Taking Aim At The Nightmare Bug

A Pentagon program seeks to zap germ weapons of the future

David J. Ecker is at war with bacteria. Armed with $6 million in Defense Dept. grants, he and his colleagues at Isis Pharmaceuticals in Carlsbad, Calif., are seeking a drug that could smash any microbe that might infect a human body--even those that haven't yet been seen. They're trying to find a bacterial Achilles' heel--a universal element that no bacteria can do without--and to craft a drug to disable it. That would be an antidote to one of Ecker's worst nightmares: a biological weapon made from genetically engineered germs. There's just one problem. No one knows whether this universal Achilles' heel even exists.

Ecker's research is one of 34 highly speculative projects in bioweapons defense being funded by the Defense Advanced Research Project Agency (DARPA). Biological weapons have been around since medieval days, when warriors hurled plague-ridden corpses over city walls hoping to wipe out resident populations. Today the thought of germ warfare is even more unsettling. The molecular-biology techniques that promise cures for disease could also be used by rogue governments or terrorists to produce supervirulent pathogens.

BLUE SKY. DARPA launched its Unconventional Pathogen Countermeasures program in 1996. It now spends roughly $50 million each year on research on radically new vaccines and antiviral and antibiotic drugs. It's a risky venture; Commander Shaun B. Jones, the program's director, describes the projects as "blue-sky ideas." Our approach has a "high tolerance for failure and the potential for high-payoff success," he says.

Critics question whether the gamble will prepare the nation for a biological attack. But even the program's detractors admit that if any of the projects pan out, peacetime medicine will benefit as much as military readiness.

Seven of the DARPA projects, including Ecker's, aim at developing so-called broad-spectrum antibiotics, effective against a wide range of microbes. Ecker's target is bacterial ribonucleic acid (RNA), a vital communication link in cells that helps translate their genetic codes into proteins. Because RNA seems to adopt just a few basic shapes, Ecker believes it is possible to design small molecules to cripple such general structures.

To fight viruses, DARPA is looking for wide-spectrum antiviral drugs and fast, effective vaccines. Scientists at the University of Wisconsin are exploiting three key events in every virus' life cycle: penetrating cells, making copies of itself, and attacking other cells. They hope that blocking one or more of these steps will kill any virus. Meanwhile, at the University of Texas' Southwestern Medical Center in Dallas, Dr. Stephen A. Johnston and his colleagues are trying to identify elements of viruses that provoke the strongest immune responses. They chop up the virus' genes, inject them into mice, and check for a response. The resulting vaccines should be safer and more effective than traditional vaccines and could be developed "in months, rather than a lifetime," Johnston says.

DARPA's high-tech approach to bioweapons defense has its critics. Monica Schoch-Spana, project coordinator at the Center for Civilian Biodefense Studies at Johns Hopkins University, would rather see money spent on refurbishing the nation's public-health infrastructure and preparing hospitals to cope with an attack. "If you don't take care of the basic point-of-care issues, it isn't going to make a bit of difference if you have a state-of-the-art antibiotic or a state-of-the-art vaccine," she argues.

Richard A. Falkenrath, a bioweapons expert at Harvard University, agrees that biological security requires readiness on many fronts. But he adds that DARPA's research could do more than boost our security. With infectious disease still the leading cause of death worldwide and the third leading cause in the U.S., "these projects have real potential to deal with ordinary disease," he says. That may be the best result of this unconventional program: Our fear of an elusive enemy may help us develop ways to take better care of ourselves.

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