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On February 6, 2007, executives from 454 Life Sciences showed 78-year-old James Watson a first draft of his own genome. There was something downright poetic about this. Watson, of course, had won a Nobel Prize 45 years earlier for his role in discovering the double-helical structure of DNA; he was also a prime mover behind the Human Genome Project, which by its completion in 2003 had spent nearly $3 billion over 13 years extracting the blueprint that those helices encode. Now 454 had moved a step beyond that megaproject, which pooled many people’s DNA to determine the genetic sequence of what amounts to a model human. The company and its so-called next-generation sequencing machine had single-­handedly read the genetic code of an individual–one whose work had done so much to make the achievement possible.

But Jonathan Rothberg, who founded 454 in Branford, CT, with the dream of producing a sequencing machine more efficient than those available to the Human Genome Project, does not mention poetry when he recounts his meeting with Watson. Rather, he talks about money, speed, and a future in which ordinary people carry around their personal genomes on discs–an increasingly plausible scenario. “It cost us $200,000 to do Jim Watson,” points out Rothberg. “And we did it mostly in December and January.”

Rothberg, who now chairs 454’s board of directors, emphasizes that “Project Jim” remains a work in progress and will require more time and money. As of February, the company had sequenced Watson’s DNA only three times (each run increasing accuracy and filling gaps); nine passes were required to produce the Human Genome Project’s final draft sequence. But still.

Rothberg’s company is just one of several, including ­Illumina of San Diego and Applied Biosystems of Foster City, CA, developing machines that can decode DNA faster than ever before. And just as the cost of computer power has plummeted with the steadily increasing density of transistors on chips, the price of sequencing DNA has fallen rapidly with the advent of these machines. Today, the price tag on a human genome decoded with sequencers of the type used in the Human Genome Project would be $25 million to $50 million. It drops to around $1 million with next-generation machines available today and could be as low as $100,000 by 2008.

As the history of computers has shown, more processing power for less money can lead to unanticipated applications. In the wake of the Human Genome Project, researchers faced difficult financial decisions about which genomes to sequence next: chimpanzee or macaque, cow or dolphin, rice or cassava. The new machines make it ­possible to sequence nearly everything of interest. And as ever more sequence data flows into databases, whole new areas of research are opening up. Scientists now have an unprecedented ability to make comparisons between species, shedding light on everything from evolutionary questions to genetic reasons for individual differences in disease resistance and susceptibility. Research done with 454’s machines and published in top journals includes the partial sequencing of a Neanderthal genome and the development of new tests for cancer-causing genetic mutations–technology that may help doctors tailor treatments to their patients.

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Credit: Steve Moors

Tagged: Biomedicine

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