Brave New Pharmacy

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Promising as all these projects seem, they're really only the first stage of the revolution in genomics-based drug discovery. The ultimate payoff of genomics will be a drug resulting from an entirely novel, as yet undiscovered class of compounds. And that will come about only when scientists have assembled a road map laying out not just the functions of individual genes but the dizzyingly complex network of enzyme reactions, receptor interactions and protein-binding patterns that result--not just the building blocks of human life, in short, but the entire working machine. "When we understand that in great, gory detail, we'll be someplace," says Alfred Gilman, a pharmacologist at the University of Texas Southwestern Medical Center at Dallas and winner of the 1994 Nobel Prize for his work on cellular signaling mechanisms.

Gilman and some 50 investigators at 20 different universities have banded together to form the Alliance for Cellular Signaling, whose goal is to trace the maze of chemical pathways in working cells and then use that knowledge to create a "virtual cell" inside a computer. This electronic cell will, in theory, allow researchers to test potential drugs for safety and effectiveness with much less need to resort to mouse, monkey or human subjects. Says Gilman: "You'll be able to take a library of millions of hypothetical chemical compounds and let the computer watch them interact with the theoretical models of drug targets. It will be a fantastic drug-discovery engine for the future."

The task, he admits, is extraordinarily daunting. A typical cell has perhaps 50 different receptors, and the cell doesn't pay attention to just one receptor at a time. "How," asks Gilman, "does it know how to interpret the signal from one hormone when it's listening to 45 other ones at the same time? How does the whole signaling system work as a network? That's what we want to find out."

Leading-edge genomics firms aren't waiting until all the answers are in. Companies like Myriad Pharmaceuticals in Salt Lake City, Utah, Human Genome Sciences in Rockville, Md., and the British company GlaxoSmithKline, along with dozens of others, are moving equally aggressively to plumb the genome for whatever secrets it's ready to reveal.

For its part, Millennium--both on its own and in collaboration with its partners--has identified 121 potential targets, developed 17 drugs currently being tested in animals and moved six drugs into Phase I human trials, four into Phase II and one into Phase III. Says company CEO Mark Levin: "We're going to understand the mechanism of diseases much better, so eventually, obesity, asthma and schizophrenia will be seen not as single diseases but as a subset of 10 to a dozen conditions. That means breakthrough products that have better efficacy and therefore more value to patients than the drugs we have today."

The drugs will have more value for drugmakers as well. With its largely automated, computer-driven searches for new medicines and the cost saving from tightly targeted human trials, Millennium chief technology officer Mike Pavia estimates, the company can cut the cost of developing a new medicine from about $500 million to $200 million while shaving the development time from more than 10 years down to six or seven. These savings, the firm hopes, will translate into pure profit for investors.