 percent of the population will make more of the CYP2D6, and so they will convert the codeine much more quickly, whereas if you go to the UK, maybe up to ten percent of the white population in the UK just wonāt be converting codeine to morphine at all, so they wonāt get any benefit from the drug. So at both ends, you have some people that donāt respond and some people that respond a little bit too much so that they need either an alternative drug or they need a different dose.
Vivienne: So, all those people who say, you know, āMy headache hasnāt been touched by this painkiller,ā and we say, āWhat a wimp youāre being,ā actually, itās to do with genetics.
Bill: Yeah, absolutely. Thereās a biological reason why people donāt ā not for everybody, but for a significant number of people, thatās absolutely right, and we can be far more tailored in how we prescribe medication, and get people onto painkillers that work for them much more quickly.
Vivienne: And thatās so interesting that it varies by where you come from in the world, because that means we need to give particular attention ā and Iām thinking, Anita, to working with patients from different community groups, to make sure that they understand the need for pharmacogenomics.
Anita: I think thatās really important, Vivienne, and I think we are now having discussions with the likes of Canada SJS awareness group, and also people have been in touch with me from South Africa because people have requested the passport now to be used in different countries, because they think itās a wonderful tool, and itās about raising awareness of pharmacogenomics and the potential benefits of that, and being able to share the tools that weāve got to help patients once theyāve experienced a serious reaction.
Vivienne: So, pharmacogenomics clearly is important in the prevention of adverse drug reactions, better and more accurate prescribing, reduced medicines wastage. Does this mean that itās also going to save money, Bill, for the NHS?
Bill: Potentially. It should do if itās applied properly, but thereās lots of work to make sure that not only are we using the right evidence and using the right types of tests in the laboratory, but weāre getting the information to prescribers, so to GPs, to pharmacists, to hospital doctors, in a way that is understandable and meaningful, such that they can then act upon that information. So, the money will only be saved and then can be reused for healthcare if the whole process and the whole pathway works, and that information is used effectively.
Vivienne: So, a lot of research to make sure that all of that is in place, and to demonstrate the potential cost savings.
Bill: Yes. I mean, there are very nice studies that have been done already in parts of the world that have shown that the savings that could be accrued for applying pharmacogenetics across common conditions like depression, like in patients to prevent secondary types of strokes, are enormous. They run into hundreds of millions of pounds or dollars. But there is an initial investment that is required to make sure that we have the testing in place, that we have the digital pathways to move the information in place, and that thereās the education and training, so that health professionals know how to use the information. But the potential is absolutely enormous.
Vivienne: Matt, can I turn now to the yellow card. So, people will be very familiar with the yellow card system. So, if you have an adverse reaction, you can send a yellow card in ā I mean, literally, it is a yellow card [laughter]. It does exactly what it says on the tin. You send a yellow card to the MHRA, and they note if thereās been an adverse effect of a particular medicine. But Genomics England is teaming up with the MHRA to do something more with yellow cards, and weāre also doing this with the Yellow Card Biobank. Tell us a bit more.
Matt: So, yellow cardās a great scheme that was set up decades ago, initially starting off, as you said, with literally yellow cards, but now actually most submissions actually come online. And itās important to note that submissions can come not just from healthcare providers, but majority of submissions actually come from patients themselves, and that people should feel free, if they feel theyāve had an adverse drug reaction, to report that themselves rather than necessarily depending on a medical practitioner or the healthcare provider to create that report. So, Genomics England is partnering with the MHRA in building whatās called the Yellow Card Biobank, the goal of which is to identify genetic markers for adverse drug reactions earlier than has occurred in the past, so that we can then introduce genetic tests to prevent these adverse drug reactions much sooner than has occurred previously.
So, what weāre doing is basically at the moment weāre doing a pilot, but the ultimate plan is that in future, patients who report a serious adverse drug reaction through the Yellow Card Biobank will be asked to provide a sample, a blood sample, that we then screen. We do a whole genome sequence on it, and then combine these with patients whoāve had like adverse drug reactions and identify genetic markers for that adverse drug reaction medication earlier, that can then be introduced into clinical practice earlier. And this should reduce by decades the amount of time between when adverse drug reactions first start occurring with medications and us then being able to translate that into a preventative mechanism.
Vivienne: And will that scheme discover, do you think, new interactions that you didnāt know about before? Or do you expect it to turn up what you already know about?
Matt: No, I really think thereās a lot of discovery that is yet to happen here. In particular, even for drugs that we know cause adverse drug reactions, mostly theyāve only been studied in people of European ancestry and often in East Asian ancestry, but in many other ancestries that are really important in the global population and in the UK population, like African ancestry and South Asian ancestries, we have very little data. And even within Africa, which is an area which is genetically diverse as the rest of the world put together, we really donāt know what different ethnicities within Africa, actually what their genetic background is with regard to adverse drug reactions.
The other thing Iād say is that there are a lot of new medications which have simply not been studied well enough. And lastly, that at the moment people are focused on adverse drug reactions being due to single genetic variants, when we know from the model of most human diseases that most human diseases are actually caused by combinations of genetic variants interacting with one another, so-called common disease type genetics, and that probably is similarly important with regard to pharmacogenomics as it is to overall human diseases. That is, itās far more common that these are actually due to common variants interacting with one another rather than the rare variants that weāve been studying to date.
Vivienne: So, itās a kind of cocktail effect, if you like. You know, you need lots of genes working together and that will produce a reaction that you may not have expected if youād looked at a single gene alone.
Matt: Thatās absolutely correct, and thereās an increasing amount of evidence to show that that is the case with medications, but itās really very early days for research in that field. And the Yellow Card Biobank will be one of many approaches that will discover these genetic variants in years to come.
Vivienne: Now, Mattās a research scientist. Bill, youāre on the frontline in the NHS. How quickly can this sort of finding be translated into care for people in the NHS?
Bill: So, really quickly is the simple answer to that, Viv. If we look at examples from a number of years ago, thereās a drug called azathioprine that Matt has used lots in some of his patients. In rheumatology, itās used for patients with inflammatory bowel disease. And the first studies that showed that there was a gene that was relevant to having bad reactions to that drug came out in the 1980s, but it wasnāt until well into this century, so probably 30-plus years later that we were routinely using that test in clinical medicine. So, there was an enormous lot of hesitancy about adopting that type of testing, and a bit of uncertainty. If you move forward to work that our colleague Munir Pirmohamed in Liverpool has done with colleagues in Australia like Simon Mallal around HIV medicine, there was this discovery that a drug called abacavir, that if you carried a particular genetic change, that you had a much higher risk of having a really severe reaction to that. The adoption from the initial discovery to routine, worldwide testing happened within four years.
So, already weāve seen a significant change in the appetite to move quickly to adopt this type of testing, and I see certainly within the NHS and within other health systems around the world, a real desire to adopt pharmacogenetics into routine clinical practice quickly and at scale, but also as part of a broader package of care, which doesnāt just solely focus on genetics, but thinks about all the other parts that are important in how we respond to medication. So, making sure weāre not on unusual combinations of drugs, or that weāre taking our medicine at the right time and with food or not with food, and all of those other things that are really important. And if you link that to the pharmacogenetics, weāre going to have a much safer, more effective medicines world.
Vivienne: I think one of the joys of working at Genomics England is that you see some of this work really going into clinical practice very fast indeed. And I should say actually that the Wolfson Centre for Personalised Medicine, the PPI group that Anita looks after so well, theyāve been very important in recruiting people to Yellow Card Biobank. And if anyoneās listening to this, Matt, and wants to be part of this, how do they get involved? Or is it simply through the yellow card?
Matt: So at the moment, the Yellow Card Biobank is focusing on alopurinol.
Vivienne: So, thatās a medicine you take for gout.
Matt: Which I use a lot in my rheumatology clinical practice. And direct acting oral anticoagulants, DOACs, which are used for vascular disease therapies and haemorrhage as a result of that. So, the contact details are available through the MHRA website, but I think more importantly, itās just that people be aware of the yellow card system itself, and that if they do experience adverse drug reactions, that they do actually complete a report form, ācos I think still actually a lot of adverse drug reactions go unreported.
Vivienne: Iām forgetting of course that we see Matt all the time in the Genomics England office and we donāt think that he has any other home [laughter] than Genomics England, but of course he still sees some patients in rheumatology clinic. So, I want to now look to the future. I mean, Iām, as you both know, a huge enthusiast for pharmacogenomics, ācos itās the thing that actually, when you talk to patients or just the general public, they just get it straight away. They canāt think why, if you knew about pharmacogenomics, why you wouldnāt want to do it. But itās not necessarily an easy thing to do. How can we move in the future, Bill, to a more proactive approach for pharmacogenomics testing? Where would we start?
Bill: Yes, so I think weāve built up really good confidence that pharmacogenetics is a good thing to be doing. Currently, weāre doing that predominantly at the point when a patient needs a particular medicine. Thatās the time that you would think about doing a genetic test. And previously, that genetic test would only be relevant for that specific drug. I think weāre moving to a place where, rather than just doing that one test that might be relevant to one drug, weād be able to do a test which at the same price would generate information that could be relevant at further points in your life if you were requiring different types of medicine. So, that information would then be available in your hospital record, in your GP record, that you could have access to it yourself. And then I think ultimately what we would really love to get to a point is where everybody across the whole population just has that information to hand when itās required, so that theyāre not waiting for the results of a genetic test, itās immediately within their healthcare record. Thatās what weād call pre-emptive pharmacogenetic testing, and I think thatās the golden land that we want to reach.
Vivienne: So for instance, I might have it on my NHS app, and when I go to a doctor and they prescribe something, I show my app to the GP, or something pops up on the GPās screen, or maybe itās something that pops up on the pharmacistās screen.
Bill: I think thatās right. I think thatās what weāre looking to get to that point. We know that colleagues in the Netherlands have made some great progress at developing pathways around that. Thereās a lot of public support for that. And pharmacists are very engaged in that. In the UK, the pharmacists, over the last few years, have really taken a very active role to really push forward this area of medicine, and this should be seen as something that is relevant to all people, and all health professionals should be engaged with it.
Vivienne: And on a scale of one to ten, how difficult is it going to be to implement in the NHS?
Bill: So, thatās a difficult question. I think the first thing is identifying what the challenges are. So I have not given you a number, Iāve turned into a politician, not answered the question. So, I think what has happened over the last few years, and some of our work within the NHS Network of Excellence in pharmacogenetics and some of the other programmes of work that have been going on, is a really good, honest look at what it is we need to do to try to achieve pharmacogenetics implementation and routine use. I donāt think the challenge is going to be predominantly in the laboratory. I think weāve got phenomenal laboratories. I think weāve got great people doing great genetic testing. I think the biggest challenges are going to be about how you present the data, and that data is accessible. And then ensuring that health professionals really feel that this is information that isnāt getting in the way of their clinical practice, but really making a difference and enhancing it, and of benefit both to the healthcare system but more importantly to the patients.
Vivienne: Now, when I hear you both talk, my mind turns to drug discovery and research, and Matt, Iām quite sure that thatās right at the top of your mind. Tell us how pharmacogenomics can help in drug discovery and research.
Matt: So, pharmacogenomics, I think actually just genetic profiling of diseases in itself just to start off with is actually a really good way of identifying new potential therapeutic targets, and also from derisking drug development programmes by highlighting likely adverse drug reactions of medications that are being considered for therapeutic trials, or targets that are being considered for therapeutic development. Pharmacogenomics beyond that is actually largely about ā well, it enables drug development programmes by enabling you to target people who are more likely to respond, and avoid people who are more likely to have adverse drug reactions. And so that therapeutic index of the balance between likely efficacy versus likely toxicity, genetics can really play into that and enable medications to be used where otherwise they might have failed.
This is most apparent I think in the cancer world. A classic example there, for example, is the development of a class of medications called EGFR inhibitors, which were developed for lung cancer, and in the initial cancer trials, actually were demonstrated to be ineffective, until people trialled them in East Asia and found that they were effective, and that that turns out to be because the type of cancers that respond to them are those that have mutations in the EGFR gene, and that thatās common in East Asians. We now know that, wherever you are in the world, whether youāre East Asian or European or whatever, if you have a lung adenocarcinoma with an EGFR mutation, youāre very likely to respond to these medications. And so that pharmacogenomic discovery basically rescued a class of medication which is now probably the most widely used medication for lung adenocarcinomas, so a huge beneficial effect. And that example is repeated across multiple different cancer types, cancer medication types, and Iām sure in other fields weāll see that with expansive new medications coming in for molecularly targeted therapies in particular.
Vivienne: So, smaller and more effective trials rather than larger trials that perhaps seem not to work but actually havenāt been tailored enough to the patients that are most likely to benefit.
Matt: Yeah, well, particularly now that drug development programmes tend to be very targeted at specific genetic targets, pharmacogenetics is much more likely to play a role in identifying patients who are going to respond to those medications. So, I think many people in the drug development world would like to see that, for any significant drug development programme, thereās a proper associated pharmacogenomic programme to come up with molecular markers predicting a response.
Vivienne: Weāre going to wrap up there. Thank you so much to our guests, Bill Newman, Anita Hanson, Matt Brown, and our patient Jane Burns. Thank you so much for joining us today to discuss pharmacogenomics in personalised medicine, and the benefits, the challenges and the future prospects for integrating pharmacogenomics into healthcare systems. And if youād like to hear more podcasts like this, please subscribe to Behind the Genes. Itās on your favourite podcast app. Thank you so much for listening. Iāve been your host, Vivienne Parry. This podcast was edited by Bill Griffin at Ventoux Digital and produced by the wonderful Naimah. Bye for now.
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In this episode, we delve into the impact of the new groundbreaking research uncovering the RNU4-2 genetic variant linked to neurodevelopmental conditions. The discovery, made possible through whole genome sequencing, highlights a genetic change in the RNU4-2 gene that affects about 1 in 200 undiagnosed children with neurodevelopmental conditions, making it more prevalent than previously thought. This discovery represents one of the most common single-gene genetic causes of such conditions.
Our host, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Lindsay Pearse who shares her journey through the diagnosis of her son Lars. They are also joined by Sarah Wynn, CEO of Unique, and Emma Baple, Clinical Genetics Doctor and Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub.
We also hear from the 2 research groups who independently discovered the findings:
Dr Andrew Mumford, Professor of Haematology at the University of BristolLink to the research paper: Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders Assistant Professor Nicky Whiffin, Big Data Institute and Centre for Human Genetics at the University of OxfordLink to the research paper: De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndromeTo access resources mentioned in this podcast:
Unique provides support, information and networking to families affected by rare chromosome and gene disorders - for more information and support visit Unique's website.Connect with other parents of children carrying a variation in RNU4-2 on the RNU4-2 Facebook group."I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future."
You can download the transcript or read it below.
Naimah: Welcome to Behind the Genes.
Lindsay: So, this feeling that like weāve been on this deserted island for eight years and now all of a sudden, youāre sort of looking around through the branches of the trees. Itās like, wait a minute, there are other people on this island and in this case actually there's a lot more people on this island. Yeah, itās very exciting, itās validating. It gives us a lot of hope and, you know, it has been quite emotional too and also a bit of an identity shift. Being undiagnosed had become quite a big part of our identity, and so now thatās kind of shifting a little bit that we have this new diagnosis and are part of a new community.
