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In an office in Munich, an ordinary mortal has caught a glimpse of what it might feel like to be God. The examiner at the European Patent Office must decide whether Harvard University is entitled to intellectual property rights on a mouse tailor-made for research. ¿ìè¶ÌÊÓƵs at Harvard modified the mouse’s genes to make the animal susceptible to cancer. The university was granted a patent in the US three years ago, and Du Pont, the chemicals company, now has a licence to sell the mouse to anyone interested in cancer research. In Europe, however, the mouse has become the focus of the whole vexing question of whether life forms in general, be they animals or plants, should be patentable.

The debate has intensified since the European Commission proposed, in a draft directive that is about to come before the European Parliament, that all genetically engineered plants and animals should be patentable. The biotechnology industry with an eye on the hugely lucrative markets that genetically engineered crops and animals promise, has mustered a powerful lobby to persuade the parliament to endorse the directive. An equally determined group of campaigners, including environmental, farming, legal and religious organisations oppose the directive. They say that the public has been kept in the dark about the consequences of patenting life and they want to open up the debate to public scrutiny.

One of the main fears of the directive opponents is the broadness of Harvard’s claim for its ‘OncoMouse’, which has been made more likely to develop tumours by the presence of an oncogene in its cells. If the EPO grants the patent Harvard could charge royalties on any non-human mammal developed for cancer research by injecting its embryo with an oncogene. The opponents question the right of one organisation to hold such a monopoly on genetically engineered animals. They say that nobody should be allowed to ‘own’ life in this way.

The current scrutinising of patent laws in Munich as a result of Harvard’s application follows a bout of equivocation by the patent office itself. In 1989, an examiner at the EPO decided that the mouse could not be patented. Clause 53B of the European Patent Convention of 1962 prohibits patents on ‘varieties’ of plants and animals – and the examiner ruled that the mouse was a variety of animal. But when Harvard disputed the ruling, the EPO’s appeals board decided that the clause does not necessarily cover all animals. The convention allows the patenting of microbiological inventions, and the board looked on Harvard’s mouse as just such an invention. The board said Harvard’s application should be considered in the light of a section of the convention that prohibits patents on inventions found to offend public morality; the sectiion has been used in the past to prohibit patents on contraceptives. It is this question that the patent examiner in Munich is now pondering. The appeals board, to the alarm of patent examiners everywhere, has brought into the debate all the thorny moral and ethical issues that surround the engineered mouse. Patent examiners say it is not their job to pass moral or ethical judgments.

These issues have moved to the top of the agenda in part because of the human genome project, an international effort to work out the coded sequence and, as far as possible, the functions of all the genes that help to determine the characteristics of human beings (‘Making sense of the genome’s secrets’, ¿ìè¶ÌÊÓƵ, 4 August 1990). ¿ìè¶ÌÊÓƵs hope to be able to determine genetic predisposition to certain diseases, which could affect people’s long-term health and chances of employment. Such information would be useful to potential employers or private insurance companies. As this project progresses, scientists and industrial companies will apply for patents on any useful section of the genome that they uncover. They will try to patent sections with industrial applications, such as the manufacture of therapeutic proteins or prenatal probes to detect genetic disorders.

Lawyers will have to decide whether scientists, in making use of stretches of DNA, have invented something and are therefore entitled to patent rights, or whether they have merely discovered a sequence of genes and have no such entitlement. There are only a few judgments in the field to help them resolve such legal questions.

In July, the State Supreme Court of California decided that patients have no property rights over tissue removed from their bodies with their consent during medical treatment, as long as they were fully informed of how their genetic material might be used. The case dealt with John Moore, a sufferer from hairy-cell leukaemia that had caused his spleen to increase in weight from 500 grams to nearly 6 kilograms. During treatment at the medical centre attached to the University of California, Moore’s diseased organ was removed and he recovered. ¿ìè¶ÌÊÓƵs at the university later found that the spleen produced a remarkable blood protein. They discovered that the protein induces the growth of two types of white blood cell that fight bacteria, and possibly cancer. The scientists managed to persuade these white bloodcells to reproduce indefinitely, in a process known as ‘immortalising the cell line’. These so-called ‘Mo’ cells will be useful for studying leukaemia.

