BioTech Nation ... with Dr. Moira Gunn

Sir Rory Collins is a Professor of Medicine and Epidemiology at the University of Oxford and the Principal Investigator of the UK Biobank. With data from half a million people, it has served 30,000 scientists around the world, giving special support to young researchers and scientists in emergent countries.

What is BioTech Nation ... with Dr. Moira Gunn?

Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.

Dr. Moira Gunn:

The frontiers of science can only be driven by data, while the continual emergence of new technology expands what data can be collected and therefore analyzed. When it comes to understanding the human condition, both anticipating how disease develops and diagnosing and treating medical conditions, what is essential is collecting data from a broad spectrum of humanity over time and continuing to tend that mission as technology and science develops. Also key is inviting analysis, not for just a few, but for the great global body of scientists pushing out the frontiers of science for the betterment of all. That in just a few words is the concept and mission of the UK Biobank. Today, I speak with sir Rory Collins.

Dr. Moira Gunn:

Doctor Collins is the UK Biobank's principal investigator and a professor of medicine and epidemiology at the University of Oxford. Well, doctor Collins, welcome to the program.

Sir Rory Collins:

Thank you very much for having me, Moira.

Dr. Moira Gunn:

We'll just start with some first principles here. Many people don't know about the UK Biobank. In fact, many people don't know exactly what a biobank is. What is a biobank? And what's the UK biobank?

Sir Rory Collins:

Well, UK biobank is an act of altruism by half a 1000000 people across Britain, and an act of vision really by the UK funders of research. Back at the beginning of the century, the Medical Research Council, our equivalent of the National Institute of Health and the Wellcome Trust Charity decided that they wanted to set up a very large, what we call a prospective cohort. That is, they were going to ask, half a 1000000 people from around the UK to answer lots of questions about their lifestyle and the way in which they live, the environments in which they live. To have measurements done on them, things like height and weight and blood pressure and their lung function. And biological samples collected, so samples of blood, and urine.

Sir Rory Collins:

And to agree to allow them to be followed through their health records in our National Health Service. So everybody in Britain, has free point of care through the National Health Service. And all of the data about their health is recorded in their systems. And these half 1000000, men and women, aged 40 to 69 at baseline, agreed to us following their health through those systems. So that we could look to see what is it in their questions?

Sir Rory Collins:

What is it in those physical measurements, and what is it in their biological samples that lead to one person developing a particular disease and another person not.

Dr. Moira Gunn:

Well, sir Rory, your English is excellent as one would expect. I'm not sure everyone knows what the word altruism means.

Sir Rory Collins:

Altruism is a generosity of spirit. So these half 1000000 people have agreed to answer lots of questions, allow us to make lots of measurements and collect their biological samples, their blood and their urine. And to have access to all of their health records, going back in time before they joined the study through the National Health Service records. And forward in time as they develop disease in the long term. They're not getting any benefit from that.

Sir Rory Collins:

They're not getting feedback of any of their individual results. What they're doing is creating a resource that researchers from around the world can use to study many different diseases and understand the causes of those diseases and ways to prevent them and treat them.

Dr. Moira Gunn:

Now it's a biobank. Does that mean that you keep the biological samples? I mean, at what point does it become digital? Because that's what we work with today.

Sir Rory Collins:

Yes. So, obviously, the questions we ask and the physical measurements we make are are various, data points. What we're doing now is with the biological samples, the blood in the urine that we stored, in big automated freezer facility, is pulling out those samples and turning the samples into data. So people will be familiar with the idea of measuring your blood cholesterol level or blood glucose level. So we've measured lots of biochemical measures, like cholesterol and glucose.

Sir Rory Collins:

But we've gone on. We've now done genotyping of all half 1000000 people. Genotyping means measuring, genetic variation across the whole of the genome. So you have about 3,000,000,000 markers across your genome. And genotyping, you probably measure about a1000000 of them.

Sir Rory Collins:

But because you inherit your genetic material in kind of lumps, if you measure a variant at one point, you can actually estimate what the variants are near to it. And that can allow you to look at associations with part of the genome with, diseases, but also with risk factors such as obesity or blood pressure or blood cholesterol.

Dr. Moira Gunn:

Now is everyone in the UK, are they served by the National Health Service? And and what are the demographics of of the people that are part of this study?

