"Fighting Chance" by Siddhartha Mukherjee, in The New Republic (Jan. 21, 2002), 1220 19th St., N.W., Washington, D.C. 20036.

Last fall, in the wake of the anthrax had discovered a means of blocking the toxic attacks on several news organizations and effects of anthrax, pointing the way toward an Capitol Hill offices, Harvard University biol-eventual antidote. The Pentagon and the ogist John Collier suddenly found himself Department of Health and Human Services thrust into the national spotlight. Just a few set aside nearly $2 billion for antiterror months before, Collier and his colleagues research, and Senator Max Cleland (D-Ga.) called for a Manhattan Project-style assault on weapons of bioterror. Mukherjee, a doctor at Massachusetts General Hospital who teaches at Harvard Medical School, believes such targeted research will likely waste money and yield few results. "Scientific discoveries often happen when they are least expected," he points out.

Collier’s case is instructive. He began studying anthrax in 1987, intrigued by the manner in which the bacterium attacks human cells. He did not set out to find an antidote but rather to delve "deeper and deeper into the basic biology of anthrax toxin." (U.S. Army researchers at Fort Detrick, Md., began working on anthrax in the 1960s but made no comparable contribution.) Collier’s approach unlocked a critical method in the microbe’s attack, leading to the discovery of the drugs that could interrupt the process.

Almost the opposite approach was tried with HIV research. In the early 1990s, AIDS activists put tremendous pressure on scientists at the National Institutes of Health (NIH) to produce results. And they got them. Adopting a "mission-oriented" approach, the researchers were able to develop effective antiviral therapies, "even before much of the basic biology of the virus was fully understood." The cost, however, was enormous. A 1999 study by NIH found that the federal government had spent proportionately more money (in dollars per year of life saved) on AIDS than on any other disease. Collier explained to Mukherjee that declaring war on a disease invites "bad science—a lot of junk aimed at getting some of that pork-barrel money."

Ironically, NIH and the National Science Foundation were established to provide federal backing for exactly the kind of "curiositydriven" basic science that Collier represents. Important discoveries more often come about by synthesizing results from seemingly disparate fields than emerge as the end product of goal-oriented research. The protease inhibitors that have been the most effective weapon against AIDS were only found because of earlier work by scientists studying kidney disease.

"Examples of such serendipitous breakthroughs abound in the folklore of science," says Mukherjee. But "the more narrowly you define a scientific goal—hoping to focus and streamline discovery—the more you potentially logjam the discovery process itself."