Objection #3: Impossible to Do

doi:10.1126/science.291.5507.1186

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Science 16 February 2001:
Vol. 291. no. 5507, p. 1186
DOI: 10.1126/science.291.5507.1186

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Objection #3: Impossible to Do

Robert F. Service

Perhaps the most surprising thing about the human genome project is that it was begun at all. In the mid-1980s, the technology for decoding DNA's sequence of chemical bases was in its relative infancy. State-of-the-art labs could sequence only about 500 bases a day, working day in and day out. And the computer technology that came to play such a vital role in the project wasn't even invented yet. "In retrospect, the optimism that the project could be done on a 15-year timetable was striking," says Maynard Olson, who directs a sequencing center at the University of Washington, Seattle.

Unexpectedly, however, says Stanford University geneticist David Botstein, sequencing technology didn't need a revolution to make the leap in speed. "In the early days, it was believed that a radical new technology would be required" to sequence the full human genome, says Botstein. "But it didn't turn out that way."

Incremental but vital improvements in manipulating DNA and chemical probes enabled researchers to switch from identifying bases with radioactive probes to fluorescent ones. That eased the way for detectors to read and catalog the sequence of bases automatically. That automation was then honed with the advent of high-speed machines that pushed snippets of DNA through dozens of capillaries, reducing the sequencing time and cost of reagents. "It was definitely evolution," says molecular biologist David Baltimore, president of the California Institute of Technology in Pasadena. "But you can go a long way with evolution."