Naimah: My name is Naimah Callachand and Iām Head of Product Engagement and Growth at Genomics England. On todayās episode, Iām joined by Lindsay Pearse whose son Lars recently received a genetic diagnosis, made possible by research using data from the National Genomic Research Library, Sarah Wynn CEO of Unique, and Emma Baple, a clinical genetics doctor. Today weāll be discussing the impact of recent research findings which have found a genetic change in the non-coding RNU4-2 gene, to be linked to neurodevelopmental conditions. If you enjoy todayās episode, weād love your support. Please like, share and rate us on wherever you listen to your podcasts.
Naimah: And first of all, I would like everyone to introduce themselves. So, Lindsay, maybe if we could come to you first.
Lindsay: Great, thank you. So, thank you for having me. Iām Lindsay Pearse, I live outside of Washington DC and Iām a mum to 3 boys. My oldest son Lars who is 8, he was recently diagnosed with the de novo variant in the RNU4-2 gene.
Naimah: Thank you. And Emma?
Emma: My name is Emma Baple. Iām a Clinical Genetics Doctor which means I look after children and adults with genetic conditions. Iām also a Professor of Genomic Medicine in the University of Exeter and the Medical Director of the Southwest NHS Genomic Laboratory Hub.
Naimah: And Sarah?
Sarah: Hi, thank you for having me. Iām Sarah Wynn, Iām the CEO of a patient organisation called Unique, and we provide support and information to all those affected by rare genetic conditions.
Naimah: Great, thank you. Itās so great to have you all here today. So, first of all Lindsay, I wonder if we could come to you. So, you mentioned in your introduction your son Lars has recently been diagnosed with the de novo variant. I wondered if you could tell us a bit about your story, and what itās been like up until the diagnosis.
Lindsay: Sure, yeah. So, Lars is, heās a wonderful 8 year-old boy. With his condition, his main symptoms he experiences global developmental delays, heās non-verbal. Heās had hypertonia pretty much since birth and wears AFOās to support his walking. He has a feeding disorder and is fed by a G-Tube. Cortical vision impairments, a history of seizures and slow growth, amongst other things.
So, that's just a bit of a picture of what he deals with day to day. But heās my oldest child, so first baby. When I was pregnant, we were given an IUGR diagnosis. He was breech, he had a hernia soon after birth, wouldnāt breastfeed. But all of these things arenāt terribly uncommon, you know. But once he was about 3 or 4 months old, we noticed that he wasnāt really able to push up like he should, and we were put in touch with early intervention services for an assessment. So, we went ahead and did that when he was about 4 or 5 months old. And as parents, we could just kind of tell that something was off from the assessors. And, you know, they were very gentle with us, but we could just get that sense that okay, something is off, and theyāre worried here.
So, that kind of kickstarted me into making appointments left, right and centre with specialists. The first specialist that we saw was a neurologist. And yeah, again, that's another appointment that Iāll never forget. She referred us to genetics and to get an MRI and some lab work but at the end of the appointment, she said to us, āJust remember to love your child.ā And, you know, that was quite shocking to us at the time because it wasnāt something that had ever crossed our mind that we wouldn't do or felt like we needed to be told to do this. But on the other hand, it certainly set off a lot of worry and anxiety of okay, well, what exactly are we dealing with here?
So, fast forward, we saw genetics and that was about when Lars was about 8 months old. We went through a variety of genetic testing, a chromosomal micro-array, a single gene testing, then the whole exome testing. Everything came back negative, but it was explained to us that what was going on was likely an overarching genetic diagnosis that would explain his like, multi-system symptoms.
And so meanwhile as he was getting older his global delays were becoming more pronounced and we were also in and out of the hospital a lot at this time. At first, he was in day care and, you know, any sort of cold virus would always turn into like a pneumonia for him. So, we were just in and out of hospital seeing a myriad of specialists, trying to put together this puzzle of what's going on and it was really hard to accept that nobody could figure it out. That was just, you know, sort of mind-blowing to us I guess. So, we applied for and were accepted into the Undiagnosed Diseases Programme at the National Institute of Health over here. The NIH as itās commonly referred to. So, we first went there when Lars was 2. He was one of their youngest patients at the time. But that was a really great experience for us because we felt like they were looking at him holistically and across a bunch of all of his systems, and not just seeing a specialist for sort of each system. So, we really appreciated that.
We also did the whole genome sequencing through this research study. Although that also came back negative and so at that point, we were told to kind of keep following up symptomatically. Keep seeing the specialists and eventually maybe one day weāll find an overarching diagnosis, but that science just hadnāt quite caught up to Lars. It was hard for me again to believe that and to sort of wrap my head around that. But certainly, it was an education from all of the doctors and geneticists and everyone we saw at NIH, to realise like how far there still was to go in terms of genetic research. How it wasnāt also that uncommon to be undiagnosed in the rare disease community. I would say that being undiagnosed sort of became part of our identity. And itās, you know, it was something that, you know, you had to explain to like insurance companies and to his school, and it became part of our advocacy around him. Because without being able to say oh, itās this specific thing and if it was someone who hadnāt met Lars before, trying to explain to them that, you know, yeah, within the range of this community you can be undiagnosed, and they just havenāt found it yet, but I promise you there is something going on here.
And Iād say the other thing too without a diagnosis you have no prognosis, right? And so, trying to figure out what the future would look like. Also, family planning. We waited 5 and a half years before we had another child and, you know, it was certainly an anxiety ridden decision. Ultimately after seeing as many specialists as we possibly could, we still were left with the same answer of well, we just donāt really know if it will happen again. So, that was a big decision to make. But again, it just kind of became part of our identity and something that you did eventually accept. But I would say in my experience I feel like the acceptance part also of Larsā disabilities perhaps took me a little bit longer. Because again, I didnāt have a prognosis, so I didnāt exactly know what we were dealing with. Only as he has become older and, you know, youāre sort of getting a better sense of what his abilities might be than being able to understand, okay, this is what Iām dealing with. I need to accept that and do what I can to care for him and our family in the best way that we can.
Naimah: Thanks so much for sharing that, Lindsay. I feel like youāve touched on a lot of really, you know, a lot of complications and difficulties for your family. Especially, you know, with regards to keeping hopeful and things about the prognosis as well, Iām sure it was really difficult. Youāve mentioned that Lars was able to be diagnosed recently due to recent research efforts. So, Sarah, I wonder if you can tell us a bit more about these and what the findings have meant for patients with neurodevelopmental conditions.
Sarah: Yes. So, I think we know that there are lots of families that are in Lindsay and Larsā position where they know that there is almost certainly an underlying genetic condition, and it just hasnāt been found yet. And so, I think we know that lots of researchers are working really hard to try and find those causes. I think over time we know that as time goes on and research goes on, weāll find more of these new genetic causes for neurodevelopmental conditions. I think particularly as we start to look at regions of the genome that we havenāt looked at so much so far. But I think one of the things that's really extraordinary about this one is that actually it turns out to be much more common than we might have expected, for one of these new conditions that we havenāt found before. But I think itās about one in 200 of those undiagnosed children with neurodevelopmental conditions, have this diagnosis so that's not a small number. That's not a rare finding at all actually, that's much more common than we could ever have anticipated.
But I think one of the things that we do know is that as we look further and deeper into that genomic sequence, so, weāve started off looking at the bits of the sequence that are genes that code for proteins. This changes in a gene that actually doesnāt code for protein, so itās less obvious that it would be important but clearly it is important in development because we know when it has a spelling mistake in it, it causes this neurodevelopmental condition. But there will be as researchers look more and more at these kinds of genes, and also the other part of the genome that is not genes at all, weāll find out more and more the underlying genetic causes of these neurodevelopmental conditions.
I think itās also really important to stress why this is so important to find these genetic changes and itās because families really need a diagnosis. Lindsay talked quite eloquently and a lot about that knowing something was off and really wanting to know the reason why. Getting these diagnoses might change care management or treatment, but actually really importantly it just gives an answer to families who have often been looking for an answer for a really long time.
Naimah: I just wanted to go back to the point that Sarah made that actually this genetic change is relatively common. Emma, I wondered if you could tell us a bit more about maybe why it took us so long to discover it?
Emma: That's an interesting question actually. I suppose the sort of slightly simplified answer to that question is we havenāt been able to sequence the whole of a personās genetic information for that long. And so, children like Lars would have had, as Lindsay described lots and lots of genetic tests up until they had a whole genome sequencing which is what Sarah was talking about. The types of tests that we had up until the whole genome sequencing wouldn't have allowed us to look at that bit of the genetic code where this RNU4-2 gene can be found. So, we can only really find that using whole genome sequencing. So, before that existed, we wouldn't have been able to find this cause of developmental condition.
Naimah: Okay, thanks Emma.
Naimah: Now weāre going to hear from one of the two research groups who are responsible for these research findings. First of all, letās hear from Nicky Whiffin.
(Clip - Nicky Whiffin)
Naimah: How were the findings possible using the Genomics England dataset?
Nicky: So, most previous studies have only looked at genetic variants that, in genes that make proteins, but only a subset of our genes actually do makes proteins. The Genomics England dataset we have sequencing information on the entire genome, not just on these protein coding genes and that means we can also look at variants in other genes. So, those that make molecules other than proteins. And RNU4-2 for example, makes an RNA molecule.
Naimah: These findings translated to direct patient benefit for patients like Lars who were able to receive support from Unique. How does this demonstrate the value of the dataset?
Nicky: Yes. So, it was incredible that we could find so many patients with RNU4-2 variants so quickly. This was enabled by access to Genomics England data but also to other large sequencing datasets around the world. So, we worked with people in the US, in Australia and also in mainland Europe. These large datasets enabled us to spot consistent patterns in the data and by looking across multiple datasets we can also make sure that our findings are robust. When we realised how significant this was and how many families would be impacted, we very quickly contacted Sarah at Unique to see if we could direct patients to them for support.
(End of clip)
Emma: There's one thing I wanted to raise. Itās important to recognise the way that was discovered was through the National Genomic Research Library that Genomics England hosts. To highlight the value of that, and the value of having this centralised resource where families have been kind enough really to allow their data to be shared with some limited clinical information that allowed these researchers to be able to pull this out. And I think it highlights the power of the National Health Service in that we were able to create such a resource. Itās really quite astounding that weāve found such a common cause of a rare genetic condition, and it wouldn't have happened in the same timescale or in this way without that resource. And then to just say that as Sarah talked about the fact that weāve been able to get that information out there, also the researchers were able to get out there and contact the NIH and all of these other programmes worldwide. In Australia, America, everywhere in the world and quickly identify new patients who had this condition and get those diagnoses out really rapidly to people.
But all that came from that power of sharing data and being able to have that all in one place and making it accessible to very clever people who could do this work and find these answers. Itās so important for families like Lindsayās, and all the families in England and around the world that have got these answers. So, I guess itās a big plug for the value of data sharing and having a secure place where people feel that itās trusted and safe, that enables these diagnoses to be made.
Lindsay: If I could just echo that, weāre so grateful that that exists in the UK. Just acknowledging like the privilege here that we have had to be able to, I mean for our family in the US, that weāve been able to, you know, get ourselves into the NIH study and into the study at Childrenās National. That takes a lot of work. I feel like not everybody has that opportunity to be able to spend the time to do these applications and to go to all the appointments and get the testing done and have the insurance to cover it. So, very grateful that the system exists in a way in the UK that made this sort of research possible. I just hope that that can be replicated in other places, and also to what Emma was saying earlier, come up with a lower cost test as well for this to further the growth of the community and of course then the corresponding research.
Sarah: I think firstly we have to sort of thank all of those families that took part and do share their data, because I think itās not always clear why you might want to do that as a family. I think this is really a powerful example of the benefit of that. I also think the data sharing goes one stage further. So, itās partly about getting the diagnosis, but the data sharing going forward about how this condition impacts families, both clinically and sort of day to day lived experience, is how weāll be able to learn more about these conditions. And so, when families get this diagnosis next week or next year, not only will they get a diagnosis, but theyāll get a really good idea about what the condition is and how it might impact their child.
Naimah: And Lindsay, coming back to you. So, weāve talked about, you know, what it meant for your family before the diagnosis, but what has it meant to have a diagnosis and how did you feel? And what happened whenever you received the diagnosis?
Lindsay: Sure. Lars was again part of the NIH Undiagnosed Diseases Research study. So, once you attend this programme and if you are not diagnosed like at the end of your stay, they keep your details on file and youāre part of this database at the NIH Undiagnosed Diseases Programme. So, if youāre undiagnosed after your sort of week-long work up, your samples stay within the research programme. We were also part of a research programme at Children's National Medical Centre, the Rare Disease Institute. So, our samples were sort of on file there in their database as well.
And so, at the end of March I was really quite shocked to receive a call from our long time and trusted geneticist at Childrenās National that they had found a diagnosis. It was quite emotional. I really kind of didnāt believe it. I just kept asking, you know, āAre you sure? Is this it?ā you know, āHow confident are we?ā Because I think in my head, I sort of always thought that we would eventually find a diagnosis, but I thought that Lars would be, you know, a 30- or 40-year-old adult. I thought it would be decades from now. Like I felt like for whatever reason we had to wait decades for the science to sort of catch up to him.
So, we were very, very grateful. It felt very validating, I guess. I had always kind of had this intuition feeling that we were sort of missing something and itās more that the science just hadnāt quite caught up yet. But, you know, it was validating to know that okay, Lars is not the only person in the entire world with this, it is something that is relatively common in fact within the rare disease community. That is also very exciting to me personally because Iām hopeful that that will lead more researchers to be interesting in this, given how, quote on quote, common it is. Iāve sort of been describing it as like a mass diagnosis event but also more so this feeling that like weāve been on this deserted island for eight years and now all of a sudden, youāre sort of like looking around through the branches of the trees. Itās like, wait a minute, there are other people on this island ad in this case, there's actually a lot more people on this island.
Yeah, itās very exciting, itās validating. It gives us a lot of hope. And, you know, it has been quite emotional too and also a bit of an identity shift. Because I spoke earlier about how like being undiagnosed had become quite a big part of our identity. So, now that's kind of shifting a little bit that we have this new diagnosis and are part of a new community. But yeah, weāre just very grateful that the research had continued. And, you know, I think sometimes you sort of have this feeling of okay, our files are up on a shelf somewhere, you know, collecting dust and are people really looking at them? And actually, it turns out that the research was ongoing and yeah, weāre just very grateful for that.
Naimah: Thanks so much for sharing, Lindsay. It sounds like itās been a real rollercoaster of emotions for your family and Iām glad to hear that, you know, youāve got some hope now that youāve got a diagnosis as well. So, moving onto the next question. Emma, I wanted to ask you then, how will these findings improve clinical diagnostic services for those for neurodevelopmental conditions?
Emma: So, you asked me earlier about why it had taken so long to find this particular cause of neurodevelopmental condition, and I gave you a relatively simple answer. The reality is one of the other reasons is that almost eight out of ten children and adults who have RNU4-2 related neurodevelopmental condition have exactly the same single letter spelling change in that gene. So, actually that in itself means that when researchers are looking at that information, they might think that itās actually a mistake. Because we know that when we sequence genetic information, we can see mistakes in that sequencing information that are just because the machine has, and the way that we process that data, itās not perfect. So, sometimes we find these little mistakes and theyāre not actually the cause of a personās problems, theyāre just what we call an artefact or an issue with the way that that happens.
