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Keeping the Peace

While the startups jockey for advantage, the government-backed projects plan to assemble a body of common knowledge that could help all researchers-public and private-gain access to protein structures. In mid-April, the Wellcome Trust, the giant British biomedical research foundation, hosted a meeting of government scientists and academics in Cambridge, England, to work out ground rules for a coordinated worldwide effort to discover protein structures en masse. The NIH hopes that 10,000 proteins, carefully chosen, will be enough to catalogue roughly 1,000 different protein “folds,” the basic types of loops and twists common to all proteins.

Once every fold is in their library, scientists should be able to use computers to predict, with reasonable accuracy, the structure of any of the remaining 90,000 or so human proteins directly from DNA sequence. That will be a critical step in giving meaning to the raw DNA data generated by the genome projects. “In the past, we found the function of a protein and then found the structure,” says the NIH’s John Norvell. “Now we’ll be in the position to find the structure and ask, ‘What does this protein do?’”

With both private and public sectors diving into structural genomics, some worry that a poisonous competition will develop. An obvious precedent: the Human Genome Project versus Celera Genomics, the Rockville, Md., company that appears poised to win the race to complete the human DNA sequence (See “The Gene Factory,” TR March/April 1999). Efforts to work together were dashed by Celera’s refusal to share its private data on the government’s terms.

Could the same scenario unfold in structural genomics? “I suspect there will be some friction,” says Phil Bourne, who co-directs the Protein Data Bank. Open publication of data will likely again be the flash point for conflict. The NIH (and its international partners) agreed at the Cambridge meeting on quick release of information into the public domain.

SGX executives say they will have to protect their structures, through both secrecy and patents. Stevens, however, says Syrrx is moving to avoid conflict by taking the extraordinary step of depositing much of its data into the Protein Data Bank. “There’s a lot of lessons we can learn from Celera and the Human Genome Project,” says Stevens. “We would like not to make those mistakes….The information should become public.”

Not that Syrrx is giving away the store. The company will keep certain structural details important for drug development under wraps, and it has also filed patents on its robots. But Stevens has promised that Syrrx will let the government use these for a nominal fee. “This is a two-way street with the public effort,” he insists.

Whether or not it’s possible to avoid public-private strife, it’s clear that structural genomics is acquiring tremendous momentum. For crystallographers, that means dramatic changes ahead. Lynn Ten Eyck, who has been a card-carrying member of this insular field for thirty years, sees the writing on the wall. “These automated systems will just steamroll anyone who’s not using them,” he says. “It’s like the Industrial Revolution.”

Ten Eyck does not intend to fight progress. In fact, he’s joined a group of fellow academics seeking a structural genomics grant from the NIH. As Ten Eyck sees it, mass production of protein structures is the inevitable next step in biology’s rapid transformation from a basic science into an “engineering discipline.” The payoffs should include not only structure-based drugs, but also better diagnostics and perhaps even the ability to reverse birth defects. “There’s a vast array of things you can do if you actually understand the biology well enough,” says Ten Eyck. “This is not something that’s going to happen tomorrow, but we’re watching the transition start.”

Structural Genomics Becomes International Big Science Initiative Highlight Protein Structure Initiative $125 million-plus effort funded by the U.S. National Institutes of Health to solve 10,000 protein structures in 10 years Protein Structure Factory The German Ministry for Research and Technology is funding several academic teams to perform high-speed structure analysis of medically important proteins NMR Park Project Japan’s Institute of Physical and Chemical Research (RIKEN) is using NMR to determine the structure of mouse proteins Structural Biology Industrial Platform Several major European pharmaceutical firms are part of this 16-company consortium in structural genomics Structural Diversity Pilot Academic collaboration led by Rockefeller University Project

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