The university has patented the white blood cells, and two companies, Genetics Institute, a biotechnology company in Massachusetts, and Sandoz Pharmaceutical in New Jersey, intend to develop drugs from the cells. It was Moore’s claim to a share in the future profits of the research that the Supreme Court quashed. The ruling implies that patients sign away such rights when they agree to tissue being removed after being told of its potential usefulness. The patient can however add a rider, saying how they would like their material to be used in future.

Though the case does not strictly deal with genetic manipulation of human material, it does set a legal precedent of relevance to patenting. Researchers and the biotechnology industry alike breathed a sigh of relief at the outcome of the case, as their future will depend increasingly on such mammalian cells in the development of new drugs.

Many human cells have already been granted patents in the US on the basis that they would not exist but for the intervention of the ‘inventor’, who extracted and manipulated them to reproduce indefinitely. The US patent office has said it does not intend to allow patents on human beings, drawing on slavery amendments to US law that prohibit ownership of human beings. But the office has not made clear how it intends to distinguish between human cells and human beings. As it stands, the European Commission’s draft directive does not explicitly exclude human beings. This omission has increased concern over the implications of allowing patents on any animal at a time when great advances are being made in areas of research such as gene therapy, which might one day allow scientists to correct defective genes in a human fetus. Individual scientists, universities and companies may eventually have the power to design the genetic make up of a fetus. Should they then be able to patent the DNA that allows them to confer certain traits on a child, or to own rights to the process by which they manipulate the genes of a fetus?

According to Kevin O’Connor, a senior legal analyst at the US Office of Technology Assessment, few people have thought through all the arguments and the many different ways of interpreting existing law. O’Connor says the Moore case illustrates the problems thrown up when new technologies collide with old law. Derek Wood, head of the biotechnology patents group at the Patent Office in London, agrees. He says the European directive will eventually contain a clause excluding human beings from the patents system, but concedes: ‘This is clearly an area that is going to prove a pretty horrendous problem in the future. The difficulty is in deciding where to draw the line between genetic material and human beings per se. Until we have a specific case in front of us we have to make some pretty delicate judgments.’

For a process or product to be patentable it must be novel, produced by human intervention and capable of industrial application. The work must also be ‘unobvious’, the exact interpretation of what is and is not obvious being left to the patent examiner. But the fundamental legal argument over patenting life is whether genetically manipulated plants or animals are inventions or discoveries. The distinction depends on the degree of human intervention in the process. Opponents of the EC’s directive say that its wording on human intervention erodes some of the most basic tenets of patenting in order to fit biotechnology and the patenting of life forms into the patents system.

The European Patent Convention states that ‘essentially biological processes’ cannot be patented. However, the European Commission’s draft directive classes all products of biotechnolgoy – apart from traditional breeding practices – as not essentially biological, and therefore patentable. This means that the tiniest and most standard piece of genetic engineering could render a process patentable, even if the bulk of that process takes place by straightforward biological means.

The directive clashes with the EPO’s existing guidelines, which say that human intervention must play ‘a significant part.’ It argues that even the process of purifying a natural substance to identify its genetic sequence constitutes human intervention and so renders the product patentable – even though the sequence is unchanged. This argument is dismissed by David King, a molecular biologist and now head of the Genetic Forum, a British pressure group interested in biotechnology issues. He says purification involves only standard cloning techniques, which are the staple diet of biotechnology, and is not enough on its own to constitute ‘significant’ human intervention.

Perhaps even more controversial is the proposal in the directive that any undiscovered substance is new ‘for the purpose of patentability’ simply because it has not been mentioned in the scientific literature. This could conceivably set a legal precendent allowing patents on any substance – whether from a tomato, mouse, human or any other living source – so long as it has not previously been purified and discussed in the literature.

Opponents of patents on plants and animals also argue that the system delays the free flow of information, particularly in Europe, where a company is not allowed a patent if it has already disclosed details of the work it wants to protect. Industry says the opposite: that patents encourage the free exchange of scientific knowledge because a patent application will be approved only if it contains enough information for anybody with a reasonable level of skill in the field of research to reproduce the results.

The directive classes any manipulation of a plant or animal as ‘microbiological,’ and therefore patentable. This runs counter to the traditional scientific definition of microbiology as the study of single-celled orgnaisms, such as yeasts or bacteria. Such fuzzy definitions alarm the directive’s opponents because the ethical difficulties of patenting microbiological organisms are different from those surrounding the patenting of modified cells capable of generating whole animals.

