nomena have advanced dramatically in the past 20 years and will almost certainly become even more powerful in the future. As a consequence of these capabilities, novel approaches to biomedical research have emerged. Techniques have been developed to render viruses safer to use in laboratory studies and to provide new animal models with which such studies can be performed. Because variola virus is the only uniquely human orthopoxvirus, it offers the potential for understanding aspects of human biology that may have considerable biomedical significance. Thus variola virus, once considered an agent of human pestilence, may in the future be viewed as a potential source of knowledge and of reagents to support advances in cell biology and immunology. In particular, research using variola virus could assist in understanding the inflammatory response, which is a key process of cell-mediated defense.
In preparation for international deliberations concerning whether all variola virus stocks, stored clinical materials containing variola virus, and live variola virus genome DNA held in the international repositories are to be destroyed, this committee was asked to assess future scientific needs for live variola virus. The committee was not asked to make a recommendation about destruction or retention of variola virus stocks, and such a determination involves information beyond the purview of the committee.
In carrying out its charge, the committee recognized that the knowledge likely to be obtained from future research using live variola virus must be assessed within a broader context that has changed dramatically since the eradication of smallpox. This broader context encompasses three major global conditions.
First, since the cessation of vaccination programs following the successful eradication of smallpox, the entire global population has become more susceptible to the disease than ever before. Widespread inoculation during the eradication program produced a high level of immunity within the general population that protected those exposed to the virus. A smallpox outbreak occurring today in a highly mobile and susceptible population, in contrast, might spread widely before being recognized and before effective countermeasures could be put in place. If large enough, an outbreak could quickly overwhelm medical response capabilities.
Second, the significant number of individuals in many parts of the world who are immunocompromised as a result of HIV infection, an organ transplant, or chemotherapy limits the potential widespread use of the current smallpox vaccine because it is made from live vaccinia virus. Smallpox vaccination with the vaceinia vaccine, the workhorse of the eradication program, was terminated primarily because of eradication, but also because of concern about rare but