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Vol. LVII, No. 16
August 12, 2005
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Speaker Probes Concept of Microbes as Weapons

On the front page...

It wasn't the kind of seminar where a terrorist might slip in with a tape recorder and furtively learn how to create biological mischief; they don't offer that sort of fare over the NIH videocast system after all. Rather, Dr. Arturo Casadevall of Albert Einstein College of Medicine offered a sweeping intellectual consideration of how we view risk in a July 14 talk in Bldg. 50 titled, "The Weapon Potential of a Microbe."

Continued...

 
Dr. Arturo Casadevall of Albert Einstein College of Medicine  
In an immune-compromised patient, for example, something as otherwise innocuous as brewer's yeast or yogurt (containing, respectively, S. cerevisiae and L. acidophilus) could be pathogenic, argued Casadevall, who also displayed a slide of his humble sedan alongside a caption, "The civilian car is the most effective weapon of war in Iraq." If cars, yogurt and yeast have "dual use" as potential weapons, what lines can modern society draw as to their availability?

In the good old days, a weapon was defined as a club, knife or gun. But biological weapons come in a staggering variety not subject to the usual restraints imposed by the laws of physics. It is na´ve, Casadevall said, to pick and choose among the many thousands of microbes, labeling this one a danger and another harmless; after all, most organisms are only one "virulence factor" away from being pathogenic. (Using the metaphor of playing cards, he showed that most pathogens represent a hand that is only one card — or virulence factor — short of becoming significantly more dangerous.)

Granted, the bugs on the government's Select Agents and Toxins list and its various categories are undeniably prime candidates for weaponization and should be guarded against, he said. But it makes more sense to craft a broader framework for evaluating risk, taking into account the intricacies of host-microbe interaction, including communicability, stability, inoculum (the actual material that transmits disease such as spore or bacteria) and symptoms.

Casadevall and his colleagues have constructed a simple formula to determine the virulence potential of a biological agent. The calculation yields numbers that, in themselves, are not especially meaningful, but enable one to rate relative danger. Time is a crucial variable in the math — a virus such as HIV might rate low on the communicability scale, but given many years to work its way through a given population can eventually claim cultures and continents, as is happening in Africa, Casadevall said.

Ironically, science's successes in wiping out biological threats eventually serve to create new ones: "In 2020, measles and polio will have weapon potential (because vaccines eliminated them in earlier generations) — every public health success generates a new weapon."

In summary, Casadevall noted that "all pathogenic microbes are potential weapons." He argued that regulations inhibiting research on biological agents invariably leave society more vulnerable to them, and that the weapon potential of microbes changes over time. "The line that we draw in the sand [with respect to microbes] can't be fixed," he concluded.

Casadevall offered a postlude on the role of fungi as a cause of disease. There are some 1.5 million fungal species, but only
It is naïve to pick and choose among the many thousands of microbes, labeling this one a danger and another harmless; after all, most organisms are only one “virulence factor” away from being pathogenic.
about 10 are common pathogens; most can't survive the 37 degree Celsius (body temperature) barrier. Fungi, he theorized, might have contributed to extinction of the dinosaurs in the following scenario: millions of years ago, at the Cretaceous-Tertiary Boundary, a global dusk set in, caused by Earth's collision with an asteroid (Alvarez hypothesis) or by a spate of volcanic eruption. The event turned the planet into a compost heap, teeming with fungi. Any surviving animals would have been exposed to large numbers of spores, but those that developed higher core body temperatures (such as mammals and birds) might have been better able to survive fungal invasion via a process known as "endothermal exclusion." Assuming that the dinosaurs did not enjoy high body heat, they could have succumbed over time to fungi. Mammals, on the other hand, flourished.

"We're hot on the inside and this helps keep out fungi," explained Casadevall. "Most caloric intake is used to maintain body temperature, not to yield the energy for walking around. That's the reason we eat three times a day — to keep fungi away."

The entire talk can be viewed at www.videocast.nih.gov.

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