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Genomics New Scientist 21 Mar 98

In sickness and health: patients will benefit from better treatments and preventive care

IF YOU go to your surgery twenty years from now complaining of rheumatism, your doctor may well check out the relevant section of your personal genome CD-ROM rather than reach straight for the prescription pad. Any medicines you are eventually given will be designed specifically for you. The days when everyone suffering from the same disease took the same drug will be long gone. This is not a pipe dream. Pharmaceuticals companies are already preparing for a healthcare revolution based on genomics. Its foundations are being built by the Human Genome Project, which will have mapped and sequenced tens of thousands of human genes by 2007. The project, which involves scientists in more than 50 countries, has the potential to change medicine like no previous scientific advance. As the DNA sequence of every human gene is revealed, we will learn what each one does, how genes vary from person to person and how we might manipulate them with new drugs to beat disease. But these advances will not come cheap. The drugs companies are facing a massive investment in the task of putting each sequenced gene under the spotlight. They need to discover its role and the protein it makes, then check its potential as a drug target. The huge cost of this research is causing massive upheavals in the industry One example is this year's merger bid between Glaxo Wellcome, already Britain's biggest drugs company, and its rival SmithKIine Beecham (SKB). Although the deal collapsed, others seem sure to follow. "There are 100 000 human genes and each is a potential drug target," says George Radda, chief executive of Britain's Medical Research Council (MRC). "Drugs companies have still got 85 000 or so to investigate. That is what's going to be expensive." Hunger for research funds is not the only driving force behind the changes, says Juan Enriquez, a Harvard economist specialising in biomedical research policy. Companies fear being locked out by their competitors' patents and licensing deals. One way to avoid this, he says, is to own your competitors. For patients, a major benefit of genomics research will be more effective treatments.

But the biggest change, and the most significant for health spending, will come from radically improved preventive medicine. Sequencing the human genome will give doctors and scientists powerful tools for assessing a particular patient's risk of certain diseases. Companies will be able to develop more effective drugs by expressing specific genes in cell cultures and working out the structure of the proteins they produce. This could result in earlier detection and treatment for Alzheimer's, cancer and diabetes. It will also provide new opportunities for DNA vaccines, which are longer-lasting, more effective and easier to make than conventional protein vaccines.

The full treatment

In a speech to the meeting of the American Association for the Advancement of Science in Philadelphia last month, Enriquez noted that biotech firms such as the Frenchbased Genset are already using genetic information to identify which individuals are most likely to benefit from a particular medicine, and which are likely to suffer the worst side effects. The logical conclusion to this line of research, he says, will be to provide different drugs for different patients. The drugs companies are already directing considerable resources towards genetics research. Last year, Glaxo Wellcome set up a genetics directorate and recruited Allen Roses, then director of the Center for Human Genetics at Duke University in Durham, North Carolina, to head it. SKB, meanwhile, is spending a quarter of its budget for drug discovery on genomics. But success is not guar anteed. Sceptics fear that the interaction between our genes and drugs could tum out to be more complex than imagined. Neutralising a gene in order to inhibit a harmful biochemical process could affect other, unsuspected beneficial processes. The sums required for medical genetics research far exceed what most drugs companies can currently afford. Even the biggest-Merck in the US and Glaxo Wellcome-are dwarfed by the top oil companies and motor manufacturers. Perhaps most significantly, the world pharmaceuticals market is fragmented, with the industry's two biggest players only commanding about 5 per cent each. "The volume and speed with which genomics and other molecular technologies are providing basic information, coupled with the enormous costs of bringing a drug to market, dwarfs most companies'budgets, labs and knowledge base," says Enriquez. So drugs companies need to grow. The result has been a frenzy of alliances, mergers and takeovers. "Trying to map what is occurring at the company level in biotech and genomics is a little like trying to follow the lines in a Jackson Pollock painting," says Enriquez. "Mergers, information purchases, partnering, are taking place at a staggering speed." Less than ten years ago, SKB was the world's third-largest drugs company, he notes. By 1996 a series of mergers, including that of the Swiss-based Ciba and Sandoz to create Novartis, had pushed it down to tenth place. While Glaxo Wellcome's attempt to merge with SKB ended acrimoniously, other mergers and takeovers are being plotted in boardrooms in the US, Britain and Switzerland. Meanwhile the big players have been staking their claims to smaller, specialist businesses to gain instant expertise in key areas of genetic research. Glaxo Welcome, for example, has linked up with Powderject, an Oxfordbased biotech group, to develop DNA vaccines and cancer treatments.

The effects of the new medicine are being felt beyond the boardrooms of pharmaceuticals groups. Funding of genetic research in universities has rocketed, with state grants being dwarfed by money from industry. In the US, Duke University is launching its own biotech company. Stanford and Cornell are restructuring their generics departments to focus on genomics. It is also likely that some countries will reap the benefits more successfully than others. Britain has discovered a disproportionate share of basic genomic technologies, "yet seems unable to generate as many start-ups as the US", Enriquez notes. "The rest of Europe is further behind." Radda says this is partly because companies fail to convert the science into practical medical advances. "They rely on pure research," he says. "We need to do a lot more than just sequence the genes." Analysts point out that new biotechnology firms do not necessarily result in new advances: the emergence of 1400 such companies in the US has resulted in just 50 successful drugs.

The MRC is attempting to change this with the launch last month of UK Medical Ventures. The company, which has City and drugs company backing, aims to provide capital for new ventures in genomic technology. The idea is to stimulate research that drugs companies can then translate into practical medical advances. So come the healthcare revolution, who will benefit? Kevin Fehr, head of extemal scientific affairs at Glaxo Wellcome's Canadian division, says that the new techniques will lead to shortened hospital stays and will ultimately save money. But first, companies must persuade the public that the new techniques are ethical and safe. Enriquez notes that "trust in big medicine has collapsed". Researchers, doctors and health officials, he says, will have to avoid any BSE-type cover-ups with genomics, or risk sacrificing its potentially huge benefits to scandal. Michael Day