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Answers on Anthrax
Crowd Jams Special Grand Rounds on Bioterror

By Rich McManus

On the Front Page...

You would have thought that Katie Couric came back to Masur Auditorium by the number of NIH'ers who jammed the hall Oct. 31 for a special edition of Clinical Center Grand Rounds on the topic of bioterrorism; even guest speaker Dr. Anthony Fauci, director of NIAID, admitted afterward he was stunned by the audience's size. But that's because with 17 documented cases of anthrax up to that date, including the death that day of an unusually suspicious case, everyone was passionately interested in what NIH had to make of the emerging public health crisis.


Unlike most Grand Rounds, which on a good day might fill Lipsett Amphitheater for two sober half-hour presentations, this version gave Fauci and NIMH director Dr. Steven Hyman — who addressed the physiology and psychology of terrorism — 20 minutes each to roar through the fast-developing story and devoted the last 20 minutes to Q's and A's from a crowd whose scientific literacy might well have proved too lofty for those who tuned in to the event via live broadcast on cable television's C-SPAN network.

"Unfortunately, [the anthrax outbreak] is turning out to be quite an historic event with regard to public health in our nation," Fauci began, but cautioned, "This is no surprise. There is a long history of bioterrorism in the United States and other nations dating back to the 1980s," including the well-publicized cases of tampered-with Tylenol on store shelves in 1982. He said the good news is that NIH "had programs in place long before the threats became real."

Confining himself to the medical and public health aspects of bioterror, Fauci said the major threats are from smallpox, anthrax, plague and botulism, though there are a host of other possible agents.

"With anthrax, the problem is that very few physicians ever saw it before in clinical practice, though everyone who goes to medical school learns all about it," he said. "Rapidly, we're becoming the world's experts."

Anthrax is caused by Bacillus anthracis, a rodlike gram-positive bacteria that, fortunately, does not transmit from person to person; rather, one has to come in contact with its spores, which Fauci called "the real bad guys in all of this."

Determined entirely by its portal of entry, anthrax infection can be either cutaneous, inhalation (or pulmonary), or in rare cases, gastrointestinal. "It was thought that it would require some 10,000 spores of 1 to 5 microns in size to reach the alveolar macrophages in the lungs and produce infection," Fauci reported. "That was all textbook stuff until this happened."

The cutaneous form of infection is "progressive but controllable," Fauci said; the mortality rate for this form is 20 percent without antibiotic treatment. Of the inhalation form, he said the minimal amount of spores needed to produce infection is "open to debate. One or two won't do it, but 50,000 will. Somewhere in between is the right number." Inhalation anthrax is "close to 100 percent fatal if not treated," he said, and secondary infections such as meningitis are common.

The first vaccine against anthrax was produced in 1970, and required six doses taken over 18 months, Fauci noted. "It might still be useful if administered post-exposure," he said. As it was produced primarily for the armed forces, "the Department of Defense essentially owns all of it."

The next generation of vaccines will use recombinant technology; a version called recombinant protective antigen (rPA) is currently being developed. Fauci saluted two recent papers in Nature that report specifically how the bacteria harms the body. "We should be proud of the research that NIH and its grantees are doing."

Regarding smallpox, Fauci said, "We are a victim of our own successes in public health": the disease was virtually wiped out in 1977 via a worldwide eradication program; the last reported case was from that year in Somalia. Routine vaccinations against smallpox ended in the U.S. in 1972. It was thought that only two laboratories, one in the U.S. and the other in Russia, had stores of smallpox under careful guard. But Fauci reported, "It is highly likely that Russia made large amounts [of smallpox virus], and the question becomes, 'Did it get into other hands?'"

He said the government is adopting a vaccine approach to smallpox on immediate, intermediate and long-term bases. At the moment, the federal government owns 15 million doses of vaccine. NIAID has begun a "dilutional study" to determine if those doses can be fractionalized by one-fifth and one-tenth and still yield a "take rate" of immunity that would result in potential dosages for 75 million to 150 million people. "Seventy-five million doses are potentially available for January, when the study ends," Fauci said.

A new and better vaccine for some 300 million people is in the works for the end of 2002, he reported. But he warned that smallpox vaccines "are not without toxicity. It is unusual, but it can be severe."

Of NIH's role in late October's climate of "extraordinary havoc," Fauci said, "We'll have to do what we do best, which is provide the scientific basis for whatever public health efforts ensue...Our role is substantial. We cannot rush the science, but we can accelerate the translation." He concluded by citing a useful web site on bioterrorism,

NIMH's Hyman talked about the emotion of fear, and how the brain processes it; fear is fundamentally a survival function, giving organisms a way of appraising the relevance of potential threats in the environment. The cliche of "freezing like a deer in headlights" began as a survival instinct; predators who use motion to hunt prey are unlikely to detect an immobile object. "But this became a less adaptive strategy after the invention of the automobile," said Hyman, in one of his trademark dry quips.

Fear's immediate sequel is fight or flight, as many learned in Psychology 101. The next stage, if all goes well, is vigilance and coping. "The goal of terror," Hyman explained, "is to undercut one's coping mechanism and to keep us in fight-or-flight.

"Terror exploits two aspects of the human brain," he continued. "It takes advantage of the stress we feel in novel and uncontrolled situations. And it exploits our normal empathy with others — we identify with the relatively small number of victims, and are not very good at doing a dispassionate risk analysis."

He said, "Fear is contagious, unlike anthrax...what we have to do as a nation is learn what is happening, and learn coping strategies that reassert our level of control over circumstances. We don't normally do risk-analysis in our day to day lives. The key is to deal with real risks, not imagined risks."

Hyman said that sending anthrax via mail to the media "guaranteed emotional contagion." He then spoke about those most severely affected by terrorism, those who develop post-traumatic stress disorder (PTSD). Because traumatic experience literally "rewires the brain so that synapses are physically altered," extreme stress can lead to illnesses such as PTSD, which is characterized by intrusive reliving of the trauma, and hyperarousal. He urged that people use their social networks and get back as quickly as possible to normal routines. He also counseled against permitting children to be excessively exposed to repetitions of the horror on the nightly news. Lastly, he advised, "Don't communicate fear to your kids through your own behavior. Try to increase the time you spend with family and friends."

During the question session, which ran to a half-hour, the audience learned that PTSD can develop within several days, not the month predicted by textbooks, said Hyman; his data came from a study following the Oklahoma City federal building bombing in 1995. Fauci ended up giving a mini-symposium on diagnosing infectious diseases — including what triggers his "index of suspicion" — as he answered questions on when it is appropriate to prescribe antibiotics. "It is important to continually consider the risk versus the benefit in clinical decisions such as these," he said.

Asked whether it was good policy for the FBI to put the nation on high alert over an unspecified threat, Hyman answered, "I don't think anyone knows whether it's a good idea or a bad idea. It's one of those cases where you're damned if you do, and damned if you don't." Someone else asked him if NIMH had any psychological insight into the minds that could perpetrate this kind of terror, and Hyman observed: "I really can't speculate about the motives of terrorists. NIMH has not studied terrorists as part of its public health mission."

Since many in the audience were old enough to have been vaccinated against smallpox prior to the end of that practice in 1972, Fauci was asked if they still might harbor some immunity. "After 10 years, you don't have significant immunity — that's the standard wisdom," he answered. "But I think it's better to have been vaccinated than not to have been. I can't believe it won't help in some way." Later, in response to a similar query, he said people have varying degrees of immunity post-inoculation. "We all live under the bell-shaped curve," he concluded.

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