Science: WHOSE GENES ARE THEY ANYWAY?; GENES PART 1: THE PATENT DEBATE

The blueprint for life is up for grabs. But should we allow our genes to be patented? It's an argument with all the twists and complications of the double helix itself, says Hilary Bower

The notion of patenting "life" has been bandied around all summer, with the troubled passage of legislation through the European Parliament which deals with how patent law is to be used in protecting genetic advances. The idea of patenting "life" is a strongly emotive one which plucks at our feeling of human identity, but will this much-fought- over legislation actually allow companies to have monopoly control on parts of the human genome or not?

The simple answer is yes; the debate over whether it should is not so simple. The arguments for and against patenting DNA have all the switch- backs and twists of the famed double helix itself. At the heart of the conundrum is not so much the question of whether the principles of patent law do or do not allow the patenting of genetic material, but the philosophical question of whether DNA - deoxyribonucleic acid - is a collection of chemicals or something more.

The European Parliament and Council directive on the legal protection of biotechnological inventions is an enormous document exploring the implications of patenting law on everything from human cloning (unpatentable) to whether farmers may retain the right to re-sow part of a harvest grown from genetically modified seed (patentable). The directive has caused a furore in many quarters and was passed on to the next stage of the legislative process - national consultation - by the European Parliament, with 66 amendments to discuss. The part that is firing the argument about patenting life is a passage of less than 100 words that many people, including MEPs, say expressly denies the patenting of life.

Article Five says: "The human body, at various stages of its for- mation and development, and the simple discovery of one of its elements including the sequence or partial sequence of a gene, cannot constitute patentable inventions."

The problem is that it is followed by an apparently contradictory clause: "An element isolated from the human body or otherwise produced by means of a technical process including the sequence or partial sequence of a gene may constitute a patentable invention, even if the structure of the element is identical to that of a natural element."

Paradoxically, genetic material and information must be "isolated" from the body by means of some sort of technical process before any scientific work can be done. But what the clauses mean is that while an organisation can patent a stretch of DNA and charge royalties for its use in any commercial product - a diagnostic test or an artificial organ - they can't charge royalties to us for having it in our bodies.

So, if at this month's meeting, the Council of Ministers passes the directive as it now stands, it will allow the patenting of DNA.

Is there a problem with this? Genetic tests and therapies are the great hope of the future and companies are pouring millions of pounds into researching their functions and potential applications. Is it wrong for them to want to protect their source material?

Let's step aside from ethics for a minute and concentrate on patent law which exists to protect novel inventions. Opponents of the directive say when vulcanised rubber was found to be the perfect material for tyres, the patent granted did not cover rubber, but did cover the process of vulcanisation, the structure of the tyre, the pattern of its tread, in other words the "inventions" that made rubber into a tyre.

Opponents of the directive say patents should not be granted on genetic material itself because it is discovered, not invented. Patents should, they say, be restricted to the applications that make use of genetic material. Proponents offer a different example: many antibiotic agents existed in nature, they say, and no one knew they were there. But once they were isolated or "discovered", they were patented and developed and have contributed hugely to modern healthcare.

Genetic material, isolated from the body, is the same as any chemical compound isolated from nature, says David Roberts, senior vice president for intellectual property with SmithKline Beecham, one of the largest players in the biotech industry. Chemical compounds are patentable under long-standing patent law. Amino acids isolated from the body are patentable, why should DNA be any different?

In fact, says Roberts, the case for genes is even stronger, because a gene doesn't exist as a discreet chemical entity in the body. "To isolate a gene you have to use processes far more substantial than purification of chemicals." On a less controversial plane, Roberts points out that 100 years ago Bayer, a major pharmaceutical company, patented an analgesic they christened aspirin. "The natural source of aspirin is the willow tree. The equivalent in genetic terms is the human body. Bayer didn't attempt to patent the willow tree but did patent the compound it isolated. We wouldn't attempt to patent the human body but do want to patent the compound we isolate from it."

To do otherwise is to make different rules for genetic developments than any other area of science and technology. Plus, since so much work, inventiveness and money goes into isolating genetic material and extracting information, companies like SB argue they must recoup funds in the traditional way, via patent licenses, or it's not worth the risk. Much of the biotech industry wants to remain able to patent DNA sequences without specifying function or application - a position they say is justified by the investment they put in before either of these is visible. Without this protection, they say, European industries will not be able to compete internationally - in the US and Japan DNA sequences or genes are patentable.

"You have to ask whether investment can be justified when the fruit of that investment can be copied by anyone. The more you close down the availability of patent protection, the less attractive the biotech industry is going to be. Stopping the patenting of genetic material would send a very negative signal to anyone doing biotech research in Europe and one would expect a steady drift of investment away from Europe and towards the US and Japan," says Roberts.

SmithKline Beecham is not a disinterested player: it spends US$1.3 billion a year and has 4,000 scientists working on genomic research. It also controls one of the largest databanks of raw DNA sequences. The biotech industry also argues that if the directive is passed, it won't introduce anything not being done already.

This is true: patents are being granted on genes in many European countries including Britain (see box), and the right to patent genetic material is enshrined in US law. The US is so keen to see world- wide acceptance of this, that it has threatened not to renew a hugely funded collaborative research programme with India if it refuses to change its anti-patenting stance. The European directive will allow broader patents than US law, as companies filing for them will only have to specify a sequence's function, not its commercial application. This would enable companies to buy up rights to stretches of un-identified DNA and control research and dev- elopment on them. Opponents insist patenting on this basis will damage access to the potential benefits of the genetic revolution and give immense power to a handful of commercial companies.