Sir Rory Collins:

Everybody in the UK, has access to the National Health Service. And almost all of health care that's provided in the UK is through this public service. I mean, private health care is available. But the vast majority of health and particularly, serious health outcomes are picked up through the National Health Service and through the National Health Service Record Systems. So, that allows us to follow all of the participants in UK through these record systems to find out whether they die and what they die of, to find out about cancers and what kind of cancer they have, and also all of their, hospitalizations for various conditions.

Sir Rory Collins:

And increasingly, we're now able to link into their primary care, records, which go into even greater detail about what investigations they've had, what drugs they get. And then, we can go one step further because there are then many disease specific, datasets. So we can look at imaging for someone who's had a stroke, sequence data for someone who's had cancer. So So we can get very, very precise information about many different health outcomes and combine that with a very detailed information that we have about the participants and their lifestyle, their genetics, their environment to really hone down on what it is that causes a particular disease and how we might be able to prevent it.

Dr. Moira Gunn:

And what are the demographics?

Sir Rory Collins:

So the participants were aged 40 to 69 when they joined the study from across England, Scotland and Wales. Men and women, about 50% each. And then we located our recruitment centers in places that helped us to increase the diversity of the participants who joined the study. So people from urban and rural areas, people from different socioeconomic strata and also to recruit people from ethnic minority groups, in accordance with the proportion in the UK population. So they are minorities.

Sir Rory Collins:

They're smaller numbers, but still really quite large numbers of people from very different backgrounds that we're able to study within the UK Biobank cohort.

Dr. Moira Gunn:

I don't want people to get the idea that well, that's it. That's what you do. You just keep collecting this data. There are many different biobank initiatives. And I see one that has a goal of a 100000 participants.

Dr. Moira Gunn:

They have their brains, hearts, and abdomens, which I I I'm guessing are many of their vital organs, image with MRI scan. Tell us about that.

Sir Rory Collins:

So among the half 1000000 participants in UK Biobank, what we're doing is trying to get as much information about as many of them as possible. So we've done biochemical, analyses looking at things like cholesterol and blood glucose. We've done hematological assays, so looking at people's hemoglobin levels, looking at their white cells and their red cells and things like that. We've genotyped everybody, which means measuring about a million of the 3,000,000,000 markers across the genome. But we've then gone on to analyze the exomes within the genome.

Sir Rory Collins:

So this is the 2% or so of the genome that actually is directly producing proteins that then are relevant to the development of particular health conditions. And finally, we've done sequencing of the whole cohort. So all 3,000,000,000 markers across all half 1000000 people in UK Biobank have been measured, with funding from the UK government, charity, and from industry. Why are we doing that? Because the more data we have, the more researchers can understand the causes of many different conditions because all of this information by the participants is then linked to their health outcomes.

Sir Rory Collins:

And these data in UK Biobank are being made available to researchers around the world for any kind of research that's in the public interest. And there are now some 30,000 researchers using the data, some 10,000 of whom are in the US.

Dr. Moira Gunn:

Now you are in the midst of recruiting, the 100,000 participants to have their brains, hearts, and abdomens, scanned. And I understand you were the 60,000th participant. But tell us about what that was like. What did you go through?

Sir Rory Collins:

Well, we were very much aware that we had very detailed information from the questions to participants. And, of course, having blood and urine samples, we can do very, very detailed, analyses of those samples, such as genetic analyses, analyses of proteins and things like that. But the physical measurements we made were relatively crude. So, how heavy are you? What's your height?

Sir Rory Collins:

So what we wanted to do for at least a large percentage of the UK Biobank cohort was to get very much more detailed information about people's measurements, if you like. So, 100,000 of participants are undergoing a special imaging protocol. They come back and spend 5 hours, in one of our 4 U. K. Biobank imaging centers.

Sir Rory Collins:

They do the whole of the baseline assessment again, the questions, the physical measurements, the blood and urine collection. But then they spend time in magnetic resonance imaging of their brain for about half an hour, of their heart and their body for about half an hour. We use low power x-ray to look at their bones and joints. And then carotid ultrasound, which allows us to look at their arteries in their neck to see whether there's evidence of flaring up of the arteries. So it's incredibly detailed physical characterization of the participants.

