SCIENCE : Whose gene is it anyway?

Quietly and unobtrusively, governments and drug companies are staking claim to the ownership of human DNA. Should the double helix of life be patented for research like any other chemical? Tom Wilkie reports

LATE IN pregnancy women's bodies undergo radical changes to ease labour during childbirth, triggered by a hormone called relaxin; its genetic recipe is carried in every woman's DNA. But this human gene, whose action helps reshape the birth canal and soften the cervix just before delivery, is the intellectual property of Genentech, a US biotechnology company.

In the US, some 600,000 women carry a gene which may predispose them to develop breast cancer or ovarian cancer. Last year, Mark Skolnick and his colleagues at the University of Utah sorted through human DNA samples and found the gene. It is now the intellectual property of Professor Skolnick's associated company, Myriad Genetics.

In the forests of Panama lives a Guyami Indian woman who is unusually resistant to a virus that causes leukaemia. She was discovered by scientific "gene hunters", engaged in seeking out native peoples whose lives and cultures are threatened with extinction. Though they provided basic medical care, the hunters did not set out to preserve the people, only their genes - which can be kept in cultures of "immortalised" cells grown in the laboratory. In 1993, the US Department of Commerce tried to patent the Guyami woman's genes - and only abandoned the attempt in the face of furious protest from representatives of indigenous peoples.

Nor is it just genetic material that is "owned". In the information age, data is a commodity too. Last month, a unique catalogue of human genes was published in the scientific journal, Nature. It was, one researcher wrote, "the largest body of information about the physical structure of our genetic apparatus that has ever been published". It marks a milestone in humanity's view of our basic biological composition, comparable with the first anatomical atlas of the human body compiled by the Renaissance surgeon Andreas Vesalius in 1543. Though the catalogue was openly published, it represents but a short guide to a far larger computer database holding the bulk of the genetic information. This resource is owned and operated by a private company, which reserves the right to patent developments made by researchers who log on to its computer.

Quietly and unobtrusively, government departments and international corporations have been staking claim to the ownership of human DNA. Those taking out the patents argue that, without this protection, essential life-saving research won't be possible. Others see this growing trend as a violation of one of civilisation's guiding principles: that human beings and their body parts cannot be "owned".

The rise of the biotechnology industry over the past 20 years is changing the ground rules. Human genes are no longer to be held in common - everyone's property, and no one's. Human genes are big business. Entrepreneurs across America are starting up biotechnology companies whose sole assets are the genes they have dissected out of the double helix strand of DNA, genes whose biochemical instructions their researchers have decoded.

John Gillott, of the Genetic Interest Group, which represents the families of those affected by genetic disease, is shocked by the trend. "Private ownership of a naturally ocurring part of the human body is repugnant," he says. "Somebody seeking privately to co-opt a discovery, not an invention, relating to a human body part is something we'd oppose." The GIG doesn't oppose the biotechnology industry, which offers the best hope of a cure or treatment for genetic disease, but its members do believe privatising human genes "is overmonopolistic. It gives a company the ability to control future developments, which creates dangers if that company doesn't develop a product. Information disappears from the public domain."

Like DNA itself, the story has two entwining strands. As researchers deprived of public funds turn to commercial companies to pay for their research, those companies seek to protect their intellectual property for their shareholders' benefit. The privatisation of science has led to the privatisation of genes. This has affected even those scientists still working in publicly funded laboratories, so that governments too are staking their claim to human DNA.

There are striking parallels with the enclosures movement which swept across the English landscape from the 17th to the 19th centuries, parcelling up for private profit what had once been common land over which individuals had rights but nobody had ownership. But while the enclosures were legitimised by the passage of parliamentary bills, it is the officials of the European and American patent offices who have overseen the appropriation into private hands of humanity's genes, extending patent protection from industrial chemicals to DNA, the very blueprint of human life itself.

It is all a far cry from 1953, when, in the Cavendish Laboratory in Cambridge, two brilliant young men - an American birdwatcher turned microbiologist, James D Watson, and an English physicist, Francis Crick - discovered that the molecule of heredity, DNA, had the structure of a double helix. Theirs was the scientific discovery of the second half of the century, rivalling relativity and quantum mechanics in the pre-war years. The structure of DNA provided the key to its function: DNA could replicate itself by unzipping the two strands of the double helix, then building two new strands on each of the originals, using them as templates.

Four decades on, Watson returned to the forefront of genetics research on a project vastly more ambitious in its scope: to read along the twist of human DNA, find each and every one of the 100,000 or so genes written there, and decipher the instructions each contains. The hope is to identify a complete specification for a human being: the genetic "essence" of humanity (if there is such a thing), loaded on to computer databases, and stored on a small boxed set of CD-Roms. International in scope, the research is called the Human Genome Project (the compendium of all human genes is known, scientifically, as the human genome).

Watson agreed in 1989 to head the American contribution to this endeavour. Though much of the work was to be conducted in America, it was conceived as an international enterprise researched by universities and public-sector laboratories worldwide - such as the Medical Research Council here in Britain. Watson emphasised the public character of the enterprise in an article in the journal Science: "Early sharing of the human DNA database is much more likely to occur if large-scale... efforts are undertaken by all those major industrial nations that want to use this data... The nations of the world must see that the human genome belongs to the worlds' people as opposed to its nations."

In 1992, just two years after Watson wrote his article for Science, the human genome project was in effect privatised. The leading figure in the transition from public to private was the American geneticist J Craig Venter. He started out in the public sector, working for the National Institutes of Health (NIH), and hit upon a novel way of identifying the genes active in human brain cells. Every cell in the body contains a copy of all the genes, but "reads" only a few: brain cells don't need to make insulin, for example, as that is the business of the pancreas. Brain cells copy these genes from the double helix into a messenger chemical, RNA, which instructs the cell to produce the protein.

