Behind the Genes

Helen White, Professor Ian Tomlinson, Claire Coughlan and Dr David Church: Can genetic discoveries revolutionise bowel cancer care?

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 cancer’s 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 wouldn’t 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 we’re seeking to realise now. But, you know, it’s not a given when we treat people in the clinic so we’re 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 we’ve found could be useful in preventing cancer and it doesn’t necessarily matter that they’re rare, even if they’re 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 I’m the Participant Panel Vice-Chair for Cancer at Genomics England. Today I’m 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 today’s 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. We’re 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 let’s start by hearing from my guests. Could each of you please introduce yourselves. 

Ian: I’m Ian Tomlinson, I work at the University of Oxford and most of my work is research into bowel cancer, it’s 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, I’m Claire Coughlan, I’m 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 we’re 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. I’m 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: I’m David Church, I’m 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 we’re discussing today of course. 

Helen: Great, thank you. Now let’s 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 you’re 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 you’re 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, it’s really important that we diagnose at the earliest possible stage which is why studies such as the one we’re 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 it’s still a disease of older people, you still have a greater chance of getting bowel cancer as you get older but it’s really, really important that we’re 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, we’re 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 it’s a common disease and staging an early detection is vital.

Helen: That’s 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 we’ve known for many years actually, for much longer, that cancer is a genetic disease, it’s 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 don’t 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 don’t 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 it’s 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 we’re 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 we’ll 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 weren’t 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 we’re 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 we’re 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 don’t want to look at patients and say that looks an interesting change, we may be able to use that if it’s present in all of the normal cells in that patient’s 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: That’s 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 cancer’s 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 wasn’t done is to look at other molecule tests or essays, looking at RNA wasn’t 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 we’ve 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 we’ve 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 it’s just the complexity of the disease.  

So, as we’ve mentioned we know that cancer is a genetic disease, that it’s driven by genetic alterations, alterations in genes which regulate the growth of cells or the death of cells or the spread of cells. And we’ve 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 we’ve hugely extended our understanding of the genes that drive bowel cancer and in fact we’ve 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 we’ll 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 we’ll 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: That’s 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 I’m 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 they’re 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 we’ve found could be useful in preventing cancer. And it doesn’t necessarily matter that they’re 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 we’re 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 we’re 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 we’ve 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 it’s really exciting that you’re 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 it’s not 100% guaranteed. And I don’t suppose it ever will be but having the vaccination in that armoury would be fantastic I think for future generations, it’s very exciting and we look forward to hearing more about it.  

Thank you Ian and David. I mean we’ve heard a lot there about preventing bowel cancer but I think moving back now to potential treatments, you know, we’ve 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 I’m 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 it’s 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 it’s not a tiny number either. But it would mean investment at that level to benefit let’s say 1 to 2% potentially of all patients with bowel cancer but I think that’s 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, we’re 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 don’t 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 aren’t in the real world which of course they are.  

But it’s 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, it’s 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 don’t 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 … 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 they’re 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 don’t 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, that’s 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 we’re talking about that and you mentioned lynch syndrome earlier, so there has been a lynch syndrome project as I’m sure you’re aware where we’re 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 that’s 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 hasn’t yet and the funding hasn’t quite followed in the way that we need it to enable that to happen. It’s 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, it’s 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 you’ve 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 that’s a very good example of, you know, it doesn’t 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 haven’t heard of it, so yes it’s really, really important.  

And that patient forum, you’re probably aware of Lynch Syndrome UK, I don’t 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 we’ll 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 wouldn’t 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 we’re seeking to realise now. But, you know, it’s not a given when we treat people in the clinic so we’re 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 we’ve 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 won’t have helped them but by donating their data, you know, it has allowed this work to happen and potentially it could change lots of people’s lives in the future, so thank you to them. 

Ian: Could I also just emphasise and agree with what David has said, I won’t 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. It’s quite difficult in a way to find a formal way of thanking them for all of this but without them it wouldn’t have happened. 

Helen: On that note I think we’ll 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. 

Adrianto Wirawan: What does 'no primary findings' mean?

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

You can download the transcript or read it below.

Florence: What does ‘no primary findings’ 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 ‘no primary findings’. 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. 

Mathilde Leblond: What do parents want to know about the Generation Study?

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

You can download the transcript or read it below.

