Glitz steals glory off gene

The Sequence
September 14, 2001

When President George Bush Sr presented the National Medal of Honor to two elders of the American scientific establishment, he paid tribute to the Human "Gnome" Initiative. He may have imagined a tiny robot directing our thoughts and actions from within the cell. The president's grasp of biology probably reflected the general level of public understanding of the matter.

The Human Genome Project has also been misunderstood and disparaged inside the camp. One biochemist saw it as witless: imagine, he said, a planet on which all experiments had worked; nobody could think of any new research, so they decided to sequence the human genome. Some feared that the ruinous costs would drain support for more modest designs, and others asserted that we would learn nothing from such a huge collection of data - that a display of the parts that go to make up a watch could never reveal how the contrivance worked. But the sceptics misunderstood the purpose behind the venture. James Watson, its true begetter, did not envisage a transcendental revelation of man's nature, only a far-sighted investment in the future of biology, of research into genetics, cancer, hereditary diseases, ageing and evolution.

Nor was it the effulgent conceptual advance that its sponsors, public and private, and the press have made it out to be. Sydney Brenner, whose influence has pervaded molecular genetics for four decades, hit the nail on the head, as always: "The idea that this is a tremendous scientific accomplishment is simply ridiculous. It is an entrepreneurial accomplishment, a great managerial achievement, but there isn't any new science in it."

The hard sell, though, and the slightly specious glamour of the undertaking caught the beady eyes of a number of opportunists and arrivistes . As the physicist Leon Lederman said of the moguls of particle physics, "some of these gentlemen would also have done well in the retail garment trade". Worst of all, it attracted the attention of the pharmaceuticals and biotech industries. Companies sprang up, eager to patent the more alluring genes, a proceeding that a French geneticist likened to patenting the moon.

The public initiative was quietly started by the US Department of Energy, but was soon absorbed by the National Institutes of Health. In time, an international consortium emerged, with participating laboratories in England (with a large investment by the Wellcome Trust), Germany, France and Japan. But no drama is complete without its villain, and Craig Venter, a man given to bombast and thumbing his nose at authority, was cast for the role. Spurned by the NIH, Venter set up his own company, Celera, to compete with the publicly funded programme. It would fuel its research by selling the sequence information that it accumulated. This, and his promise to beat his competitors to the finishing line and get there more cheaply, infuriated the leaders of the public programme. Venter had also developed a method (EST, for expressed sequence tags) of identifying active (expressed) genes - for some 95 per cent of the human genome consists of "junk DNA", which appears functionally inert and is perhaps mere evolutionary detritus. This, much derided at the time, proved its worth and so further inflamed the genome establishment. As Ambrose Bierce observed, success is the only unforgivable sin against one's fellows.

Celera benefited hugely from the advance of sequencing technology. Automation supplanted the tedium of manual analysis, which Brenner once suggested could be pursued in scientific penal colonies by academic delinquents. Celera determined the complete genome sequences of fruit flies, nematode worms (both creatures of urgent interest to geneticists and developmental biologists) and of a succession of bacteria and made them freely available. Business World dubbed Venter the "gene king" and Celera shares rose into the stratosphere. The share price had reached $5 when President Bill Clinton and prime minister Tony Blair issued a statement urging that the human genome sequence be made available gratis to all. This modest proposal struck panic in the investors and the shares plunged to $100, carrying Nasdaq and the entire biotech market with them. Days later, Clinton, evidently overcome by remorse, said he had not meant it, and the shares again began their ascent. Eventually, Celera moderated its conditions of access, and an uneasy truce with the public programme ensued.

On June 26 2000, celebrations were held to mark the completion of the human genome sequence - except that it was actually quite far from complete. Someone (the NIH and the Wellcome Trust perhaps) had judged that the time had come for a little public chest-thumping or, perhaps, the suggestion went, it was the only gap in Clinton's and Blair's diaries. The press gushed, the director of the Wellcome Foundation hazarded that the achievement would prove more important that the discovery of the wheel, and Richard Dawkins declared that he was now proud to be human.

Watson's expectations have been vindicated: all areas of biology are already benefiting from the flow of riches, and the practical rewards will surely follow. To whom then the credit? Venter has made good his boast: Celera has apparently the more complete sequence, but it was able to assimilate all along the data emerging from the public programme. The public programme would have got there by itself, but without Venter's intervention would have taken years longer.

Kevin Davies chronicles the events with verve and authority. He gives many striking examples of what DNA sequences have already taught us - about diseases and populations, the kinship of the Cohens and the Jewish heritage of the African Lemba tribe, the prospects of pre-implantation embryo screening and the creation of designer babies. An abiding impression is how much science has changed since 1978 when Fred Sanger sequenced the first genome (a bacteriophage) with the aid of filter paper, gels and a few associates, and never a thought of patents or profits. For all the glitter, the glory has somehow faded.

Walter Gratzer is emeritus professor of biophysical chemistry, Kings College London.

The Sequence: Inside the Race for the Human Genome

Author - Kevin Davies
ISBN - 0 297 64698 2
Publisher - Weidenfeld and Nicolson
Price - £20.00
Pages - 310

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