Dr Gareth Evans is a consultant in medical genetics in Manchester and part of a group of geneticists and representatives of patients with rare genetic diseases (the Genetic Interest Group). The group is pleading with British Government officials to make a stand at the Council of Ministers, and Dr Evans says that even putting aside the ethics of owning something that exists in life, patents on DNA will add another level of royalties and make any developments more expensive and less accessible to those who most need them.

Even if a hospital designs its own DNA test for a genetic condition it will be liable to pay a royalty to the sequence owner every time it uses it, he says. If the owner sells its own test kit, that royalty could be prohibitive. A patent holder could also decide it wishes to control all development itself and deny all other licenses. Patenting raw DNA will place control of research and development of the human genome with a handful companies who own huge databases of genetic sequences, says Dr Evans. Far from encouraging investment, he believes this will discourage development because it allows companies to make money from doing nothing but identifying a sequence.

"It gives them a broad brush claim on everything that emanates from that gene - anywhere in the world if America gets its way. And unless compulsory licensing measures are beefed up, the patent owner could just refuse licences. Companies that do develop a commercial product could find they are not able to use it.

"We are creating a field day for patent lawyers and biotech companies. The losers are the taxpayers and people with genetic diseases."

Smithkline Beecham's David Roberts bats this back: "This is superficially the most powerful argument, but this argument applies to all areas of industrial development. The patent for aspirin covered use as an analgesic. If someone wanted to use it as a flame retardant, it would still be covered by the patent. In theory I could refuse to license it. In the real world I wouldn't do that - I would make a contract that was agreeable because it would bring in money. And if I decided to abuse my monopoly and refuse all licensing, then the laws of every country in Europe have compulsory licensing."

Dr Evans argues it is unnecessary to patent actual genetic material: "If you create something that is not there in nature, like a diagnostic kit, you can patent it anyway. And secondly, in developing a therapy, you would never use the gene in its natural state anyway - it would be manipulated or changed in some way that you could patent."

John Gillott, policy officer for the Genetic Interest Group puts it this way: "We should be able to create a framework in which people can protect genuine novelty and their investment. This is found at the interface between function and therapy. It's this that should be patentable. Patents would specify the function and drug, but the sequence itself would stay free for others to work with. Companies should have confidence in their own innovativeness and seek patents at this interface where the hard intellectual work takes place."

Warnings from industry that restricting patents to applications will stem the flow of investment and push biotech companies over the Atlantic are false threats: drug companies have always developed new substances on spec which they have then tried to find a use for - why would they stop now, asks Dr Evans?

Directive proponents also argue that without security of investment people with rare genetic diseases will be denied any hope of treatment because it won't be financially viable to develop therapies in a competitive environment. Indeed the industry's battle-cry of "no patent, no cure" became one of the most influential over the summer, as MEPs, already blitzed by the mind-numbing combination of genetics and patent law, and under intense pressure from commercial players wielding jobs and investment, also found themselves faced with patients in wheelchairs waving banners backing patents.

Dr Evans says the biotech industry has sold these patients a lie too. "Cures will be less likely with patenting because it screws up research, makes it more secretive and syphons off money. Biotech companies have the cheek to say 'you are being very ungrateful by not allowing us to patent genes when we've done you this great service of finding them.' The vast majority of single genes have been found by charities, academic institutes and the like. As for the rest, they will all be discovered by 2005 without any help from the biotech industry because of the Human Genome Project which is non-commercial."

Confusingly, both sides argue that if they don't get their way, science will become more secretive and wasteful as people duplicate research. Opponents say conflict with commercial sensitivity will kill the tradition of publishing to share information, while proponents insist scientists, unable to patent, will take refuge in trade secrecy.

There are a welter of other objections. Clinicians note most genetic samples have been donated by volunteers to non-commercial research institutes who may feel differently if a commercial company is to profit. The Church of Scotland earlier this year deemed regarding any aspect of the human body as intellectual property "abhorrent".

For their part, Greenpeace says patenting genes will promote "biopiracy", by enabling companies to take over crops or animals bred by local producers to have useful traits such as hardiness or resistance, then charge those same producers royalties for using the product of their own ingenuity or circumstance. The same could happen with traditional medicine - an attempt has been made to patent turmeric used in Indian Ayurvedic medicine for centuries.

There is a third corner to stand in and that is "defensive" patenting. Professor Mike Stratton of the Institute of Cancer Research in London, together with the Cancer Research Campaign has just been granted a British patent on BrCa2, the second gene for breast cancer. He says patenting, backed by licensing agreements which bind users to a code of practice, may not only offer clinicians an ethical way out, but also allow money to flow back into non-commercial laboratories.

"For clinicians, a key worry is how a company who owns the rights to a gene might behave in the future. Clinicians are going forward slowly, offering gene testing only to those who really need it and who will benefit most, but financial imperatives could mean a company would want to offer testing to as many people as possible. There is huge potential for clinical, ethical and financial conflict."

The implications of this could include individuals being pushed into having tests which they don't need, tests where there's nothing that can be done, and the anxiety of being told of pre-disposition to a disease which you may never develop. All this has ramifications on insurance. The one thing everyone agrees upon is that exactly what will and won't be done with patents must be clarified. Banishing the directive for another five years simply will not wash. So are our genes more than the sum of a collection of chemical parts?