Naimah: 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 — 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 ‘How has design research helped shape the Generation Study?’, 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 Alzheimer’s, 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?’ 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 ge-newborns@genomicsengland.co.uk, or you could find out more on the Generation Study website www.generationstudy.co.uk. 

Thank you for listening.

Callum Morris: What happens in a clinical trial?

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

You can download the transcript or read it below.

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. 

Nicole Chai: How does X-linked inheritance work?

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

You can download the transcript or read it below.

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. 

Arina Puzriakova: What is a polygenic disorder?

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

You can download the transcript or read it below.

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. 

Öznur Özkurt, Mathilde Leblond, Rebecca Middleton and Sandra Igwe: How has design research shaped the Generation Study?

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, Öznur Özkurt, 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.

 

"It’s not enough to just ask people afterwards. It’s also not enough to engage just at the beginning and then stop listening once we’re live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn’t 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 Bick

You can download the transcript or read it below.

Öznur: Welcome to Behind the Genes. 

Sandra: Every community’s 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 it’s really important to have representation because the lack of it in research can overlook communities’ specific concerns and needs. 

Öznur: My name’s Öznur Özkurt and I’m the director of design and research at Genomics England. On today’s episode, I’m joined by Mathilde Leblonde, senior design researcher at Genomics England, Rebecca Middleton, and Sandra Igwe, CEO and founder of the Motherhood Group. Today we’ll be discussing how design research was used in the Generation Study by involving participant and users’ voices to address ethical considerations, implementation and consent. If you enjoy today’s episode, we’d 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, let’s start with you. 

Sandra: Hi everyone, I’m Sandra Igwe and I’m 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. 

Öznur: Great to have you on the podcast, Sandra. Rebecca? 

Rebecca: Hi everyone, I’m Rebecca, I’m a rare condition patient, and I also have the pleasure of chairing the recruitment working group of the Generation Study. 

Öznur: Fantastic, thank you, Rebecca. And over to you, Mathilde. 

Mathilde: Hi, I’m Mathilde. I’m 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. 

Öznur: Fantastic, thank you. Mathilde, let’s start with our first question. What is the Generation Study? 

Mathilde: Sure. So, whole genome sequencing is a technology that’s improving. We’re finding new ways of using that, and there’s 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 they’re not having two different departments trying to figure out what’s wrong with them. And because we can look for hundreds of conditions with whole genome sequencing, it’s really much more efficient, and we’re able to look at these rare conditions, so it’s really exciting. There’s still a lot of questions about implementing this operationally within the NHS, and so the Generation Study is aiming to explore this. We’re 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. 

Öznur: Thanks Mathilde. And if you’d 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 didn’t know this would be called the Generation Study and we weren’t 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. 

Öznur: And how have we implemented design research in the Generation Study? 

Mathilde: Yep, so we’ve 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 we’ve been involving users in regular rounds of codesign and usability testing to understand what works and what doesn’t work. It’s been around 105 people now that have taken part, and it’s 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 I’m proud to say that user perspectives have been central to the decisions of the programme throughout.  

Öznur: That’s fantastic to hear. I’m going to come to Rebecca and ask, why is it important for us to be guided by the patients and the participants? 

Rebecca: It’s 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 that’s exactly what we’ve 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, ‘cos 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.

Öznur: 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, “Sandra, black mothers are so hard to reach, they don’t really get involved in research.” 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 it’s not knowledge, it’s experience. It’s, you know, having someone go through the experiences without necessarily studying it, but again lived experience to me, it’s more crucial than any other experience that you could possibly have. 

Öznur: 100 percent, lived experience is really, really crucial for us to make the services that we’re 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, “Gosh, I’m going to have to (inaudible 0:08:54) to go through this.” 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 didn’t understand it, and I needed somebody to help me unpack this, and translate it. And I’m pleased to say that our consent process and our recruitment process is very different to this, which is a fantastic thing.

And what’s 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 that’s 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 weren’t 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, “Well, I don’t know what this actually means.” 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 we’ve asked parents and patients as well.

So, we know the challenges and we’re trying to address them head on, and that’s essential. It’s essential in building trust, and that’s 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.

Öznur: 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 that’s a topic that’s 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 it’s 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, you’ve already done the first step in building trust.

And consent conversations should be guided by what matters most to each parent within each community, ‘cos every community’s 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 it’s really important to have representation because the lack of it in research can overlook communities’ specific concerns and needs.

