CNS Occasional Papers: #9

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Commentary

by

Peter B. Merkle, Ph.D., P.E.
Sandia National Laboratories
Albuquerque, New Mexico
October 3, 2002


Thank you for providing a forum for this type of "forensic epidemic analysis." Dr. Zelicoff has done a great service by careful research of the actual circumstances of the outbreak. I think such studies are critical to meeting the many challenges of defending against biological warfare (BW) and bioterrorism. In all these matters, I commend the editors for your restraint with the press. Panic and fear will be equal adversaries to the virus itself if a new epidemic emerges.

I wanted to share my thoughts on this, especially regarding Dr. Zelicoff's "unanswered questions." The prevalence of hemorrhagic-type disease in a smallpox epidemic is not necessarily indicative of selection for virulence. In a 1945-46 hospital-centered outbreak among U.S. military personnel in Japan, Agerty reported 17 adult cases, with 10 fatalities of the hemorrhagic type. Many of the deceased had been vaccinated within three years of the outbreak, presumably with faulty technique or degraded vaccine, according to Agerty.[1] I analyzed this outbreak as reported, and supplied some figures and comments to Dr. Zelicoff after the New York Times article of June 15, 2002.[2] For the 1999 modeling study by John Bombardt I managed at DTRA[3], Dr. Horst Agerty was interviewed (then nearly a centenarian, but sharp as a tack). The outbreak he reported upon was extremely unusual. He noted that smallpox was endemic in the area among the local and transient population of post-war Japan.

Having 10 hemorrhagic cases out of 17 total in a hospital-centered outbreak is by any standard an outlier. I do not know why some outbreaks are more virulent than others, aside from the "host factors" reason that is the commonly accepted theory. Logically, the Agerty outbreak was either "natural" or "unnatural." I have no reason to believe that the index case(s) were deliberately infected with a strain especially selected for virulence, or that the strain in circulation was somehow unnatural, other than pure conjecture. I do know that genetic technology to enhance the virus did not exist at that time. I must conclude that, absent new findings about smallpox in post-war Japan, there were a completely natural series of epidemics in progress. In comparison with the Agerty outbreak, I cannot conclude even qualitatively that the Aralsk outbreak involved "an especially virulent strain" with its 2 hemorrhagic cases out of 10 cases. Note that it is reasonable to assume that any BW program would select strains of any disease organism for virulence, if that indeed were the weapon's intended characteristic.

In the context of the Aralsk smallpox virus strain, the "unanswered question" section comments that our reliance on a "single vaccine (unmodified vaccinia) represents a serious potential vulnerability." However, all wild and thus presumed natural strains of smallpox virus were extinguished as epidemics by such vaccines, including the Agerty strain. It is regrettably unclear from this portion of the text if the implication is that the Aralsk strain, or perhaps others in the Soviet program, have been genetically modified to evade the vaccine, or that there were wild strains that were known to have overwhelmed potent vaccine when administered properly, repeatedly, and in advance of infection (as was done for WHO personnel in epidemic eradication). I defer to those with field experience in smallpox eradication on this point.

The "unanswered questions" section includes the statement "...the Soviets not only 'weaponized' smallpox but succeeded in aerosolizing it and, it appears, 'hardening' the virus so that it maintained its infectivity..." The vocabulary used here does not reflect the terminology of former offensive BW practitioners, to my knowledge. It implies that "weaponization," "aerosolizing," and "hardening" the virus are distinct activities. In fact, they are not. This same imprecise vocabulary caused a great deal of confusion during the anthrax mail attacks. The process of "weaponization" encompasses the entire process of strain selection, strain enhancement, and strain compatibility with aerosolization mixtures and environmental factors upon release. The text implies "weaponization" is something separate; is it solely this genetic modification or strain enhancement, as in "new forms never encountered"? Weaponization is not synonymous with genetic modification or even strain selection for virulence. As a process, it may include genetic modification. Aerosolizing the formulation is integral to the weaponization process, as is making the aerosol robust against environmental stress during dispersal. At its simplest, infecting someone with the variola virus and sending them to a target population or onto an airplane is "weaponization," albeit nontechnical. I think this vocabulary issue is something that needs to be communicated to researchers in the policy field. Not understanding BW-related terminology can lead to tremendous misunderstandings and, in the press, outright mistaken reporting.

I must comment further on the statement "That smallpox is still with us is obvious, perhaps in forms we never encountered..." It is obvious that smallpox virus cultures exist in the two authorized repositories. To suggest that new unnatural forms exist is to suggest that someone has genetically modified the variola virus in some fashion, unless the contention is that natural outbreaks or reservoirs still exist where the smallpox virus is undergoing genetic change, or that undiscovered strains exist. I think the intended meaning is to suggest that genetic manipulation or assisted selection of some kind has taken place. I agree that this would be an extremely dangerous situation, yet I know of no public and substantiated reports of any specific individual or organization in any location having done so, or even holding an unauthorized natural variola virus culture today. I would welcome education on this point. If there is nonpublic information of this kind, I think that anyone not otherwise restricted should report it openly so that the threat may be addressed directly by the international community.[4]


References

[1] Agerty, H.A. "An Outbreak of Smallpox in American Military Personnel in Japan." N Engl J Med 237:305-09 (1947).

[2] Merkle, P.B. ''Observations on Models and Outbreaks,'' presentation to the 2002 DIMACS Working Group on Mathematical Sciences Methods for the Study of Deliberate Releases of Biological Agents and their Consequences, May 2002.

[3] Bombardt Jr., J.N. "Smallpox Transmission and BW Casualty Assessments," Institute for Defense Analyses Paper P-3550 (Defense Threat Reduction Agency, Advanced Systems and Concepts Office, Fort Belvoir, VA, 2000).

[4] The opinions expressed here are the author's own and do not necessarily represent those of the U.S. Government or the Sandia National Laboratory.


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