From the Academy: Discovery of antivirals against smallpox

Smallpox, a devastating infectious disease dreaded throughout much of recorded history, is caused by the variola virus, a member of the poxviridae family. In the 20th century alone, smallpox deaths worldwide numbered in the millions. In 1980, after an intensive program of immunization with vaccinia virus, a related but relatively nonpathogenic virus, the World Health Organization (WHO) declared the disease eradicated. By 1983, all known stocks of variola virus were in two WHO collaborating centers: the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta and (after a transfer in 1994) the Russian State Research Center of Virology and Biotechnology (the Vektor Institute) in Novosibirsk. The WHO Committee on Orthopoxvirus Infections voted on several occasions to recommend destruction of the stocks, but each time the decision was deferred to permit more research on live variola virus. A 1999 National Academies report summarized and assessed scientific needs for live variola virus (1). The concern that undeclared stocks of variola virus might exist and that they might be used as a bioterrorist weapon (2) was heightened in late 2001 by the deliberate release of Bacillus anthracis, the agent of anthrax, in the weeks after the September 11, 2001, attacks. That concern prompted a voluntary national-preparedness effort to vaccinate healthcare workers, first responders, and members of the military against smallpox. However, given the substantial side effects, the risks associated with the smallpox vaccine, and the absence of information about an imminent bioterrorist attack, vaccination was not accepted by all members of those groups, nor was it recommended for the general public by the government (3). Whatever the likelihood of covertly held variola virus stocks, an intentional release of the virus would pose a serious health threat and would probably provoke a global health crisis. The lethality of the disease (up to 40%) and its ease of transmissibility place variola virus at the top of CDC's list of high-threat (Category A) agents. For that reason, the federal government rapidly increased its support of research related to the discovery of antiviral drugs against smallpox. In addition to providing potential therapy for infected people, the availability of antiviral drugs could decrease the risks associated with the smallpox vaccine by providing a treatment for vaccine-associated complications. Ultimately, the development of antiviral drugs against smallpox could deter rogue states and terrorists from releasing variola virus because its impact would be diminished. Moreover, the same new therapies are likely to be useful in other poxvirus diseases, such as monkeypox.