1. Dual-Use Examples Lecture No. 15 Applied Version

2. 1. Outline The meaning of dual-use today –Slides 1-7 Typical examples of dual-use research –Slides 8-11 The Fink Report –Slides 12-20 The NSABB 2007 Oversight proposals –Slides 21-22 The 2008 Israeli Report –Slide 23 University of Maryland project on Controlling Dangerous Pathogens –Slides 24-26 Emerging concept of dual-use research –Slides 27-30

3. The term dual-use technologies, primarily applied to technologies with both military utility and viable commercial applications, has acquired a second meaning in the context of potential weapons development: the tools, skills, equipment, and knowledge critical to conducting legitimate research and development that could be subverted to malicious use. Rapid advances in biology, chemistry, and the information sciences will produce even more of these dual-use technologies, in both senses of the term, by 2020. Julie E. Fischer Senior Associate The Henry L. Stimson Center 2. The meaning of dual-use today

4. Oct 5, 2008 Yomiuri Newspaper) Who do you select in the context of the scientist who damaged the earth most? US scientist James Conant (1893 - 1978) Took the initiative to produce poison gas in World War I Became the president of the Harvard University at his age of forty The chairperson of the National Defense Science Committee: Promoted the project of developing atomic bomb US chemist Thomas Midgley (1889 - 1944) Invented leaded gasoline to suppress car knocking Succeeded in synthesizing dichlorodifluoromethane: cooling media of refrigerators and air conditioners, abstergent of electronics, gas for sprays Air pollution and the destruction of ozone layer Benevolent inventor may become the worst destroyer. To what extent should scientists take responsibility to their discovery or invention? 3. Scientists honor and destroyers dishonor

5. 4. Start point of the problems Good research projects, Excellent results But … we cannot exclude the possibility of hostile misuse Dual use dilemmas

6. 5. Why do the life scientists need to know the dual-use issue? 1.The development of science and technology, especially in life science such as biotechnology and recombinant DNA technology, is closely related to the development of new generation biological weapons. 2.Benevolent and civil research can be used for not only military purposes but also deliberate applications, and it could happen independently of researchers opinions. Dual use dilemma 3.Now is the age of high-speed internet and anyone can obtain the information of science and technology very easily from websites. Therefore, the scientists need to be responsible for the information that they provide also they have to foster their foresight about dual use research. 4.Regarding the publication of research results and new findings, researchers free and voluntary activity should be maintained. Governments or independent authorities are not the only responsible framework of this issue. Therefore, scientists themselves must tackle on the problems of dual use dilemma. 5.In the Biological and Toxin Weapons Convention, no reliable framework or methods to verify the compliance are established so far. That is the biggest problem in the Convention and simultaneously the life scientist can provide their knowledge to this issue. 6.If the life scientists themselves have an interest in the dual-use issue and participate in related frameworks, it will enhance the comprehensive resolution of this issue.

7. 6. Biosecurity is needed in the life science research Prevention of unauthorized or risky use of microbes that could be used for the development of biological and toxin weapons or bioterrorism. The process or countermeasures to suppress it. It is time to consider new measures for dealing with dual-use life science. Current goals To strengthen the protection of Biosecurity To recognize the importance of dual-use issue

8. 1.Genomics and proteomics 2.Bioinformatics 3.Human Genome Project and human diversity 4.Gene therapy 5.Virulence and pathogenicity 6.Vaccines and novel therapies 7.Recombinant protein expression 8.Toxins and other bioactive molecules 9.Detection and identification technologies 10.Human infectious disease patterns 11.Smallpox destruction 12.Drug resistance 13.Disease in agriculture 14.Pest control in agriculture 15.Global initiatives to tackle disease 16.Molecular biology applications and crops 17.Trends in protein production technologies 18.International co-operation and biosafety: activities under the Biodiversity Convention 19.Means of delivery of agents and toxins 20.Use of pathogens to control weeds and criminal crops 21.Bioremediation: the destruction of material 22.Countering the threat of BW terrorism 23.Impact of the entry into force of the CWC Useful in protecting against disease and BW Many were seen as causes of concern The UKs detailed science and technology review covered 23 separate topics Biological and Toxin Weapons Convention; The Fifth Review Conference of 2001-2002. 7. Dual-use concern is not an unrealistic issue but a real problem

9. 8. Sign of dual-use problems in life science research - Concerns about hostile misuse of bioscience (1) Genetic manipulation of anthrax vaccine (2) -endorphin production in Francisella tularensis Combination of biological agent and bioregulator The possibility of making a new bioweapon? The title appears as if An improvement in anthrax vaccine But … the truth was the addition of toxin genes to the anthrax vaccine Pomerantsev, A.P., Staritsin, N.A., Mockov Yu, V. and Marinin, L.I. (1997) Expression of cereolysine AB genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection. Vaccine, 15, 1846-1850. Borzenkov, V.M., Pomerantsev, A.P. and Ashmarin, I.P. (1993) [The additive synthesis of a regulatory peptide in vivo: the administration of a vaccinal Francisella tularensis strain that produces beta-endorphin]. Biull Eksp Biol Med, 116, 151-153. Examples of dual-use research (Papers in a gray zone)

10. 9. A typical example of dual-use dilemma in scientific research

11. 10. Genetically manipulated new virus showed unexpectedly strong virulence to kill the mice Refer to Lecture 13: Dual-Use Example 1: Mousepox Originally the virus was constructed for other purpose (Contraceptive vaccine for mice) The vaccine was developed to raise the antibody response to zona pellucida glycoprotein 3, and mousepox virus was used as a simple vehicle to carry it. Genetically-manipulated mouse virus Unexpected toxicity Inefficacy of present vaccine programme If similar technique were used, it stimulates the development of ultimate biological weapon? Human smallpox virus Analysis of the mechanism Dual-use research?

