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Library Science

For Christopher Austin at Merck, it began with a simple question: “Chris, how would you like to come help us figure out what to do with the genome?” The proposition came from Francis Collins, who as director of the National Human Genome Research Institute at the National Institutes of Health (NIH) had led the effort to complete the Human Genome Project. It was mid-2002.

Austin, then director of genomic neuroscience at Merck Research Laboratories, jumped at the opportunity. This would be a chance to take a leading role in translating genomic research and new drug targets into novel, more effective therapies. “The genome presents an enormous problem, if you’re a pharmaceutical company,” Austin explains. “The failure rate is higher if you take on unprecedented targets.” That’s why drug companies tend to focus on a narrow set of targets and compounds they already understand.

In an effort to broaden the playing field, NIH announced in June that it is opening a Chemical Genomics Center. Headed by Austin, the center is part of a four-year “molecular libraries” initiative whose $32 million annual budget is expected to grow to about $100 million. The plan: to fund a nationwide network of centers to screen small molecules for their effects on cells and proteins and aggregate the results in a public database. “If we can populate the scientific literature with data on small molecules,” Collins says, “that could set off light bulbs towards therapies that wouldn’t otherwise happen.”

Until now, most academics have not had access to the industrial-strength technologies required to synthesize and screen small molecules. And drug companies don’t share data on their compounds. The hope is that, with this effort, academics will systematically explore small molecules, and drug companies will use the public results to better fight cancer, diabetes, and rare diseases that they currently have little financial incentive to pursue.

To jump-start the initiative, Collins and Austin signed a deal worth up to $30 million to license a molecular-screening system from Kalypsys, a San Diego, CA, startup. The system represents the state of the art in combinatorial chemistry for making small molecules, the hardware for screening them, and the informatics software for analyzing the results. More broadly, it represents an important step in turning the science of chemical genomics into practical technology that companies and research groups can use. “In terms of technology development,” says Austin, “we are about where the Human Genome Project was in 1988” – two years after the invention of the automated DNA sequencer. But chemical genomics is vastly more complicated, he says. “This will make DNA sequencing look like child’s play.”

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Tagged: Biomedicine

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