Öznur: Absolutely, and that inclusion is really important for the study. Is there anything you’d 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 it’s been really important because, yes, the moment of consent - you know, during pregnancy, you’ve 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 there’s 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 we’re 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 we’re thinking about where we’re using the word genomic and how are we using that, this is a word that’s actually really scary for a lot of people. And we might be very proud of the cutting edge technology that we’re 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. It’s really been looking at this whole journey holistically.

Öznur: 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. There’s a lot of language. There’s written words in there, there’s 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 community’s 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 didn’t 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 didn’t speak directly to our community. They also expressed that seeing more black parents and more black families represented signals for us too as well – 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: It’s really exciting how much this feedback has pushed all of us in the team and the designers – pushed us to think about how to talk about the Generation Study, what narratives to use, what tone of voice, but also you’ll see on the posters there’s space there to have photos of several different family types and people of different backgrounds. It’s not just one photo. And there’s also some very small tweaks, it seems like, but it actually has a very big impact, about what it is that you’re trying to say and what people understand in a split second when they’re seeing that.

Öznur: 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. I’m curious about how will design research continue to shape the Generation Study going forward.

Mathilde: Yep, so we will have an iterative process, where we’re still listening to the sides as they’re launching to hear what are the questions that are being raised, what are some of the challenges that they’re 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 we’ve 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 it’s critically important that we have this always learning philosophy. It’s critically important that now, you know, the rocket has launched, how will it land, and we don’t know until we’ve 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 won’t know until the project goes live and that feedback comes through. And that’s what we’re 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, it’s 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.

Öznur: Thanks Rebecca. I’d like us to reflect on the importance of continuous learning. What’s the importance of continuous learning in this project? I’ll 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 there’s been a lack of trust from the community, and that means transparency. It also means honesty, and it also means continuous involvement as well. There’s 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, it’s 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.

Öznur: Thank you. And Mathilde? 

Mathilde: I think there’s only so much that we could really cover in theory before we launched, and now, you know, it’s going to go out into the world, and there’s many things that we couldn’t have predicted that will happen. We have that humility to understand that. And what’s super important going forward is that we have a team there to keep kind of staying on our toes, listening to what’s happening, to make sure that we respond to that, so that, as Sandra said, it’s not enough to just ask people afterwards. It’s also not enough to engage just at the beginning and then stop listening once we’re live, once it gets hairy and a bit difficult. So, we are very excited to find out all the things that we hadn’t 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 you’d like to hear more episodes like this, please subscribe to Behind the Genes on your favourite podcast app. I’ve been your host, Öznur Özkurt. This podcast was edited by Bill Griffin at Ventoux Digital, and produced by Naimah Callachand.

Amanda Pichini: Which healthcare professionals are involved in my genomic healthcare journey?

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

You can download the transcript or read it below.

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.  

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?  

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?  

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. 

Maili Raven-Adams, Niharika Batra, Trupti Patel and Naimah Callachand: How can we ensure equitable access to genomic medicine?

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, they’re being completely transparent, they come with you with clear benefits, how it’s 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 I’m the Head of Product Engagement and Growth at Genomics England. On today’s episode, I’m 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, we’re 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 today’s episode, we’d love your support, please like, share and rate us on wherever you listen to your podcasts.  First of all, I’m going to ask each of our guests to briefly introduce themselves.

Maili: I’m 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 they’re 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, I’m Niharika Batra, I’m 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 I’m really passionate about working with the immigrant communities in the UK.

Naimah: It’s lovely to have you.  And Trupti, can we come to you?

Trupti: Hi, I’m Trupti Patel, I’m 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 we’re talking about those of non-European ancestry, and there are very specific reasons as to why that is.  So firstly, there’s 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 we’re 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 there’s a lack of financial investment as well within developing economies.  So it’s 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 there’s 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 we’re 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 can’t always accurately predict whether or not someone does or doesn’t have a condition.  So we’re 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 doesn’t 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.  That’s one of the tensions that we’re playing with at the moment, especially when it comes to providing genomic healthcare via a healthcare service.  Understanding people’s 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 it’s also important to understand things like timing, so the decision around whether or not someone decides whether or not they’re 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 they’ve 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.  There’s also been examples where research has been actively untrustworthy in the past.  You know, there’s well known stories of Henrietta Lacks, whose cancer cells were taken without her consent, and then used to develop research.  And there’s 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 aren’t 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?  It’s 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 they’re 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 weren’t even aware what they were consuming.  And it was in the name of research.  So there’s 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 it’s 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 sevā 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 it’s not just donation, but it’s 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 sevā 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 it’s important to be cognisant of the cultural sort of ideas.  And this is something that can be used with South Asian communities, sevā and giving back to the communities.

