The human genome project-molecular biology’s international extravaganza that seeks to decode all of humankind’s estimated 100,000 genes-is on track to be completed in 2005. Researchers know that each of those genes contains a precise molecular script for making a different protein. But after spending several billion dollars on the Genome Project over a decade and a half, scientists will simply have gathered the cast of characters for another fundamental mystery: What in the heck do all these proteins do?
On biology’s stage, proteins are the leading players-as well as the producers and directors. Acting alone and in groups, proteins do just about everything in a cell, from shuttling urgent messages to controlling the cycle of growth and death. It’s the role of proteins that scientists need to know to unravel the secrets of life-and to develop potent new drugs. In fact, in one sense the Human Genome Project and its counterparts for other organisms, such as flies, worms, viruses, and bacteria, are simply precursors of a great Human Protein Project. Yet the efforts to decode the genes of less complex creatures are bringing advance notice of just how poorly lit the world of proteins really is.
Take baker’s yeast. A staple of genetics labs, researchers finished sequencing its genome-all 6,000 genes-in 1996. Each of the strings of genetic “letters” predicts the basic makeup of a protein. “But we still have no idea whatsoever what nearly half of those proteins do,” laments Roger Brent, a geneticist at the Molecular Sciences Institute in Berkeley, Calif. “And yeast is one of the most intensively studied organisms.”
Today’s research techniques are woefully inadequate for explaining the function of so many proteins. Typically researchers will breed “knock-out” mice missing a particular gene, then study what effect the loss of the corresponding protein has on the animal-an approach that is like trying to understand how a carburetor works by removing it and checking to see whether the car still runs. Thanks to the rapidly growing
availability of the DNA sequences of genes, scientists are gaining a neatly labeled inventory of parts. “What we need now are fast ways to find where and how all those parts fit,” says Brent. “We need to apply high-throughput approaches to studying proteins.”
The field developing these approaches is called “protein genomics,” or, more catchily, “proteomics,” and it’s one of the hottest areas of biotech. Over the past year, research in this sector has spawned an array of high-tech startups, including Genome Pharmaceuticals, a spin-out from Germany’s Max-Planck Institute, and Hybrigenics, a Paris-based venture. Established gene-hunting firms are also moving aggressively into proteomics. Cambridge, Mass.-based Millennium Pharmaceuticals, Genome Therapeutics, and Incyte Pharmaceuticals of Palo Alto, Calif. all have research groups. These genomics companies bring to the protein game qualities honed over half a decade of searching for genes: a taste for big projects and an aptitude for automated, high-speed science.