Last September, Rory Collins stepped into a firefight. Becoming a principal investigator is never an easy task, but taking the job at a national project designed to last several decades, and which has elicited a steady stream of criticism since its inception seven years ago, takes some nerve.
The UK Biobank, a £61m government-sponsored medical project designed to study the interaction between genes and the environment in affecting health, is meant to inform our knowledge of how diseases such as cancer, heart disease, diabetes and Alzheimer's develop in populations. It will collect blood and urine samples from volunteers aged 45 to 69. By looking at the medical records and genetic profiles of those who develop disease, scientists want to correlate which environmental factors are involved. At the end of last month, the project began recruiting for its pilot phase, the first 2,000 or so of its eventual goal of 500,000 people.
Critics have taken great pleasure in lining up to bemoan the project ever since the idea for it was announced in the government's 1999 comprehensive spending review. Some argued that it would result in false leads in linking genes and health. Others raised questions on what use Biobank's results could have for the public. Lack of debate
In 2003, the House of Commons science committee slammed Biobank, arguing that it got the green light before coming up with a proper scientific mandate. A report published in the Lancet that same year claimed that, among the scientists it had canvassed, "the only point everyone seems to agree on is that sufficient debate about the project has not taken place".
It was into this environment that Collins stepped up to take charge. Already an epidemiologist of some renown, as co-director of the clinical trial service unit and the epidemiological studies unit at the University of Oxford, he donned a flak jacket to take on Biobank's critics. Their comments, however stinging, never seem to ruffle his feathers.
"I am aware of uninformed criticism but I'm not aware of informed criticism," he says, a statement that seems designed to both bring his detractors out of the woodwork and pacify them by implying that any bad feeling is simply a misunderstanding. "There have been claims that many scientists oppose Biobank. Personally, I don't know where the evidence for that is. Scientists I talk to have been very positive. If you look at some of the public health errors that have been made, they have been chiefly through not having studies like Biobank."
He cites the example of the once common advice that lowering cholesterol in old people was not a good idea. "The reason was that they hadn't been studied in large enough numbers to identify that cholesterol was just as important a risk factor in the elderly as it was in young people."
One of Biobank's most vocal critics has been the geneticist Sir Alec Jeffreys of the University of Leicester. He has claimed that for Biobank to achieve its aims would cost billions of pounds and that, because so much information would be stored for each volunteer, the chance of getting false positives - where a genetic marker or environmental factor appears to be a cause of a disease but is, in fact, a blind alley - was astronomical. He added that studies intended to link genes with environment in the development of disease should be smaller and more focused. Biobank was all wrong for genetics, in his opinion.
These comments, made to the Guardian just before the official launch of Biobank in March, prompted Collins to give the geneticist a call. "It wasn't about me saying 'you can't say these things'. Alec Jeffreys is not worried about what I think," he says.
Collins deals with the false positives issue first. "Everything else being equal, a big study is unlikely to produce spurious results compared with a small study. If you take a coin and toss it 10 times, getting six heads, four tails, [that's a] 50% increased risk of getting a head. Does that mean it's a biased coin? No, that could easily occur by chance. If you have 600 heads and 400 tails, that's unlikely to occur by chance."
He goes back to his initial assertion - that there is too much of what he calls uninformed criticism about Biobank. He agrees Jeffreys had concerns, but says this was only because he did not understand the true intent of the project.
"It's not a genetic study, it's not a DNA study," says Collins. "It's an epidemiological study, a study of public health, and it's looking at a range of different factors. If you're interested in genes, then why do a prospective study? If you're solely interested in genetics, then you do family-based studies to identify new genes that are causing disease."
In Collins's experience, once this is explained to critics, their minds change. By the time Biobank was launched last month, Jeffreys seemed to have done an about-turn. "Biobank is a straight epidemiological project. It does not have a focus on genetics, which is my real concern," he said. "As soon as you view Biobank in that sort of light, then I have no major problems with it."
Jeffreys wasn't alone. Ian Gibson, Labour MP for Norwich North, a former biologist, and chair of the Commons science committee that criticised Biobank in 2003, told the Guardian the project needed serious examination to see whether it was money well spent. He added that the delay in getting the project going was also a worry.
But in a statement issued at the launch of Biobank, Gibson said: "I am very confident that it will succeed and be an extraordinarily valuable resource for public health in the UK. It has my full backing."
