A spotlight on smallpox.

Naturally occurring smallpox was eradicated in the late 1970s after a carefully organized worldwide public health initiative coordinated by the World Health Organization (WHO). In what might be the most momentous public health achievement of the twentieth century, a virus that had killed more people than any other pathogen in the history of mankind, was relegated to the test tube. Although some authorities have considered it to be an unlikely candidate for a biologic weapon, recent hypothetical scenarios such as the “Dark Winter” exercises have revealed the profound vulnerability of the United States civilian population to smallpox attack.1–3 Moreover, the events of September 11, 2001 and subsequent spread of weaponized anthrax spores through the U.S. Mail have heightened anxiety among civilians and increased concern among public health officials over our lack of preparedness against future acts of bioterrorism. Smallpox is especially worrisome because it is highly contagious via droplet infection, causes a painful and disabling febrile illness, and has a case-fatality rate of up to 30%.4,5 The famous British historian Macaulay referred to it as, “the most terrible of all the ministers of death.” The majority of smallpox survivors were left with disfiguring scars and blindness occurred in up to ten percent of cases. With the eradication of smallpox, routine vaccination of civilians and international travelers was abandoned.6,7 Consequently, the great majority of the U.S. population, even those previously vaccinated, are now considered vulnerable to infection. The loss of widespread immunity in a population, ie, so called “herd immunity”, allows a higher proportion of primary contacts of an infected individual to contract a disease. Each primary contact can then infect a greater percentage of secondary contacts, etc. This permits exponential spread of the disease in a population. Our vulnerability is further heightened by increased population density and mobility and the likelihood of delayed recognition of new index cases by two generations of physicians who have no experience with variola. A recent mathematical model suggested that if 100 individuals in the U.S. population were initially infected, quarantine and vaccination would eventually control the outbreak but there would be 4200 cases and an entire year would be required to stop the outbreak. One can only speculate as to what effect such an outbreak would have on the national psyche, the economy, tourism, etc.8 After the eradication of variola, remaining viral stocks were sequestered at 2 laboratories, one at the U.S. Center for Disease control (CDC) in Atlanta and the other in the former Soviet Union. Although the WHO Committee has advocated destruction of remaining viral stocks, it has been repeatedly postponed so these stocks are still in existence.9 The disquieting possibility that clandestine stockpiles might exist and anecdotal reports that the former Soviet Union probably produced large quantities of smallpox virus are cause for concern.9,10 Dr. Kanatjan Alibekov, former First Deputy Director of Biopreparat, the former Soviet Union’s biologic weapons program, from 1988 to 1992, defected to the U.S. in 1992. He alleges that the former Soviet Union successfully bioengineered a number of biologic weapons including smallpox, plague, anthrax, Venezuelan equine encephalitis, tularemia, brucellosis and was working on several hemorrhagic fevers.11 It has also been proposed that smallpox virus could potentially be genetically altered or recombined with other pathogens such as Ebola to produce even more dangerous bioweapons; as if smallpox itself were not a great enough threat. During the 1991 Gulf War, stocks of camelpox virus, which is very similar to smallpox virus, were discovered in Iraq and allegedly were intended for biologic warfare use.12 Moreover, outbreaks of monkey pox, another orthopox virus, have been reported in Africa with case fatality rates of about 10%. Although humanto-human contagion of this agent is thought to be too limited to sustain significant epidemic spread, genetic manipulation of this virus could conceivably increase its transmissibility.13 A team in Australia recently reported the inadvertent creation of an unusually deadly form of mousepox.14 They had been trying to create a contraceptive vaccine, using a benign mousepox virus to express genes for proteins carried on mouse eggs. To boost the antibody response against these proteins they added the gene for interleukin 4 (IL-4). The augmented IL-4 expression down regulated cell-mediated immuFrom the Department of Dermatology, Mount Sinai School of Medicine, New York, New York. Address all correspondence to: Donald Rudikoff, MD, Box 1048, 1 Gustave L. Levy Place, New York, NY 10029. Email: RNAhybrid@aol.com.