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The End Of a Long Race

Andrew C. Thomas

An event of no small importance happened earlier this week that went largely unnoticed by the general public: the Human Genome Project was officially declared completed. The project, collaborated on by a public consortium of universities and research facilities, most notably Washington University, the Sanger Centre in Cambridge, England, and MIT's own Whitehead Institude, sought to craft this golden blueprint and make it publicly available in the interests of science.

What is so fascinating to me, and other interested observers of the politics and economics of the scientific community, is that without corporate greed, we likely would not have had the benefit of this information for several years to come. The project became a race between the public consortium and Celera Genomics, who, according to the musings of Professor Eric Lander, director of the Project’s efforts at Whitehead and noted celebrity instructor of Introductory Biology (7.012), had somehow arrived at the conclusion that the public effort wasn’t moving quickly enough. Craig Venter, the head of Celera at the time, had declared that they could do it in an astonishing three years -- setting a completion time of mid-2001.

What followed was a remarkable surge from the public effort, which wasn’t entirely unanticipated; the project had set a reasonable schedule for progress in 1990. Prof. Lander’s popular hypothesis, which he has put forth to an attentive audience on several occasions, is that Celera had not taken into account the possibility that the project could be scaled up with the advent of newly developed technology. Noting that Prof. Lander has a terrific sense of humour, most in the audience at the time likely realized that he was simply trying to take a fun poke at the competition. Prof. Lander’s sense of fair play is certainly not in question; the consortium and Celera managed to call a truce in late 2000 to celebrate the accomplishment of both groups, that a draft sequence had been completed and analyzed. The draft had very interesting ramifications in itself -- for example, the total number of genes that the genome is believed to carry reduced substantially, from 100,000 to 30,000.

The finish line of this race, it turns out, was when the entire genome had been sequenced and covered ten times -- since most methods cannot determine the entire sequence at once, a considerable degree of overlap is required in order to ensure both that all sequences are in order, and acceptably error-free (since, as in cells, the ability to read DNA is far from perfect).

Celera’s bold move was no small gamble. By finishing first, they would have indisputable control over the marketplace. Their method, the “whole genome shotgun”, was considered unreliable in its early stages for the human genome, despite its success in the sequencing of Drosophila melanogaster. But by late 2001they had declared absolute victory, claiming that they had available a “golden draft” with 10X coverage, and they would begin taking orders from laboratories, universities and other research institutions for use of the completed sequence.

Celera might have won the race, but they had a powerful silent partner -- the public consortium itself. Their 10X coverage could only have been achieved in the speed it had if they made use of the public sequence in order to accomplish the overlap. So Celera was in fact marketing 5X coverage, which was at the time necessary to make sure the information was reliable, and using the beneficent policy of freedom of information as an advantage.

However, with the release of the public consortium’s data this week, Celera’s ready-to-order genome sequence is now a white elephant. This does not mean that the money and effort is wasted; the Celera machine has proven itself on the battlefield, and will no doubt hold a monopoly on future sequencing efforts. They aren’t without competition. The genome of the virus that is believed to cause SARS was recently sequenced in a matter of days -- an astonishing increase in speed -- by several companies. And so even with the profit motives of Celera, and the next generation of sequencing startup companies, we are seeing a genuine benefit to society. For now, though, it remains to be seen whether the completed human genome sequence will grow a trunk and tusks of its own.