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MSU postdoctoral researcher Xinghong Yang studies the organism that causes brucellosis in bison and cattle. The work, done indoors in a special lab, requires a protective suit and respirator.

Bioterrorism Research - Thinking the Unthinkable

Long before last year's spate of postal anthrax infections, a number of scientists and public health officials were already thinking the unthinkable: bioterrorism.
The Centers for Disease Control and Prevention, for example, issued a list of three dozen agents that could be used to purposely spread disease. The agency mandated tighter security for U.S. laboratories working with them.

The world's two remaining official stocks of smallpox-in the U.S. and Russia- remained heavily protected, and diplomatic pressure was focused on countries known to harbor chemical and biological weapons. Quietly, scientists have been learning all they can about some of the world's most infectious microbes, with an eye toward developing better detection methods, antidotes and vaccines. Those efforts include the work of several Bozeman scientists.



David Pascual
David Pascual is leading the brucellosis research. Brucella is considered a potential bioterrorist agent.
Sitting behind a mound of papers in a cramped, tunnel-shaped office, Associate Professor of Veterinary Molecular Biology David Pascual wondered out loud how a potential bioterrorist could unleash deadly agents onto an unsuspecting population without killing him- or herself first.

After all, Pascual uses a special laboratory to work with the organism he studies. Brucella abortus, which causes brucellosis in cattle and bison and an intermittent fever in humans, is a Level 3 infectious agent in a federal classification system where Level 1 means a low-risk organism to Level 4, which includes exotic, deadly agents like Ebola virus.

"In our lab, we need a protective suit and personal respirators," Pascual explained. "We disinfect ourselves when we come out of the facility and then shower. Everything else is autoclaved."

His point is one echoed by other scientists: bioterrorism isn't something that just anyone can do.

Pascual has been drawn into the now-national topic because the microbe he studies is closely related to Brucella melitensis, one of the potential bioterrorist agents identified by the Centers for Disease Control. The organisms are so closely related that a vaccine against one would likely work against the other.

"It's on the CDC's list because there is no vaccine, the organism is readily available and it can be aerosolized," explained Pascual. "It's not lethal, but it can cause illness and there's no cure. That makes it a potential weapon."

Endemic in sheep and goats in Mediterranean countries, B. melitensis typically is passed to humans in unpasteurized cheese and milk. The undulate fever it causes is treated with long-term antibiotics.

"If one potential method of delivery is to aerosolize an urban area it could be an issue," Pascual said.

Pascual's approach to developing a vaccine is to find the proteins on the outside of the bacterium that would make the body's immune system jump into action and create a protective immunity.

Once he finds those proteins, his collaborator-Bozeman-based LigoCyte Pharmaceuticals, Inc.-would develop a replica of those proteins to act as a vaccine. LigoCyte has a Department of Defense contract to develop vaccine delivery systems and microbe detection methods for B. abortus and two other organisms.

MSU and company scientists are eyeing the mucosal surfaces-the vast system of cells that line the nose, mouth and gut-as the place to create immunity in the body because most microbes must cross a mucosal barrier in order to cause disease.

Without giving away details, Pascual said his studies already have shown "some evidence" of protection against B. abortus in bison, the most sensitive animal to brucella infections. In other words, he has a potential vaccine candidate that could take another five years to refine. More advanced animal studies and human clinical trials would all be done elsewhere, as neither LigoCyte nor MSU has the proper facilities.

The vaccine needs to be simple, unlike the current anthrax vaccine that requires repeated doses over 18 months and brings some nasty side effects with it.

And even if never used on the behalf of U.S. troops or civilians trapped in an evil execution of germ warfare by a nefarious dictator or extremist political regime, a brucellosis vaccine would still be a useful tool on behalf of the American bison, whose management on the Yellowstone National Park/Montana boundary remains highly controversial.

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