UK Biobank Requires Earth's Geneticists To Cooperate, Not Compete

Aug 31, 2019

There's an astonishing outpouring of new information linking genes and health, thanks to the efforts of humble Englishmen and women such as Chritopeher Fletcher. The 70-year-old man recently drove 90 miles from his home in Nottingham to a radiology clinic outside the city of Manchester.

He is one of half a million Brits who have donated time, blood and access to their medical records to a remarkable resource called UK Biobank. The biobank, in turn, has become a resource for more than a thousand scientists around the world who are interested in delving into the link between genes, behaviors and health.

Popularity of the resource is snowballing. Just this week, a major study using the data explored the genetics of same-sex sexual behavior. And as researchers discover the biobank's value, there's a strong incentive to add to the database to make it even richer.

That's why Fletcher finds himself at a radiology clinic. A decade ago, he had donated a blood sample to the nascent UK Biobank and told scientists they were free to poke around in his medical records.

The scientists have now asked him back, to contribute medical scans that will help medical researchers correlate imagery with health conditions and genes.

Fletcher will get a scan of his heart and internal organs, to look for buildup in his arteries and fat deposits around his organs, as well as a brain MRI.

He will spend half a day at the clinic, donating his data to science.

"I'm in the fortunate position that I have very little wrong with me, and I got to 70 years old, and I just thought I should give a bit of public spiritedness, really," Fletcher says. "Nothing more, nothing less, really."

"So far, 10,000 researchers from around the world have registered with the resource and we've now gone past 1,000 different research projects that are ongoing." - Dr. Rory Collins, Chief Executive, UK Biobank

What makes UK Biobank valuable is not only the half-million volunteers, whose health will be followed for decades, but also its community-spirited scientific strategy. Chief scientist Dr. Cathie Sudlow says the organizers, in a break from their usual ways, aren't out to answer their own scientific questions, but to serve their colleagues.

"I'll freely admit that when I first started out in the biobank I couldn't really believe that we were all going to work really hard to make data available for other people," she says. "And that is because I came from this traditional, kind of slightly paranoid, somewhat territorial, academic background."

The scramble for research funds creates competitive incentives in much of academic science today. This biobank is different.

Between 2006 and 2010, the biobank organizers hit the pavement to recruit middle-aged volunteers. Their medical data are stripped of personal information and put into a database that scientists with a legitimate request can download and study.

The project was not an immediate hit with scientists.

"The thing that really changed the landscape from the point of view of use was when the funders – the Medical Research Council and the Wellcome Trust — decided to provide us with the funding to genotype all half-million of the participants," says Dr. Rory Collins, the project's principal investigator.

A genotype is essentially a snapshot of a person's genetic variants. Using that, scientists can look at people with specific traits or medical conditions and search for a matching genetic pattern.

One of the most significant discoveries so far is a new understanding of Type 1 diabetes. It used to be called juvenile diabetes, but that's a misnomer.

"Type 1 diabetes is far more common and relevant in middle age than had been previously appreciated," Sudlow says. "It's always been thought to be a disease of younger life onset." A study based on UK Biobank samples found a genetic signature of people at high risk of developing this condition, and recognized that a lot of adult-onset diabetes was Type-1 disease.

Once scientists around the world discovered that they could use the biobank to do this kind of research without even drawing a blood sample, Collins says interest took off.

"So far, 10,000 researchers from around the world have registered with the resource and we've now gone past 1,000 different research projects that are ongoing," he says.

New research papers appear in the scientific literature almost daily. And though the subjects themselves are primarily Brits, researchers from all over the world are welcome to probe the data.

Collins says the idea is to democratize research so scientists who might struggle to get funding and other resources can also make important contributions, using this dataset.

In Queensland Australia, Prof. Peter Visscher has plenty of resources and a lab teeming with scientists interested in exploring human genetics. They have downloaded data repeatedly from UK Biobank. In one project, they found a genetic signature that illuminates why people tend to select mates with similar height and educational attainment.

"I thought it was quite cool because the theory of that's been known for more than 100 years, but we've never been able to demonstrate that, because we've never had this kind of data," Visscher says.

He uses other genetic repositories for his studies, including a big one managed by the U.S. National Heart Lung and Blood Institute. He says the downside is it has less detailed information about the people who donated that DNA.

"That's what's so special about the U.K. biobank," Visscher says. "All individuals have been measured for all traits, essentially."

Visscher does what's called genome-wide association studies, which are a bit controversial. It's often not clear how to make use of the correlations that come from this kind of analysis.

Sudlow acknowledges that figuring out how to use that information is still a work in progress, "but the biobank has opened this major possibility to interrogate these kinds of questions at [an enormous] scale."

And in the process, it's expanded imaginations about what else this collection can yield. The U.S. pharmaceutical company Regeneron offered to sequence the genes of all half-million participants. (Genes make up 1-2% of a person's DNA, and a genes-only sequence is called an exome.)

Company scientists get an exclusive first-look at this data, but it will soon be made available to everyone who has access to the biobank.

That kind of deal adds value to the data, and biobank executives are willing to accept the trade-off that gives the company donating those services an exclusive preview of the findings.

As Sudlow watches the biobank's success feed on itself, "it's made me realize how fun it is to do stuff that actually makes things happen," she says. "That's a really legitimate and interesting thing to do," and is rewarding, she says, even though she is not actively pursuing her own research agenda in the process.

Sudlow expects collaboration, rather than traditional competition, will be what really drives medical science forward.

You can reach NPR Science Correspondent Richard Harris at rharris@npr.org.

Copyright 2019 NPR. To see more, visit https://www.npr.org.

