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Biodefense Effort Firms Up in Post-Attack Year

By Rich McManus

Photos: Bill Branson

As NIH prepares to absorb its largest budget increase in history, chiefly to conduct research to defend against bioterrorism attacks, one of the lead architects of the preparedness plan, NIAID director Dr. Anthony Fauci, offered a sweeping view of the steps that have been taken since 9/11 to defend the country against such ravages. Speaking at a special hour-long Grand Rounds session in Masur Auditorium on Sept. 11, he addressed everything from the philosophy of bioterror versus biowarfare, to the agents most likely to be used as weapons, to the broad federal response to the threat (from basic research to "deliverables"), and concluded with a bedrock rationale for NIH to be at the center of things: "The worst bioterrorist of all could be nature itself...The next pandemic flu worries all of us. The same research that goes into [preparing for emerging and reemerging pathogens] should go into our bioterrorism work...The country is looking toward us at NIH. We're going to be in this for a very long time."

NIAID Director Dr. Anthony Fauci

Unlike biowarfare, which is essentially troop-targeted, bioterrorism is aimed broadly at the civilian population, meaning that defensive measures must take into account not the homogeneity of an army made up mostly of healthy men ages 18-50, but a staggering diversity of ages, degrees of healthiness and susceptibilities. This is particularly true of vaccines against potential agents of bioterror, Fauci suggested. Too, the nature of a biological attack is insidious; the name of a potential agent alone — Ebola, Lassa, or Marburg viruses for instance — is enough to unleash panic. Thus, even though last fall's anthrax attacks, which resulted in 18 confirmed cases and five deaths, were, epidemiologically speaking, limited, the result was nonetheless chaos: Congress was closed and no hearings could be held until buildings were cleansed, post offices closed, everyone was afraid of the mail for a while, and more than 30,000 people were put on antibiotics, more than 10,000 of them for more than 60 days. "The fear and disruption had more impact than the biological effect," Fauci said, adding that he in no way discounts the tragedy of those who suffered personally.

Lessons from the anthrax attacks were both academic and grim: we can correct the old textbooks that speculated inaccurately about the volume of spores needed to induce disease; Fauci reported that anywhere from a few to likely 1 million or more spores are required to produce infection, depending on the subject. Each of the letters used in the anthrax attacks contained 2-3 grams of spores, Fauci continued. "If that amount had been put into the ventilation system of a large building, there would possibly have been hundreds if not thousands of deaths...Anthrax is still very high on the list of our homeland defense strategy."

Fauci reviewed the history of smallpox, noting again that fear of the agent "likely outpaces its actual biological impact." Despite a vaccine supply large enough to protect all Americans (if the problem of delivery could be solved), and the fact that victims are only infectious after a rash has appeared some 10 to 12 days after initial infection ("That's at least a positive in our favor," Fauci noted), not to mention that smallpox was declared eradicated in 1980 by the World Health Organization, the likelihood is "pretty strong," Fauci said, that remaining stores of smallpox virus from the old Soviet Union "may have fallen into the wrong hands...Is it a real bioterrorism threat? Yes."

Fauci shares recent research findings offering hope in the war on terror.

That there is enough smallpox vaccine to go around in the U.S. is tribute to a science that moved "in absolute record time," Fauci said. Researchers using samples from an original store of 15 million doses of smallpox vaccine, in addition to another store of approximately 70 million doses that was recently identified, found through dilution studies that more than 360 million doses can be wrought from our reserves, and would still likely offer good protection. A second-generation vaccine is in the works. The very rare, but still lethal, toxicity of the old vaccine is the only reason it has not yet been offered on a voluntary basis to anyone who wants it, Fauci said. He hinted that an official policy on smallpox vaccination is forthcoming from the Bush White House.

Fauci touched briefly on a raft of research highlights: NIH, the CDC and the Department of Defense are working on a better anthrax vaccine, one that will employ a recombinant protective antigen; following "very impressive" animal trials, a phase I trial in humans of a new Ebola virus vaccine is expected in coming months, largely a tribute to the "spectacular job" done by Dr. Gary Nabel at NIH's Vaccine Research Center (a combination vaccine is also planned to combat not just Ebola but also Lassa and Marburg viruses, which also cause viral hemorrhagic fever); four new Biosafety Level 3 or higher laboratories are in the works (a BSL-3/4 lab and animal facility at Rocky Mountain Laboratories, a BSL-3/4 clinical facility at Ft. Detrick, a BSL-3 lab and vivarium in NIH's new Bldg. B and a BSL-3 lab at the Twinbrook facility in Rockville); a new polyvalent inhibitor of anthrax toxin is being developed; and perhaps most dramatically, Fauci showed a brief film clip from the laboratory of Dr. Vincent Fischetti demonstrating a new bacteriolytic agent that kills anthrax bacilli with remarkable speed and efficiency.

Fauci also expects big payoffs in unexpected areas from biodefense work, which NIH is pursuing in partnership with industry and academia. "There will be important spinoffs for things having nothing to do with biodefense," he predicted.

He reported that the proposed Department of Homeland Security is budgeted at over $30 billion, 16 percent of which ($5.9 billion) is devoted to bioterrorism work. "NIH has assumed a substantial responsibility for this work that all of us take very seriously," Fauci said. The President's FY 2003 request for NIH biodefense spending is about $1.75 billion — "the largest annual increase in the history of NIH."

NIH director Dr. Elias Zerhouni introduced the Grand Rounds session on bioterrorism, and recounted his own activities of 9/11

Addressing fears that some of the work could end up compromising U.S. interests, Fauci called for a "culture of responsibility" among scientists and declared that "unless it is proven otherwise, we should keep science the way it is, which is totally transparent. There may be exceptions, but transparency must be the rule."

The session ended with questions from the audience, during which Fauci offered evidence that smallpox vaccination, even if it occurred decades ago, is still somewhat protective. "You might still be susceptible to infection, but chances are better compared with people who were never vaccinated that you might not die if you were infected."

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