Anthrax stands apart in the rogue’s gallery of bioterror diseases: the bacterial spores that cause it are relatively easy to acquire, mass-produce, and disseminate. They are extraordinarily lethal when inhaled, and antibiotic-resistant strains are easy to make. Moreover, as the five mail-attack deaths grimly demonstrated in 2001, modern medicine is powerless against late-stage anthrax, in which bacterial toxins cause deadly blood poisoning and organ damage.“Biological weapons are the biggest national security threat facing the nation,” says Tara O’Toole, director of the Center for Civilian Biodefense Strategies at Johns Hopkins University. Anthrax, she adds, is “a much more serious threat than smallpox. I think it’s much easier to imagine terrorists getting hold of the bug, the technology, and disseminating anthrax than doing all this with smallpox.”
But against these realities, significant progress is afoot. A host of rapidly emerging approaches promises to save lives in future anthrax attacks, whether on the battlefield or on the home front. New treatments that kill the bacterium-Bacillus anthracis-and deactivate the deadly toxins it produces should become available within the next year or two. And better vaccines are on the way to replace the 18-month-long vaccination regimen that is already standard for hundreds of thousands of military personnel.
The first mission: combating antibiotic resistance. Anacor Pharmaceuticals in Palo Alto, CA, is developing a new class of antibiotics that block an enzyme certain bacteria-including Bacillus anthracis-need to replicate their DNA. Although the difference between this approach and the way some existing antibiotics work is subtle, it is significant enough to “increase the difficulty [for terrorists] by an order of magnitude,” says Anacor CEO David Perry. That’s because each new line of antibiotic attack makes it less likely that the bugs will have evolved the means to escape or that rogue states or terrorists will have engineered the right type of resistance, he says. Anacor, which last year won a $21.6 million grant from the U.S. Department of Defense to develop new compounds, has already started animal tests and expects to have drugs in human trials within three years.
Another antibiotic approach pits a virus against anthrax. Rockefeller University microbiologist Vincent Fischetti identified an enzyme from a virus that infects only anthrax-causing and closely related bacteria. In test-tube experiments, the enzyme kills about a hundred million bacteria in two minutes or less. “It drills a hole in the cell wall, and the organisms explode,” Fischetti says. He adds that the treatment should boost the power of existing antibiotics against anthrax, as well as kill resistant strains of the bacteria. His group is currently performing animal experiments to test the enzyme further.
Such superantibiotics could play a critical role should an anthrax attack use an antibiotic-resistant strain. But what’s needed most urgently is a treatment to counteract the potent toxins produced by Bacillus anthracis. These toxins attack the cells of those infected; in fact, researchers believe they are what killed the five anthrax victims in 2001, despite the patients’ treatment with powerful antibiotics. Experimental anthrax infections in monkeys show that “there comes a point of no return,” says Michael Mourez, who, as a postdoc in biochemist R. John Collier’s lab at Harvard Medical School, studied anthrax toxin. “You can treat the animal and get rid of the bacteria, and yet the disease will progress towards death.”
Collier’s group has developed several molecules that effectively protect animals against the toxins. Rats typically die within 90 minutes of being injected with anthrax toxin. If the rodents are given one of these antidotes, however, they survive. Even before the 2001 attacks, Collier had formed PharmAthene, a Potomac, MD-based company, to develop one such antidote into a drug. The treatment the company is testing is a mutant version of one of the proteins that make up the toxin; it binds to the other components to prevent the formation of active toxin. This protein could act as both a vaccine and a drug. If testing goes well, Collier anticipates that the treatment may be available in limited quantities next year.