So, that is part of the reason for why it was tricky for us to know whether this was, or rather the researchers to know whether this was or was not the cause of this particular condition. But that in itself is quite helpful when we think about how we might identify more people who have this going forwards. Because unlike in Larsā case where we didnāt know what the cause was and so we were still searching, and we didnāt know where to look in the billions of letters that make up the genetic code to find that answer, we now know that this is really very common. Itās unbelievably common. I think we didnāt think we would be finding a cause of a rare genetic condition that was this commonly occurring at this stage. But the fact that itās just a single, itās commonly this one single change in the gene means that we can set up pretty cheap diagnostic testing. Which means that if you were somewhere where you wouldn't necessarily have access to whole genome sequencing, or a more comprehensive testing in that way, we could still be able to pick up this condition. And itās common enough that even if you didnāt necessarily recognise that a person had it, you could still have this as part of your diagnostic tool kit for patients who have a neurodevelopmental condition. Itās common enough that just doing a very simple test that could be done in any diagnostic lab anywhere in the world, you would be able to identify the majority of people who have this.
Naimah: Now letās hear from the other research group who are responsible for these findings. Here is Dr Andrew Mumford.
(Clip - Dr Andrew Mumford)
Naimah: Why are these research findings significant?
Andrew: It offers genetic diagnosis not just for a handful of families but potentially for many hundreds of families, who we all know have been searching often for many, many years for a genetic diagnosis. But actually, there are other gains from understanding how this gene causes neurodevelopmental disorder. We know that there's GRNU4-2 in codes, not a protein actually, but a small nuclear RNA which is unusual for rare, inherited disorders. Itās a component of a very complicated molecule called the spliceosome which in turn regulates how thousands of other genes are regulated, how theyāre made into proteins. So, fundamentally this discovery tells us a lot about the biology of how the spliceosome works. We already know that some other components of the spliceosome can go wrong, and result in diseases like neurodevelopmental disorders. This gives us an extra insight and actually opens the door to, I hope, a whole load of more discoveries of genetic diagnosis possible from other components of this complicated molecule.
Naimah: Your research group used a mathematical modelling approach. Can you tell me a bit about this, and what this means for other rare conditions, Andrew?
Andrew: So, identifying relationships between changes in individual genes and different kinds of rare, inherited disease is notoriously difficult because of the volume of data that's involved and the need to be absolutely certain that observed genetic changes are actually the cause of different rare, inherited disease. So, applying statistics to that kind of problem isnāt new. But what my collaboration group have achieved here, is to develop, actually developed some years ago a completely new approach to applying statistics to genetic data. We call that BeviMed and weāve been working for many years on the genes in code that make individual proteins. Most rare disorders are caused by genetic changes in genes that make proteins.
What this discovery comes from is actually weāve applied the BeviMed statistical technique to genes that donāt make proteins, theyāre non-coding genes. For example, genes that make small nuclear RNA, itās just like RNU4-2. What's unusual about the BeviMed approach is that itās very sensitive to detecting links between genetic changes and rare diseases, and it can detect statistical associations really driven by very, very small numbers of families.
So, we apply it to datasets like the 100,00 Genomes dataset and identify associations using statistics that have got a very high probability of association. Other members of the team then seek to corroborate that finding by looking at if we can see the association in other datasets, and we certainly achieve that with RNU4-2. But also, assessing biological plausibility by investigating what we understand already about in this case, a small nuclear RNA, and how it can possibly result in a disease. And we normally try and employ other independent evidence such as experimental investigation. Or going back to our families and asking for additional data to help really test this sort of theory that changes in this particular gene have resulted in a problem with neurodevelopment.
(End of clip)
Naimah: Emma, are there any other ways that we can identify these conditions based on their clinical presentation?
Emma: So, Lindsay and I were talking with you just yesterday, wasnāt it? And I asked Lindsay about what sorts of things Lars had in common with other children and adults who have been diagnosed with this condition? I actually think Lindsay probably gives a better summary than I would, so I might ask you to maybe repeat what you said to me yesterday. But the bit of it that really stood out to me was when you said to us that a lot of parents have said, āI'm not sure how we werenāt all put together in the first place because you notice so many things that were in common.ā So, maybe if you can give that summary and then I can translate that back into medical terms, if thatās okay Lindsay.
Lindsay: Sure, of course. Yeah, it been again, kind of mind blowing, some of the similarities. Especially as weāve exchanged pictures and such, and baby pictures especially where some of the children like look like siblings. So, definitely some similarities in facial features, you know, everyone seems to experience some of the slow growth, so a short stature or quite skinny. There's feeding issues also that seem to be quite common. Also, you know, things like the global developmental delays, that's certainly across the board and histories of seizures, that's also quite common. Some people have experienced also some, like, bone density issues, that's not something that weāve experienced so far, but that also seems to be quite common.
But then also, behaviourally, there's a lot of similarities which has been, I think, quite exciting to a lot of us because youāve always thought okay, so this is just my child. And of course, some of that is true but itās also interesting to find out some of these other things that are, you know, are quite similar. So, a lot of people have mentioned their child having, like, an interesting sense of humour. Kind of like a very slapstick sense of humour which is quite interesting. Or everyone seems to love water, everybody loves swimming pools and bathtime, and all of that. Lars loves a windy day. Something about the wind, he just loves it and plane noises and things like that have also come up with other people. So, yeah, itās been really interesting and cool to see.
Emma: So, I guess Lindsayās sort of very beautifully summed up what is written in the research publication. So, there's only two research publications so far on this condition, itās all really new. And I am definitely not claim to be a clinical expert on this condition, and I don't think there are any yet. It will take people time to see lots of children and adults who have this particular condition. But ultimately what Lindsay summarised was the common clinical features that have been described by parents. In my job as a clinical genetics doctor, part of what we look at is a personās appearance. So, Lindsay described the photographs of children particularly when they were little, looked very similar. In the photographs that Iāve seen, I would agree with that. And so obviously those children look like their mum and dad, but they have other features that are in common. They have a characteristic appearance and that helps doctors like me to have an idea as to whether a child or an adult might have a particular condition.
Then put together with the sorts of information that Lindsay gave us around the low tone, so being a little bit floppier particularly when theyāre little. The slow growth and growth problems, problems with eating, also with seizures. Those are all common things that were pulled out of both of the two research publications on this condition and putting that all together into one picture helps doctors to have an idea whether somebody may have a particular condition. That would help us in this case to potentially request that simple test I was talking about, if maybe we were practicing in a part of the world where we wouldn't have the resources that we thankfully do have in the United Kingdom, and in the USA.
Naimah: So, Sarah, just coming to you next. How does this research spread awareness and help other patients with these conditions?
Sarah: So, I think one of the things that's been really great about research now is that we are able to, you know, social media and things like that mean that we can spread this information really quickly across the world basically. I think what that does is that as well as helping bring people together that theyāve got this diagnosis, what it does is I think it provides hope for all of those people that Lindsay was talking about at the beginning who don't have a diagnosis. So, that piece around people are still looking, the researchers are working hard and that even if you don't have a diagnosis today you might get one in the future. Lindsay talked about your sample being dusty and not being looked at. I think it gives lots of families, not just those that get this diagnosis but all of those that havenāt got a diagnosis, hope, that hopefully in the future they will get a diagnosis.
I think one of the things we really hope will come out of diagnoses like this is that we will then be able to build up more of that picture about how families are affected. So, that we can give families more information about not only how their child is affected but how they might be affected in the future. That prognosis information that Linsday said is really missing when you don't have a diagnosis. And I think the other thing that hopefully is the next stage in this journey with this discovery is that those two science publications that Emma talked about, what we will want to do here at Unique working with the researchers and those families that have got a diagnosis, is to produce a patient family friendly information leaflet about this condition.
One of the things we know is really important about those patient leaflets is including the photos. Because as both Emma and Lindsay have said that idea that they have facial features in common. And so, if you look at a leaflet and you can recognise your child in it, and you can see others that look like it, that can be a really sort of quite heartwarming experience in what often is a lonely experience with a rare condition.
Naimah: And I think kind of on that point about it being a lonely experience, I wondered Lindsay if you could talk a bit more if this research has allowed you to connect with other parents and families who have received a diagnosis, and what impact that's had on your family?
Lindsay: Yeah. I mean, and I think everything that Sarah has said was spot on. Itās wonderful to have resources like Unique to connect families and have those diagnoses on the platform, so other clinicians can look for it and sort of grow this group. I think that has definitely been the highlight of getting this diagnosis at this stage, right. Because there's not much more you can do with it, with someone so brand new so being able to connect with the other families has been wonderful. One amazing mum who with this diagnosis set up a Facebook group, RNU4-2 Family Connect. And, you know, itās just been amazing to see people from all over the world joining this as they receive this diagnosis, you know, sharing their stories. Weāve spent countless hours on the weekends over the past couple of months on Zoom calls with total strangers, but just you find that you can just talk for hours and hours because you have so much in common.
Itās great to see what has worked well for other families and, you know, what has not worked. Sharing resources, just kind of all learning together. Also seeing the spectrum of this diagnosis, I think most genetic disorders have a spectrum and this seems to be the same here. So, that's been very interesting. And of course, our son is 8, Lars is 8. There's now a 33-year-old and a 29-year-old in the Facebook group. Speaking for me personally itās just amazing to see them and like itās very cool to see where theyāre at. That sort of helps you answer some of those questions about that before were quite unknown when you were thinking about the future. Obviously, everybodyās development whether you have a genetic disorder or not, it is going to be what itās going to be, and everybody is going to do their own thing. But being able to see what a path might look like is just so helpful. And, you know, we all want community and connection, and so this has been really, really great to have that now.
Sarah: I don't think there's much more that I can add because Lindsay articulated so well. But itās really heartwarming for us to hear the benefits of those connections because that's really why Unique and other support groups exist. Is to provide, partly to provide information, but I think predominantly to put families in touch with other families so that they can find a new home and connect and share experiences. And, you know, stop feeling as alone as they might have done before.
Naimah: Okay, weāll wrap up there. Thank you to our guests, Lindsay Pearce, Sarah Wynn and Emma Baple for joining me today as we discussed the research findings which found a genetic change in the RNU4-2 gene which has been linked to neurodevelopmental conditions. If youād like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iāve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin of Ventoux Digital.
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Genomics has changed considerably over the past 10 years, and we are now exploring how to integrate it into routine healthcare. In this episode, our guests reflect on this evolution and discuss how the key learnings from the past 10 years can shape the genomics ecosystem of the future. They highlight the importance of partnership across teams, organisations and participants, emphasising the importance of keeping participant and patient benefit at the heart of research, whilst also addressing the ethical and safe storage of patient data.
In this episode, our host, Helen White, who is the Participant Panel Vice-Chair for cancer at Genomics England, speaks with Dr Rich Scott, CEO of Genomics England.
"Thereās a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care."
You can download the transcript or read it below.
Helen: Welcome to Behind the Genes.
Rich: Thereās a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer, and thinking as we do that, about how we structure the system to generate evidence, and to respond to it, and have a conversation about what the right balance of evidence for patients to make a choice about their own care.
Helen: My name is Helen White and I am the Participant Panel Vice Chair for Cancer, at Genomics England. On todayās episode Iām joined by Dr Richard Scott, Chief Executive Officer for Genomics England. And today weāll be discussing Richardās recent appointment as CEO, lessons learnt from the last ten years in the evolution of genomics in healthcare, and how these learnings will be taken forward in the next ten years. And weāll also visit the importance of keeping participant and patient benefit at the heart of research, as well as the ethical and safe storage of patient data. If you enjoy todayās episode we would love your support: please like, share and rate us on wherever you listen to your podcast.
Before we dive into the interview with Rich, I wanted to take a moment to share my story and tell you a little bit about myself. I have been a member of the Participant Panel at Genomics England since 2018. It was the year before that when I was diagnosed with endometrial, or womb cancer, and was offered the chance to join the 100,000 Genomes Project, which felt like something positive at what was otherwise quite a scary time. It turns out that I have something called Lynch syndrome, thatās a genetic condition that increases my chance of developing certain cancers, particularly womb and bowel cancer, which is actually a really useful thing to know as there are things I can do to reduce my chance of getting cancer; things like having regular colonoscopies and taking daily aspirin. I have now been on the participant panel for six years and one year ago I was appointed as Vice Chair for cancer. This is a new and developing role and I am excited to have so far helped recruit more people with lived experience of cancer to the panel and to be assisting Genomics England with connecting to organisations that advocate for people whose lives have been touched by cancer.
So thatās enough about me. I am delighted to be joined today by Richard Scott, and I am very much looking forward to our conversation. Welcome, Rich.
Thank you. So Rich, youāve recently been appointed CEO of Genomics England. Can you tell me a bit about your background and what brought you to this role?
Rich: Itās a really good question and itās one that doesnāt have a really very simple answer. I guess what it boils down to is I guess Iāve always had an interest, even as a child, for whatever reason, in genetics and genomics. I have also then always been drawn to things where I can have an impact and particularly the impact in healthcare and thatās what took me to being a medical student. And I guess itās that combination of that particular interest in genetics and being able to see, even when I was at medical school I qualified in 2000 that this was an area of medicine that was going to be really important in the future. And then as I trained, as I did a PhD and as I saw the technology develop and change and then when I saw the UK government and the NHS investing in genomics in a really foresighted way, I found myself eight or nine years sitting at Great Ormond Street as a consultant in clinical genetics where I still practice, I still do one clinic a month there as a clinical genetics consultant seeing families with rare conditions.
But I could see when Genomics England was established that this was something, as I said, really foresightful where we could really collectively across the country make more of a difference together in terms of patient and healthcare outcomes. So I joined GEL eight or nine years ago initially in a subject matter expert role, and really found myself the more time it passed, understanding how working in my role at GEL and helping GEL be a really productive part of what is a busy genomics healthcare ecosystem in the UK, we can make a big difference, and thatās the thing that just wakes me up in the morning, is realising how much there is left to do, being proud of the stuff weāve done, the difference weāve made to participants in our programmes already, but realising that many of those still need our support to do better and the big distance left to go before we really deliver on I think the long-term promise of genomics, and I feel my mixture of skills and experience make me really excited to be in the middle of that.
Helen: Thank you. Yes, it sounds like youāve brought many skills and experience, and interesting to hear that as a child you already had that interest in genetics and where thatās taken you. Can you tell me what being CEO Genomics England means for you? What are your aspirations for your first year in this position?
Rich: Well, I guess, as you can tell, Iām really excited to take on this role. As I said, as a doctor Iām always focused on the impact for patients and our participants and ultimately itās the broader health of the nation. And the role I see Genomics England playing and being able to play in the future, sort of building on that, the leadership position the UKās always had in genomics ā you know if you look back to the discovery of the structure of DNA, the invention of sequencing technologies and also the clinical implementation coming from that government investment and the NHS investment, what excites me most about GEL is that we can be there, playing a critical role alongside others in that ecosystem, whether thatās in the NHS, whether itās our participants and the patients who weāre aiming to support academia and industry, to create a whole thatās greater than the sum of the parts, and I genuinely feel that the UK remains uniquely placed to live out that potential that genomics has, engaging in the questions, not just you know, the scientific questions of: what could genomics test for? Or, how could this be implemented and is it cost-effective?
But also being able to have the nuanced conversation of what we all and our participants in the public and general, expect in terms of the care we receive or how our data is looked after, and getting that really balanced view on how we chart a path forwards where we can really see big differences being made in the future, and I think always being honest to ourselves about where we are today and that things donāt come in spotting some position a long time in the future that we want to navigate to, but also being really focused on the here and now and what is possible and what is evidenced, and what the next set of evidence or discussions or conversations in the public we need to have to help navigate ourselves there and thatās where at the moment our focus at Genomics England is both being very clear sighted on where Genomics could go, and also thinking very clearly about where we are today, and so very much at the moment for us itās about focusing on the life service we offer to the NHS and weāre really proud to be part of a world-leading whole genome sequencing service, the first national health service in the world to be providing that in the context of cancer and rare disease, and so offering and providing our service that contributes to that.