SCOTT SIMON, HOST:

Scientists announced the results of a study on sexuality this week. They say they found a genetic link to being LGBTQ, but it's spread widely across the genome and not limited to a single gene. To reach that conclusion they used a repository called the UK Biobank which has quietly become a major resource for scientists around the world. NPR's science correspondent Richard Harris has the story about how this unique research tool came about.

RICHARD HARRIS, BYLINE: The UK Biobank is a collaboration of scientists and civic minded Brits, including a 70-year-old man from Nottingham.

CHRISTOPHER FLETCHER: Hello. My name's Fletcher, I have an appointment at 1:30.

HARRIS: Christopher Fletcher has driven 90 miles from home to a radiology clinic outside Manchester. A decade ago he had donated a blood sample to the nascent UK Biobank and told scientists they were free to poke around in his medical records. And now he's adding more valuable information to this treasure trove of health data - medical images. Before he goes in the scanner a technician runs down a list. No metal implants? Good.

UNIDENTIFIED TECHNICIAN #1: So anything like tattoos or piercings?

FLETCHER: Certainly not.

HARRIS: Fletcher will get a scan of his heart and internal organs to look for buildup in his arteries and fat deposits around his organs as well as a brain MRI.

UNIDENTIFIED TECHNICIAN #1: At the end of our brain scan, if we have time, we actually get you to complete a little functional task, a little game we get you to play. I just need to make sure that you'll be able to see it plainly, so if you could please have a look at the chart on the wall.

FLETCHER: Yes.

UNIDENTIFIED TECHNICIAN #1: Reading...

HARRIS: Fletcher will spend half a day here donating his data to science.

FLETCHER: I'm in the fortunate position that I have very little wrong with me and I've got to 70 years old. And I just thought I should give a bit of public spiritedness really. Nothing more, nothing less, really.

HARRIS: After a change of clothes he's ready to start.

UNIDENTIFIED TECHNICIAN #2: Gonna get you to pop these earplugs in. OK. And then we'll take you through to the scanning room, OK?

FLETCHER: OK.

(SOUNDBITE OF MEDICAL SCANNER SCANNING)

HARRIS: What makes the UK Biobank valuable is not only the 1/2 million volunteers whose health will be followed for decades, but its community spirited scientific strategy. Chief scientist Cathie Sudlow says, in a break from their usual ways, the organizers aren't out to answer their own scientific questions, but to serve their colleagues.

CATHIE SUDLOW: I'll freely admit when I first started out in Biobank I couldn't really believe that we were all going to work really hard to make data available for other people. And that was because I came from this traditional kind of slightly paranoid, somewhat territorial academic background.

HARRIS: That's the reality of the scramble for research funds. Between 2006 and 2010 the Biobank organizers hit the pavement to recruit middle aged volunteers. Their medical data are stripped of personal information and put into a database that scientists with a legitimate request can download and study. Principal Investigator Rory Collins says it started off slowly.

RORY COLLINS: The thing that really changed the landscape from the point of view of use was when the funders decided to provide us with the funding to genotype all 1/2 million of the participants.

HARRIS: A genotype is essentially a snapshot of a person's genetic variants. With that, scientists can look at people with specific traits or medical conditions and search for a matching genetic pattern. Dr. Sudlow says one of the most significant discoveries so far is a new understanding of type 1 diabetes. It used to be called juvenile diabetes, a misnomer.

SUDLOW: Type 1 diabetes is far more common and relevant in middle age than had been previously appreciated. It's always been thought to be a disease of younger life onset.

HARRIS: When scientists around the world realized that they could use the Biobank to do this kind of research without even drawing a blood sample, Dr. Collins says interest took off.

COLLINS: And so far 10,000 researchers from around the world have registered with the resource and we've now gone past a thousand different research projects that are ongoing.

HARRIS: New research papers appear in the scientific literature almost daily. And though the subjects themselves are primarily Brits, researchers from around the world are welcome to probe the data. Collins says the idea is to democratize research so scientists in relatively neglected fields still have a shot at doing world class research.

COLLINS: Also people who are working in countries where perhaps they don't have the resources.

HARRIS: In Queensland, Australia Peter Visscher has plenty of resources and a lab teeming with scientists interested in exploring human genetics. They have downloaded data repeatedly from the UK Biobank. In one project they found a genetic signature that illuminates why people tend to select mates of similar height and educational attainment.

PETER VISSCHER: I thought it was quite cool because the theory of that's been known for more than 100 years, but we've never been able to demonstrate that because we've never had this kind of data.

HARRIS: Visscher uses other genetic repositories for his studies, including a big one managed by the U.S. National Institutes of Health. The downside is it has less detailed information about people who donated that DNA.

VISSCHER: And that's what's so special about the UK Biobank, that all individuals have been measured for all traits essentially.

HARRIS: Visscher does what's called genome wide association studies which are a bit controversial. Chief Scientist Cathie Sudlow acknowledges it's often not clear how to make use of the correlations that come from this kind of analysis.

SUDLOW: So I would say the jury is out, but Biobank's open to this major possibility to actually interrogate these kind of questions at scale.

HARRIS: And in the process this has expanded imaginations about what else this collection can yield. The U.S. pharmaceutical company Regeneron offered to sequence the genes of all 1/2 million participants. Company scientists get an exclusive first look at the data, but it will soon be made available to everyone who has access to the Biobank. And the richer the collection becomes, the more valuable it is and the greater the incentive to make it even richer. Chief Scientist Cathie Sudlow says it's satisfying even though she's not pursuing her own research ideas.

SUDLOW: It's made me realize how fun it is to do stuff that actually makes things happen. That's a really legitimate and interesting thing to do.

HARRIS: She expects collaboration, rather than traditional competition, will be what really drives medical science forward.

Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.