meaningful data. There are gaps in our understanding of the factors that affect biological agents’ dispersal and uptake by humans, animals, and plants. For example, uncertainties of a factor of 10 or more in the LD50 values and a factor of 2 or more in the probit slopes (i.e., the dose-response curves) for different agents are common. These uncertainties are even greater if strain type is not known or the mechanism and magnitude of environmental decay rates for different agents are not well understood. Moreover, the incubation period (and its dose dependence) for different agents can vary by factors of 2 or more; and diurnal and weather variations can easily affect the contaminated area by an order of magnitude or more for open-air releases (typically the highest-casualty scenarios). Finally, uncertainties surrounding the amount and purity of the agent, the aero-solization efficiency for 1- to 5-micron particles, reaerosolization for agents that have settled onto the ground versus other surfaces, protection factors associated with buildings, and breathing rates can easily affect the inhaled dose by an order of magnitude or more.

These factors produce an irreducible uncertainty of several orders of magnitude in the number of people who will be infected in an open-air release. Moreover, the onset of disease may occur several times faster or more slowly than predicted, and this can have a significant impact on the efficacy of medical prophylaxis administered at a specific time after release. When bounds on these uncertainties are taken into account, the mean and variance of different attack outcomes may yield a different picture of the magnitude of the medical response required to cope with attacks—it is possible, in other words, that response options may be relatively insensitive to these uncertainties. However, the psychosocial consequences of a biological warfare attack (i.e., the disruption and terror caused by the event) will likely remain very large and difficult to quantify. Other transmission modes (water, food, animal vectors) create similar uncertainties, as do attacks directed at livestock or crops. Nonetheless, modeling and scenario building will be essential for cities and states to evaluate and improve their capacity to respond.

Recommendation 3.6: Agencies with relevant expertise (such as NIH, CDC, and DOD) should develop and support the development of models—taking into account a range of incubation periods, transmission dynamics, and variables of climate, population, and migration—to simulate the release of contagious and noncontagious agents. Such modeling may resolve many of the uncertainties about the effects of biological weapons.

Substantial uncertainties regarding mechanisms of pathogenesis would still remain, however; the only way to resolve them is through new experiments that involve virulent organisms and animal models of human disease. This fundamental work, which has been neglected in the age of molecular biology, underlies much of what must be done to develop new vaccines, broad-spectrum antibiotics and antivirals, and preclinical and traditional diagnostics. And, work must

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