Collins says the delay is easily explained. Biobank's steering group had told the management to take its time in developing the project. "There's been lots of consultation on exactly what measurements to make, what questions to ask. There's been a whole series of experiments done on what samples to collect, how to collect them, in order that the widest range of things can be measured in the future.
"One of the things about a study like Biobank is that it doesn't have hypotheses at the beginning. It has the general hypothesis that you want to study the relationship between a whole range of different factors and their effect on particular diseases. It makes it difficult because you have to think of the future, think of questions you want to have asked in 10 years' time. And have samples that allow you to measure things with methods that may not even exist now."
Collins cites the example of the eminent epidemiologist who, in 1951, began a survey of doctors in order to find a link between smoking and lung cancer. "Richard Doll didn't know that smoking was going to cause this huge range of diseases. He hadn't even thought of it; he was only trying to confirm results for lung cancer. The observations that emerged over time were not expected. But he built a resource that could do it."
Did it surprise Collins that people as prominent and well-informed as Jeffreys and Gibson were so vocal about the project? "Not really. It's very difficult to keep everyone informed about everything that's going on."
It is an odd conclusion, given that Biobank has been discussed, consulted on and reported for almost seven years. Despite this, and by Collins's own assertion, there is a lack of information on the project's aims. Can this be the fault of scientists alone? Is the Biobank management not partly to blame for a lack of information? Collins concedes that the public relations exercise could have been better. Conspiracy theory
He dismisses a conspiracy theory that many researchers have resisted speaking out publicly against Biobank because the two main funding agencies behind it - the Medical Research Council and the Wellcome Trust - also provide the vast majority of academic funding for epidemiologists and geneticists in the UK. "I don't believe it. I've no evidence that the Wellcome Trust or the MRC work like that or scientists work like that," he says.
The controversy is unlikely to die away completely. Pressure groups such as GeneWatch continue to gnaw at the project, insisting that the scientific rationale needs re-evaluation. Continuing these debates will clearly be part of Collins's beat - he has already arranged discussions with GeneWatch so it can air its concerns directly - but he sees his main task as recruiting his 500,000 volunteers.
A secondary task is to come up with ways of keeping the database accurate and full of as much interesting information as possible. "If I take blood from you today, then the levels of various things will differ tomorrow. We have to do repeat assessments in quite sizeable samples: tens of thousands every two years or so. That gives us an opportunity to do more detailed assessments in that subset in order to inform the whole collection," he says.
These limited repeat assessments can also be used to enhance the information on the entire cohort of volunteers. "One neat thing you can do is say, in 10,000 of them, let's do some extra things that inform us about diet. In another of the 10,000, let's do things that inform us about exercise. What they're doing is informing the whole cohort."
Though he will not be swayed by any argument on the scientific validity of Biobank, he admits the project is not perfect. "If there was a problem with Biobank, it was in the structure put in place, which didn't use the expertise of the regional collaborating centres," he says. While the central store and offices are in Manchester, the project put out tenders for several "collaborating centres" around Britain to collect the samples. Collins says the tendering process excluded some groups he now wants to involve.
Collecting half a million people will take at least four years and, if all goes to plan, it will be done just a year before the £61m funding runs out. Collins's job then will be to find more cash. "There is an opportunity, once the resource is established, to go to a wider range of funders. Cancer Research UK and the British Heart Foundation and the big charities, who may be first to benefit, may well be interested in supporting it," he says.
And he is not averse to tapping the pharmaceutical industry, which is likely to start benefiting from the results of Biobank in the next decade or so. "The intention is that the resource will be open to all, including the pharmaceutical industry. After all, it is the pharmaceutical industry that develops the drugs that treat diseases," he says. "Industry, health service, charities are all potential sources of money."
Beyond that, Collins is more circumspect about his and Biobank's future. Ideally, the 500,000 people would be followed to their natural death, meaning several decades of follow-ups. I ask what that means for his future and, for the first time in the interview, he cracks a smile. "I'm not planning to do what Richard Doll did and write a 50-year follow-up."
Curriculum vitae
Name Rory Collins
Age 51
Job Codirector of clinical trial service unit and epidemiological studies unit, University of Oxford; British Heart Foundation professor of medicine and epidemiology; principal investigator and chief executive, UK Biobank
Likes When years of research turn into clear results that save lives and prevent disability
Dislikes Unnecessary obstacles to such research
Married
