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Audacious Goals

Although structure-based design has led to some breakthrough medications, such as HIV protease inhibitors (including Vertex’s Agenerase) and Glaxo’s flu treatment Relenza, the list quickly dwindles after that. Drug firms still largely rely on the mass screening approach, in part because protein structures are so hard to come by.

Mass production of protein structures could change all that. Today, even the biggest pharmaceutical companies only manage about twenty new protein structures a year. Yet, by 2003, SGX proposes to solve that many each week-every week. It’s an incredibly audacious plan, but Harris is confident. “I know that if we don’t do it, some other bugger would,” he says. “Because it’s absolutely there waiting to be done. It’s the next step.”

In fact, Harris already has competition. Less than a mile away as the crow flies, but separated from SGX by a deep ravine, is the Genomics Institute of the Novartis Research Foundation, a non-profit with close ties to Swiss drug giant Novartis (See “The Bell Labs of Biology,” TR March/April 2000). As TR went to press, scientists at the Genomics Institute were about to unveil a new spin-off venture called Syrrx that plans to harness automation and robotics “to solve [protein] structures at what would be considered, in years past, almost an impossible rate,” says director of business development Ned David.

Other contenders include Astex, in Cambridge, England, and Princeton, N.J.-based Structure Function Genomics. More are coming. “It’s going to be very crowded,” says Harren Jhoti, acting CEO of Astex.

Nor is it only the private sector that’s interested. The National Institutes of Health (NIH) recently launched the Protein Structure Initiative, which will spend up to $125 million in its first five years. The governments of Canada, Germany and Japan are also planning major structural genomics initiatives, and overall spending could eventually rival the multibillion-dollar Human Genome Project. The NIH alone hopes to generate 10,000 structures by the end of the decade.

The startup companies are even more ambitious. By 2003, Syrrx projects, it will be solving about 1,000 structures a year. SGX, if it meets targets, will be doing 1,350. The numbers go up from there. These are truly bold figures given the painfully slow pace at which three-dimensional protein structures have been unraveled in the past. For perspective, consider that in almost half a century since the first protein structure was solved in 1957 (the muscle protein myoglobin), a total of only about 2,000 unique protein structures have been deposited in the Protein Data Bank, the international structure repository.

Indeed, the promises being made by SGX and Syrrx are so far out of line with past experience that in the eyes of some experts they amount to fantasy. “Completely unreasonable,” says prominent University of California, Irvine structural biologist Alex McPherson. “The technology is simply not there, and it’s not going to be there for a fairly long time. I just don’t understand where they’re getting numbers like that.”

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