Smallpox Eradication and Storage

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Smallpox Eradication and Storage

Introduction

Smallpox is a disease caused by the smallpox virus, also called the variola virus or simply variola. The World Health Organization (WHO) of the United Nations declared smallpox eradicated in 1980 after a decades long program of global vaccination. However, specimens of smallpox virus are still held in the United States, Russia, and possibly other countries. Samples of variola DNA may also be recoverable from old medical samples, such as the century-old smallpox scabs discovered in an envelope tucked in a nineteenth-century medical textbook in a New Mexico library in 2004. Since the 1990s, there has been ongoing debate about whether or not remaining stocks of smallpox should be destroyed. Issues include the morality of deliberately causing the extinction of a species; whether continued possession of the virus might someday result in its escape, potentially causing millions of deaths; whether the virus might be used to develop biological weapons; and whether keeping the virus intact is necessary as a precaution against the possible use of smallpox as a biowar or bioterror weapon or its accidental or natural re-release into human populations. The WHO has authorized some research with existing variola stocks, but faces continued controversy over the continued existence of the smallpox virus.

History and Scientific Foundations

The eradication of smallpox began with the discovery in 1796 by English physician Edward Jenner (1749–1823) that inoculating a person with pus from a cowpox lesion could prevent smallpox. This fact had been noticed before by a number of people, as had the possibility of inoculation using scabs or pus from people with milder cases of smallpox (variola minor). However, Jenner was the first person with professional standing to discover inoculation with the harmless cowpox virus, and so he was able to publish his findings and make them a standard part of medical knowledge.

Widespread vaccination led to the disappearance of smallpox from industrialized countries. In the United States, for example, the last case was reported in Texas in 1949. From 1967 to 1980, the World Health Organization oversaw a global campaign, the WHO Intensified Smallpox Eradication Program, to eliminate smallpox entirely. The program was declared an official success in May 1980, almost three years after the last case of natural smallpox on Earth was seen in 1977 in Somalia.

The eradication strategy had two basic features. First came mass vaccination campaigns in each target country, coordinated with that country's government. The goal was to vaccinate at least 80% of the population of each target country. Smallpox vaccination is a simple procedure involving multiple skin punctures in the side of the arm with a two-pronged metal tool resembling a lobster fork. The tool, termed a bifurcated needle, is dipped once into a vial containing liquid smallpox vaccine and then repeatedly stuck into the skin over a small area. Earlier, less-convenient methods were displaced by the bifurcated-needle procedure during the global eradication campaign.

The smallpox vaccine does not contain smallpox virus, but live vaccinia virus. Vaccinia virus almost never causes fatal disease; the reported death rate from smallpox vaccination is approximately one death per one million vaccinations. An immune system that has learned to recognize and attack the vaccinia virus will also recognize and attack the variola virus at its first appearance. Smallpox virus may enter the body of an immunized person, but is destroyed by the immune system before it can gain a foothold.

The second aspect of the eradication strategy was termed “surveillance and containment.” Since some percentage of the population in most countries remained unvaccinated even at the height of the eradication campaign, smallpox still occurred. Surveillance and containment involved keeping a lookout for outbreaks of smallpox and then selectively, intensively vaccinating people in the vicinity of the outbreak.

This two-part strategy was successful. Smallpox was eliminated in Brazil in 1971 and in Indonesia in 1972. A few outbreaks in Europe were caused by travelers, but were rapidly contained. The last case of the more severe form of smallpox, variola major, occurred in Bangladesh in 1975. The last case of natural smallpox occurred in Somalia in 1977. After several years with no reported cases of the disease, the World Health Organization declared smallpox eradicated in 1980. As of 2007, no cases had been reported worldwide in 30 years.

Following eradication, the World Health Organization requested that all laboratories in the world either destroy their smallpox virus stocks or transfer them to one of two reference laboratories, the Institute of Viral Preparations in Moscow or the United States Centers for Disease Control and Prevention in Atlanta, Georgia. The stocks of the Institute of Viral Preparations were transferred in 1994 to the State Research Center of Virology and Biotechnology of the Russian Federation in Siberia, now the WHO Collaborating Centre for Orthopoxvirus Diagnostics.

WORDS TO KNOW

BIFURCATED NEEDLE: A bifurcated needle is a needle that has two prongs with a wire suspended between them. The wire is designed to hold a certain amount of vaccine. Development of the bifurcated needle was a major advance in vaccination against smallpox.

BIOSAFETY LEVEL 4 FACILITY: A specially equipped, secured laboratory where scientists study the most dangerous known microbes. These labs are designed to contain infectious agents and disease-causing microbes, prevent their dissemination, and protect researchers from exposure.

COWPOX: Cowpox refers to a disease that is caused by the cowpox or catpox virus. The virus is a member of the orthopoxvirus family. Other viruses in this family include the smallpox and vaccinia viruses. Cowpox is a rare disease, and is mostly noteworthy as the basis of the formulation, over 200 years ago, of an injection by Edward Jenner that proved successful in curing smallpox.

VACCINATION: Vaccination is the inoculation, or use of vaccines, to prevent specific diseases within humans and animals by producing immunity to such diseases. The introduction of weakened or dead viruses or microorganisms into the body to create immunity by the production of specific antibodies.

VACCINIA VIRUS: The vaccinia virus is a usually harmless virus that is closely related to the virus that causes smallpox, a dangerous disease. Infection with the vaccinia virus confers immunity against smallpox, so vaccinia virus has been used as a vaccine against smallpox.

