He was looking for a major project that would “put Santa Cruz on the map,” as he said. The original plan was to build the world’s biggest telescope at Santa Cruz, but when this fell through, Sinsheimer had the novel idea of setting up an institute to sequence the human genome. At the meeting, he sought the views of 12 leading researchers on whether such a project was feasible. The meeting concluded that sequencing the human genome was technically possible, but the participants were evenly split on whether it would be worth doing or not. Although Sinsheimer’s grand vision of a sequencing institute went no further, there were other, more immediate ripple effects from the meeting, particularly for two participants who were to become key players in the human genome story.
One was Walter Gilbert, who came away convinced that sequencing the human genome could—and should—be attempted straightaway. He tried to set up his own Human Genome Institute that would devote itself to sequencing, though concentrating perhaps on known genes and other regions of importance. When this came to nothing, Gilbert took a step in 1987 that sent shock waves through the world of molecular biology. He proposed forming a new company, called, rather provocatively, Genome Corporation, that would create a database containing all human genes, and allow customers to interrogate it.
For example, customers might ask where a particular protein-coding sequence was located on the human genome. “The company will say, for a price, that the gene is on chromosome 21, 1,300,000 bases from the left,” Gilbert explained. Equally, “a user can call up any part of it and read it. Or a pharmaceutical company might like a copy of the whole sequence; we would license it.” The only thing a user could not do was download the database and then sell it. Gilbert noted: “You can buy a book but you can’t sell it. It is exactly that distinction.”
Gilbert’s inarguable scientific prowess made an otherwise preposterous idea look at least possible. The fact that he had already been involved with a start-up before—the biotech company Biogen, founded in 1978—made it seem downright plausible. The ramifications were wide-ranging. Although Gilbert accepted that there was always the risk that someone else might emulate the company, he also noted that “once someone has done it, it is in no one else’s interest to do it again. It would be cheaper to pay for it.” As a result, if Genome Corporation succeeded, it would probably end up with a monopoly on the digital code underlying life. Clearly, privatizing this unique resource would have a huge impact on pharmaceutical companies and the healthcare industry. But the effects of such a monopoly would be just as profound on the biological sciences community. Jealously guarding the knowledge that it would spend so much to gain—$300 million was the expected price tag—it seemed inevitable that Genome Corporation would effectively become the gatekeeper of all genomic research.
Gilbert nearly pulled it off. In July 1987, Science reported he was “still shy of the $10 million in venture capital he says he needs, but he expects to be in business by mid-summer,” and hoped to finish the sequence in about a decade. His confidence proved misplaced. Monday, October 19, 1987—which came to be known as “Black Monday”—saw the largest single percentage drop in the history of Wall Street. Approximately $1 trillion was wiped off the value of stocks. It was hardly the right atmosphere for brilliant but risky ideas like Genome Corporation. As Gilbert recalled later: “Venture capitalists weren’t interested.” In particular, they wondered how a genome company of the kind Gilbert proposed “could make commercial sense.” Although this was the first time this question was posed, it would certainly not be the last.
Commercializing genomics was not the only area in which Gilbert was ahead of his time. His other innovative idea—the central role of computers in molecular biology—proved far less controversial. With each passing year, as the databases of GenBank steadily filled with sequences, it became clearer to everyone involved that the only way of dealing with this rising digital tide was through fast algorithms running on high-speed computers.
Gilbert himself played a part in starting the flood of DNA data when he developed a sequencing technique that could be applied systematically; in practice, however, Sanger’s method proved more important in the long term. If one person can claim the credit for setting the pace at which the tide was rising, it was another of the participants in the Sinsheimer gathering who came away profoundly influenced by it: Leroy Hood. “The meeting totally clarified my thinking about these things, and I went out a passionate minister of the genome,” Hood told me.
Genome Delight
