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New Genes, New Drugs

If Kalypsys is building the gateway, then NIH is the gatekeeper. From the fourth floor of NIH’s building 31, Francis Collins’s office looks out over the institute’s tree-lined campus in Bethesda, MD. It is a sweltering August day. Pictures of Collins and his family, his diplomas, and countless awards line the walls and shelves. But Collins is nowhere to be found.

It seems he has passed the day-to-day direction of what could be called the Human Genome Project, Act Two, to his deputies. In walks the Chemical Genomics Center’s Austin with Jim Inglese, who is second in command and likewise a former Merck researcher. In a dress shirt and slacks, Austin has a casual air that belies the depth of his experience in genomics and drug discovery. He makes football analogies about where the “handoff” should occur between academic research and industrial drug development. He refers to Collins as “king” and “big guy.” He jokes that he chose Kalypsys because of the San Diego weather.

When the talk turns to the NIH initiative, though, Austin is all business, armed with charts and timelines to make his points. “The question of the day is, how do you make functional and therapeutic sense of the whole human genome?” he says. “It takes time and capital. Academia has time but lacks capital. Pharma has capital but no time.” The right technology, he says, could change the terms of that equation. Once the NIH-funded network is up and running (Austin plans to fund five or six centers by next year), academic groups will compete for the opportunity to use the Kalypsys machines and other screening technologies – gaining capabilities previously reserved to industry.

That could lead to a wider variety of drug compounds for industry to work on, says Inglese, an expert on biomolecular screening. Instead of chasing frivolous cash cows like anti-impotence pills, companies might be able to derive huge benefits from developing treatments for cancer, diseases of the immune system, and other ailments. And because the new drugs will be based on small molecules, scientists know they will work, instead of knowing that they should work, as is the case with many large-molecule biotech drugs in development.

But Austin and Inglese bristle at the suggestion that their initiative signals a government move into drug development. They maintain that companies will still do the vast majority of the work needed to refine and develop drugs. Instead, what the NIH effort seems to demonstrate is that the border between basic science and technology development is shifting. Perhaps that shift is overdue; the biotech industry, for one, has suffered from premature efforts to translate molecular biology into useful therapies.

Whatever the implications, this follow-up to the genome project is near and dear to Collins. Big questions remain, he says: “How does the one-dimensional genome function in four-dimensional space and time? How does that go wrong? What can be done to fix it?” Asked to predict how the effort will play out, Collins answers as both a scientist and a physician. “In a decade, we’ll learn a substantial amount about how genes work together and how a cell does what it does,” he says. “We’ll understand the hereditary contribution to diseases such as diabetes and mental illness.”

Will this new marriage of genomic science and drug discovery be a happy one? What bodes well for it is that, ultimately, the two disciplines have a common goal. Back at Kalypsys, McKearn is gathering himself for an off-site meeting. One might ask, in the end, what is really special about what he’s doing. “The end customer for us is the patient,” he says. “We can touch the lives of millions of people in a way that’s unparalleled. That’s what’s keeping us going. We’re not in it for the glory. It’s a quest.”

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Tagged: Biomedicine

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