VARIOLA VIRUS: Variola virus (or variola major virus) is the virus that causes smallpox. The virus is one of the members of the poxvirus group (Family Poxviridae). The virus particle is brick shaped and contains a double strand of deoxyribonucleic acid. The variola virus is among the most dangerous of all the potential biological weapons.

By United States law, smallpox virus can be stored and handled only at Biosafety Level 4 (BSL-4) facilities. Such a facility consists of a separate building or architecturally isolated section of a building specially equipped for biological isolation. Persons entering and leaving the facility must take sterilizing showers; air and sewage leaving the building must pass through special filters to remove any possible disease-carrying particles, and separate air supply and exhaust must be arranged for workers inside the laboratory space. The building must be ventilated so that air flows into the building and toward the part of the building where the most hazardous materials are kept. The building must also remain sealed in the event of a power failure. There are approximately 10 BSL-4 facilities in the United States as of 2007.

Applications and Research

Following eradication, the World Health Organization set 1999 as the deadline for the destruction of all variola virus stocks. However, both the United States and Russia failed to carry out this directive, citing the need for further research on the virus. The World Health Assembly (WHA), the governing body of WHO, accepted the continuing existence of the virus and established a Variola Advisory Committee to oversee variola virus research until the end of 2002. After that time, the virus stocks were to finally be destroyed. Some ethicists have raised the question of whether it is permissible to deliberately cause the extinction of any species, even a malignant virus, but this has not been a major concern in WHO or governmental debates on the fate of the variola virus. In 2002 the WHA decided, under combined United States and Russian pressure, that not enough research had been accomplished and that the deadline for variola destruction would be extended indefinitely.

The goals of variola virus research are said by workers in the field to be a better understanding of the genome of the virus, the proteins produced by the virus, and the precise means by which the virus infects cells in order to prepare for accidental, natural, or deliberate rerelease of the virus in human populations. The genomes of several dozen varieties of variola virus were completely sequenced by 2007.

In 2004, the Variola Advisory Committee decided to allow the creation of genetically modified varieties of the variola virus, in particular, some containing reporter genes (genes that make it easy to identify the presence of the virus, such as a protein that glows green when exposed to blue light). In 2005, the advisory committee also voted to allow the transfer of variola DNA fragments up to 55 base pairs long between laboratories, the manufacture of gene chips containing smallpox DNA, and the splicing of smallpox genes into other orthopoxviruses.

Impacts and Issues

Research using the surviving smallpox virus stocks has been controversial for decades. The World Health Organization's Director-General opposed WHO's decision in 2005 to allow the transfer of smallpox genes to other viruses, a move also opposed by South Africa, China, the Netherlands, and a number of other countries. Developing countries, which would be more vulnerable to a new smallpox outbreak, are particularly keen on final destruction of virus stocks. Two groups, the Third World Net-work and the Sunshine Project, mounted campaigns in the early 2000s against continuing smallpox research of this type.

Also in 2005, a bill passed by the United States Congress made it illegal to “produce, engineer, [or] synthesize” the variola virus from scratch. The possibility of from-scratch (also called de novo) manufacture of smallpox virus is not farfetched. Poliovirus was first synthesized from scratch in 2001, starting solely with a record of its genome and without the aid of preexisting RNA, DNA, or living cells. In 2006, Sandia National Laboratory, an arm of the U.S. government, began experiments that involved inserting synthetic (de novo) variola genes into other organisms. Some critics of the continued existence of variola stocks say that since Sandia's historical mission has been the production of nuclear weapons and the laboratory has no biomedical mission, its research with variola virus genes is inappropriate and signifies deteriorating WHO control over smallpox research.

In January 2007, the WHO Executive Board adopted a draft smallpox resolution to be sent to the WHA in May 2007. The resolution asks the Director-General of the WHO to forbid genetic engineering of the variola virus and calls for the topic of setting a definite date for the destruction of variola virus stocks to be placed on the agenda of the WHA's 63rd or 64th session in 2010 or 2011.

BIBLIOGRAPHY

Books

Carrell, Jennifer Lee. The Speckled Monster: A Historical Tale of Battling the Smallpox Epidemic. New York: Dutton, 2003.

Koplow, David. Smallpox: The Fight to Eradicate a Global Scourge. Berkeley, CA: University of California Press, 2004.

Periodicals

Cohen, Jon. “Leaks Produce a Torrent of Denials.” Science 298 (November 15, 2002): 1313–1315.

Enserink, Martin. “WHA Gives Yellow Light for Variola Studies.” Science 308 (May 27, 2005): 1235.

Halloran, M. Elizabeth, et al. “Containing Bioterrorist Smallpox.” Science 298 (November 15, 2002): 1428–1432.

Normile, Dennis. “WHO Gives a Cautious Green Light to Smallpox Experiments.” Science 306 (November 19, 2004): 1270–1271.

Web Sites

Centers for Disease Control and Prevention. “The Pink Book: Smallpox.” November 15, 2006. <http://www.cdc.gov/nip/publications/pink/smallpox.pdf> (accessed February 22, 2007).

World Health Organization. “Smallpox.” <http://www.who.int/mediacentre/factsheets/smallpox/en/> (accessed February 20, 2007).

Larry Gilman

Infectious Diseases: In Context