Iceland's gene pool holds the key to curing diseases. But drug firms will

BYLINE: BY ROBIN MCKIE

BODY:
INSIDE the Reykjavik headquarters of DeCode Genetics, a guard stands on permanent duty outside a small, panelled room containing a double-locked steel safe. Only a handful of staff have keys. The safe, however, is no mere repository for financial secrets or bonds. They are the genetic records of tens of thousands of Icelanders and their value is inestimable, said DeCode's president, Dr Kari Stefansson.

A former Harvard researcher, Stefansson set up DeCode this year to collate his countrymen's DNA records - and sell them as sources of future medicines. International pharmaceutical companies will use them to pinpoint genes that dispose people to disease, he predicted. And he was right. Tightly inbred populations such as Iceland's are invaluable for tracing disease genes and have led to the creation of a generation of 'gene prospectors', scientists who have begun poring over the world's isolated peoples - in Tristan da Cunha, Easter Island, the Brazilian highlands and, of course, Iceland - in search of DNA that can be linked to ailments such as asthma, multiple sclerosis, diabetes, schizophrenia and cancer.

These populations have limited pools of genes, which makes it much easier for researchers to pinpoint the genes that predispose people to individual disease. And medicines created in the wake of these discoveries will be worth millions of dollars.

The drug companies' efforts, however, have not been universally welcomed. Gene prospecting has been labelled the ultimate exploitation of the Third World, with companies - such as Sequana Therapeutics of La Jolla, California; Millennium Pharmaceuticals, of Massachusetts; and Genset, of Paris - being accused of acquiring the DNA of indigenous peoples in order to fill corporate coffers without thought, concern or benefit to natives.

In addition, some scientists say companies are freezing access to specimens and information. While academics freely exchange data, companies - concerned about securing patents for their discoveries - maintain tight secrecy and insist that university scientists who collaborate with them sign complex agreements that ensure their silence. Medical research suffers as a result.

'It's helicopter science,' said Stefansson. 'Companies fly in, take what they want and then fly out again. When I was at Harvard, I saw this happening and I decided no one was going to do that to Iceland.'

So he set up DeCode, with the backing of local government and academics, and funded by $ 12 million ( pounds 7.5m) of international venture capital. Already tens of thousands of Icelanders have given blood and their family histories. Eventually Stefansson hopes most of his 270,000 countrymen and women - even Bjork - will contribute.

Companies will then have to pay for access to Iceland's unique genetic heritage, formed when the island was settled by Vikings 1,100 years ago and distilled through two subsequent population crashes - an outbreak of bubonic plague in the 1400s and an eruption of the volcano Heckla, which triggered famine in the 1700s.

The reduction in Iceland's gene pool has been dramatic and the usefulness of this limiting effect to science is revealed through the first ailment that was tackled by scientists using DeCode's database. In only 10 weeks they were able to pinpoint the gene for the world's most common neurological movement disorder - 'familial essential tremor', an inherited shakiness of the limbs.

Now projects aimed at pinpointing genes associated with multiple sclerosis, pre-eclampsia and alcoholism are being established between DeCode and various pharmaceutical companies.

And once these genes are found, the abnormal proteins that they are responsible for manufacturing can be isolated and studied. Drugs can then be made to counter their effects, tested and eventually marketed round the world. This technology offers drug companies a chance to save lives and make money - though not in Iceland, for one of DeCode's stipulations is that all medicines made from use of its DNA database must be provided free to Icelanders.

'We are going to make sure Icelanders can exploit their own genetic heritage,' said Stefansson. 'That is the whole raison d'etre of DeCode. There will be no DNA exports from this country.'

This position, however, contrasts with many other parts of the world. In Tristan da Cunha, for example, scientists working for the University of Toronto have used local populations to unravel a gene which they have linked to asthma.

Although the disease has clear environmental causes, scientists have long suspected that asthma also has a strong inherited component, and on Tristan da Cunha they found the perfect laboratory. In the Sixties, the tiny island's interbred population was evacuated to Britain after a volcanic eruption. To their amazement, doctors discovered that half of them had a history of asthma, at least three times the asthma rates in normal populations.

Scientists believe that the island's original settlers - a family who remained after the British garrison quit Tristan in 1817 - were asthmatics. Now their interbred descendants - all 300 are cousins - are riddled with the disease. However, as several genes appear to be involved in disposing people to asthma, the severity of the condition still varies among the population.

Nevertheless, Toronto researchers Noe Zamel and Arthur Slatsky have isolated one of the genes they believe causes asthma on the island.

But because their institution had suffered cuts in government funds, a deal was signed between the university and Sequana Therapeutics. Sequana has invested an astonishing $ 70m in asthma research and, thanks to its support, Zamel and Slatsky were able to carry on.

'We simply could not have done this without Sequana's backing,' said Dr Slatsky.

But Sequana's backing has a price. Although the Toronto team has found and cloned the first gene to be linked to asthma, it cannot publish details until Sequana has established patent rights for the discovery and for any medicines that might be developed from it.

Nor is Tristan Sequana's only target. It has set up deals to use DNA from populations in Easter Island, Brazil and China, and there is no provision for native people to be provided with drug discoveries derived from their DNA.

These developments alarm some researchers, although Dr Slatsky defended Sequana and other pharmaceutical companies. 'Yes, companies force us to keep quiet about our work for longer than we normally would. But scientists always think before they rush to print. All we are doing is extending the period a little bit. And as for Tristan da Cunha, Sequana has promised that islanders will be given free supplies of any asthma drugs developed from their DNA.'