about losing experimental material that could provide important information regarding viral pathogenesis in humans, as well as about establishing a precedent for the deliberate destruction of an archived species and the associated loss of genetic information. These concerns are implicitly seen as outweighing the risks of keeping the virus. Many participants in the COI discussions have found themselves in broad agreement in perceiving merit in both points of view. Efforts to reconcile the two incompatible policy stances have been a continuing challenge for COI and others.

Starting in 1977, the number of laboratories known to be holding stocks of variola virus was reduced until by the end of 1983 all known stocks were held in only two WHO Collaborating Centres—the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the Research Institute for Viral Preparations in Moscow, Russia [1]. The Russian stocks were transferred in 1994 to the State Center of Virology and Biotechnology (VECTOR) in Kotsovo, Russia, which subsequently became the WHO Collaborating Centre for Orthopoxvirus Diagnostics.

Use of these remaining variola stocks at CDC and VECTOR is restricted to approved Biological Safety Level 4 (BSL-4) conditions (see Box 5-1). WHO periodically conducts safety and security inspections of the facilities. Inventories of the samples at each institution are on file at WHO. COI recommended that cloned fragment libraries of selected strains be prepared and that selected prototypical strains be sequenced [15].

In addition, handling of cloned DNA fragments of the variola virus genome follows the recommendations issued in a 1994 COI report [16]:

• The two international repositories for storage, maintenance, and distribution of cloned DNA fragments of variola virus are CDC and VECTOR.
• Each sample is identified by nucleotide sequence determination.
• A register of cloned material is maintained, containing full descriptive and sequence information.
• Clones are distributed to research laboratories requesting them if:
• •  The clones will not be further distributed to third parties.
  •  The clones are not to be used for insertion of variola DNA into vaccinia virus or related poxviruses. No laboratory other than the international repositories is permitted to hold clones representing more than 20 percent of the variola virus genome at any one time.