Sir Rory Collins:

And I went through that a couple of weeks ago, as a participant in UK Biobank. And I was incredibly impressed by the team doing it. It was so well managed, and actually very interesting. The 5 hours just flashed by, during this process. But these data, these imaging data, like the biological samples, are also being turned into data points.

Sir Rory Collins:

So the images are being provided to kind of engineers, digital scientists, data scientists. And they turn the images into data points in the same way that say, a laboratory scientist turns the blood into data points. And then that data, thousands of measurements about the brain or about the heart, are made available to researchers to understand, are there things that we measured back in 2,006, 2010 when the participants joined that predict differences in the brain or heart or body images? And also then, are those measurements in the brain and heart and body associated with subsequent disease? The body image is really interesting.

Sir Rory Collins:

So you can have somebody with the same body mass index, essentially the shape based on their height and weight, but have very, very different magnetic resonance images of them, showing very different fat distribution. It might be superficial under their skin or it may be associated with their body organs. And you can only pick that up with the magnetic resonance. And that's likely to be very differently associated with disease.

Dr. Moira Gunn:

It seems to me that this is unprecedented.

Sir Rory Collins:

Oh, absolutely. I mean, the biggest imaging studies in the past were a few 1,000 people. The idea of doing a 100000 people being imaged is, yeah, absolutely unprecedented. But so is half a 1000000 people being sequenced. You have to remember that 20 years ago, the first person was sequenced.

Sir Rory Collins:

Now we've sequenced half a 1000000 people. And all these data are being made available to researchers around the world. And they're making extraordinary discoveries because they have a combination of large scale exquisite detail. And now, of course, nearly 15 years of follow-up of people's health outcomes. So there are large numbers of individuals who've developed various conditions, so that one can really understand what's the cause of those conditions and therefore, find ways in which to prevent and treat them.

Dr. Moira Gunn:

Now I see that 30,000 researchers have actually accessed this data bank, this biobank, and, that they've done work with it. Who are these scientists? And how do they get access?

Sir Rory Collins:

So they accessed de identified data. So they don't know who anybody is in in the study. And, they they have to show that they are bona fide researcher and that their institution agrees to comply with the rules of engagement that, to look after the data and to use it for health related research in the public interest. The researchers then provided with access to these data to do their research. And really, the only requirement, in that respect is that they put their findings into the public domain.

Sir Rory Collins:

They publish them in medical journals or they make them public in some other way, so that they benefit medical science. And there'd be some really interesting findings that have come out. I think increasingly what we'll see is new targets for treatments and the work with exome sequencing which focuses on the part of the the genome that produces proteins has already found some new targets for conditions, for example, anti obesity treatments which are now starting to be developed. But I think, perhaps the most striking observation in my my mind is the finding that if you combine dozens or hundreds of genetic variants across the whole genome, each of which has a small effect on disease. But if you combine many of them, then you can identify a few percent, maybe 3 to 5 percent of the population that have a risk of that particular condition equivalent to somebody with a single gene disorder, the kind of disorders like, BRCA 1 and BRCA 2 that many listeners will be used to hearing about with respect to breast cancer.

Sir Rory Collins:

Now, that's about 10 times less common. So the idea that this genotyping, where you measure variance across the genome, can identify 10 times as many people with equivalent risk of breast cancer. But also identify, 10 times as many people with equivalent risk to heart disease as someone with so called familial hypercholesterolemia. And it's been shown that, you can identify people in the top few percent of about 16 conditions in about a quarter of the population. So that means that this very simple test, this genotyping test, which probably costs about $10 can identify a lot of people who are high risk of different conditions.

Sir Rory Collins:

And you can imagine how that could get rolled out into healthcare systems. For example, breast cancer screening is typically offered to women when they get to a certain age. Well, if we could find 5% who were at particularly high risk, one could offer breast cancer screening to them at a younger age. And the same would be true, say colorectal cancer or prostate cancer screening. And then from the cardiovascular perspective, I do cardiovascular epidemiology and clinical trials.

Sir Rory Collins:

So I'm particularly interested in this. The idea that, we give cholesterol lowering therapy to people largely when they get to a particular age. If you could identify 5% of people who are age 30 were at very high risk of heart disease, then again, you could offer them protection against getting heart disease, when they get older. The data are available to researchers around the world, on the basis of just the cost of processing their application to access the data and providing the data to them. We've now put all of the data onto a cloud based research analysis platform that's hosted in Britain by the Amazon Web Services.