According to the opponets, there is an unworkable clash between the new directive and the European Patent Convention. Many of them want the convention revised to take account of advances in fields such as biotechnology. Others suspect that this will lead to even more problems. According to Tim Roberts, who has worked on patents for ICI Seeds for the past 30 years, ‘it is not clear that there is a consensus even within the industry on what to do about the convention, but if you do try to amend it you could end up unravelling the whole thing.’

While work on genetically manipulated human tissue is still a long way from yielding products that developers might consider worth patenting, the agricultural industry is already confronting the issue of patents and intellectual property rights. The manipulation of plants, which is far more advanced than that of animals, could turn agricultural practices upside down. Several patents have been granted, in the US and in Europe, on techniques for engineering plants and on the modified plants themselves – each containing some useful new trait, such as resistance to pests.

ICI is currently trying to secure a patent on a genetically engineered tomato that does not go squashy when ripe. A rival company in the US, Calgene, alrady has a patent on a similar tomato. ICI disputes that Calgene was the first to confer this non-squashiness on a tomato. ICI’s claim, like Harvard’s mouse patent, is very broad. It wants rights to the stretch of DNA it uses in its tomatoes. If the patent is granted, seed producers or farmers wanting to use that stretch of DNA to develop their own variety of any crop would have to pay ICI a royalty. ‘We were the first to clone the necessary gene and we consider that to be an invention,’ says Ed Dart, resarch director of ICI Seeds.

The dispute over the patenting of specific genetically engineered plants and animals centres on the interpretation of the word ‘variety.’ Do such plants and animals fall into the ‘varieties’ clause of the European Patent Convention (clause 53B), in which case they are not patentable? Or does the word ‘variety’ refer only to plants or animals produced by traditional breeding processes, which would allow patents on those produced by other means?

In Europe, the EPO granted its first patent on an engineered plant in 1989. The application came from a large American biotechnology company called Lubrizol Genetics, and sought rights on a technique that modified the genes of sunflower, alfalfa and soya bean plants so that they store more protein. But even this ruling, which is being challenged by a coalition of Dutch organisations, including environmental and human rights pressure groups and trade unions, still left the definition of ‘variety’ open to interpretation, says Wood of London’s patent office. At least in Britain, he says, the Plant Varieties and Seeds Act of 1964 contains a definition of new plant variety, drawn up by knowledgeable plant breeders. Wood now wants a parallel definition for new varieties of animal.

In the US, the momentum for patenting life forms has been greater than anywhere else in the world. In the important test case of Diamond v Chakrabarty, in 1980, the US Supreme Court decided that a bacterium, genetically engineered to digest oil slicks, could be patented. The decision reversed earlier rulings that did not allow patents on ‘products of nature’ and paved the way for the granting of patents on plants. By 1987, the US Patent and Trademark Office considered all non-human multicellular living organisms, including animals, to be patentable. This followed a ruling from the Board of Patent Appeals and Interferences that polyploid oysters, which contain more than twice the normal number of chromosomes, could be patented. A year later, the first patent on a ‘manipulated’ animal, Harvard’s OncoMouse, was granted. But it remains the only one: the decision so fuelled the debate over patents on life, and on animals in particular, that the US patent office has not granted another patent on an animal.

Since 1988, Congress has faced at least eight bills on the patenting of animals. These bills fall into two categories. The first, which Congress has consistently rejected, argues for a moratorium on patents on life forms and, in some cases, a total prohibition on patents on any kind of animal. The second type, which has had a more favourable reception in Congress, suggests that patents on non-human animals should be granted so long as the law is amended with two clauses. One must state explicitly that patents on human beings are prohibited. The other must give farmers the right to breed from patented animals. While the debate continues, more patent applications are lining up in the wings.

Farmers say that patents on new crops already threaten their livelihoods, taking away rights enshrined by international convention to keep and re-sow seeds. They add that patents on modified animals would also put a stop to traditional breeding practices, whereby a farmer who pays for the services of a breeding animal owns the offspring. Animals bred from a patented animal would belong to the person who owns the patent, not the farmer.