Supporting researchers so that we can keep the flow of discoveries coming and also for example, making sure that our participants in existing programmes continue to get new answers as the science evolves. So, the last year more than 2,000 families had new findings fed back because of new knowledge thatās accumulating, keeping that flow going. And then weāve got three big research initiatives going on at the moment where weāre really focusing on delivering around them. Weāve got a diverse data initiative where weāre really focused on making sure the research library, the National Genomic Research Library, our participants are representative of the UK population, so the discoveries that weāre supporting are relevant to everyone; our cancer initiative which is exploring the use of new sequencing technology in the context of cancer, and also looking at the use of image data and other modalities of data, alongside generic data to drive new discoveries.
And then the third initiative is our newborn genomes programme, where weāre asking a big question through a research study to generate evidence to ultimately answer the question: should every baby when theyāre born be offered whole genome sequencing? Most pressingly to improve and broader the range of conditions that we can look for that are severe and treatable. So, this year weāre very much focused on delivering on those promises that weāve made to our participants and our partners and through those programmes and very much with an eye to the future thinking about what we need to change in terms of the use of underpinning technology, so that we know that weāve got the potential to scale, to think about the broader use of genomics in years to come as evidence evolves.
Helen: So Rich, there have been many advances in genomics in the last ten years. What do you think are the big lessons from those last ten years, and what do you think the next ten years will look like for the genomics ecosystem, what impact will this all have on healthcare as we know it?
Rich: So, genomics has changed extraordinarily in the last ten years thanks to shifts both in the technology, particularly the sequencing technology but also some of the computing technology thatās there to deal with the scale of data. Ten years ago we were talking about the 100,000 genomes project and beginning the project itself, but it was still very early in the use of whole genome sequencing, thatās gone from something where the big question around the 100,000 genomes project was: can this technology be used in routine care in cancer and for rare conditions, and if so, how do we do that?
And weāve learnt both I think about that specific question and as I mentioned, weāre enormously proud to be part of enabling the NHS whole genome sequencing clinical service, so that has entered routine care. I think along the way the biggest lesson for me is actually one about this being about partnership and about working as a team across many different organisations and with our participants, and recognising that this isnāt just about one set of questions, or itās not just about clinical or scientific questions, itās about joining everything up together back to that point around, so a discussion about what people expect ā this is about doing stuff together and learning often quite complex lessons about practicalities is one things, for example, one of the really big lessons we learnt around the use of whole genome sequencing in cancer are just practical lessons about handling of tissue samples and the need to make sure the right fridges are available on the right corridor of a hospital, with plugs available to plug them into, through to questions around, as I say, peopleās expectations around how their data is stored, which itās used for, which again thereās really strong precedent for, and as we explored, different uses of genomic technology, we shouldnāt just take those previous answers for granted, we need to make sure we validate and check with people what their expectations are.
So I think thatās the big one for me is sort of the number of different angles with which one explores questions and the fact that this is very much about doing it together. I think just one other piece which is so easy for us here to take for granted is that doing things at national scale with national scale investment from government, from other funders and from the NHS is absolutely critical and when you look across the world, we are in an extraordinarily privileged position here in this country because of that investment and because that investment recognises the need critically to join clinical care and research in a whole, where you recognise that youāre doing multiple things at once, but joining them up rather than them being two worlds, is really, really critical, and weāre really lucky to be able to do that at national scale.
So then thinking about what the next ten years might look like for the genomics ecosystem, I think lots of those things continue, so I think national scale and the need for ongoing investment to keep up our position at the forefront in terms of answering these big questions about the use of genomics in healthcare, and to where the evidence supports their implementation to roll them out and keep that link there between healthcare and research, and so making sure the systems talk to each other and I mean that in a digital sense as well as a human sense is absolutely critical.
And then, so in ten yearsā time what are the areas of healthcare that will have been impacted, or could have been impacted by genomics, Iām really pleased that weāre doing a better job for families with rare conditions and people with cancer than we were ten years ago, I think thereās a long distance left to run even in those settings for us to do better and to continue to learn, so we expect our major focus to continue to be in those areas where we know they can have an impact and thereās more to do. We also then have the different areas where if the evidence pans out to support the use of genomics or if we can implement systems that can support it there can be a big sort of area of growth. For example, our newborn genomes programme is asking questions and developing evidence so that in the future policymakers can decide should that become part of routine care, and I think thatās something that could have become part of routine care in the next ten years if the evidence supports it and if thatās something that the public support.
If I were to pick one other area where thereās a real potential for growth in the coming handful of years itās in something we refer to as pharmacogenomics. What that means is looking at your DNA code (genomics) to help make decisions about prescription of medicines and sometimes thatās about avoiding these medicines in people who are at a higher risk of having an adverse reaction, or itās about tailoring the dose because of something about for example the way the person metabolises, chews up, the medicine and so can influence how much dose they need. That actually has an enormous potential; we all have variations in our DNA code that influence how we respond to or metabolise medicines. If you look across primary care, GPs and so forth, primary care physicians and in secondary care, hospital care, I think thereās good evidence that actually probably half of all appointments, interactions in those settings, if you were to have DNA data available that could influence how prescription choices are made; sometimes thatās about knowing that youāre doing the right thing, giving the normal prescription, but sometimes it's about modifying it, thatās an area where I think thereās a real potential for growth and thatās an area that the NHS also really recognise and weāre exploring ways in which we might look into that and think about how that might be implemented, because actually a lot of the questions there are about how you make sure the right data, the right information is available to clinical teams and patients at the time that prescriptions are being made.
Thereās also real potential more broadly in thinking about more common disease settings, thereās lots of work going on from various research studies looking at the value of what people sometimes refer to as polygenic risk scores or integrated risk scores, where we use genomics as an element of estimating risk for common diseases like heart disease or cancer, thatās something where the evidence is being worked on and is developing, I think weāll see a lot of evidence come out in the coming years and I think that will then influence how we implement genomics to help as part of that risk estimation process, which is routine now in GP practices where you go for an NHS health-check they do it with lots of complicated stuff, at the moment not genomics, and weāll see how that plays out in the years to come.
So I think thereās enormous room for growth where genomics where at the moment itās making an important difference to people with certain conditions that we can do better on. In the future I see it becoming very much more part of the routine day to day of healthcare. As we make that transition thereās lots to work through about the evidence, the order in which thatās done and the way in which we, for example, store data, and make people part of the choice about how their data is used and what Iām really excited about in Genomics England is the role we play in the middle of that, bringing our particular expertise around what we call bioinformatics, which is sort of managing genomic data at big scale, particularly national scale to support healthcare and research, generating evidence that can help inform policy, and also critically drawing things together into the conversation amongst different players in the ecosystem and participants in the public so that we can not just think about evidence in a sort of terribly scientific way but we think about it in the round.
Helen: Thatās really interesting to hear you speak a lot about getting that evidence because thatās critical, but that takes a long time doesnāt it, so for example with the generation study, the newborn study itās really important to measure the benefits of that if youāre testing young babies, newborn babies for diseases that if you pick up a condition that condition can be treated and something can be done about it early rather than poor parents going through this diagnostic odyssey, but also itās that balance isnāt it with not leading to any harm, so if a number of parents come out of that thinking their baby might get a condition and it never happens thereās potential there isnāt there. But I think in terms of the public understanding of how long it takes to get evidence and everything else that needs to go on in the background I donāt think itās always particularly clear that thatās a massive process that has to be gone through and thereās a lot of work going on behind the scenes ā you canāt just do these things.
I think as patients/members of the public weāre eager to get on and for change to happen and things to be better but itās a big, big process, but also good to hear that you talk about it being a collaborative approach, itās not just Genomics England, itās the NHS, itās members of the public and patient voices, itās other organisations working in partnership, itās a big undertaking.
Rich: No, it is and I think that one of the words you used there was impatience, and I think thatās healthy and important to recognise, it can be easy, particularly for example as a doctor, sat in a clinic room to accept the status quo, and at the same time, one needs to recognise the complexity of the questions, the balance, the need to generate high-quality evidence to inform those opinions and I think combining both that sort of impatience and dissatisfaction with the status quo, and that mind-set about thinking really thoroughly and collaboratively about the right evidence that is needed to change policy.
Helen: Yes, really important that those patient voices are there from the beginning, from the planning of obtaining this evidence and that youāre measuring the things that matter most.
Rich: One of the areas where I think weāve seen that play out, another area where I really see the potential for growth in the future is much more genomics-enabled treatments. We and you and the participant panel have helped us think about thereās a whole new era I see coming in terms of the therapies that are directed at the causes of genomic conditions, both in rare conditions and in cancer and thinking as we do that about how we structure the system to generate evidence and to respond to it and have a conversation about what the right balance of evidence for patients to make a choice about their own care, but also policymakers to make choices about funding, decisions and safety decisions, is really important and weāve been supporting to a wider work in cancer in the UK called the Cancer Vaccine Launchpad, and likewise weāre part of something we call the Rare Therapies Launchpad, where in those two areas weāre exploring that, and thatās another area I think of real potential in the coming years, and also real nuance as we construct a way of navigating that together and making the most of the potential, but not just sort of rushing in and pretending we know all of the answers at the outset.
Helen: And those launchpads are of particular interest to participants in the wider patient population, there are a lot of people and children with rare, ultra-rare conditions who are desperate for treatments that just arenāt available right now, equally for cancer patients thereās a big need isnāt there for more effective treatments, fewer side effects, that target that personās particular cancer, so itās good news I think for the wider public.
It does seem that innovation and partnerships are crucial to Genomics Englandās activities so how does Genomics England ensure that participant and wider patient benefit are at the heart of these activities?
Rich: I think one of the really important things is actually governance is sometimes a boring word, sounds like it, but I think thinking about how weāve structured the organisation and placed you, as the participant panel, as part of our governance to make sure that when weāre thinking about for example access to data in the National Genomic Research Library, participants are sort of driving those decisions, itās an independent committee that makes those decisions with representation from our panel. One of the things is thinking about the governance and making sure that you as our participant panel hold us to account for the decisions that weāre making, which I think is really critical.
I think then also as weāve learnt a lot over the years, not always getting it right, about how we make sure that participants, or potential participants in the public are involved from the outset in the design of programmes because it always helps. I think certainly before I joined Genomics England I think I would have been unsure about the best ways of going about that and that brings with it sometimes a nervousness. I think the main advice I would say to people listening is to have confidence that just getting stuck in and have conversations is the way to do it. There are then also all sorts of expertise that weāve really benefited from being to bear in terms of ways of doing that engagement work and that will come; the first thing is to have the confidence and the desire to put that at the centre of how you decide where your focus should be and how you design programmes.
Helen: I think Genomics England has been very successful with that by integrating that patient voice from the very early days and here we are what eight years on I think now, and yes, hopefully weāll be there for some time to come yet, as long as Genomics England exists.
So Rich, with more and more health data being stored, how do we ensure that this sensitive personal data is stored and used safely and ethically across the genomics ecosystem. And actually while weāre on this question, can you just explain what genomics ecosystem means, because we use that term I think quite a lot, but I think itās not necessarily understandable to the wider public?
Rich: What I mean when I talk about it is I mean the mixture of different people, whether thatās sometimes organisations, us, Genomics England, the NHS, the NIHR, National Institute for Health Research; industry partners whether theyāre people who are from pharma companies or from biotech, academic researchers, participants in programmes ā everyone who comes together to work on genomics in the UK and a bit like the word as itās used in biology, itās a sort of busy ecosystem with all sorts of people playing their own role and then working together, and so I think itās a really important thing to recognise that weāre part of that and in fact itās one of the things I love most about my role at Genomics England is thinking about all of the different partners that we need to work with and to those outside it I think it can also be a bit intimidating, because itās hard to keep up with who on earth everyone is.
So then thinking about the question of how we make sure that dataās stored and looked after and used in the ways that people expect and safely and so forth, I think thatās absolutely at the heart of my role and our role. And I think one thing is actually always sort of starting at the: why are we doing this? What benefits are we seeking to bring to people? Is that what they expect? What have they signed up for if you like? But thatās in a research study or when theyāve decided to say yes to having a particular test, which is the same in any part of medicine. And if we use that to drive our decisions, thatās whatās so critical. And so thatās where thinking about programmes we run, and also the things that we think might be worth something that we should prioritise in the future is always first driven by the benefit that you might be bringing, weighing up the costs and the potential downsides and harm that might be caused by the use of genomic data in that way and thatās what should always drive things, and there isnāt a one-size-fits-all, you know, genomic data should be used and stored in this way and thatās one of the things that I think making sure that participants and the public are at the centre of the conversation is absolutely critical, it turns out that genomic data is very much like health data at large in many senses and itās very precious for those reasons.
It is also special in a few ways. One of the ways thatās sort of peculiar if you like is that pretty much the DNA sequence, the genome, that youāre born with, is the same one that you hold throughout your life, thatās different from say if you do a blood count or something that varies for various reasons over your life and most things in medicine do change quite meaningfully over a much shorter time period. One of the things about the DNA code: A) it makes it more precious because itās very much about you, your whole life; also it makes it more useful and reuseable in many ways, so one of the things that we think about a lot more in genomics is about the storage and reuse of data on an ongoing basis through the lifetime. And I do think that that model in certain settings and potentially more broadly as evidence accumulates, may well be the path that we take forward where you consider your genomic data part of your health record where it can be used and reused.
And what we need to do is explore why you would in the first case generate someoneās DNA sequence, and what sort of sequence, is it a whole genome or less than a whole genome? What would you use it for in the first place when you first generate it? And what other uses could there be to support the healthcare and have you involved them or the public more generally in decisions about how itās used? Because we do, as I said, see the potential for genomics being just becoming part of the fabric if you like of healthcare, good healthcare, the best healthcare.
Linked to that is the point on research as well, like where people are happy for it, holding their genomic data and understanding how that impacts on longer term health outcomes, something weāll continue to learn about for years and years. So I think the first point is about focusing on the why and whose data it is, oneās own genome belongs to you, it doesnāt belong to anyone else, what people are happy with and consent to and expect and then always holding that in mind as one makes the choices is critical. Iāve talked about how we think the governance and the involvement of the participant panel is really critical for that as well. And then it also comes down to doing in various ways, the job that people would expect in terms of, for example, that safety piece, using the very latest tooling to make sure that itās held in a secure way, that itās backed up so that it wonāt be lost etc. and bringing sort of the right, very good minds around some of those more technical questions, but always with the expectations of the people whose genomes they are in mind and to say are we living up to their expectations, are we doing what they would expect?
So, Helen, I wondered if I could ask you a couple of questions. The first one I wanted to ask is what youāre hopeful for in the coming years as a participant panel member?
Helen: Thank you. Iāve actually already posed these questions to some of the other panel members, so Iāll try and make sure I include their responses here as well as mine, but I think itās important to hear from everybody, not just me, Rebecca Middleton and Emma Walters have recorded their responses as well. I think the four main things that panel members are hopeful for is the coming years, the first is equitable access to whole genome sequencing, basically everybody who needs whole genome sequencing should get access to it regardless of where they live, their income, ethnicity or disability, so thatās something that weāre hopeful will get better over the years.
We know this is essential to improving healthcare, to improving outcomes for patients and generally for sort of greater inclusivity and in genomic research, we want as well as Genomics England, the data is the National Genomics Research Library to be representative of the population as a whole, not just the people who 1) are offered, and 2) agree to have their data in the library. And also, obviously the more data that is held in that library, the more opportunity there is for research across those rare and ultra rare conditions and rare and less common cancers, where itās all about numbers, you need numbers of sets of data in order to draw things together and make conclusions to look for patterns.
