October 2001

The Proteomics Payoff

Continued from page 2

By Jon Cohen

Human Proteome Project?

Humphery-Smith heads Glaucus Proteomics in the Netherlands and cofounded the Human Proteome Organisation, a nascent effort to get a human proteome project underway. "When you look at the start of the Human Genome Project, you had all this rhetoric about why it wouldn't work," says Humphery-Smith. "And I'm sure that we're ahead of where the Human Genome Project was in 1988. For one thing, we don't have to wait for funds: there are two billion dollars available now in industry and academia."

In June, the organization named its first president, Sam Hanash, a cancer proteomics researcher at the University of Michigan. Hanash tries to frame the group's mission in realistic terms. "It's impossible to conceive of a human proteome project that would be exhaustive, that covers everything that one would want to know about in relationship to the proteome," says Hanash. "But even if we cannot define a project that has an end, there's still a needto define some components of an ill-defined project."

To Hanash, a human proteome project would describe all of the proteins and in what quantities they are expressed in all of the tissues of the body. Another way to look at the problem, then, is that each tissue has its own proteome. "You're talking about doing the Human Genome Project hundreds of times over," says Hanash. "It's very unrealistic to want to have as an objective for any one group or any one body to accomplish that. You're not going to see anyone say, We plan to complete the human proteome project,' the way Celera did with the genome project. It's not going to happen. If someone makes claims of that sort, they're misleading the world."

The Human Proteome Organisation's vision is to accomplish what one group cannot by coordinating what amount to multiple proteome projects that can feed off each other. Its goal is to catalogue every distinct human protein, all protein-protein interactions and levels of proteins in different cells and tissues. The organization would like to see all of this done in both healthy and diseased tissues and cells. "There's a need to deconvolute this complexity," says Hanash. "Things are disorganized. If there's no consensus to emerge, no coordination, it will be too much of a frontier mentality."

Still, the prospect of a human proteome project is held back by a fundamental problem. Proteomics suffers from a technology gap that does not yet allow for the high-throughput, "massively parallel" analyses that have become the trademark of genomics. "The Human Genome Project was a particularly simple and get-your-hands-around-it definable goal, while proteomics is a far more amorphous and expandable area where we don't have breakthrough technologies yet," says biochemist Roger Tsien, whose own lab at the University of California, San Diego, is pushing forward the ability to image proteins as they move about cells (see "Candid Camera," sidebar).