Smallpox on death row, but research is yielding fruit

"If smallpox is outlawed, only outlaws will have smallpox." Peter Jahrling, civilian advisor to the United States Army Medical Research Institute of Infectious Diseases.1

Once very near execution, smallpox remains on death row. Eradicated in nature, the infamous killer survives in two official repositories in the United States and Russia.

After the global eradication of smallpox was confirmed by the World Health Organization (WHO) in 1980, a series of philosophical and scientific discussions began about the fate of the remaining stocks of live virus. In the mid-1980s, the WHO consolidated the world’s known stocks of live virus in two locations: the Centre of Virology and Biotechnology (VECTOR) in Koltsovo, Russia; and the Centers for Disease Control and Prevention (CDC). At that time, the first recommendations to destroy the stocks came forward, sparking the aforementioned debates about the research value of keeping the virus alive.

In 1990, a WHO ad hoc committee recommended the destruction of the smallpox stocks by Dec. 31, 1993. As debate continued about the wisdom of the action, the deadline was extended repeatedly. In May 2002, the WHO approved resolution WHO55.15, the most recent clemency granted for the live viral stocks of smallpox. The resolution called for "temporary, retention of the existing stocks of live Variola virus at the current locations . . . [with] the understanding that steps should be taken to ensure that all approved research would remain outcome-oriented and time-limited and periodically reviewed and a proposed new date for destruction should be set when the research accomplishments and outcomes allow consensus."

Though the virus famously described as the "demon in the freezer" has been close several times to being thawed and killed, it appears the research agenda is bearing fruit. The most recent progress report on smallpox research was presented at the fifth meeting of the WHO Advisory Committee on Variola Virus Research, November 2003.2 The current variola virus stocks at CDC include 451 isolates, of which 49 have been selected for viability studies. Of those, 45 isolates could be propagated in tissue culture.

Of the 120 samples at VECTOR, 55 were tested for viability and 32 could be propagated. The WHO committee recommended that isolates shown to be non-viable should be destroyed and removed from the inventories, with DNA being isolated if this was considered useful for future studies. The committee recommended that the WHO should approach the responsible authorities within the collaborating centers to implement the recommendations concerning the destruction of these virus isolates.

The WHO committee reported progress in developing a primate model for smallpox in the United States using macaque monkeys. Essential research on an animal model of smallpox is needed to meet the efficacy rules for the licensing of new antiviral compounds. In additional research with the smallpox virus, antiviral treatment with cidofovir was shown to protect monkeys against variola-induced death if given 24 hours before infection. The WHO committee acknowledged "the need for continued research" toward treatments and better vaccines, meaning that for the foreseeable future smallpox lives to fight another day.

References

1. Preston R. The demon in the freezer. The New Yorker, July 12, 1999: 44-61.

2. World Health Organization Advisory Committee on Variola Virus Research, Report of the Fifth Meeting. Geneva; 2003. Web site: www.who.int/csr/resources/publications/en/WEBWHO_CDS_CSR_GAR_2004_15.pdf.