And the other thing which I guess comes more under the umbrella of the NHS is that the panel is quite keen, they want everybody whoās undergoing genomic testing to receive good support and after care, I think regardless of whether that testing is via the NHS or as part of a research study, sometimes it will be both, but thatās for the patients at the coal face that is obviously critically important.
The second, I think broad theme, coming from the panel membersā responses is that I think youāve mentioned this already, is increased understanding of genomics amongst the general public is really important ā thereās a need to demystify genomics and to generally improve public awareness of its benefits and to get those conversations going around its regulation and its ethical use, but to do that you need to get meaningful engagement from a wide range of people, you know, thatās not always straightforward, there are lots of challenges there, itās all about prioritising inclusivity, accessibility, to make sure you get diverse views and perspectives on genomics and on genomics research.
The other thing that came out very strongly from the responses which we have talked quite a bit about already is about this individualised healthcare. I think we as a panel are very hopeful that there will be this shift towards treatment strategies that are tailored more to the individual and their specific health condition, rather than a one-size-fits-all approach, we want effective treatments that will minimise side effects but also through the use of pharmacogenomics, to make sure if thereās a risk of a severe, sometimes life-threatening side effect that that can be identified and that individual doesnāt have that treatment either at all or has a lower dose, so itās not so toxic.
And letās hear from Emma who talks about this.
Emma: My hope is that we move to a truly individualised healthcare system and Iām really excited to see how in particular pharmacogenomics changes the healthcare landscape. For a long time weāve gone with a one-size-fits-all approach, and thatās easy to deliver on a large scale basis that the NHS works on, but we know fundamentally thatās not how patients work, so to be able to consider individualising medication and knowing which wonāt work, interests and excites me.
Helen: So the panel is also very hopeful about the development of those innovative therapies, and you talked about the rare therapies launchpad and the cancer vaccine launchpad, because those offer real hope for treating previously untreatable conditions and generally improving accessibility to treatments. And weāre also hopeful that there will be a much better understanding of diagnosis of cancer, through things like the multi-model programme, because although thereās lots and lots of research going on with cancer thereās still a long way to go to have more effective treatments and to improve diagnosis of cancer.
And then just finally just in response to your question, patient and public involvement, this is what the participant panel is all about, we are a group of individuals whose lives have all been touched by either a rare condition or by cancer currently, either weāve had that condition ourselves or itās affected our loved one, and we do bring these diverse views and perspectives to Genomics England and I think we have a crucial role in influencing its decisions about what it does with participant data and who has access to that data. Itās critically important that Genomics England listens to what matters to the people whose data it holds and who do that, as Rebecca here explains.
Rebecca: Genomics is a fast-moving science and it has the impact to change lives and healthcare for future generations, but genomics is a science of people and therefore the only way you can truly understand the limitations and opportunities of it is to talk eye to eye to the very people it will impact, and not everyone will agree on everything. But how we understand genomics and its power to transform healthcare, our own and that of our children and the ones we love, can only progress at the pace of the people that it will benefit. Itās a simple equation but itās not maths and indeed not science: we are all different and unique, our emotions, experience and history will be wrapped up in our viewpoints and thoughts, and thatās where the panel comes in, representing and advocating for the very many different voices of genomic healthcare, ensures Genomics England is stronger, healthcare design is more meaningful and research is more impactful.
I have no doubt that the panel of the future will continue to be heard and understood at Genomics England, and I hope it continues to grow to reflect more diverse voices and experiences and continues to be the people inside the science.
Helen: Finally, the panel is also hopeful for increased public and patient involvement in genomics research, this is integral for shaping research both academic and commercial, it helps with identifying research priorities, developing new treatments, basically getting that voice of the patient in there to tell researchers whatās the most important and what matters to them.
Rich: So another question Helen, how do the panel feel about the changing genomics landscape?
Helen: A good question and I think overall itās a balance between excitement and hope on the one hand, and a bit of apprehension and caution on the other. So the panel is really excited about the advances going on in healthcare, weāre entering an age now where weāre promised a much more proactive, as opposed to reactive approach to healthcare. You were talking earlier Rich, about having your genome sequence, and this is something that you have for life, itās like your passport, your fingerprint, so from infancy to old age youāve got this data which is held somewhere which holds so much promise of predicting if you might develop a disease, whether you might react badly to a drug, so ultimately it offers great potential to improve outcomes for patients, their families and the NHS. Again, we spoke earlier about this holds so much promise for producing the diagnostic odyssey that so many parents go through when the children are born with a condition that doesnāt have a diagnosis, potential to diagnose things like cancer a lot earlier where itās more treatable and to prevent disease as well, I know thatās something Genomics England isnāt specifically looking at, but through screening programmes, using things for example like circulating DNA which may be able to pick up that there are things going on and picking things up earlier means that those things can be dealt with earlier.
I mean thinking of my own personal example, I know I have Lynch Syndrome, I know that I am at risk of developing bowel cancer now, but that means I can do something about it. So I have my colonoscopies every two years, I take aspirin every day because that reduces my chance of getting bowel cancers and Iām much more symptom-aware, so having that knowledge up front is very helpful in being able to move forward and reduce my chance of getting an advanced cancer.
The panel is also very excited about the ongoing collaborations and the novel therapies that are being developed through the rare therapies launchpad, these offer a lot of hope for treating previously untreatable conditions, and improving accessibility to treatments, and obviously more targeted treatments for cancer, you know, weād need more effective treatments for cancer but with reduced side effects, so that in a nutshell, those are the other positive sort of things that the panel feel excited about. Where theyāre slightly more apprehensive or concerned, I mean they do acknowledge that there are challenges ahead and there are big concerns about the NHSās ability to cope with increase in demand for genomic testing and particularly worries about education and training of healthcare professionals in genomics, how do they effectively communicate research findings or results to patients if they donāt have a broad understanding of genomics?
And then finally, letās hear from Emma.
Emma: I think Iām excited but cautious. I think itās really important to acknowledge that the research being undertaken is groundbreaking and the vast majority of clinicians have very little to know genomics education, and translating these findings into tangible benefits for participants is so very important, and something I think weāve really got to make sure we donāt lose sight of.
Helen: We talked earlier about awareness among the public about genomics and we do feel that thereās a need to drive education forwards, you know but this is challenging, given the rapid pace of developments that weāve spoken about, I think even for the panel members who I would say are relative experts in genomics now itās hard to keep up to date, so how do we do that moving forwards? Weāve talked about security of data, we understand there are moves to link more genomic data sets both nationally and internationally and that clearly has significant benefits because that brings bigger numbers of patients data together, but opens up potential risks in terms of security, so how do we make sure that the security of that data is as good as it is currently when itās held in one pot in Genomics England Research Library.
And just a couple of final concerns that were flagged by panel members, there is some apprehension regarding potential misuse with genomic data by insurance companies; weāre given a lot of reassurance about that but there are concerns that could potentially lead to the most vulnerable in society being unable to get affordable cover if theyāre found to have genomic changes that mean they are at risk of conditions or have certain conditions and there are also concerns about the ethical implications of AI in diagnosis and clinical decision making, you know, AI is obviously a fantastic thing for looking at patterns amongst a big lot of data, but how accurate is it and where does the human come in, in terms of decision making?
So those are, I think, the broad concerns from the panel. I donāt know if you have any thoughts on those, Rich?
Rich: I think the big thing to say is I think having the participant panel there, you said in the middle of that, become collectively quite expert and you recognise that. Having the ability to have these complex nuance conversations and have people share that and speak directly to us about it I think is the biggest thing ā lots of those points there made by the panel, I think both things that we have very much in our mind about things that one needs to balance and focus on, and there are also things that we already talk about which is reassuring I think as well, we talk about with the panel. I think one of the things for us as well is sort of being clear on some of the things where there are really clearly well-established red lines, for example, that point on insurance, but that is very clear and part of our role is making sure that that is there and people can feel comfortable in that context to understand that.
I think the main thing that I would say is thank you to you Helen, and to all of the panel and all of our participants because I said earlier, this is a team thing and you are all very much part of the team and we would not be able to do our jobs in any way, I wouldnāt even say effectively, I would say with the relevance, which is the thing that we drive for, the relevance to have impact for peopleās lives whose data we hold and will hold in the future. And so thank you for being part of the team.
Helen: Thank you. And I think thank you to Genomics England for having the foresight to create the participant panel in the first instance, it was there from the get-go and I think a really great opportunity for all of us to be involved in this, to have our voices heard and listened to, so thank you.
Weāll wrap up there. Thank you for joining me today and thank you for discussing your appointment as CEO for Genomic England, and your view on what the genomics ecosystem might look like over the next ten years. If you would like to hear more like this, please subscribe to the Behind the Genes, on your favourite podcast app. Thank you for listening. Iāve been your host, Helen White. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
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In this explainer episode, weāve asked James Duboff, Strategic Partnerships Director at Genomics England, to explain how genomic data can be used in drug discovery.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Naimah: How do pharmaceutical companies use genomic data for drug discovery? Today, Iām joined by James Duboff, a Strategic Partnerships Director here at Genomics England, to find out more.
So James, first of all, what is genomic data, and how does this relate to our genes?
James: Letās start with a simple explanation of what we mean by genomic data and our genes. So, every cell in our body contains a complete copy of our genome. Now, genome is kind of a mini instruction manual that describes exactly how to make you. Now, those instructions are written in a language called DNA, which is over 99 percent identical in every single human on the planet, so you and I are actually genomically very, very similar. The differences, however, are called variants, and theyāre what make us unique. Now, some of those variants can actually be very dangerous, and they can code for things like rare genetic diseases or even cancer. So, we need to read in detail exactly whatās going on in your DNA and in your genome to see where changes are and where those variants really are, and we do this by sequencing the genome. So, if you get a DNA sequence, thatās effectively an electronic readout of your genomic data, which is your genome in computational form.
Now, understanding that and working with that is still a relatively new field, so what we try and do is connect the genomic data, your genome, with health information, such as hospital records and what youāre presenting with in clinic, if youāre in a patient setting, and look at those together to give context to those variants in the genome. So, genomic research is actually where we look at how genes and physical outcomes could be linked. So thinking of, you know, biology and physiology term, what does a variant exactly do and how might it cause a disease.
Naimah: You mentioned both the genome and whole genome sequencing, and if our listeners arenāt too sure exactly what they are, they can listen to some of our other explainer episodes with Greg Elgar, who explains these concepts. So James, next could you tell me why are pharma and biotech companies interested in genomic data?
James: Ultimately, pharma and biotech companies are interested in genomic data because that really tells them whatās going on within the blueprint or that mini instruction manual of an individual. So, pharma and biotech have dedicated research teams that focus on genomic research, and they look through genetic databases across the world, such as Genomics England and others, to really understand the role of the genome in their target disease areas. By looking at those, that helps them develop new drugs and tools to specifically diagnose, treat and also even cure these diseases.
Naimah: So, how exactly do they do that? Can you explain it in some simple steps?
James: I think there are four key areas that they need to focus on. So, starting with the first, where, whereabouts on a genome should they focus? Now, the way that a pharma company would do this, or any researcher really, is by taking two populations of people. So, youād take a population who have a known disease, and youād compare that to people without. Now if youāre looking at the genomes of people with the disease and those without the disease, you can kind of play spot the difference between those two, and understand whereabouts on the genome variants appear for the disease population and not for the healthy or undiseased control group. Now, when you do that, you can kind of pinpoint exactly whereabouts you see variants only in that patient population. That helps you identify your target, and thatās known as target identification, which is essentially pinpointing that spot on the genome thatās linked only to the disease. Once you know that, you can use that as a potential target for a new drug.
So, once youāve found that variant, the next step was, what does that variant do? Is it potentially overproducing something? Is it activating a promoter and therefore making more and more and more of a gene product that, you know, might be toxic inside a person if you have too much? Even too much of a good thing could be a bad thing. So, is that the case? Or does that variant cause an underproduction or something to just be not actually made by your body at all? So, if that variant kind of interferes with a piece of genetic code, it could stop that gene from producing anything, and therefore you might be effectively detrimented and deprived of that particular gene product. And both of those, an overproduction or an underproduction, could lead to a disease. So, to understand that in more detail, you might need to look at gene products as well.
The next step, once you know whereabouts in the genome youāre looking and what exactly a variant does, the next step really for a pharma company is how could you fix that. So, if youāre looking at too little of something ā so, if a variant stops a gene from actually developing into a gene product then you might need a drug to boost or to compensate for that, so potentially a supplement or having some kind of drug that can get the body to make more of that product. If on the other hand your body is making too much of something in a way that could be toxic, you kind of want a drug to reduce those levels, so a drug that could potentially breakdown that gene product so that you donāt have too much of it, or stop it from working effectively, so that it doesnāt seem as if you have too much of it, or otherwise prevent it being made altogether.
Now, one example of this prevention is actually a gene silencing drug, or an ASO, as theyāre effectively known, which can be used as a genetic mask. So, that sits on top of a gene and hides it, so the body canāt actually make that dangerous varied gene product. Now, if youāre going to make something like that, you need to be absolutely sure that masking that entire gene and stopping even a varied form of it isnāt dangerous, so that last step really is making sure that your drug is safe and wouldnāt cause any other issues. So, traditionally, that would have been done using animal models as kind of a surrogate organism, but now using genomic databases, you can use human genomics as kind of real world examples of applying say a genetic mask and hiding an entire gene or genetic section, and you can look through genetic databases to have a look for individuals who are alive and hopefully healthy in the population, who donāt express a certain gene. So, if you can find people who are healthy, who donāt have that gene or have variants that stop that gene from being produced, you kind of can be confident that you can make a drug to cover that and it would be considered safe.
Naimah: Okay, so thatās really interesting. So, what youāre saying is, by using human genomic data, we can test the impact and safety of gene targeting drugs directly in humans.
James: Yes, exactly. So, you can ask that question of would hiding that gene entirely cause any other health issues or any adverse effects really from a drug that hides it. And the really useful thing about that is that weād know the impact of a gene targeting drug before youād say start a clinical trial, so that really stacks the odds in your favour of the drug working safely, which is really powerful for a drug company that would otherwise invest a lot of money in a clinical trial that could be a risky endeavour for the company and also for participants. So, this is very useful for patients, and also fundamentally itās a lot more useful for a company to be assessing safety using humans and human genomics directly as opposed to using a surrogate organism like a mouse, which many people would argue is not a good reflection of what would happen in humans.
Naimah: Can you tell me briefly if genomics can be applied to other stages of the drug delivery pipeline?
James: Yes, in fact genomics can be applied all along the drug discovery and development R&D pipeline. So, as an example, biomarker identification. A biomarker is a biological product or a chemical signal thatās associated with a disease, that you can find and monitor inside the
body. So, you can look at an increase in that biomarker or a decrease in that to monitor whether a drug is working as youād expect. Is the drug increasing levels of something being produced, or is it decreasing that product being produced? And you can use that to understand whether itās possible to potentially develop that treatment, would that treatment actually work. So, thatās really important in monitoring drug impact and also understanding clinical endpoints for a trial.
You can also look at biomarker identification to look for genes and variants that are associated with a disease that could help you understand who best to enrol in a clinical trial. So, clinical trial recruitment is another key area, where if you involve the genome in your enrolment criteria, you can essentially just recruit the most suitable people where you know the drug will work best, and also youāre sure that the drug would be most safe and effective at treating their condition. And then actually to go a step further on the clinical trial point, clinical genomic datasets are actually really useful, if you think about it, in the opportunity to recontact participants too where theyāve consented. So, what I mean by that is, a pharma company could directly find and recruit optimal patients with either a rare disease or a cancer where their drug would help most, based solely on their genome, and thatās a really, really exciting point, because that offers the opportunity for pharma to both develop a drug based on that genomic dataset, but also then deliver the drugs to treat those same exact people.