Sir Rory Collins:

And, that platform that has been developed for us by an American company called DNAnexus allows researchers to go to the data rather than us having to provide data to them. And that really democratizes further access because the data are very big now. And therefore, to to have the data come to you means you have to have a big computer and lots of analytic power on your computer. Whereas, you can now come to our research analysis platform, and have all the compute power you need for your project without having to invest in large computers. So it makes it even more, accessible to researchers around the world.

Sir Rory Collins:

And indeed, we have, free compute from Amazon for researchers from low and middle income countries and for all early career researchers, again, to facilitate access, to the data.

Dr. Moira Gunn:

Well, I see that in 2021 alone, there were 1700 publications in such journals as Nature, Science, and many others. So obviously, there's a tremendous amount of output that goes right into the scientific community.

Sir Rory Collins:

Absolutely. The success of UK Biobank, is down to the research community around the world using the data in extraordinarily imaginative ways. And what we're seeing is an increasing range of researchers from around the world using the data. So one of the problems, of course, with health data is getting access to it. Well, for the first time, really, a very large, very detailed, health research database is available to researchers.

Sir Rory Collins:

And what we're trying to do is encourage you really clever scientists out there, perhaps not the ones who are most used to using health data, to come and use it. We really want to see the people who do fantastically interesting things with astronomical data or physics data, other data scientists who may be not used to working in the biological field coming and solving major health problems by accessing these data. They're now readily available at scale and in-depth, which is unprecedented.

Dr. Moira Gunn:

Well, I would imagine that once COVID appeared on the scene, that the UK Biobank sprung into action. What did you do?

Sir Rory Collins:

Well, one of the things we had to do, of course, was stop our imaging study, because we couldn't invite healthy individuals to come in to the imaging centers. So we thought, well, what are we going to do with all our imaging staff and with our imaging centers? And because we had already imaged 50,000 of the participants, we decided with the support of the Medical Research Council and the Wellcome Trust to swivel towards studying COVID. And so, we invited back a 1,000 of the previously imaged participants who had been infected and a1000 of the previously imaged individuals who had not been infected. And we re imaged them.

Sir Rory Collins:

So we created a unique data source where we have a thousand people with pre and post infection imaging and a 1,000 match controls. There is no such data available anywhere else in the world. And then we've made those data available to everybody. And the value of that is that you can look at the effect of infection on change because you have a pre infection measurement. And and that, is being used increasingly.

Sir Rory Collins:

We also made the data available to researchers all around the world to look at, what were the determinants of a bad outcome with infection. And there were about 200 publications, on UK Biobank related to COVID, identifying some of the major determinants of a bad gap outcome. Some related to ethnicity, to body shape, to other underlying conditions in those individuals. And again, by making those data readily available, rapidly identifying important determinants of bad outcome and the imaging study helping us to identify what the infection does to people in terms of their brain function, their heart function, etcetera.

Dr. Moira Gunn:

So doctor Collins, where does the UK Biobank go from here? Are there plans?

Sir Rory Collins:

Absolutely. The next phase of UK Biobank will be about studying other aspects of these blood samples, the proteins, the metabolites, the changes that occur in response to exposures to your environment, to your genes themselves, so called epigenetics. All of these things will help us to understand how it is that risk factors, be they genetic, lifestyle or environment, lead to disease. To understand the pathways and the mechanisms, and therefore, really understand better how to prevent and treat those conditions. And I think that will be the next phase of UK Biobank.

Sir Rory Collins:

We'd like to bring back all of the UK Biobank participants so that we can get measurements in all of them. And therefore, we can look at change in risk factors on disease. So there's plenty more to do to make UK Biobank more valuable for for researchers. And the great thing is that we have half a 1000000 really altruistic, really engaged participants that want to make this resource as good as possible for the benefit of of humanity.

Dr. Moira Gunn:

Well, doctor Collins, thank you so much for joining me. And, truly, I hope you will come back and see us again.

Sir Rory Collins:

I'd love to do so. Thank you very much, Maura.

Dr. Moira Gunn:

My guest today is sir Rory Collins. Doctor Collins is the principal investigator of the UK Biobank. More information is available on the web atukbiobank.ac.uk. For Tech Nation, I'm Moira Gunn.