Maili: I was just going to say, I completely agree with that, like 100%, it’s really important as well that the global majority don’t feel pressurised into giving that data because of the language that’s 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 that’s 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, it’s important when we’re using language like genetic ancestry that those aren’t 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 we’ve got translators, or there’s investment in making sure that the resources are there to make the engagement and also the research accessible to people.  There’s 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 there’s not too many barriers to become involved if they want to be.  I think that’s 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 don’t 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 don’t 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 there’s been a history of eugenics, and at the moment, that’s quite a big area that lots of universities, especially in the UK, are going through eugenics inquiries.  It has effects upon people’s 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, there’s 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 there’s transparent governance mechanisms in place and they can understand how their data is being protected, you know, that goes right through data access committees.  There’s 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, that’s one thing.  Another could be through consent processes.  So there’s different sorts of consent models that could be explored with communities to figure out which one they’d be more comfortable with.  So broad consent I think is the one that’s 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 it’s not always clear to people what those purposes are, or where that might be used over time.

So there’s 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 there’s different options of people that they’d 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, “Yes, my data can be shared with nonprofit organisations or research organisations affiliated with universities or the government, but I don’t want my data to be shared with private companies.”  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 we’re engaging with and a lot of these communities that we’re 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 that’s 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 they’re 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 that’s something that you’ve 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 they’ve 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 God’s 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 God’s 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 there’s 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 they’re uncomfortable with any aspect of research.

Maili: I was just going to say something else about consent models.  When we’re thinking about different forms of consent, like dynamic consent, it’s 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 we’re exploring those models, we need to make sure that people have access, and if they don’t have access that there’s other ways that that sort of consent model might be able to be replicated, or there is an alternative way, so that people aren’t 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 that’s 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 that’s through analogies or visuals that convey information, I think that’s 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 wasn’t 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, it’s 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 they’re not just consenting for themselves, they’re 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 shouldn’t 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, it’s 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 that’s something to be considerate of.  And it might influence their decision making as to whether or not they or their family members should or shouldn’t 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, they’re 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 there’s this skewed power dynamic over them as their white man or white doctor asking for the consent.  But also, they don’t know what exactly to do in that moment, they’re very frustrating from the long waiting line.  And they feel they’re 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, it’s 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 they’re trained, once they have enough knowledge about genomic research and how it can benefit their communities, they’re 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 it’s 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 that’s 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 they’re talking with so that that information can be translated or got across in the best possible way.   

 

And that’s even more important I think where there is a lack of diverse data that’s 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 it’s 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 we’re 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, there’s 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: You’ve 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, there’s 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 we’re 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 there’s 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 we’re also known for being a very highly secure biobank, compared to others.  So that’s 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 there’d 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 we’re looking at in the near future is whether or not these principles could be used in order to guide some of our international partnerships’ 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 doesn’t just happen once but is embedded into whole research practices.  So there’s 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 they’re giving and the time that they’re 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, it’s really important that that’s done in a really equitable way, and that those conversations are had between different researchers to figure out what’s going to work well.   

 

We need to avoid instances of things like helicopter science, and sometimes it’s 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 that’s something that we really need to avoid, especially in the UK, we don’t 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.  There’s 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 there’s constant anxiety around your DNA or genetic data.  So it’s important that the researchers maintain utmost transparency.  There’s 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 they’re 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 people’s 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 they’re based off again is that European genetic ancestry data, and therefore is not accurate or applicable to lots of communities.  And it’s not just genes that we need to be aware of, it’s people’s 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 aren’t perpetuated and existing health inequalities aren’t continued to be exacerbated. 

 

Naimah: Okay, we’ll 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 you’d like to hear more like this, please subscribe to Behind the Genes on your favourite podcast app.  Thank you for listening.  I’ve been your host and producer, Naimah Callachand, and this podcast was edited by Bill Griffin at Ventoux Digital.

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

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

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

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

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

 

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

 

You can download the transcript or read it below.

Marie: Welcome to Behind the Genes. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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