Naimah: So, how do pharmaceutical companies access this data?
James: Well, there are different datasets, and each different dataset has a different population within those, and each of them have their own consent models and governance rules on how that data can be used and who can access it, and how they access it. So, some of these datasets just hold genomic data, while others would have additional biochemical data and also health information potentially on participants. So, depending on the different types of data, thereāll be different access limitations and restrictions. So, some entities and some datasets can be simply downloaded, and that could be very useful for pharma and biotech companies, because that means that they could use them inhouse. Other datasets and groupings of genomic data and libraries of sorts would operate a TRE or an SDE model, so that stands for a trusted research environment or a secure data environment, and these are essentially ā you could consider them as libraries, like a reading library, where you can come in and read the books but not take out those books, or genomes in this case.
Naimah: Can you tell me, what impact does the use of genomic data for drug discovery have on the public or patients?
James: Oh, thereās huge impact on drug discovery, and ultimately genomic research really helps drug companies make better treatments for patients and the public. So, weāve already seen the benefits of genomics used in drug discovery, and I think we will do more and more as DNA sequencing is used more in clinic, and also thatās going to keep happening the more cost keeps dropping, which is making genomic medicine really and genomic healthcare increasingly feasible at scale. So, 20 years ago, it cost over Ā£100 million and it took years to sequence a genome, but today you can sequence a genome within a few hours for under Ā£1,000.
Naimah: What are the benefits of having your genomes sequenced in a healthcare setting?
James: Ultimately, genomics enable a faster and more accurate diagnosis. That enables early intervention, which can really maximise the treatment impact and improve outcomes. So, what I mean by early intervention, if you can give a drug before someone shows symptoms then you could prevent them ever getting the disease, so thatās moving towards preventative medicine, which is really exciting and absolutely enabled through genomics. So, genomics really help pharma companies make also better drugs and target the underlying disease directly rather than just addressing symptoms, so this helps them make more effective and safe treatments to really improve overall outcomes for patients.
Another thing to think about is that some drugs are already on the market but used for different reasons. Genomics can help pinpoint the root cause of that disease within a genomic setting, so that can highlight repurposing opportunities for existing drugs. Now, existing drugs are those that have already been proven safe in humans and approved for use, albeit potentially in a different setting. Now, if a drug could be shown by genomic research to be targeting the same root cause within the same biological pathway, they could very easily be repositioned and applied in an entirely new disease.
So, I guess to finish, through genomics, drug development can help us move towards precision healthcare, and by that I mean making targeted treatments for specific patients. That will be far more effective and have significantly fewer side effects. In the case of participants in clinical genomics sequencing programmes open to researchers, that also means matchmaking opportunities for companies to diagnose and treat unique patients. In the case of ultra rare conditions, that means they can create a treatment specifically for that patient and then work with their doctors to deliver the brand new drug just to them, to ultimately save lives.
Naimah: That was James Duboff explaining how pharmaceutical companies can use genomic data for drug discovery. If youād like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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Ethical considerations are essential in genomic medicine and clinical practice. In this episode, our guests dive into the details of ethical principles, highlighting how they can be brought into practice in the clinic, whilst considering the experiences and feelings of patients and participants.
Our host, Dr Natalie Banner, Director of Ethics at Genomics England, speaks to Professor Sir Jonathan Montgomery and Dr Latha Chandramouli. Jonathan is the Chair of the Genomics England Ethics Advisory Committee, and a Professor of Health Care Law at University College London. Latha is a member of the Ethics Advisory Committee and the Participant Panel at Genomics England, and is a Consultant Community Paediatrician working with children with complex needs.
"You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You donāt want to have separate discussions of things."
You can download the transcript or read it below.
Natalie: Welcome to Behind the Genes.
Jonathan: The first difference is that the model weāve traditionally had around clinical ethics, which sort of assumes all focus is around the patient individually, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions. Families differ enormously, some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approaches to genomic issues must respect everybody in that.
Natalie: My name is Natalie Banner and Iām the Director of Ethics here at Genomics England. On todayās episode, Iām joined by Chair of our Ethics Advisory Committee, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli, member of the Ethics Advisory Committee and the Participant Panel, whoās also a community paediatrician working with children with complex needs.
Today weāll be discussing why ethical considerations are crucial in genomics research and clinical practice and what consent means in the context of genomics. If you enjoy todayās episode, weād love your support. Please like, share and rate us wherever you listen to your podcasts.
At Genomics England, we have an Ethics Advisory Committee, which exists to promote a strong ethical foundation for all of our programmes, our processes, and our partnerships. This can mean things like acting as a critical friend, an external group of experts to consult. It can mean ensuring Genomics England is being reflective and responsive to emerging ethical questions, especially those that arise as we work with this really complex technology of genomics that sits right at the intersection of clinical care and advancing research. And it can also ensure that we are bringing participant voices to the fore in all of the work that weāre doing.
Iām really delighted today to welcome two of our esteemed members of the ethics advisory committee to the podcast. Professor Sir Jonathan Montgomery, our Chair, and Dr Latha Chandramouli, member of our Participant Panel. So, Jonathan, if I could start with you, could you tell us a little bit about your background and what you see as the role of the ethics advisory committee for us at Genomics England?
Jonathan: Thanks very much, Natalie. My background professionally is Iām an academic, Iām a professor at University College London, and I profess healthcare law the subject that Iāve sort of had technical skills in. But Iāve also spent many years involved in the governance of the National Health Service, so I currently chair the board of the Oxford University Hospitalās NHS Foundation Trust.
Iāve spent quite a lot of time on bodies trying to take sensible decisions on behalf of the public around difficult ethical issues. The most relevant one to Genomics England is I chaired the Human Genetics Commission for three years which was a really interesting group of people from many backgrounds. The commission itself primarily combined academics in ethics, law and in clinical areas, and there was a separate panel of citizens think grappling with things that are really important. Genomics England has a bit of that pattern, but itās really important that the ethics advisory committee brings people together to do that.
You asked why ethics is important and how it operates, I suppose the main thing for me is that these are tricky questions, and you need all the voices, all the perspectives, all the experience in the room working through at the same time. You donāt want to have separate discussions of things. My aim as Chair of the advisory committee is essentially to try and reassure myself that weāve heard all the things that we need to hear and weāve had a chance to discuss with each other as equals what it is that that leads us to think, and then to think about how to advise within Genomics England or other people on what weāve learnt from those processes.
Natalie: Fantastic. Thank you, Jonathan. And as you mentioned, the necessity of multiple different perspectives, this brings me to Latha. You have lots of different hats that you bring to the Ethics Advisory Committee, could you tell us a little bit about those?
Latha: Thank you, Natalie, for that introduction. Iām Latha Chandramouli, Iām a Consultant Community Paediatrician and Iām based in Bristol employed by Siron Care & Health. Iām a parent of twins and from my personal journey, which is how I got involved, my twins are now 21 so doing alright, we had a very, very stormy difficult time when they were growing up with our daughter having epilepsy, which just seemed to happen quite out of the blue sometimes. It started to increase in frequency the year of GCSE, to the point that she would just fall anywhere with no warnings and hurt herself. This was difficult for me because as a clinician, I was also treating patients with epilepsy. I also was looking at the journeys of other people and was able to resonate with the anxiety as a parent. Worry about sudden death in epilepsy, for example, at night, these were the kind of difficult conversations I was having with parents, and I was now on the other side of the consultation table.
I was also doing neurology in those jobs in a unit where there was epilepsy surgery happening, so it was, in very simple terms, very close to home. It was quite hard to process, but equally my job I felt was I should not separate myself as a parent but also as a clinician because I had information, I had knowledge, and we had conversations with my daughterās clinician.
We were then recruited into the 100,000 Genomes Project which had just started, so we were just a year after it had started. That was an interesting experience. We were in a tertiary centre with a lovely clinical geneticist team, we had the metabolic team, we had loads of teams involved in our daughterās care. We could understand as a clinician, but there was also my husband, although a clinician, not into paediatrics and was in a different field. It was important that it was the whole family getting recruited into the journey. My daughter also was quite young, so obviously we have parenting responsibility, but we were very keen to make sure they knew exactly what they were getting into in terms of the long-term issues. Despite being informed, at times there were things that we went in with without understanding the full implications because life happens in that odyssey.
I think that was my biggest learning from those exercises when I began to question certain other things because I then had a breast cancer journey, but obviously I was not recruited as part of that process for the 100k. Those were kind of some of the questions coming in my head, how does the dynamic information sharing happen, and thatās how I got involved, found out a bit more about the participant panel, and thatās how I got involved from 2018 which has been an interesting experience.
Firstly, I think with Genomics England they are probably one of the groups of organisations having a big panel of people, genuinely interested in wanting to make a difference and represent thousands of participants who have got their data saved in the research library, recruited under the two broad arms of cancer and rare disease. We were under the rare disease arm, although I could resonate with the cancer arm because of my own experience.
At various times there were lots of opportunities to think about how data is accessed, are we getting more diverse access to data, all those different issues. At various points we have been involved in asking those questions. We all have different skillsets, you see, in our group. Some have got information governance hats; some have got data hats and PR hats. Iāve got a clinical hat and a clinical educator hat. I am a paediatrician, so I have recruited people for the same, for the DDD, for CGH etc, and Iāve always gone through the principles of consenting, confidentiality, the ethics. I also work in a field, Natalie, where there is a huge, as you are aware with the NHS resource issues, thereās huge gaps and waiting lists, so itās trying to make sense of what is the best thing to do for that patient or that family at that point in life. Are we obsessed by a diagnostic label? Are we going down a needs-based approach? Itās having always those pragmatic decisions to be made. Thatās one of my clinical hats.
I also am an educator so Iām very keen that young medical students, be it nursing students, everybody understands genomics and theyāre signing up to it so that we can mainstream genomics. Those are some of my alternative hats which kind of kick in a bit.
Natalie: Fantastic, thank you, Latha. As you say, there are so many different perspectives there. You talk about kind of the role of the whole family as part of the journey. You talked about consent, confidentiality, data access issues, lots of questions of uncertainty. Perhaps, Jonathan, I can come to you first to talk a little bit about what is it about the ethical issues in genomics that may feel a little different. Are they unique or are they the same sorts of ethical issues that come across in other areas of clinical practice and research? Is there something particularly challenging in the area of genomics from an ethical perspective?
Jonathan: Thanks, Natalie. I think all interesting ethical issues are challenging, but theyāre challenging in different ways. Iām always nervous about saying that itās unique to genomics because there are overlaps with other areas. But I do think there are some distinctive features about the challenges in genomics and I suppose I would say they probably fall in three groups of things that we should think about. The first youāve touched on which is that information about our genomics is important not just for the individual person where you generate that data but itās important for their families as well. I think the first difference is that the model weāve traditionally had around clinical ethics, which sort of assumes it all focuses around the patient individual, is not enough to deal with the challenges that we have, because we also have to understand how we support families to take decisions and families differ enormously. Some families are united, some families have very different needs amongst them, and we have to recognise that our ethical approach is genomic issues must respect everybody in that, so I think thatās the first difference.
I think the second difference is that the type of uncertainty involved in genomics extends much further than many other areas. Weāre talking about the impact on peopleās whole lives and itās not like a decision about a particular medication for a problem we have now or an operation. Weāre having to help people think about the impact it has on their sense of identity, on things that are going to happen sometime in the future.
And then thirdly, I think the level of uncertainty is different in genomics from other areas of medicine, and the particular thing I think is different that we have to work out how to address is that we canāt really explain now all the things that are going to happen in the future, because we donāt know. But we do know that as we research the area, weāre going to find out more. So, what are our obligations to go back to people and say, āwe worked with you before and you helped us out giving data into the studies. We couldnāt tell you anything then that would be useful to you, but actually we can now.ā. Now, thatās different. That continuity sometimes talked about, you know, what are our obligations to recontact people after a study. You donāt usually have those in the ethical areas weāre familiar with; youāre usually able to deal with things in a much more focused way.
I think those differences, that itās not just the individual, itās the family, that itās not just about a specific intervention but itās about an impact on peopleās lives and that we will need to think about what we had to do in the future as well as what we do immediately. They make it different in genomics. Some areas of healthcare have those as well, but Iām not aware of anywhere that has all of that in the same position.
Natalie: Latha, Iām wondering if that kind of resonates with your experience, particularly the navigating of uncertainty over time?
Latha: Yes. I would say thatās exactly what youāve said, Jonathan. I think itās the whole process of consenting with the view that you do not know much more beyond what you know about the situation here and now. Part of that is like any other situation, thatās why we have evolved from I would say penicillin to the SMA gene therapy. If we did not do this, we wouldnāt reach frontiers of medicine and kind of thatās how I explained to families when Iām recruiting and Iām also very clear that itās not all about research but itās combination of the tool and focusing on your, but itās also helpful for research even if you do not get answers. I think itās very important at that stage, Natalie, that we have to be clear we may not get many answers at the very outset and also when do we really look at data, do we have that kind of realistic pragmatic resources to be able to relook every time? Is there a method of dynamically having that information from our NHS spine if somebody of the trio has contracted a condition, would that be fed in.
Those are the kind of questions parents and families ask. I cannot honestly answer that, and I often say that is optimal plan. If things go to plan, that will be the area weād be heading towards, but currently I canāt give you timelines. I think itās important we are honest at the outset and manage expectations. Thatās how you engage families and, in my case, itās more these children and families, so engaging is crucial. As you mentioned, itās also the question that gets asked is very simply in my mind, you know, sometimes there is that conflict because of my own personal recruitment to the 100k project, I have an interest in genomics and, therefore, I would be very keen to embark on that journey and I feel that is the way forward.
I also understand as a member of my clinical team, for example, where I know thereās a huge waiting list, how am I best using the taxpayersā money thatās been entrusted to us. If I think the waiting list is so high, can I see two further patients in that time that Iām using to consent which is not going to add much more to that childās journey, for example, with autism or ADHD. Itās trying to be careful where is the ethics in doing an investigation, and thatās like in any situation as a clinician. I think thatās not much different, but it is kind of similar, but it opens up a huge area of uncertainty. As you would with any investigations, if you just went and did scans on everybody, you might pick things up which you donāt need to do anything about. Itās being sensible and being honest.
Jonathan: And for me, Latha, that raises two areas which I think are really interesting about genomics. The first of those is the language weāve tended to use about consent I donāt think captures all the ethical issues that we raise, because weāve tended to think about consent of something that happens once and then gives people permission to do things. Whereas what youāve described, and what we find ourselves often thinking about, is that we have to get a respectful relationship with people, so the consent is not to doing certain things, itās to agree to part of what I think about as a common enterprise. So, patients and families are partners with the clinicians and the researchers, and itās not that they sign a form and then the consent issue goes away, which is how lawyers tend to think about it, itās that weāre starting something together and then we need to think about how do we keep the conversation going with mutual respect to make sure that everybodyās values are there.
