Reading Room Production — page 374

From: "Mclinnes, Pamela (NIH/NIAID)" </O=NIH/OU=NIHEXCHANGE/CN=NIAID/CN=PMCINNES> To: "Fauci, Anthony (NIH/NIAID)" <AFAUCI@niaid.nih.gov> Cc: "Gruber, Robin (NIH/NIAID)" <M @niaid.nih.gov>, "Heilman, Carole (NIH/NIAID)" HE @ visid. nih. gov> Subject: Mark Buller and so called US develops lethal new viruses Date: Thu, 30 Oct 2003 13:09:33 -0500 Importance: High Embedded: unnamed Tony: Background on Mark Buller presentation in Geneva re so-called US development of lethal new viruses In 2000, Australian investigators, while pursuing a contraceptive development program for controlling mice, serendipitously discovered that by engineering ectromelia (mousepox) to include mouse IL-4, the new virus was more virulent and could evade normally protective vaccination (Dryvax). These data were published (Jackson RJ, et al. J Virol. 2001 Feb;75(3):1205-10. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox.) The data created some disturbance in the poxvirus research community, in the national security community and in the press because of the possible implications for engineering a smallpox virus with human IL-4. Given that the data were in the public domain and the study design was not optimal from a virologic perspective, it was felt to be both important and appropriate to verify these data and to explore ways to control this new virulent virus, utilizing either a vaccine or a therapeutic. Under Contract NO1-Al-15436, Dr. Mark Buller of St. Louis University implemented a study in mice utilizing a mouse pox virus engineered with mouse IL-4. (Carole sent you the attached e-mail 7/16/2002 informing you of progress on the study.) The MOUSE part of each component is critical and adds two levels of safety. Both the virus and the IL-4 used were mouse species specific. This study confirmed the Australian findings and Dr. Buller has presented these data in several forums including the International Poxvirus Meeting held in Lake Placid in summer 2002, and down at DHHS. Shift to Geneva. Last week a meeting organized by Acambis was held in Geneva. DA was prominently involved in the meeting and honored at a dinner. Larry Kerr (DHS) , Bernie Moss, Peter Jahrling, Jim Meegan, Mark Challberg were among other meeting attendees. Mark Buller had been assigned the topic of "The Potential Use of Genetic Engineering to Enhance Orthopoxviruses as Bioweapons". Jim Meegan reports that in the first half of Mark's talk, he discussed hypothetical scenaria and tried to show that these would not add to the general body of knowledge in a meaningful way; e.g. engineering monkey pox. In the second half of his talk, he presented his data that confirmed the Australian findings with engineered ectromelia. The only new data presented were partial protection against the engineered virus with antivirals (cidofovir). He acknowledged funding of the work from NIAID. At the end of his talk, Buller said that in partnership with Jahrling, he was going to create a cowpox virus mouse IL-4 construct and a vaccinia virus mouse IL-4 construct for testing of antivirals in the mouse system. Following his talk, Jim Meegan immediately jumped up and stressed that the Australian data were already published, that it was important to confirm them, that safety issues had been fully considered and embraced in the design of the experiment, and no aspect of the study had been covert. The next individual to comment from the audience (US person, unknown name) expressed relief that Dr. Meegan had clarified those issues because that eased his concerns re the experiment and the data and the chance that we were "giving terrorists a recipe for a bioweapon." At the end of the session, Dr. Meegan instructed Dr. Buller not to initiate work on the cowpox virus mouse IL-4 or vaccinia virus mouse IL-4 construct experiment without discussion and express permission if NIAID money was proposed for use. The reason for his concern obviously was that one of the two safety barriers (cowpox and vaccinia can infect humans) would not be in place for such an experiment. Dr. Buller yesterday sent an e-mail to Dr. Meegan asking for clarification on this. Dr. Meegan has not yet responded. However, within the last 24 hours we have discovered that Barney Graham has already created and tested a vaccinia virus mouse IL-4 construct. (There is some similar work published almost a decade ago.) We hear that this virus was also more