Clinical genetics have been transformed since the mapping of the genome. Patrick Butler reports on a Scottish case that could have far-reaching repercussions

Talks between the Department of Health and a small Scottish biotechnology firm called Rosgen over the past few weeks have attracted little publicity. Yet the outcome could have an explosive impact not only on clinical genetics in the UK, but on the very future of the NHS.

The negotiators will try to agree the terms on which the NHS can access a genetic test for predisposition to breast and ovarian cancer, a test carried out on around 1,200 women each year by the UK's 15 regional genetics centres.

The talks have infuriated many in the clinical genetics community, as well as patient groups. They believe any agreement will massively inflate the costs of the test, radically limit the numbers of women able to get the test on the NHS, and undermine the regional genetics laboratory network. They fear it has also set a dangerous precedent over commercial patenting - the controversial ownership of genes by genomics companies.

The government hinted last year that it would attempt to block 'gene entrepreneurs', but it now appears to have abandoned the fight. 'What will the costs be to the health service if the costs for genetic testing have to include royalties to the holder of the patent for that gene?' asked Liberal Democrat MP Richard Allan in a House of Commons debate in March.

'What will be the effects on public research if the incentive to develop novel applications is tempered by the knowledge that those applications cannot go to market? Or that they are used for the public good in the public domain without negotiating with, and making payment to, the gene patent holder?'

There are fears that as more 'disease genes' are identified and patented the agreement prefigures a time when effective control over genetic diagnosis - and over time, disease prevention and therapy - is passed from the integrated, clinician-led NHS system to commercial companies in the US and elsewhere.

'I think it [the Rosgen agreement] is enormously important, ' says Rob Elles, head of the north-western regional genetics laboratory in Manchester, and secretary of the British Society of Human Genetics. 'It's one of the most serious issues to affect NHS genetics.'

In March Rosgen acquired a five-year UK licence from Myriad Genetics Inc, a US genomics firm. This will allow Rosgen to provide private genetic testing services for mutant breast cancer genes.

Myriad has identified and patented in the US the two genes for predisposition to breast cancer - BRCA-1 and BRCA-2 (pronounced Bracker-1/2).

Controversially, it is soon expected to be given the UK patent for BRCA-1.

The Cancer Research Campaign holds the UK patent for BRCA-2.

But whereas the charity allows NHS genetics centres to practise BRCA-2 testing free, Myriad is expected to charge. Soon it will be able to levy a royalty fee on each test, and demand that certain stages of the testing process are carried out by Myriad laboratories in the US or Rosgen in Scotland.

There are also worries that when the patent is granted - and the DoH believes that will be soon - genetics centres (and their parent NHS trusts) could be sued for what the DoH says are 'substantial damages' by Rosgen or Myriad for BRCA-1 tests it has carried out over the past five years.

A recent memo to NHS managers from NHS Executive health services director Sheila Adam says: 'Department solicitors advise that the NHS laboratories which offer BRCA-1 testing are potentially infringing Myriad Genetic's intellectual property rights. If Myriad Genetics is successful in gaining patent protection in the UK, either Myriad Genetics itself, or Rosgen, could choose to take action against NHS laboratories, claiming damages back to the date on which the patent claim was filed (August 1996).'

The talks on price and access between the DoH and Rosgen are secret - a Rosgen spokesperson said it would have been happy to discuss the issues, but the DoH insisted on confidentiality.

NHS geneticists believe the cost to the NHS of Myriad being awarded the BRCA-1 patent could make the test prohibitively expensive, severely restrict access, and create a two-tier system in which well-off women will be able to access the test privately.

According to Dr Elles, Rosgen originally set the UK price per test at£2,000 - more than the US price of around£1,500.At the higher rate, his department's budget would be rapidly eaten up. It tested 173 women in 1999-00, but if the price was£2,000, its test capacity would shrink to just 20 women.

Fiona Macdonald, clinical molecular geneticist at Birmingham Women's Healthcare trust , says : 'As far as we can see, it means fewer patients will get the test.'

Geneticists are not averse to paying royalties - a royalty of up to£5.40 is exacted by pharmaceutical company Hoffman La Roche on a technique used in the gene testing process called preliminary chain reaction (PCR).But as Dr Macdonald explains: 'PCR is a technique, not a gene.'

Critics are fond of the mousetrap analogy to explain why gene patenting is so iniquitous. Mr Allan says: 'I would argue that the patenting of human genes is equivalent to securing a patent on dead mice, rather than on a mousetrap.

'If that patent were secured, the dead mouse patent holder could seek royalties from anyone else who invents other methods for killing mice. It is that exclusivity over the material rather than the applications that is the major source of concern.'

Professor Andrew Read of the department of medical genetics at Central Manchester Healthcare trust is surprised a patent was awarded: 'The point about gene patents is that they confer a natural and complete monopoly.You cannot make a better gene.' He fears the UK genetic testing system could disintegrate. Companies will suck key parts of the testing process into their own labs, and the comprehensive service offered by regional centres - seen as a model system in Europe - will be 'severely downgraded'.

John Gillott, policy officer at Genetic Interest Group, a patient lobby, says:

'The issue is that clinical geneticists could turn into people who collect blood samples and put them in the post.' But he warns: 'There's a danger of over-hyping. We will find the genes for more diseases. It's a fixed number of people and we will be able to offer these people more therapeutic options. That will be a steady process rather than a tidal wave.'

Dr Elles is angry at 'lack of leadership' by the DoH, which he feels has been 'all at sea' over gene patenting.

A DoH spokesman says: 'The view was it would have been difficult to oppose the patent application. . . The DoH is having discussions with Rosgen to ensure NHS patients will have the best possible access to BRCA1 tests in the future. We are confident women who need to have this test on the NHS will continue to receive it. It is wrong to imply the NHS is facing a big bill. The NHS has recognised it needs to move on these issues, and common sense dictates that we talk to the commercial organisations involved in these particular issues.'

But the charity Breakthrough Breast Cancer is worried about patenting.

'Will it limit access to diagnostic tests, and limit the use of new technology in the future?' asks chief executive Delyth Morgan.

'What worries me is we are just talking about breast cancer. There could be lots more gene discoveries in the pipeline, and this is setting a precedent.'

BRCA-1 and BRCA-2 are the two genes responsible for inherited predisposition to breast and ovarian cancer; mutations in these genes are believed to cause up to 10 per cent of breast and ovarian cancers. Women who carry mutations in the two genes have a 56-87 per cent chance of developing breast cancer by the age of 70, compared to the average risk of 12 per cent. Rosgen and Myriad claim the test - which involves sequencing the genes from a small sample of the patient's blood to detect mutations - is 99 per cent accurate.

A positive result means that a probable risk of the patient developing cancer can be estimated, allowing the patient to take precautions such as having regular breast examinations, preventive medicine such as the drug Tamoxifen, or breast removal. A negative test isn't conclusive evidence that the patient won't contract breast cancer.

They still have the one in eight risk shared by the population as a whole.

The DoH recently issued guidelines to GPs on referrals for genetic screening for women with a family history of breast cancer. 'High-risk' women (more than four times the average age-related risk) will be referred for specialist genetic counselling and possible testing at a regional centre. 'Moderate-risk' women (at least three times the average related risk) are deemed 'not appropriate' for genetic testing.

One fear is that UK patients, encouraged by drug companies and patient groups, will demand more BRCA tests without real evidence to suggest they are cost-effective. Rob Elles, secretary of the British Human Genetics Society, fears that carrying out out a proper evaluation of the tests could be scuppered.' The commercial imperative is crashing through the accumulation of an evidence base that would enable a thorough service delivery framework to be put into action.'