Barquet and Domingo [1] present an enthralling history of the smallpox virus but end their article with a regrettably incomplete summary of the recent scientific debate over the destruction of variola. Since the time of the most recent stay of execution of the virus in early 1996, some of the rich scientific and medical value of variola has come to light. Indeed, in the past few years, tantalizing bits of understanding of the unique propensity of the virus to induce immune tolerance or immunosuppression by way of cytokine inhibition [2] and of the structure-function relations of the genome [3] have been determined. That these properties have now been related to protein products of the virus is perhaps unsurprising given Barquet and Domingo's observation that many strains of the virus cause disease with extraordinarily high penetrance in a given population. However, the previously elusive mechanisms of action, including interference with MHC-restricted antigen presentation, strongly suggest novel models of immune modulation of relevance to other immunosuppressive agents, and the potential for exploitation for important clinical application, such as organ transplantation [4]. Ironically, this "most terrible of the ministers of death" may hold the key to selective inhibition of primary immune system responses, advancing us toward immunosuppressive regimens far less toxic to patients.

Proponents of destruction state that cloning of variola provides an adequate store of genetic material for later study. Although cell biologists have learned much from atomizing their targets, all virologists know that smashing a watch to bits does present a daunting obstacle to learning all of its integrated functionality. Immune system manipulation using the hitherto-disparaged virus requires retention of the entirety of the genome [5] or of pieces that can easily be fully reconstituted. Elimination of the virus is not only political folly; recent literature demonstrates that squandering this immensely valuable resource is scientifically imprudent at this stage of our knowledge.