Germ Warriors

In the race to find a cure for anthrax before the disease again emerges as a terrorist weapon, scientists in early July announced that they had mapped the three-dimensional structure of anthrax toxin as it enters human cells-the point at which the bacteria becomes deadly for humans. It is a major breakthrough in understanding how the lethal, spore-forming bacterium Bacillus anthracis operates within the human body.

Scientists believe the discovery will likely lead to the development of drugs that can be used to treat late-stage anthrax, for which there is no cure. Antibiotics are effective if they are taken early enough after exposure to anthrax, but they do not work after significant amounts of the toxin have entered the bloodstream.

"We really need [drugs] that would neutralize the toxin in the late stage during infection, because often it can be the toxin that kills you, even after you've taken out the bacteria with antibiotics," says Robert Liddington, director of the Center for Infectious Diseases at the Burnham Institute in La Jolla, Calif. Liddington led the study, which was funded by the National Institute of Allergy and Infectious Diseases (NIAID). The findings were published on the Web site of the journal Nature on July 4.

It could take days or longer for public health officials to determine that people have been exposed to anthrax, since the early symptoms resemble the common cold. So developing drugs that could be effective in the disease's late stages would be a major weapon in the arsenal to combat biological terrorism. Liddington expects that within a year or two, researchers could have a drug ready for testing on animals.

What's more, the anthrax research may have a direct impact on cancer treatment. Anthrax toxin uses a protein called "protective antigen" to gain entry into cells. Because this protein can bind with either of two similar receptor cells-one found throughout the body and the other found only in the cells that line the blood vessels of tumors-scientists believe they can engineer anthrax to bind only to tumor cells, thus selectively killing those cells. "You potentially have a silver bullet there to knock out tumors by depriving them of their blood supply," says Liddington.

"We've already started trying to develop the toxin as cancer therapy," says NIAID senior investigator Stephen Leppla, who contributed to the research. Leppla has been working on anthrax toxin for 24 years, Liddington for more than a decade. The new developments have been possible because the fall 2001 anthrax attacks brought a huge influx of federal funding to research on diseases that could potentially be used by terrorists. The attacks left five people dead and 23 with the disease. The cases never have been solved.

"This has been an ongoing project," says Liddington. "Initially, it was really a scientific curiosity, because it was never perceived as a public health threat; maybe as a battlefield weapon, but not as a public health threat, not in the U.S. anyway. Now we've sort of been thrust into the limelight in trying to help design drugs."

The scientists' discovery also could help researchers develop a better vaccine for anthrax, says Leppla. "If we know the exact part of the molecule that binds to cells, then we can make vaccines that would induce antibodies to that part of the molecule," Leppla says.

As if to underscore the importance of the research, the Defense Department announced this summer that it would expand its program for vaccinating troops against anthrax and smallpox. Dr. William Winkenwerder Jr., assistant secretary of Defense for health affairs, says anthrax remains one of the top biological threats to U.S. troops. Since June 2002, the Defense Department has vaccinated more than 750,000 personnel for anthrax. In a Pentagon briefing for reporters, Winkenwerder said he was unsure how many additional troops would receive the vaccine, but that it was in the "tens of thousands."