Killing a Killer: What Next for Smallpox?

Now that the 20th century has passed into the domain of history books, we can retrospectively begin to assess the relative contributions that the many advances in the realm of infectious disease have actually made to public health in general. At the top of this virtuous list will surely be the discovery of antibiotics in the 1930s and the use of vaccination to eradicate smallpox as an extant human disease in the 1960s and 1970s. As clearly pointed out in a recent book by D. A. Henderson, one of the leaders of the global smallpox eradication program, this task of ridding Homo sapiens from the curse of this ancestral disease was neither easy nor without controversy [1]. In fact, the history of the many consequences of smallpox on humankind reads like a long litany of human misery and calamitous events, but is juxtaposed with the more noble accomplishments that began with the discovery of vaccination by Jenner in 1798 and culminated with the World Health Organization (WHO) certifying the world free of smallpox in 1980 [2]. With this singular accomplishment, as many as 60–100 million individuals who would have been predicted to die of smallpox have been spared from a truly gruesome death. Nevertheless, as is intimated by the timeline in Table 1, which summarizes the history of smallpox and the orthopoxvirus that caused the disease (variola virus), the narrative of smallpox did not stop with its eradication as a pandemic human disease. Instead, we find ourselves still wrestling with an issue that intermingles public health policy, philosophy, national security, and bioterrorism, and affects our perceptions of research ethics with extreme pathogens in general. It boils down to a not-so-simple question: What exactly should the Victor do with the Vanquished? In 1980, this question seemed simpler than now. Following the smallpox eradication, all declared stocks of the live variola virus were rounded up and distilled into two WHO-approved repositories, now residing at the Centers for Disease Control (CDC), Atlanta, United States of America, and at Vector, Novosobirsk, Russia. WHO convened a standing committee to oversee these repositories and issue regulatory approval for any research studies that utilized the live virus stocks at the two sites, with the tacit assumption that the only justifiable long-term fate for these stocks was an autoclave. Then, the revelation that variola virus had been covertly weaponized and stockpiled by the Soviet military [3,4] led to escalating waves of mistrust and suspicion amongst politicians, government officials, scientists, and health policy experts alike [5]. Factions then formed, with the two sides collectively promulgating an agenda that was either pro-destruction or anti-destruction, and cogent arguments were made by members of both camps as to why the declared stocks of variola virus should be maintained or not [6–8]. In the meantime, the member states holding the declared stocks of live virus (i.e., the US and Russia) held their own internal deliberations of what to do next, in a kind of pas de trois with the WHO that continues to this day. In the case of the US, input was sought from the Institute of Medicine (IOM), which has struck two expert committees (the first issued its report in 1999, and the second committee report was released in July 2009 at http://www.iom.edu/ Reports/2009/LiveVariolaVirusContinuing Research.aspx; [9]) on the scientific rationale for any further research that would require live variola virus. It is expected that these two IOM reports will be factored into the US decision as to how to respond to any future request from WHO (expected in 2011), following a vote of member states of the World Health Assembly on the specific issue of whether the declared live variola virus stocks held at both sites should now finally be destroyed.