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Non-Toxic Emulsion Foils Deadly Anthrax; Flu Virus Succumbs, Too


James R. Baker, Jr.

With the increasing involvement of U.S. military forces in the Persian Gulf region, military authorities have become increasingly concerned about the threat that anthrax and other biological warfare agents pose to armed forces and civilian populations.

Spores of the deadly bacteria anthrax are a major concern. How do you wash them off? What if you've inhaled them? Concentrated chlorine bleach and formaldehyde are known to kill anthrax spores, but they're also toxic to humans.

A mixture of water, soybean oil, Triton X 100 detergent and the solvent tri-n-butyl phosphate developed by the University of Michigan and Novavax, Inc., a biopharmaceutical company in Columbia, Maryland, seems to offer great promise in the anthrax wars. A milky-white emulsion of tiny lipid droplets suspended in solvent, it has been shown to be remarkably effective against anthrax and related bacteria as well as certain viruses.

In studies with rats and mice in the U-M Medical School under the direction of James R. Baker, Jr., M.D., professor of internal medicine and director of the Center for Biologic Nanotechnology, the mixture, known as BCTP, attacked anthrax spores and healed wounds caused by a closely related species of bacteria, Bacillus cereus. (The letters BCTP stand for Bi-Component, Triton X-100 n-tributyl Phosphate.)

Baker describes the process as follows: "The tiny lipid droplets in BCTP fuse with anthrax spores, causing the spores to revert to their active bacterial state. During this process, which takes 4-5 hours, the spore's tough outer membrane changes, allowing BCTP's solvent to strip away the exterior membrane. The detergent then degrades the spores' interior contents. In scanning electron microscope images, the spores appear to explode." The rapid inactivation of anthrax bacteria and spores combined with BCTP's low toxicity thus make the emulsion a promising candidate for use as a broad-spectrum, post-exposure decontamination agent.

In separate experiments, Baker and his staff have found that BCTP, when inserted into the nasal passages of mice infected with live influenza A virus, and when incubated with canine kidney cells infected with the virus, greatly reduces viral antigen levels. "Our preliminary studies have shown that BTCP is a highly effective killing agent for the influenza virus both at the cellular level and in living animals," Baker says. "Equally important is that BCTP has no toxic effects on nasal or lung passages. It appears that if we treat the virus with BTCP as it enters the nasal passages, we can prevent infection in mice. The next step is to see whether we can administer BCTP and the virus separately and still prevent infection. The final step, of course, is to see whether it works in people."

In future studies Baker plans to evaluate BCTP's effectiveness against inhaled anthrax spores as well as other bacteria and viruses. The research is sponsored by the Defense Advanced Research Projects Agency (DARPA), the central research and development organization for the U.S. Department of Defense.

Baker can be reached at jbakerjr@umich.edu

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