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2
Of Mice and Men: Animal Models of Viral Infection
Our results with ferrets, so far as they have gone, are consistent with the view that epidemic influenza in man is caused primarily by a virus infection.
Smith, Andrewes, and Laidlaw, 1933 (57)
Introduction
Work with human volunteers for the study of yellow fever had created a backlash in Cuba, and Walter Reed had recognized that it was impossible to proceed. Unlike bacterial agents, which could often be grown on artificial media, viral agents required living cells in which to replicate. In viral diseases of plants, such as tobacco mosaic disease, the natural host was readily available and appropriate. The same was true of viral zoonoses, such as foot-and-mouth disease. For human diseases, such as rabies and polio, nonhuman hosts were necessary to isolate and characterize the etiological agent. Hence, efforts were made to isolate filterable viruses in a range of animal hosts. In addition, the embryonated egg was adapted from studies of embryology and physiology for the study of filterable viruses. In the case of rabies, a zoonosis that spreads from animals to humans with catastrophic results, the development of animal models might be expected to be productive. In contrast, polio and human influenza were not known to have animal hosts, nor was an animal host known for yellow fever. Yet, isolation and study of the agents for each of these diseases were achieved in experimental hosts. First for discussion is rabies.
Rabies: Dogs and Rabbits
Extensive experimental work on what would turn out to be the second human disease shown to be caused by a filterable virus, rabies, had been under way for virtually a century. The medical historian Lise Wilkinson credits Georg Gottfried Zinke’s 1804 publication as being “. . . the first description of experiments specifically intended to follow the transmission of the unknown agent of rabies” (69). Zinke reported successful transmission of rabies to several species, including dogs, cats, rabbits, and fowl (72). While certain characteristics, such as incubation time and clinical characteristics, differed from those in later reports,