Intellectual property on new crops is currenlty protected under the international convention known as UPOV (the International Union for the Protection of New Varieties of Plants). It dates from 1961 and has been signed by 18 countries. The convention is designed to provide some incentive for the creation of new plants, but at the same time to allow free access to plant material. ‘Plant breeders’ rights’ protect new plants ‘varieties,’ which the convention defines as new plants that are distinct from other species, homogeneous and stable from generation to generation. The convention allows only the breeder of the new variety to sell any resulting crops although, under the ‘breeders’ exception,’ other breeders may experiment with the protected variety. Under the ‘farmers’ exemption,’ farmers may store and re-sow seed taken from the initial protected crop.

In contrast, unde the terms of a patent, farmers and plant breeders must ask permission to use a protected plant or animal, and pay a royalty on every subsequent generation they produce. Also, patented plants or seed will not automatically become available for at least three years after a patent is granted.

In Europe, campaigners against the European Commission’s draft directive suggest a compromise. They say the directive should be amended to allow patents only on the first generation of a new plant or animal, with the proviso that breeders and farmers may freely use all genes at any time to improve species by traditional breeding techniques. In this way, the ‘inventor’ of a new plant or animal would receive a royalty in recognition of the work done, without abusing the moral and ethical concerns that the granting of ‘ownership’ of a life form would raise. The idea does not interest the multinational companies that would have to forfeit extended patent rights.

Industry’s main argument in favour of patents is an economic one. Companies claim that they would not bother to spend money on research without the protection of a patent guaranteeing financial returns for innovation. Opponents of patents on life forms disagree. They note that many biotechnology companies have conducted research on genetic modification for at least 10 years, before it was clear that they would gain patents on their work. This view was endorsed by Warren Burger, the former Chief Justice who presided over the Diamond v Chakrabarty case. Referrring to experiements with microroganisms, he said: ‘Legislative or judicial fiat as to patentability will not deter the scientific mind from probing into the unknown any more than Canute could command the tides.

Roberts, of ICI, is anxious about the prospect of Europe turning against the idea of patenting engineered plants. ‘We think we will get sensible plants, but the atmosphere in the industry now is that there are plenty of people who are willing to disinvest in this area.’ Without royalties from licensees of new varieties of crops for instance, says Roberts, the burden of industry’s research investment will be on farmers who will have to pay much higher prices for the latest, genetically modified seeds.

In Australia, opponents of the patenting of life forms seen to be fighting a losing battle. ‘We fear that the patent office is going to allow patents on processes, and then allow patents on animals more or less as an afterthought’ says Bob Phelps, a campaigner with the Australian Conservation Foundation. Phelps says the US is pressurising the rest of the world to agree to the wholesale patenting of plants and animals. He is also concerned that proposed Australian legislation does not distinguish adequately between human DNA, which it recommends should be patentable, and whole human beings, which it excludes. ‘It is not clear what the situation would be if human genes were inserted into animals .. would the result of such work be patentable or not?’ He plans to call for a moratorium in Australia on patents on life. According to John Coulter, enviroment spokesperson for the Australian Democrats, patent offices are operating to double standards that raise ethical concerns. ‘They argue that to allow the patenting of life is not a moral decision, but that to disallow it is.’

One of the biggest worries of those who reject the need for the patenting of life forms concerns the enormous power that patents place in the hands of large industrial concerns. Opposing patents is a lengthy and expensive legal process, which only large companies can afford. Small concerns have little choice but to pay royalties, or to work in areas where patents do not exist. If a patent claim is broad, as in the case of ICI’s non-squashable tomato or Harvard’s OncoMouse, whole sectors of a market are closed to competition.

The most severe impact of the widespread patenting of life forms could fall on less developed nations, where protection for intellectual property is usually weak. Industrialised countries, particularly the US, argue that their goods should have the same protection in the developing world as they do elsewhere. The US pressed this argument during the GATT negotiations that broke down last month. Developing nations countered that they should not have to accept such practices, which encourage monopoly control over areas such as food and drugs that are vital to economic growth.

These poorer nations also maintain that patents on improved crops devalue the vast genetic diversity that helps ensure their livelihoods. For centuries, farmers in the developing world have used genes from native wild plants and animals to breed crops adapted to local conditions. For many of them, such genetic diversity constitutes their best hope for developing future crops. Crops engineered by biotechnology are often based on DNA taken from species common in the developing world. If the industry were than to sell its engineered crops back to the developing world, it would be threatening the heritage of the very countries from which they obtained the extra genes in the first place.