I think the second thing you picked up is a sense of the need for a better explanation of how research and care interact with each other. Because the care we get now is built on the evidence that people have contributed to in the past, so weāre benefitting from our predecessors, and we want to contribute to our successors and our family getting better care in the future. I think one of the things about genomics is that the gap between those two things is really non-existent in genomics, whereas if you take a medicine, the research thatās been done to make sure that medicine is safe and effective will have been done on a group of people some time in the past that Iāll never meet, whereas in genomics Iām part of the production of that. I may get some benefit now, my friends or family may get some benefit, but there isnāt this sort of separation between the care and the research bit that weāre used to being able to think about. This is a much more mutual exercise and the stakes that we all have in it are therefore intertwined much more closely than they are in some areas of medicine.
Latha: I agree totally. In our case, for example, I went in in thinking we might get a targeted medication. I know there are certain levels of epilepsy medications anyway, so in principle it wouldnāt have mattered a lot. However, it was important to know what the outcome was going to be because we had various labels, potential mitochondrial disease, potentially some susceptibility disorder, so we were on a spectrum from something very minimal to the other end on neurodegenerative situation. We were left dangling and we thought it would be good to embark on this journey, at least thereāll be some outcome, some prognostic outcome, and more importantly we donāt have any answers, but we actually can be a hopeful story for someone else in that same position, and I think thatās how weāve embarked on it. Thatās kind of my personal experience.
But in just harking back to some of the ethical issues, itās again very clear educating the clinicians, as you said, itās that relationship; itās not just a piece of paper, itās that development of relationship with your families, some of whom have got very complex issues going on in their lives themselves. I work in a very, very deprived part of Bristol, which is the highest deprivation index, so they have got lots of intergenerational things going on, there is poverty, there is learning issues and crime, lots of things going on. Youāve got to time it right, what is important for this family here and now, and then work on it.
Thereās also the other issue that we may not continue to remain their clinicians after recruiting. I think thatās so important to recognise because the results might come back but you kind of discharge them and it may take a few years by the time the results come. How do you then cross that bridge if some unexpected results come, which then means contacting various other extended family members. I think thatās the bit we all do because thatās part of the journey weāve embarked on, but itās also thinking is there someone else whoās probably better placed, like a GP or a primary care person whoās actually holding the entire family and not just one person, not just the adult who has been the index patient. Itās just trying to think the ethics of it because itās all about engagement and being transparent with families.
Jonathan: I think youāve put your finger on another element thatās really important about the ethics. In the same way as in relation to the position of the individual patient, and we need to see them in families, which doesnāt fit very easily with lots of the clinical ethics that weāve been used to. Itās also the case that a lot of the traditional clinical ethics has focused on the individual responsibilities of clinicians, whereas what youāve just described is that we have to work out what the systemās responsibilities are, because it may not be the same clinician who is enabling good ethical practice to be pursued. These are both ways in which our paradigm of ethics has to be expanded from other areas of medicine.
Latha: Yes, I agree. And the other bit I think we can probably reassure quite nicely is about the ethics about information governance and we as data custodians storing information, how do we give with great ethics and discussion the access to research and being mindful that it is again thinking along the same principles GMC kind of had about the good for the common good and using resources equitably, but again being sensible with equality issues that a single condition doesnāt get forgotten. Itās that right balance that whilst we are doing common good, we might have a condition which might have a treatable medication, but we have to focus on that as well as research. I think itās interwoven, all these ethical questions.
Jonathan: I completely agree, Latha. That interwoven bit is something where we need to be able to think through, āwhat is the role of Genomics England to improving that?ā. I think weāve got issues around the good stewardship of information which canāt be left with an individual clinician, they can only do that effectively if the system supports them and their colleagues in doing that. But weāve also got to be proactive, weāve got to recognise the limitations of the system, so one of the really important initiatives from Genomics England is the Diverse Data initiative because we know that without aiming to solve the problem, we will get a skewed dataset and clinicians canāt properly look after people. That tells us that the ethics in this area has to do more than avoid things going wrong, it also has to work out what it means to do things right, and what systems we have to put in place to do that. I think thatās a particular example of a shift we need to do across our ethics around healthcare.
If speak to the sort of things that lawyers have got wrong around this in the past and some of our history, we focused a lot of our effort on stopping things going wrong. That has meant that we havenāt spent as much time as we need to on thinking about how to make things go right, because stopping things going wrong is almost always too late. What we have to do if weāre being proactive is work out how to set things up in a way that will make sure that the chances of it going wrong are quite small and the chances of doing good are much increased. I think thatās one of the key challenges that we have in Genomics England and as an Ethics Advisory Committee. The things weāve inherited tell us quite a lot about things that have gone wrong, but actually what weāre trying to do is to get our heads around what could go right and how to make sure it does.
Latha: Also, you mentioned about Diverse Data, I think thatās another important thing as we noticed in COVID as well. There were lots of disparities in the social model and the inequalities that have resulted in death, but also potentially HLA or epigenetic issues which could have contributed. We do have the COVID-19 genomic datasets, but itās again important to make sure that we donāt perceive certain ethnic minority populations. Just not accessing or considering them to be hard to reach, I would say for them Genomics England is hard to reach. Itās looking at it slightly differently and thinking, āhow can we reach them? how do we maybe use community workers and maybe even clinicians?ā, I think theyāve got the best trusting relationships with their clinicians and using them to recruit. As you say, even before things get more complicated, you recruit them earlier so that youād go down the prevention route rather than the gone wrong route and then look for answers later.
Jonathan: Latha, I think you put your finger on something really challenging for a group like the Ethics Advisory Committee at Genomics England, which is that however hard we try to get a range of experiences and voices, thatās not a substitute for getting out and hearing from people in real world situations. I think one of the things Iāve learnt over the years from my national health service work is that you cannot expect people to come to you, you need to go to them. In COVID when we were trying to understand why some groups were more reluctant to take up vaccines than others, there was no point in doing that sitting in your own places, you had to listen to peopleās concerns and understand why they were there. One of the things weāre going to have to be able to do as the Ethics Advisory Committee is work out when we need to hear more from people outside of the Genomics England system, and Iām a great believer that if itās right that we need to go where people are, you have to try not to reinvent mechanisms to do that. You have to try and learn where are people already talking about it and go and listen to them there.
Latha: Absolutely, yeah. I think they listen because I do work as a paediatrician with a safeguarding hat, and I think the same principles resonate in child death work. For example, simple messages about cot deaths, you would think that if a professional tells the same message to a parent or a carer itās better received if itās another family, a younger person, another layperson giving the same message. It comes back to whoās more receptive. It could be a community worker.
As you mentioned about vaccination, during the vaccination initiative I decided early on that Iām probably not going to do a lot because Iām not an intensivist, how do I do my bit in the pandemic. I decided to become a vaccinator and I thought with my ethnic minority hat on, if I went out there to the mass centres and actually vaccinated there or in mosques or wherever else, without even saying a word Iām giving the message, arenāt I, that, look, Iām fearlessly coming and getting vaccinated and vaccinating others, so please come. I think that has helped to some extent, just trying to reach out. Other than saying these people are not reaching us, itās got to be the other way around.
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Natalie: Iām really enjoying this conversation. In part because I think it highlights just how valuable it is to sort of think about ethics a little bit differently. Historically, and certainly I think within the research community, ethics can just be associated with consent. Consent is the ethics issue and if you solve for consent, then you donāt have any other issues to think through. I think what this conversation is really highlighting is just how much broader the ethical considerations are. Beyond that, itās still very important that consent can be that sort of anchor point for communication and engagement, but itās not simply a one-off. And to be able to think through ethics not just in terms of risk or moving forward when things have gone wrong in the past, there is actually a really positive aspect to it which I think is critically important.
Itās great to hear your thoughts about that different approach to ethics that I think does embed it much more in community thinking, in questions of equity; itās not just the individual. I want to follow-up by just asking where do you think the future lies in thinking about ethics both for Genomics England and the Ethics Advisory Committee, but in the space of genomic research and medicine more broadly, given that it sits in this kind of very interesting and quite complex space between research and care in the clinic.
Jonathan: I mentioned earlier in the conversation I think about this as a common enterprise that we have shared stakes in. Academic researchers have a stake in trying to build a better more robust evidence base, clinicians have a stake in being able to offer something to the people that theyāre looking after. Families have stakes not just in their own immediate care, but they worry about their siblings, they worry about their children, their grandchildren. There are also of course industrial players, so people trying to build a business out of making better medicines in the future. There are government players trying to use public resources more effectively. I think what we have to try to create is a mutual process where we recognise that everybody has overlapping but slightly different values that theyāre pursuing and trying to get out of it, and how can we make sure that we govern our work in a way that reflects all of those stakeholders and recognises the respect thatās due to them. I think this is more like a sort of membership of a common project. And the problem with consent is it risks us saying you can be a member of this club but only if you accept the terms and conditions that the committee has decided is there. Thatās not going to be adequate going forward.
I think we need to make sure that everybody feels that they are respected, that they feel they can place their trust in the system that weāre designing. As an Ethics Advisory Committee, we have to ask ourselves what justifies us suggesting to people that this is trustworthy. We need to make sure we have good information governance that people are not going to expose themselves to breaches of privacy if they take part in this. But we also need to make sure that we donāt waste peopleās efforts. If people are prepared to be part of the research project, we shouldnāt have rules coming down on the data usage that say that weāre going to reduce the value of that contribution by saying it can only be used for one project and canāt be used for others, because actually that would not respect properly peopleās contribution to the process.
We need to ask ourselves not just about the protective element of trustworthiness but that element that says we will make sure that you get as much as we can design of the things that you think are important from this project. They wonāt be identical for each group, and they wonāt be identical within each group. Different family members of participants will have different balances, but they all have to believe that this is a good club to be part of and that they have been part of agreeing ways of working that they think will produce a better future that they want to be part of and that they want to be proud of saying we have helped create this future.
Latha: I kind of agree with all that youāve said. I think itās most important not to forget because Iām also a participant, like my trio sample is there in the pipeline, and I know my data is sitting there. I also have trust that there is good information governance, the data is secure, so itās reinforcing that, but itās also being very honest that itās obviously the data is there, but we canāt forget the person or the persons at the centre of it, so itās not just alphabets or sequences of alphabets, but it is that whole person, and that person represents a group of individuals, family members, different generations, and they have embarked on it. Even if they know they may not get hope they might provide hope for others. Itās being therefore respectful.
I think that is the first thing I think is the principle of it and if you respect. If you think it could be the same principle that we use in clinical practice, the friends and family test, because Iāve been on both sides of the consultation table, I think Iāve become a better doctor because Iāve been an anxious mum, and my anxieties were dismissed as being an anxious mum and I donāt care. As far as my child is concerned, my anxiety was valid and so I would do everything to reach an outcome as to whatās best for that person. Itās made me a better doctor because I can see it from both the perspectives. Most of us are human beings, apart from AI technology looking at the dataset, so we all have conditions ourselves, weāve got doctors with health conditions, weāve got clinicians, academics, technicians, nurses everybody whoās got a friend or a family member or themselves having a health condition. I think its fundamental principle is that friends and family test. How would I like my data stored? How would I like my data analysed? Could it do this, could it give me some information on how I would get cured or treated or be managed? How would it affect my insurance, or will it find out data about whoās the father of this child, for example? Itās being honest and being honest about the uncertainties as well.
When Iām recruiting, Iām very clear that these are what I know that I can tell you about the risks. But then there may be other risks that I do not know about. If youāre honest about it and acknowledge what is the limit of the knowledge of science at this point in time, because you said there are so many stakeholders, there are researchers and academics whoāve got interest in some areas, it could have developed because of a family member having that problem, but whatever it is that is a great interest because that intelligent mind is thinking ahead and we need to encourage that. It could be for writing up papers, it doesnāt matter. Whatever be the reason, if itās for the common good, thatās fine. Itās also thinking how are we keeping our families in the loop, so you have newborns, youāve got young people sometimes with significant disabilities so they are relying on a parent or a carer to consent for them, but some are not so disabled but they have needs, theyāve got rare conditions, but they can make their consenting issues known when they turn 16, for example. Itās the changing policies and they can withdraw at some point in life or there may be a member of the family who doesnāt want to be part of that journey anymore. Itās allowing that to happen.
Jonathan: I think thatās a really interesting example youāve just touched on, Latha, where I may diverge a bit in terms of what I think is the key issue. The right to withdraw I think is a really interesting challenge for us going forward, because we developed the right to withdraw in the ethics of research studies that had physical interventions. Itās really clear that someone who is being put to discomfort and is having things done to her body, if she wants to stop that, we canāt justify continuing on the basis of it being a research project. But Iām less clear whether that applies to withdrawing data from data pools. I think there are a few dimensions to that which I hope as an Ethics Advisory Committee weāll have a chance to think through a bit more. One is the mutual obligations that we owe to each other. Iām not in these particular studies but I do try and take part in research studies when Iām eligible and invited to because I think research is important. When I take part in things and when our participants have taken part, theyāre doing something in which they rely on other people participating because the aggregation of the data is what makes it power.
One of the things we have to be honest about is what are our mutual expectations of each other, so I think we absolutely have to hold on to the fact that people should be able to withdraw from further interventions, but Iām not convinced that you should have the right to say the data Iāve previously contributed that other people have relied on can suddenly be sucked out and taken out of it, because I think itās reasonable for us to say if this is a sort of part of an enterprise. While youāre part of it, youāve made some commitments as well as, and thatās part of the mutuality of the respect. I think I personally would want to argue you can withdraw from new things, but provided that your privacy is not intruded on, so weāre talking about data health anonymously, you shouldnāt be able to say donāt process it anymore.
Latha: No, no, no. What I meant was from my perspective I would like to be constantly involved and get information through trickling. I donāt know what my daughter feels years down the line, she might say Iām happy for my data to be used for research, but I donāt want to know anymore. There are two aspects of that, and I think if we are clear with that and say continue with my data being used for research, but I donāt want to get anymore letters. I think those are the kind of questions I face when I tell them families that these are the uncertainties, you can have your blood stored, you may not be approached again for a resampling unless you have some other issues, but are we happy with this? I think thatās what I understand, and I try and recruit with that intention.
Jonathan: And that makes lots of sense to me. As you say, you probably canāt speak for your daughters now, and you certainly canāt speak for them when they become parents for themselves and those things, but we do need to create an ethical framework which recognises that people will change their mind on things and people will vary about what they want to do. But because we have mutual obligations, what that means and the control we can give, we have to be open and honest about what choices we can give people without undermining the enterprise and what choices we say, āyou donāt have to do this, but if you want to be part of it, there are some common mutual obligations that are intrinsicā, and thatās true of researchers, itās true of clinicians, itās true of anyone who works in Genomics England or the NHS.
But I donāt think weāve been very good at explaining to people that thereās an element of this which is a package. A bit like when I bank, I allow the bank to track my transactions and to call me if they see something that looks out of the ordinary as a part of the protections from me. I canāt opt out of that bit. I can opt out of them sending me letters and just say do it by email or whatever and I have some choices, but thereās an infrastructure of the system which is helping it to function well and do the things itās able to do. I donāt think weāve been very good at explaining that to people, because weāve tended to say, āas long as youāve signed the consent form at the beginning of the process, it doesnāt really matter what happens after that, youāve been told.ā. Thatās not enough I think for good ethics.
Latha: And I think that comes back to the other issue about training those who are consenting. I speak from personal experience within my own teams I can see somebody might say, āI donāt do whole genomic sequencing consenting; I donāt have the time for it.ā. I might even have my organisational lead saying when we had a letter come through to say now weāre no longer doing this, weāre going to be doing this test for everybody, thereās a whole gasp because itās at least two hoursā worth of time and how are we going to generate that time with the best of intentions. I think thatās where I think the vision and the pragmatic, you know, the grounding, those two should somehow link with each other. The vision of Genomics England with working with NHS England and with the future, Health Education England arm that is not amalgamated with NHS England, is trying to see how do we train our future clinicians who will hopefully consider it as part of their embedded working thinking and analysis, but also, how do we change the here and the now?
