Sequencing the genome: crusade called off.

Sequencing the genome: Crusade called off

The order and identify of all 3 billion nucleotides on every chromosome in the human genome has been -- as described by Walter Gilbert of Harvard University -- the holy grail of human genetics. Recent technological advances have brought those basic genetic units within sight, if not within reading distance, and the tantalizing view has spurred so many scientific meetings in the past year that a massive sequencing project had begun to seem inevitable. But at a July 23 meeting of many of the world's foremost geneticists, held by the Howard Hughes Medical Institute and the National Institutes of Health, both in Bethesda, Md., the idea of a full-scale sequencing crusade met, said one participant, with a "resounding lukewarmness."

The question is no longer whether the genome will be sequenced, but with what urgency--and what money. An intensive sequencing effort is generally considered to be much more than a $1 billion project. "I'm in favor of the project, but I think I can safely say everyone else at Cold Spring Harbor [CSH] is against it," says James Watson of CSH on Long Island, N.Y. "Everyone is scared that if we went toward the thing too fast ... there [would be] less money for [other research projects]."

Learning the order of the nucleotides might generate a lot of information, scientists say, without in itself adding much to understanding. "We shouldn't kid ourselves about having the sequence and [then counting on] some whiz at the computer being able to figure out the control mechanisms," Watson says.

Instead, many of the geneticists expressed enthusiasm for a phased assault on the genome, in which complete sequencing would await continued development of sequencing technology and a coordinating structure that could contain a project of multilaboratory, multination scale. There was consensus on giving priority to an intensive attempt to "map" the human genome -- which, in comparison to sequencing, is like looking at the genome's organization at the level of cities and cross-streets rather than individual addresses. According to Sydney Brenner of the Laboratory of Molecular Biology in Cambridge, England, a physical map could be achieved with a few years of concentrated effort. Only about 3 percent of the human genome has been put onto a physical map so far.

"The genetic sequence is a tool," says Eric Lander of the Whitehead Institute for Biomedical Research in Cambridge, Mass. "We should rate it ... with all the other tools we're going to need."