While legal minds are struggling to stretch patent law to accommodate biotechnology, scientists appear to have been excluded from any part of the debate. Margaret Llewleyn, a lecturer at Lancashire Polytechnic’s School of Law, has been studying patents on life forms for the past six years. She says that scientists, not lawyers, are best placed to decide issues such as what constitutes a plant, a variety, an animal or species. Few scientists, she says, are aware of the speed or force of the political and legal debate as it is shaping up in Europe under the planned directive.

Wood, of London’s patent ofice, says that patent examiners rely largely on their own technical knowledge and what they can glean from textbooks. ‘We are looking to grant patents, not to stop people getting them. We want to reward genuine technical developments,’ he says. Wood argues that patent examiners have to be wary of consulting scientists because they may rubbish patent applications from rival groups of reseachers working in a similar field to their own. The people working in London’s patent office are qualified to PhD level in biotechnology, and can speak with some experience of the field, Wood says. Privately, the biotechnology industry feels that patent examiners have been caught on the hop in coping with recent advances in this field.

Llewelyn is concerned that a group of people with only narrow expertise is deciding whether or not to patent life. Many lawyers involved in the debate have vested interests because they are involved with big pharmaceutical companies, she says. ‘These lawyers are playing word games with terms such as ‘variety’, which require a scientific defintion.’ She wants to see parliamentary debate of all the issues, including the ethical implications of decisions.

Llewelyn points out that any public debate would have to avoid what happened in the US, where the forum became so large snd sprawling that it got out of control. Subcommittee hearings in the US House of Representatives on the ethical issues of transgenic animal patents began in 1987. A wide variety of organisations contributed, including the church, scientists, industry, politicians and academics. Religious groups opposed the whole idea because, for them, life is the property of God. They disagreed fundamentally with rulings such as that in the Diamon v Chakrabarty case, which were based on the view that life forms are simply collections of chemicals. Those campaigning against patents on the grounds of animal welfare said they did so because animals may suffer physically from being genetically manipulated to serve human needs.

The lengthy debate in the US found little common ground. The closest it came to consensus was with a recommendation for a moratorium of patenting life, which the House later threw out just before Harvard was granted a patent on the OncoMouse. But seveal groups in Europe are willing to learn from the American experience. In Norwich, where much of Britain’s research on new plant is done, a study group of academic and agricultural scientists, farmers, educationalists and development economists, says the main lesson is the need for a public education programme. Alistair Smith, one of the founding members of the group, is trying to encourage such a programme, and aims to secure financial support from the European Commission, industry and governments. The group has already had some success following a series of ‘diplomatic’ seminars with ICI on the possibility of developing joint educational material for schools.

Smith says that there is one possible route out of the current stalemate. He suggests that this would be for the biotechnology industry to fund independent research to examine the viability of alternatives to patents for genetically engineered life forms. Such alternatives might include plant and animals breeders’ rights, the use of trademarks, registered designs, copyright and trade secrets, or even direct subsidies and tax incentives for the industry from governments.

Better public understanding of industry’s work on engineered crops, and convincing moves by industry to show that it cares about the effect its policies have one people’s lives, might help to allay fears over food safety and the enviromental consequences of this new technology, Smith says. He therefore believes his group’s most notable achievement has been to persuade ICI to acknowledge that its policies do have a social and economic impact. ‘I still believe that there is a point beyond which industry cannot go for either practical of ‘constitutional’ reasons’, Keith Pike, ICI Seeds’ public affairs manager, said when asked about this issue. ‘Nonetheless, it may be that we have drawn too tight a dividing line and that we should consider whether and how the line could be relaxed.’

The Norwich group’s success in nurturing ICI to acknowledge the wider impact of its policies is one of the most hopeful notes in the debate over the patenting of life. Apart from this, the opponents in the debate hold incompromising views. Roberts, a die-hard pro-patentee, represents those most fiercely in favour of patents for the industry: ‘Pasteur was patenting yeasts in the 19th century,’ he says. ‘I can’t see that simply because something is alive it should not be patentable. Patents are not to my mind a form of ownership, they simply stop somebody else doing the same work. The fact that life is involved doesn’t seem particularly relevant.’ Coulter sums up for the oppsoition: ‘Life is different to non-life. To own and commercially exploit life is the epitome of misuse of our enviroment.’

Susan Watts writes about science, technology and the enviroment for The Independent.