The more senior conservative thinking people, who are worried about how do they have to generate time to manage, weāre probably already a bit burnt out or burning out, how do they generate time? If you then discover new conditions whether there is already bottleneck in various pathways, how are we ethically managing the new diagnosis and how will they fit in in the waiting list criteria of those people on the journey who are symptomatic. I find that bottleneck when I have conversations with colleagues is the anxiety, how is that going to be addressed.
Jonathan: Latha, youāve sort of taken us around in a circle. We started off thinking what was special about genomics, and weāve reflected on āwe have to solve the problems of the health serviceā. I think that thereās some wisdom in that, because we are learning how to do things that are not unique to genomics, but thereās an opportunity in genomics to do it better and an opportunity for us to help other areas of the health service do better, too. I think weāve come around in full circle in a sense.
Natalie: Which feels like a lovely way to wrap up our conversation. I feel like weāve gone into some of the deep ethical principles but also really shown how they can be brought into the practice, into the clinic and brought to bear the thinking and the feelings, the hopes the anxieties of participants. Thereās a very, very important range of different voices so a very rich discussion.
Iād just like to thank you both very much for joining us on the podcast. Thank you to our guests, Professor Sir Jonathan Montgomery and Dr Latha Chandramouli for joining me today as we discussed ethics in genomics research and practice. If you would like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app. Thank you for listening. Iāve been your host, Natalie Banner. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.
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In this explainer episode, weāve asked Professor Matt Brown, Chief Scientific Officer at Genomics England, to explain what personalised medicine is and how it could change the way we treat genetic conditions and cancer.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Naimah: What is personalised medicine? Iām joined by Matt Brown, chief scientific officer for Genomics England, to find out more. So, first of all, Matt, can you tell me, what is personalised medicine?
Matt: So, personalised medicine is about giving the right dose of a medicine and the right medicine to the right person. So, itās exactly the opposite of one size fits all. Itās what doctors have been trying to do ever since we had effective medicines, that is generally looking at the patient, what disease have they got, what factors are there about the patient that can help judge what dose they should give and for how long, of which medicine.
Naimah: So, people often refer to this as precision medicine. Is this the same thing?
Matt: Generally, the two terms are used interchangeably. I think precision medicine is more specifically about the dose perhaps, but effectively they both mean the right medicine at the right dose for the right person.
Naimah: And how can we predict what treatment will suit each individual patient best?
Matt: Well, to some extent, of course, this depends on the disease the patient actually has. We also know from a patientās history how theyāve reacted to similar medications in the past. So for example, some patients have lots of problems with anti-inflammatories, other patients donāt, so if you give an anti-inflammatory to somebody whoās had problems with them before, youāre likely to cause the same problems all over again. So nowadays, we have much, much better ways, other than trial and error, to predict what treatment will suit a patient best, and in particular, development of genetic markers to look at how their condition is going to respond best, and how the patient is going to tolerate the medicine you give them, and what dose you should be giving them.
Naimah: How could personalised medicine change the way we treat genetic conditions and cancer?
Matt: So, Iāll talk about cancer first up. In the past, we used to treat cancers based on the organ from which the cancer actually arose, and the more weāve learnt about what the genetic mutations are that cause cancers, the more cancer treatments are being decided based on the genetic mutation which is driving the cancer, and this has proven to be more effective than just looking at the organ from which the cancer arose. It turns out then that some medications which were only being used for specific cancers, are actually useful across multiple cancers that are driven by the same genetic mutations.
In lots of other common diseases though, we now know a lot about genetic variants which predispose people to adverse drug reactions, and so we can use genetic tests to predict whoās going to get those adverse drug reactions and avoid them. And similarly, we also know about genetic determinants of how people metabolise and, in many cases, activate medications, and that helps us a lot learning about what dose to give people.
Naimah: And how far away are we from seeing this routinely in clinical care?
Matt: We are seeing it in routine clinical care in some pretty narrow settings. So, there are genetic tests available for enzymes which are involved in activation of particular chemotherapy 5 agents. So, DPYD testing, for example, is widely used to predict peopleās likely response to a class of chemotherapy agent called fluoropyrimidines, or 5-Fluorouracil is a common one, and the genetic test basically picks out a group of people, a small number of people who are likely to have severe adverse drug reactions to that class of medication, and thatās been a really big success.
We also use it for picking some other severe adverse drug reactions to medications like gout medications, HIV medications and so on, but generally itās pretty narrow. What we want to get to the point is where we have people tested in advance of them needing medications, so that when they go to the doctor to be seen about a particular condition, the doctor already has the genetic test available to them, so the doctor can say if the medication is safe and what dose to use. This is what we call pre-emptive testing.
Naimah: That was Matt Brown explaining what is personalised medicine. If youād like to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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In this explainer episode, weāve asked Will Navaie, Head of Ethics Operations at Genomics England, to explain what ethics is and why it's important, in the context of genomics.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
Want to find out more? Check out the blog 'Genomics 101: What is ethics?'.
You can download the transcript or read it below.
Naimah: What is ethics? Today Iām joined by Will Navaie, whoās Head of Ethics Operations at Genomics England, to find out more.
Will: Ethics is part of philosophy, and itās part of philosophy that talks through a set of moral principles that govern our behaviour and our conduct. So, it might be thinking about whether something is good or bad. It might be thinking about whether something is good or better, or whether something is bad and worse. So, itās about values and how we demonstrate those values kind of in a moral framework. So, I like to think of ethics as, just because you can do something, it doesnāt mean that you should do something. So, the law dictates to us what we can do, but ethics then talks about actually you need to look at the context around a law and to see whether something is reasonable, and so ethics to me is the should. So, should we do something? Just because we can do something, it doesnāt mean that we necessarily should do that thing.
So, in medical ethics, we have four pillars or four areas that we concentrate on. One is justice, and thatās making sure that something is fair and equitable and inclusive. And equity being the key here, so equity recognises that individuals have different circumstances, and equity allocates opportunities based on the needs of the individual. So, itās not about giving everybody the same, but itās recognising that to get an equal outcome for something, that some people will require more of something because of their set of circumstances. We also have autonomy, and autonomy in medical ethics is a bit of a focus sometimes, and what that is, is giving choices and respecting peopleās decisions around that choice. Consent, we talk about a lot in medical ethics, but it is not the be all and end all. Itās really important, but actually itās one principle among many that kind of make up ethics.
Another one of those four is beneficence, and thatās talking about everything we do must create benefit for people, and that benefit might be at an individual level, it might be at a societal level, so thereās lots of different ways of realising benefit. And the other, which is the flipside of that, is non-maleficence, and thatās making sure that everything we do doesnāt cause any harm to people.
Naimah: Okay, and then so if weāre thinking about ethics in the context of genomics, what does that mean?
Will: So, those four principles that we just talked about are applied to genomics as much as anything else, so thereās no exceptionalism to those, so we live by those four pillars, if you like. But what does make things complicated in genomics is that genomic data is not just about you. Itās not just about an individual. Itās about your family, itās about your future family, and what that means is that we need to take those four pillars, those four areas, and look at them through a lens of a group rather than an individual. Where it becomes more complicated is the kind of interface between the law and ethics, and the way that the laws are written in this country and in healthcare are very much around individual rights, and that becomes really tricky when the decision making of an individual can affect other people in their family. And so, what we try to do is to think about how we can influence behaviour that we want to see. So, the law says an individual has to give their consent for a thing to happen. What we do is we take a step back and we say, āokay, but because thereās other people involved, we need to respect that.ā
And so, weāre constantly thinking about how can we influence the behaviour that we want to see. So, we might say, āwhen you are thinking about whether you want to take part in medical research, or genomic medical research, you might want to speak to your family about this. You might want to speak to your children about this, because it does have implications on them.ā And so again weāre using the sort of vehicle of consent to try and nudge those behaviours that we want to see. So again, itās this kind of ethics complementing the law. So, the lawās not really working ā itās working to protect an individual, but itās not necessarily respecting everybody, and so we just try to kind of affect those behaviours as much as we can.
Naimah: Okay, and then whatās the best way to demonstrate ethics?
Will: I think thatās a really interesting question, and I think itās really important because ethics being part of philosophy means that very clever people have lots of opinions, and write lots of things, and thereās lots of words around ethics, but actually the really important thing is demonstrating that. So, in order to kind of build trust in something, you need to be able to demonstrate your trustworthiness, and i think the best way to do that is really through public engagement. If you donāt understand what people expect of you, it is not your role to tell people what to expect. Itās your role to listen and see what people expect of you, and once you understand what people expect of you, you then know how to act, how to behave in line with what people want from you, rather than telling people what to expect. So, in medical ethics, we talk about ā or in healthcare in general, we talk about doing things with people, not to people, and i think the best way to demonstrate that is to listen. Itās to engage. Itās to act upon what the public are telling you, and sometimes those arenāt the things that you want to hear. But thatās how we make improvements. Thatās how we build trust.
I think a really good example of this from Genomics England is the newborns programme. In ethics, we talk about the needs of science should never outweigh the needs of society, and scientists have said, āwe think genomics can help with newborn screening and diagnosis of rare diseases.ā So, what weāve done is said, āokay, science has said this, we think that we can make improvements, but actually we now need to go and see what society thinks about this. Is it acceptable? If it is acceptable, what are peopleās thresholds for what we can do? And so the whole programme and the generation study has all been driven by user involvement, public involvement, and we have learnt so much, and weāve adapted our approach so much to that. And i think that itās a really good way of us demonstrating that we have listened and that we have acted upon what weāve heard. Iām really proud of the way that ethics has been actually genuinely embedded in the decision making around that.
Naimah: That was Will Navaie, explaining what we mean by ethics. Iāve been your host, Naimah Callachand, and if you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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In this explainer episode, weāve asked Marie Nugent, Community Manager for the Diverse Data Initiative at Genomics England, to explain what diversity is and why it's important, in the context of genomics.
You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.
If youāve got any questions, or have any other topics youād like us to explain, feel free to contact us on [email protected].
You can download the transcript or read it below.
Naimah: Why is diversity important in genomics? Today, Iām joined by Marie Nugent, whoās an engagement manager for the Diverse Data Initiative at Genomics England, and sheās going to explain more. So first of all, Marie, letās start at the beginning. What is diversity?
Marie: I think itās sort of a fiendishly seeming simple question, isnāt it, what is diversity, and I think youāll get just as broad a range of answers as the people you might ask that question to. But for me, you know, itās really got to be about how we do things. So to me, diversity is about recognising that thereās maybe a limited way in which certain things work, or the way in which we might go about doing certain things, and itās also limited in terms of whoās involved in that and who might benefit from that. So, in the broadest sense, I think diversity means recognising the limitations of maybe what you currently do, and really looking for how can we open that up a lot more to provide the space and opportunity for a broader range of people and voices and experiences to really be brought into that and shape it.
Naimah: And can you tell me a bit more about what diversity means in the context of genomics?
Marie: I find this absolutely fascinating in the context of genomics, because genomics is really about how do we understand, you know, how our DNA, as an entire piece of information, is building us and shaping us as people, and having an impact on our lives, and, you know, for us predominantly our health. And the way in which we currently think about grouping people in genomics is unfortunately still very, very heavily influenced by social understandings of how people group together, not necessarily anything thatās really about your genetic ancestry, for example, which is very different. So at the moment, you know, itās an interesting thing to play with and think about because in genomics itās absolutely crucial that we understand the broadest sense of human diversity in terms of genetics and genomics, and only by doing that can we start to really fully understand what it means to be distinct, and therefore how small changes in DNA can have a massive impact on peopleās health.
So, diversity in the context of genomics has to actually completely change the very fundamental ways in which we currently understand how people group together, so itās really getting at the heart of that academic thinking about the topic. But itās more than that, of course, as well, because as Iāve sort of already mentioned about what diversity means more broadly, itās got to be about how we do things and whoās involved in that, and who benefits from it. So, in the context of genomics, itās playing at the ideas of how we even understand how people relate to each other and how theyāre different from each other, as well as how we do things. Itās a really complex but fascinating topic, to be honest, to be able to look at and study in some way.
Naimah: How does the inclusion of diverse populations contribute to improving genomic research?
Marie: Yeah, so following on from what Iāve just said, we fundamentally need to include everyone, you know. In order for us to really understand what genetic ancestry means and what difference looks like across different groups, and how that impacts health, we have to be able to capture, as best as we possibly can, you know, what true genetic diversity looks like in people. So, including as many people as possible who are different from what we currently understand is absolutely crucial. Itās the only way in which we can progress this area. And as I say, thatās in terms of how we think about it maybe academically and what we can do in terms of research, and what we understand, but itās got to also be about the practice and how we do things. So, thereās involving people and having good representation of people in, say, data, but we have to think about how weāre involving people in how we do things and how we understand things, and how we make decisions about these things too.
Naimah: So, for these large groups of people, what are the challenges and barriers for including everyone?
Marie: So, I think there are a lot of challenges and barriers that hinder the inclusion of a broader range of groups of people in studies. I suppose the main one that Iām going to focus on is itās actually the way in which we do research. Itās actually our culture, if you like, of work in this area. Thatās one of the biggest barriers, and thatās because, you know, research is a very fast paced, very competitive environment and area of work to be in. Quite often, you know, things need to be done at pace, and things need results, and things need to be published and all that sort of thing, and I think there is sometimes this perception of not having enough time to slow down a little bit, think a bit more carefully and outside the box about how we might approach a piece of work, for example.
So for me, I think the biggest barriers actually exist within the existing organisations and people who do this work currently. Weāre quite sort of blinkered, I think, still in terms of how we can even approach this work. And finding ways of approaching doing research in a way thatās kind of outside the traditional sort of ways of thinking is for me personally, in my experience of working in this area, one of the biggest challenges still.
Naimah: And finally Marie, how can we address these challenges?
Marie: I think itās not easy for sure, because this isnāt a new thing that people have been trying to do, you know. Thereās a big body of work, you know, in the context of the UK thatās been going on for a number of years, thatās been about sort of trying to open up and challenge, you know, existing research culture and things like that. But I think it has to be about our approach. So, for example, we have the power at Genomics England to think about how we approach the new initiatives, the new pieces of work that we would like to initiate. We talk about trust a lot in this space, but for me, it has to link back to how do we therefore change the way in which we do things so that it opens up a little bit more, people can see for themselves that weāre trustworthy and they can trust in this, rather than just saying, āObviously, you can trust us because weāre doing research,ā or, āWeāre doing something thatās going to be brought into the NHS.ā Unfortunately, that just doesnāt quite cut it for a lot of people for various fairly understandable reasons.
And I think, you know, we can make decisions about how we go about doing that work, and I think itās about your priorities and things like that. So for me, the most effective way of actually addressing some of these existing challenges and barriers is to almost be brave enough to do it differently, and take that sort of perceived risk of maybe not doing things as expected and slowing it down, and allowing that extra time and space for people to come in and shape it, and not actually feel like we have to know everything and we have to make all the decisions. Sometimes I think itās about, we hold the space, we have the resources and we have the access to the expertise, but how can we create the space where actually other people shape it and we just simply facilitate it. Thatās the kind of thing Iād like to see organisations like ours and other research institutions and things like that start moving towards as facilitators of shaping work that will bring some sort of public benefit.
Naimah: That was Marie Nugent explaining diversity in genomics. Iāve been your host, Naimah Callachand, and if you want to hear more Explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk. Thank you for listening.
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