threats. Given these concerns and recent terror attacks, there has been a surge in interest in the smallpox virus and vaccine and in the history of the disease and its eradication. The potential use of smallpox virus in bioterrorism challenges public health and health care systems in many ways. Smallpox is a disease unfamiliar to most current health care providers, the population of the United States is relatively immunologically naïve since vaccination was discontinued more than thirty years ago, and much of the clinical and epidemiologic data on the virus and the vaccine is decades-old.
The modern history of smallpox disease begins in the seventeenth century, with detailed records of cases and epidemics, as well as the earliest accounts of variolation, a precursor to contemporary immunization which involved inserting particles obtained from smallpox lesions under the skin or into the nostrils of a person who had never had smallpox. In the late eighteenth century, Edward Jenner discovered that dairy maids who had suffered and recovered from the less serious cowpox were not susceptible to smallpox infection, and he subsequently developed and refined the technique of removing material from a human cowpox lesion and transferring it to another person. Jenner vaccinated his own child as a test case, to give confidence in his technique (Fenner et al., 1988).
Jenner published a monograph on the causes and effects of cowpox, in which he speculated about the safety and efficacy of vaccination, the former confirmed by the much milder resulting disease, smaller lesions, and fewer fatalities than variolation, and the latter proven by challenge inoculations with smallpox (Fenner et al., 1988; Radetsky, 1999). Using human sources of cowpox virus presented some technical and medical challenges. Therefore, in 1864, the use of calves as a continuous source of vaccine was expanded from its origins in Italy to the rest of Europe, and then the world (Fenner et al., 1988).
Toward the end of the nineteenth century, vaccination became widespread across Europe and the world, and in the 1920s and 1930s, smallpox cases across Europe and North America dropped to a few dozen per year. The Second World War interrupted many public health efforts, including vaccination, and major epidemics again appeared in Asia and Africa. The World Health Organization (WHO) initiated a program of global smallpox eradication at the 11th World Health Assembly meeting in 1958, and revived it at the 18th World Health Assembly meeting in 1965. The Intensified Smallpox Eradication Program was established in 1967, and the invention of the bifurcated needle allowed for improved and efficient immunization against smallpox in the coordinated mass vaccination and surveillance and containment activities (for example, ring vacci-