World's biggest medical experiment
500,000 people, a span of decades - and a waste of time and money?
· Huge study of causes of ill-health starts next week
· Project likely to turn into an albatross, say critics
Alok Jha, science correspondent
Thursday February 23, 2006
The world's biggest medical experiment - an attempt to understand the interaction between genes and the environment in affecting health - will begin next week amid mounting criticism from scientists that it is a badly designed project of questionable scientific value and likely to give misleading results.
The UK Biobank, a £61m government-backed project to track participants for several decades, is aimed at understanding how diseases such as cancer, heart disease, diabetes and Alzheimer's develop in populations. Next week the project will begin recruiting the first of its eventual goal of 500,000 people.
However, many scientists believe the project is a waste of money and will end up an albatross for the medical research community.
"Most [scientists] think that it's not a terribly good way to spend that amount of money," said Hilary Rose, a professor of the sociology of science at City University. "What is the public likely to get from it? It's not very clear what its aims and objectives are."
Helen Wallace, of the pressure group GeneWatch, which focuses on responsible use of genetic technology, said her biggest concern with Biobank was the project's design and the lack of "proper discussion" of its relevance to health. She said: "There's a lot of scientific concern that it will throw up spurious links between genes and diseases and that it won't deliver the promised benefits to health."
The Biobank project will collect blood and urine from people aged 45 to 69, who will be followed for at least 10 years in the expectation that some will fall ill. The intention is to look at the medical records and genetic profiles of those who become ill, to try to correlate which environmental factors are involved.
"It's going to be a unique resource for looking at a range of different risk factors as a cause of a very wide range of diseases," said Professor Rory Collins, Biobank's chief executive.
The main criticism from scientists lies with the design of the experiment. Sir Alec Jeffreys, a geneticist at Leicester University and the inventor of genetic fingerprinting, said the project had been sold to scientists as a genetic survey but was very poorly structured.
It had a "lack of genealogy information, lack of pedigree information, [an] inability to carry out some of the standard genetic tests that one would do if you're trying to identify genes involved in a common disorder," he said.
Because so much information would be stored for each of the 500,000 volunteers, 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.
The project, in preparation for more than five years, has been criticised before. A Lancet article, published shortly after the project's funding was announced in 2003, concluded that many of the scientists interviewed were unhappy with the experiment's design. Of the people canvassed, "the only point everyone seems to agree on is that sufficient debate about the project has not taken place".
It was a sentiment echoed in an investigation of the Medical Research Council by the Commons science committee the same year. In a scathing report, the committee argued that Biobank had been funded before the scientific case for it had been properly established.
The committee's criticism seems to have been ignored. Ian Gibson, a former biologist, who was Labour chair of the Commons science committee when the MRC report was published, said he had seen no evidence that Biobank's plans had been altered in the light of his report. "They [the comments] have been suppressed completely. We wondered how many illnesses you would learn about by doing this DNA stuff. There was a lot of money going in - for what?"
Scientists have also raised questions over the quality of the medical records doctors keep on their patients, records that form a critical part of how Biobank intends to track its volunteers. Without precision the project could end up grouping together a number of diseases and lose the subtle differences in environmental factors that cause various diseases. "That's going to limit the scientific validity of those results," said Dr Wallace.
Recording the environmental conditions a volunteer experiences will also be important. How much and what people eat and drink, how much they exercise and which chemicals they are exposed to - all of this information will be crucial for producing worthwhile results. "It's really difficult to see if the same sort of effort is being put in and whether you can actually get social data which is robust enough to hold up alongside that molecular data," said Professor Rose.
Biobank would also add to the controversial idea that genes determine health, Prof Rose said. "Many would argue it is doomed as an explanation - it doesn't give an adequate account of an organism living in particular environments."
But Professor Collins says critics are misinterpreting the project's aims. "To criticise it because it's not the perfect genetic study is to miss the point. It's not a study of genetics, it's a study of a range of diseases and, as far as is possible, the widest range of factors that can influence those diseases." The proteins in the blood would be probably more interesting to researchers than the genes themselves.
But the problem with Prof Collins's attempt to reposition Biobank as an epidemiological rather than genetic study is that this was not the project's original aim.
And Dr Wallace pointed out that the only peer-reviewed scientific study for Biobank, the study that was the basis of the green light for the project, was clear in its aim - to quantify the combined risk of genes and environmental factors. If priorities had shifted, Biobank had yet to make them clear, she said.
The critics say Biobank should go back to the drawing board. Dr Wallace said biobanks were "potentially useful" but "they really need to ... have a much more open debate about issues like privacy and what the research is for".
Dr Gibson agreed. "We need to have a serious look at it to see what it's done, and what it hasn't done. Really to see whether it's money well spent."
But Prof Rose said the government might be too far down the path. "Once you've got a megaproject which is being run in the public sector, it is extremely difficult to say, actually we're not getting enough from it, it's better to stop it now. Nobody wants to be the minister who pulls the plug."
The idea for the Biobank was born in 1998, when the government asked the Medical Research Council to set up a central DNA collection available to British researchers. The resulting project was funded with £61m from the MRC, the Wellcome Trust and the Department of Health. Similar databases are being set up by governments for scientific research in Estonia, Sweden, Iceland, China and Mexico.
The EU is looking at the links between cancer and diet in a 400,000-person study called Epic, and the US is looking at plans to set up a Biobank-style database in the next few years. In the history of medicine, projects such as this have produced remarkable results - the link between smoking and lung cancer was discovered in the 1950s by the epidemiologist Sir Richard Doll (right) thanks to studying the medical records of 50,000 doctors.