Life Script (eBook)

Chapter 3: The Meaning of the Life Script

Though the two sides' claim to have sequenced the human genome sparked headlines around the world, they were celebrating victory before the battle. Each team now had to interpret its genome sequence by describing its major features and locating the genes, and from the quality of the respective reports a clear winner could emerge in the eyes of their fellow scientists.

This first analysis of the human genome was just as much a landmark in scientific history as the years spent decoding the sequence. But it was compressed into a few months' whirlwind of activity as the two sides set about interpreting the strange and enigmatic script they had wrested from the human cell. Talk of a joint annotation conference at which the two sides would compare notes in interpreting the human genome soon evaporated. Celera and the consortium worked with different groups of experts and published their reports in rival scientific journals, Celera choosing Science in Washington, D.C., and the consortium Nature in London. The sharp elbowing continued to the bitter end, with academic biologists including Eric Lander, chief author of the consortium's genome report, lobbying hard to persuade the editor of Science not to accept their rival's paper except under terms unacceptable to Celera.

The academics demanded that Celera make its genome sequence freely available through GenBank, even though GenBank could not meet Celera's condition that its commercial rivals be prevented from downloading Celera's data and reselling it. The editor of Science allowed Celera to be the custodian of its own data on condition that any part of it be made freely available to scientists for checking, a decision to which the academic biologists objected. Venter felt their real purpose was to deny him the prestige of being published in a leading academic journal.

Well before the White House announcement, both sides had started preparing to analyze their respective versions of the genome. Venter had more or less founded the art of genome interpretation when he published the first genome of a bacterium in 1995. He had learned then an important lesson: the best way of interpreting a genome is to compare it with the genome of a similar organism. He had long since decided that the mouse's genome would be a critical tool for interpreting the human genome, because comparison of the two long ago mammalian cousins would reveal by their regions of DNA sequence similarity all the features that nature had found it necessary to conserve. He had risked switching his sequencing machines from human to mouse DNA at the earliest possible moment so as to have both genomes in hand for the task of locating the human genes.

Another advantage for Celera was that its version of the human genome was much less bitty than the consortium's. Celera's vast computer, the largest in civilian use, had assembled 27 million of the 500-base pieces analyzed by the sequencing machines into long, mostly continuous scaffolds that straddled the genome. The consortium's genome was divided into thousands of the small sub-jigsaws known as BACs, chunks of DNA about 150,000 bases in length. The BACs had been completed for the two shortest human chromosomes, numbers 21 and 22, but over most of the rest of the genome were still in small pieces, many 10,000 bases or so in length. It was possible to hunt through these fragments for genes, but not at all easy. The consortium had not tried to assemble them by computer because it did not see the need to do so. Robert Waterston, director of the sequencing center at Washington University in Saint Louis, had prepared a BAC...