Venter realised that by looking for messenger RNA in human brain cells, and comparing these partial sequences of unknown function with others in a database, it would be possible to identify whole genes. He used the partial sequences as markers to pinpoint the gene's position in the chromosome. His approach had a bonus: there are about 3 billion biochemical "letters" in human DNA, but only about 3 to 5 per cent of this actually represents functional genes. Much of the rest is, apparently, junk, which is not transcribed into messenger RNA. Venter believed that, with his approach, he could identify genes much more rapidly and cut the cost of sequencing an unknown gene from $50,000 to $20. The strategy was controversial, and at the time the NIH feared it would isolate at best only about 8 per cent of active genes, so it refused to finance the scale-up of his strategy.

Venter went ahead on the limited scale with his existing funding. In June 1991, he stunned the scientific world by filing a patent application for more than 2,500 of these sequenced fragments. The result was uproar, because these were not genes but fragments - and neither Venter nor anyone else knew their function. The confusion deepened because the part of the NIH for which Dr Venter worked had supported his action without bothering to tell James Watson, the head of the NIH's National Center for Human Genome Research. Watson adamantly opposed the patent application, because he believed it would render impossible the free flow of scientific information and thus make international collaboration more difficult. The British and the French, two of the other biggest players in the international human gene project, protested. Watson resigned shortly afterwards. With him went the most forceful voice so far for the ideal that "the human genome belongs to the world's people".

The industrialisation of human genes took off within a month of Watson's resignation, when Venter received $85m from HealthCare Investment Corp to set up the Institute for Genomic Research (TIGR) in Gaithersburg, Maryland. Though TIGR is a non-profit institution, its results are channelled through a commercial company, Human Genome Sciences (HGS). A year after TIGR's foundation, in May 1993, SmithKline Beecham committed $125m to HGS, and obtained a 7 per cent equity stake in return for the rights to develop products from the TIGR database. The information in the database offers his company "an extravagance of opportunities", says Dr George Poste, chairman of pharmaceuticals research and development for SmithKline Beecham. The argument in favour of patenting echoes the old defence of the enclosure of agricultural land - that it was necessary if British agriculture was to make the transition from subsistence farming to what we would now call a market-oriented industry. Enclosed commons meant profitable pasture: so private genetic databases "will increase the pace of drug discovery", according to Dr Poste. But although the company last month opened part of its database to other scientists, it has kept the most commercially sensitive part back. As SmithKline Beecham's genetics research leader, Russell Greig, remarked: "Government funds were not available to Craig Venter. His application [for research money] was turned down. More than $100m has come from the private sector. Why should these investors return the knowledge to the public domain?" Both men acknowledge that the policy is a deliberate one to stymie rival drugs companies.

SmithKline Beecham is not the only company to get involved in genomics. Within a year of Craig Venter's departure from the US government service, more than 30 leading genome scientists who had received research grants from the NIH were involved in deals with venture capitalists leading to the founding of new sequencing companies at a rapid rate. Within a year, the human genome project had evolved from a public into a largely private enterprise.

This evolution has been tracked by Sara Crowther and Sandy Thomas at the Science Policy Research Unit (SPRU) at Sussex University, who are providing a definitive analysis of the trends. Their research documents more than 1,200 human genes that have been patented worldwide, mainly by US and Japanese companies (the European pharmaceutical giants have been surprisingly slow in patenting human genes). The SPRU researchers have found that details are astonishingly hard to come by, because there is no central register of patented human genes; the process has been uncoordinated and governed by the commercial strategies of individual companies.

But there is a firm commercial imperative, says Dr Poste, the architect of SmithKline Beecham's aggressive expansion into genetics. He points out that it costs between pounds 150m and pounds 200m to develop a new drug. "Without intellectual property protection," he says, "I do not see companies coming forward with new drug development unless they feel there is a protectable asset." But the assets being protected are not the drugs themselves, simply the genes that the company's scientists have isolated and identified. For Dr Poste, identifying a gene "allows you to understand the root cause of disease. By understanding what happens in the gene, you can focus on the events most relevant to the disease." Instead of hunting blindly for chemicals with some biological activity, then developing them into drugs, Dr Poste believes the new science of "genomics" holds the key to rationally designing the drugs of tomorrow.

Some of the drugs developed from human genetics research have been spectacular life-savers. In the mid-1980s, Amgen - an American biotechnology company - isolated the gene for erythropoetin, a key hormone stimulating the production of red blood cells. It has transformed the lives of people suffering from anaemia, particularly those with kidney failure, and is now the biotech industry's blockbuster drug with a market worth $1.5 billion a year.

Many geneticists cannot see why there should be any fuss or unease over the patenting of genes. For them, DNA is a twist of biochemicals in the bottom of a test-tube with no more moral or social significance than any other laboratory reagent. Others have their doubts about the equity of patenting human genes - most notably those clinical geneticists who have to deal with patients in the hospitals and consulting rooms, and therefore see DNA not in the test-tube but in a human being.

Dr Angus Clarke, of the Institute of Medical Genetics at Cardiff, has been involved in the successful hunt for the gene responsible for Huntington's Chorea - a devastating degenerative brain disease, whose victims include the legendary American folk singer Woody Guthrie. "In gene hunts," Dr Clarke says, "a lot of background work has been done by the scientific community as a whole, and a lot of the families have provided samples for free. Both the medical and scientific communities and the families are being pipped at the post by the commercial companies, which come in and cream off the work at the last moment." The early stages of a gene hunt depend on the goodwill of the families to provide tissue samples for genetic analysis. Patenting, in Dr Clarke's view, "is a breach of the implicit trust that this work will be for the general good of human welfare, and not for the enrichment of commercial companies".