1. Dual-Use Research: A Double Challenge for International Science Henry Metzger, MD Scientist Emeritus, NIAMS, NIH

2. Dual-Use Research Research that may generate valuable scientific knowledge but that could also be deliberately used to create serious harm to the public health or the environment

3. Resources Necessary to Misuse Research Nuclear: Sophisticated expertise and nation-state resources; damage horrific Chemical: Lesser sophistication and minimal resources; damage extensive (e.g. methylisocyanate release Bhopal, India, December 1984) Biological: Lesser sophistication and minimal resources and damage could reach pandemic proportions

4. Early example of dual use biological research Chaim Weizmann* and Acetone WWI: UK has urgent need for cordite (smokeless gun powder). Requires large volumes of acetone --manufactured by destructive distillation of wood-- which was in short supply. Weizmann introduced to Minister of Munitions, Lloyd George, and Churchill in 1915. Given use of Lister Institute lab and industrial plant at Nicholson's Gin Distillery to perfect method. Full-scale plant set up using bacterial fermentation of grain. 1912: Weizmann develops method to produce acetone by fermentation of starch by C. acetobutylicum; has no commercial value.

5. A recent example Production of an Extraordinarily Lethal Form of a Select Toxin An investigator in NIAID/NIH is developing a vaccine against a “Select”* toxin (known to be stable to boiling) *(Select agent: A biological agent or toxin that has potential to pose a severe threat to public health and safety) She purifies the toxin from a natural source by a simple but previously unpublished method When tested in mice the oral LD 50 is found to be 1000x lower than expected from literature values! Who to tell? Publish findings?

6. History A. U.S. National Research Council (NRC) Study: Scientific Communication and National Security (1982): Despite growing concern that nations may gain military advantage from new findings published in open scientific literature, U.S. decides to maintain only two options: open publication or classified B. Since then: -Discovery of nations with clandestine research on biological weapons -Increase in terrorist activities -Rapid progress in biotechnology; internet -Gary Hart/ Warren Rudman Report (Jan. 2001): Road Map for National Security:Imperative for Change -Anthrax attack shortly after 9/11/2001

7. Statement by Presidents of US NAS and UK Royal Soc. Referring to 1975 Asilomar Conference at which scientists codified their responsibilities with respect to ensuring the safety of recombinant DNA technology, the statement concludes: “Today researchers in the biological sciences again need to take responsibility for helping to prevent the potential misuses of their work, while being careful to preserve the vitality of their disciplines as required to contribute to human welfare.” (B.Alberts and R.May: Science 298:1135 (2002))

8. 2003 Consensus Statement by Journal Editors and Authors Group 1. Publication confers responsibilities on both authors and editors 2. Prospect of bioterrorism has raised legitimate concerns about abuse of published information 3. Scientists and their journals should consider appropriate mechanisms for review of papers that raise security issues 4. Where editor concludes potential harm of publication outweighs potential societal benefits, modify or reject paper Science 299:1149 (2003)

9. 2004 NRC Report Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology (Chair: Gerald Fink) Recommendations 1. Educate scientific community 2. Review plans of selected experiments 3. Review at publication stage 4. Create National Science Advisory Board for Biosecurity (NSABB) 5. Increased communication between life science, national security, and law enforcement communities 6. Convene international forum on biological security

10. Further NRC Reports Seeking Security: Pathogens, Open Access, and Genome Databases (2004) Globalization, Biosecurity, and the Future of the Life Sciences (2006) Common message: The scientific community should take preemptive steps to protect the integrity of science and to minimize the risk of misuse of dual use research of concern.

11. The National Scientific Advisory Board for Biosecurity (2004) Purpose: guide development of * Institutional and federal research reviews that allow fulfillment of research objectives while addressing security concerns; * Guidelines for identifying and conducting research requiring special attention and security surveillance; * Professional codes of conduct * Educational materials and resources regarding effective biosecurity. * Strategies for fostering international collaboration for oversight of dual use biological research. Draft Report: June 2007 (Currently under government review)

12. “World at Risk” Congressional Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism (2008) “It is essential that the members of the life sciences community…foster a bottom-up effort to sensitize researchers to biosecurity issues and concerns.”

13. Recent examples of published “contentious research” 2001: A lethal variant of mousepox virus 2002: Total synthesis of poliovirus genome 2005: Genome sequence of the 1918 human influenza virus ; effects of recreated virus in mice. 2007: Extending host range [human → mouse] of Listeria monocytogenes by rational protein design

14. Experiments/Results of Special Concern 1. Render a vaccine less- or in- effective 2. Confer resistance to antibiotics/antiviral agents 3. Enhance virulence, increase transmissibility or alter host range 4. Enable evasion of diagnostic/ detection modalities 5. Enable weaponization of biological agent or toxin

15. Two Teaching Modules 1. Federation of American Scientists (FAS) http://www.fas.org/main/home.jsp 2. Southeast Regional Center for Excellence in Emerging Infections and Biodefense (SERCEB) http://www.serceb.org

16. SERCEB Role: To develop drugs, vaccines and diagnostics for biodefense and emerging infections Support: NIAID (2003 → Experience: Of 27 proposals (2004-2007) for funding,10 contained “dual-use research of concern” Science 316:1432 (2007)

17. World Mortality Statistics Cause Incidence* Communicable diseases, maternal, perinatal, and nutritional conditions 18,400,000 Non-communicable diseases 33,500,000 Injuries (intentional and non-intentional) 5,200,000 Bioterrorism 1 * Per annum estimates (2002-2006) from WHO data

18. L J. Bomlitz and M. Brezis Misrepresentation of health risks by mass media J. Public Health Med., 2008 Number of media reports in United States on causes of death vs actual number of deaths from these causes in 2003

19. The Dual Challenges Minimizing risk of misuse Minimizing constraints on research through self- or government-imposed censorship

20. Take Home Message Recognize that there is a potential problem and that the public is seriously concerned about it Be informed about the scientific community’s efforts to minimize misuse responsibly Remain sensitive to the potential in your own research and in reviewing work of others If concern arises, know who to consult