Smallpox (variola), a member of the orthopox genus of viruses, has been extinct in the wild since 1977, and it may have the distinction of becoming the first species to be totally extinguished by world consensus. This virus, "the most terrible of all the ministers of death" (Macaulay, 1800), has plagued humans since the beginning of civilization. Until the1960s, smallpox was still common in some parts of the developing world, and the risk of an outbreak in Europe was a source of serious concern.

Smallpox was used as a biological weapon during the French and Indian Wars, when British forces distributed contaminated blankets with the intent of initiating outbreaks among the Native Americans. Persons of all ages and classes were potential victims for this indiscriminate killer. However, since 1978, the tables have been turned. Humans now control the fate of smallpox and must wrestle with ethical issues about genocide that never troubled the virus.

Orthopox viruses are large, complex viruses, with a characteristic brick-shaped structure measuring about 200 nm in diameter. Three naturally occurring members of the orthopox genus are known to infect humans: smallpox, monkeypox, and cowpox (also called vaccinia). Cowpox causes mild skin lesions. Outbreaks of monkeypox with occasional fatalities occur among people in Africa who have contact with the squirrels and monkeys that are the natural hosts of that virus. In contrast, smallpox is extremely contagious and has a high fatality rate.

Smallpox infection begins with inhalation or ingestion of the virus. The infectious dose is believed to be only a few virions. After a two-week incubation period, the patient develops a fever and a rash beginning on the face, arms, and in the mouth, and then spreading over the entire body. Pustules form and crust over, with scabs that fall off to leave severe pitted scarring on those who survive. Historically, 20 to 60 percent of smallpox victims died, usually during the second week of the illness. Death most likely resulted from the toxemia associated with circulating immune complexes and variola antigens. Other forms of smallpox—the hemorrhagic and malignant forms—were less common, which sometimes meant that these cases were not promptly identified and that quarantine of these patients was delayed. As is true for most viral diseases, there is no spe cific treatment for smallpox. All that can be done for patients is to provide supportive care.

It was long known that people who had recovered from smallpox were immune to reinfection. This led to a practice called variolation, in which people were inoculated with infectious material from patients who had had a mild case of the disease. Variolation significantly reduced the number of fatalities associated with smallpox outbreaks, but in some cases fatal smallpox infections resulted from the inoculation. Cowpox infection in humans was also known to produce immunity to smallpox, but without the risk of inducing fatal disease. In 1796, Edward Jenner was the first to demonstrate the efficacy of "vaccination" in the prevention of smallpox. The modern vaccine is a genetic hybrid between vaccinia and variola. The adoption of vaccination in Western countries eliminated the threat of massive outbreaks in those areas.

The World Health Organization (WHO), an agency of the United Nations, began a global eradication program in 1967. Massive vaccination programs coupled with disease surveillance and quick response to outbreaks facilitated its eradication. The last naturally occurring case of smallpox was reported in Somalia in 1977. However, the last recorded death by smallpox occurred because of a laboratory accident in 1978 (Kreeger, 1994). In 1979 the WHO declared the world free of smallpox, with stores of virus remaining only in two research laboratories.

The WHO Ad Hoc Committee on Orthopoxvirus Infections made a recommendation in September 1984 to destroy all remaining stores of the smallpox virus, stating that the risk of an outbreak outweighed its value for future research. Destruction was initially delayed in order to allow the viral genome to be sequenced. In May 2000 the WHO set a new deadline for destruction of

Hand of Gloucestershire milkmaid Sarah Nelmes showing cowpox blisters from which Edward Jenner developed the smallpox vaccination technique, 1798 (From the collections of the Library of Congress)

virus stocks—2002—in order to allow further international research into antiviral agents, improved vaccines, and investigations of the genetic structure and pathogenesis of smallpox. The WHO did, however, reaffirm that elimination of the virus is the organization's ultimate goal.

The key reason given for the need to destroy the last stocks of the smallpox virus is the danger of accidental or intentional release. In 1999 and 2000, WHO teams inspected the Russian and U.S. facilities where smallpox is stored. They were satisfied with the biological safety and physical security of the facilities, but there is concern that other stocks of virus might remain in non-WHO laboratories. Others have raised the concern that virus preserved in the tissues of previous victims might be the source of new epidemics, or that the virus could re-emerge as a variant of mon-keypox (ibid.).

Although the smallpox vaccine is very effective, the immunity is not permanent. Vaccination of the general public was discontinued in the 1970s because the disease was no longer considered a threat. It is believed that persons who were vaccinated more than ten years ago are susceptible to the virus, although they might not be as severely affected. In addition, the prevalence of persons with compromised immune systems caused by the human immunodeficiency virus (HIV) increases the susceptibility of some populations. Increased human mobility has made intercontinental travel rapid and commonplace, and it has the potential to disseminate contagion on a scale unknown at the time of the last smallpox outbreak (Henderson et al., 1999).

For many people there is no ethical dilemma regarding the fate of the smallpox virus: It is a threat to mankind with no known redeeming characteristics, so its destruction is justified. To others the matter is more complicated. Does mankind have the right to knowingly exterminate a species? If we wish to eliminate things that are dangerous or frightening, the list will also include many creatures that we are currently striving to protect from extinction. Are we sure that there is nothing more that we can learn from the smallpox virus, or that smallpox has no possible use that would benefit mankind? How will future generations remember this decision?

—Julie Pomerantz

See also: Five Kingdoms of Nature; Medicine, The Benefits of Biodiversity to; Viruses


Barquet, N., and P. Domingo, 1997. "Smallpox: The Triumph over the Most Terrible of the Ministers of Death." Annals of Internal Medicine 127:635-642; Henderson, D. A., et al. 1999. "Smallpox as a Biological Weapon: Medical and Public Health Management." Journal of the American Medical Association 281, no. 22:2127-2137; Joklik, W. K., et al. 1993 "Why the Smallpox Virus Stocks Should Not Be

Destroyed." Science 262:1225-1226; Kreeger, K. Y. 1994. "Smallpox Extermination Stirs Scientists." Scientist 8, no. 22: 1; Macaulay, T. B. 1800. The History of England from James II. Philadelphia: Claxton, Rem-sen, and Haffelfinger; Mahy, B. J., et al. 1993. "The Remaining Stocks of Smallpox Virus Should Be Destroyed." Science 262:1223-1224.

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