Brave New Pharmacy

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The result could be a medical revolution. Until now, doctors haven't actually been fighting illnesses like cancer, stroke and heart disease. Instead they've been intervening at the level of symptoms--the last, visible step in a complex cascade of biochemical events. And they have done it largely by trial and error--finding new medicines in exotic plant extracts, for example, or looking for chemical compounds that resemble existing drugs. The process is so woefully inefficient that the drugs currently available target only 500 or so different proteins in the body, out of the 30,000 or so we're made of. Says Collins: "We've beaten those targets to death."

Even when they have the drugs in hand, doctors have to guess which ones might work for a given patient. To treat high blood pressure, for example, physicians must choose from six different classes of medications--and it's the rare patient who hasn't had to work his or her way through several of them before finding a medicine that works.

But in the new era of genomic medicine, this halting, inefficient approach should give way to something much more rational and systematic. Doctors will treat diseases like cancer and diabetes before the symptoms even begin, using medications that boost or counteract the effects of individual proteins with exquisite precision, attacking sick cells while leaving healthy cells alone, and they will know right from the start how to select the best medicine to suit each patient.

Sifting through the human genome for therapeutically useful gems, though, requires a well-designed search strategy combined with powerful technology. At Millennium, housed in a factory that once stamped out heart-shaped candy boxes for Valentine's Day, that strategy is embodied in Zeus, whose job is to find the handful of genes among the genome's tens of thousands that are key to individual diseases--and thus key to making effective medications.

To make this search as easy as possible, Millennium chief scientific officer Dr. Robert Tepper has chosen to focus on the low-hanging fruit--going first for the most obvious targets. In looking for anticancer drugs, for example, his researchers are concentrating on monoclonal antibodies, a type of biological "smart bomb" that targets cancer cells and leaves normal cells alone. Like all antibodies, these man-made cancer missiles seek out particular receptors--molecules on the cancer cell's surface that help the cell recognize and react to nearby enzymes and proteins. Almost a dozen such drugs are already on the market, including one called Herceptin. It zeroes in on the HER-2/neu receptor that sits on the surface of some breast-cancer cells, blocking the binding of growth factors. For the 30% of tumors involving the receptor, the drug may be helpful.