isease no longer exists in humans, Army researcher Peter Jahrling, PhD, set out to create an animal model that mimicked as many aspects of human smallpox as possible, using some of the preserved strains from the CDC and the maximum containment laboratory at CDC that is sanctioned for use with smallpox. He tried infecting cynomolgus macaques, monkeys that are used frequently for infectious disease studies. He found that although the monkeys did not get sick through inhalation of the virus - the way people usually become infected - they developed many of the features of later stage smallpox, as well as features of the hemorrhagic form of this disease, from injected virus.

When Relman first learned about Jahrling's plans, he realized that the model would be a rich opportunity for exploring what goes on in the host animal's immune system during infection. "No prior information about the molecular features of the host immune response to smallpox was available," he said. "Smallpox disappeared from nature before the molecular age."

Given the devastating mortality rates of smallpox infection only a generation ago, there are some who are reluctant to revive the virus even for research purposes, said Relman. However, he added, the potential of using smallpox as an agent of bioterrorism tips the scales in favor of preparedness. To build defenses against a disease agent, its tactics must be understood. "Smallpox is known as one of the most sophisticated viruses in outsmarting the defenses of its natural host - humans," he said. "It can teach us in general about the strategies used by viruses to evade and subvert host defenses, as well as provide new insights into the workings of the human immune system."

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Contact: Mitzi Baker
mitzibaker@stanford.edu
650-725-2106
Stanford University Medical Center
5-Oct-2004

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