HEALTH / No prize for being second: Teams of scientists chasing the defective gene behind inherited breast cancer are locked in competition, says Steve Connor

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The Independent Culture
QUIETLY and determinedly, some might say secretly, half a dozen teams of scientists are racing to discover the gene responsible for inherited forms of breast cancer. In this race there are no prizes for coming second. Yet what was once thought of as a quick sprint to the finishing post has turned out to be a marathon with no end in sight. The time it is taking has raised the question of whether the scientists should now co-operate openly and fully for the benefit of women.

All the groups involved are using basically the same scientific tools and methods. In essence, it is a matter of luck who gets there first. Because the search involves the painstaking analysis of genetic material, it seems reasonable to suggest that sharing data would eliminate wasteful repetition of what is, after all, now routine work in molecular genetics. And the large number of groups involved in the race only increases the chances that several will end up fumbling over the same mistakes.

Such polemic is not merely academic. Breast cancer is the biggest killer of all the cancers that affect women. There are about 29,000 new cases in Britain each year and about 16,000 deaths. Roughly 5 per cent of cases are due to the inherited forms of the cancer, and half of these are due to the gene scientists are now trying to isolate. Finding the gene, it is hoped, may help medical scientists to understand not just inherited breast cancer but the other 95 per cent of 'sporadic' breast tumours that arise for no apparent reason.

Although it has been known since Roman times that breast cancer can run in families, it was only in 1990 that an American team of scientists, led by Mary- Claire King at the University of California at Berkeley, located the rough position of the gene on one of the 23 pairs of human chromosomes. By studying scores of families with a history of the disease, she detected evidence that the gene was in a particular region of chromosome number 17. The race duly began.

It is now known that the gene - or rather inherited defects within it - also increases a woman's chances of developing ovarian cancer. Broadly speaking, there are two groups: one with a high breast cancer risk and low (though still above average) ovarian cancer risk, and another set with a high risk of both types of cancer. In general terms, a woman who inherits defects in the gene has a roughly 60 per cent risk of developing either type of cancer by the age of 50 and a greater than 80 per cent chance of developing breast cancer before she is 70.

In spite of scientists' initial optimisim, predictions of finding the gene 'within the next few months' mutated into 'before the end of the year' - and that was last year. Today, the researchers are more circumspect.

'I think we're all at pretty much a similar stage,' says Professor Bruce Ponder at Cambridge University, who leads a British team funded by the Cancer Research Campaign. 'We've narrowed down the region of the chromosome where the gene probably lies.' In that region there are between 10 and 15 genes.

There are several reasons it has taken so long, he says. 'These are quite difficult techniques and they don't always work. They take time and patience.' Like other researchers he has to sift through thousands of letters in the genetic code to eliminate the regions of chromosome 17 that cannot be involved in conferring a predisposition to breast cancer. 'It's possible that we are mistaken,' he says, and that other groups believe the gene is elsewhere.

Although there was quite close co-operation between the different groups about a year ago, that began to tail off when more and more of the region on chromosome 17 could be eliminated from inquiries. Last October, when news of the non-cooperation emerged, one of Professor Ponder's colleagues, Simon Smith, explained: 'Things have now gone quiet because none of us wants to give information to the others. In an ideal world we'd be talking to each other and not holding back information. But our work is judged on what is published. If we are always second, it's no good.'

Professor Ponder says there was a formal arrangement whereby the different groups - scattered as they are in France, the US and Canada - could share information if they wanted. 'The rule was basically data-in, data-out. If you didn't contribute you didn't get a share.' Even this led to occasional tensions. There was sometimes a feeling, for instance, that certain scientists were 'coming to the meeting, taking away all our data but not putting all their cards on the table', he says.

'You can sometimes suspect it at conversations over coffee at one of the many scientific meetings and you can get a feel that not quite everything is being released.' He says frankly that he has himself not given out the most sensitive research data for fear of helping the competition.

A competing British group is led by Ellen Solomon of the Imperial Cancer Research Fund in London, a charity that is also competing for public donations with the Cancer Research Campaign. Like many scientists, Dr Solomon likes to play down the tensions between competing researchers, laughing it off as part of the rough and tumble of any profession. (The humour starts at the door to her laboratory, which bears a photograph of Mary- Claire King as a reminder of who else is working on the problem.)

But if they are all good friends and colleagues, why not share their data? Dr Solomon pauses before replying: 'The simple facile answer is that everyone wants it for themselves. But I think it is by no means the only answer. There isn't really good evidence that sharing things out and doing them in a structured, contract sort of way helps. Science doesn't really have a history of working well in that way.

'You might say to the BBC, why do you bother with a six o'clock or nine o'clock news when ITV does the same? The answer is you get quality control. You are much more careful of what you say if there is a programme on another channel. You can give your creative input to it, and are not stymied by the methodology that other people may be using. It acts very much as a check.'

Dr Solomon and Professor Ponder are agreed that the intense publicity surrounding their work has not been completely beneficial to close co-operation. As Professor Ponder explains, the perceived benefits of finding the gene are far greater than the intellectual challenge involved in looking for it. 'People are more likely to be jealous of others finding the gene because they think someone else could get a result that brings them fame and fortune which after all was only a matter of luck. That's the root of it.'

Dr Solomon puts it slightly differently: 'There has been amazing hype over this gene and I'm not sure that it's appropriate. I worry a lot over the public perception of this gene. There is great misunderstanding about what its importance is - it is important, but not in the way that most people would wish.'

Once the gene is found one of the earliest practical benefits will be a test which can be used by women in whose families the disease runs. Young women in these families will be able to discover if they have inherited the defect and are therefore likely to develop breast cancer in later life. It should help those with the gene to make difficult decisions about prophylactic surgery.

If scientists discover that similar defects in the same gene are involved in the far more common non-inherited forms of the cancer, then the potential exists for a test that could be applicable to all women, to pick up mutations in the gene long before they result in the development of tumours. Already one scientific group in the US involved in the race has set up a company to patent and market such a test if it finds the gene first.

But the difficulties here are enormous, and Dr Solomon dismisses the widespread belief that finding the gene will quickly lead to such a test. 'I don't think it is going to lead tomorrow to an early diagnostic test for all.'

Nevertheless, such is the fear associated with breast cancer that medical scientists may feel they have to open up their laboratory notebooks to each other a little more if the race to find the gene drags on for much longer.

(Photograph omitted)