12. 1.The purpose of this study was to improve antibody production by IL-4 gene insertion into ectromelia virus, but the recombinant virus suppressed cellular immunity very strongly. (Unexpected products for researchers) 2.The authors show the possibility of making a new pathogenic virus by manipulating the gene that directly involves in immune response. (The possibility of making new pathogenic viruses using similar concept) 3.The recombinant virus exerted strong immunosuppressive effect to the host that already has acquired immunity to the same virus strain. (Warning to the vaccine programme) 4.Novel vaccine research regarding cancers and other diseases may produce unexpected products such as killer viruses. (Similar research may produce harmful viruses?) 5.Research reports can be freely published in medical journals and anyone can read them. (Easy provision of information) 6.Simple gene manipulation may lead to the production of novel viruses. (No need of high technology and specialized knowledge) 11. Problems in this paper from the viewpoints of dual-use

13. 12. The Fink Report

14. The Committees 2004 report, Biotechnology Research in an Age of Terrorism, is usually referred to as the Fink Report. The Fink Report contained seven recommendations to ensure responsible oversight for biotechnology research with potential bioterrorism applications. One of these recommendations was to create a National Science Advisory Board for Biodefense within the Department of Health and Human Services to provide advice, guidance, and leadership for a system of review and oversight of experiments of concern. 13. The Fink Report

15. 14. Experiments of concern (Seven categories) Biotechnology Research in an Age of Terrorism, http://books.nap.edu/catalog/10827.html 1.Would demonstrate how to render a vaccine ineffective. This would apply to both human and animal vaccines. 2. Would confer resistance to therapeutically useful antibiotics or antiviral agents. This would apply to therapeutic agents that are used to control disease agents in humans, animals, or crops. Introduction of ciprofloxacin resistance in Bacillus anthracis would fall in this class. 3. Would enhance the virulence of a pathogen or render a nonpathogen virulent. This would apply to plant, animal, and human pathogens. Introduction of cereolysin toxin gene into Bacillus anthracis would fall into this class. 4. Would increase transmissibility of a pathogen. This would include enhancing transmission within or between species. Altering vector competence to enhance disease transmission would fall into this class. 5. Would alter the host range of a pathogen. This would include making nonzoonotics into zoonotic agents. Altering the tropism of viruses would fit into this class. 6. Would enable the evasion of diagnostic/detection modalities. This could include microencapsulation to avoid antibody based detection and/or the alteration of gene sequences to avoid detection by established molecular methods. 7. Would enable the weaponization of a biological agent or toxin. This would include environmental stabilization of pathogens.

16. Ensure that Research is Not Limited Educate the Scientific Community Enhance the Review System for Experiments Rely on Self-governance for Review of Publications Create a National Science Advisory Board for Biodefense Improve Communication between Security, Law Enforcement, and Life Science Organizations Review Physical Containment and Personnel Issues Coordinate International Oversight 15. Important points in the report are …

17. 16. National Science Advisory Board for Biosecurity (NSABB)

18. 17. NSABB ex officios

19. 18. NSABB Charge (1) Criteria for identifying dual use research National guidelines for oversight of dual use research at both local (e.g., Institutional Biosafety Committees) and federal levels Local review and approval processes Criteria/processes for referral of issues to NSABB Strategies for oversight of new classes of experiments and technologies Recommend:

20. 19. NSABB Charge (2) Advice on: Program for biosecurity education and training for all scientists and laboratory workers at federally funded institutions A code of conduct for scientists and laboratory workers in life sciences research National guidelines on communication and dissemination of dual use research methodology and research results Strategies for coordinated international oversight of dual use research

21. 20. Points To Consider in Assessing the Risks and Benefits of Communicating Research Information with Dual Use Potential

22. Dual-use research of concern identified Work conducted in accordance with risk management No dual use potential identified 21. NSABB oversight proposals (1) Major steps in local oversight of dual use life science research

23. CRISP (Computer Retrieval of Information on Scientific Projects) 22. NSABB oversight proposals (2) Examples of points of communication of dual use research during the research process

24. 23. The 2008 Israeli Report The Israeli government recently passed a law regarding dual use life sciences research that enforces mandatory training. (Bill for the Regulation of Research into Biological Disease Agents, 2008. Israel.) Charles Sturt University and the Australian National University recently passed legislation enforcing mandatory training. Most recently, the report of the Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism (WMD Commission), entitled World at Risk, calls for mandatory education of life scientists about dual use research. The Report of the Commission on the Prevention of WMD Proliferation and Terrorism (World at Risk) was released in December 2008. Mandatory education of life scientists about dual use research Israeli system may prove to be a better model for smaller countries

25. 24. University of Maryland project on Controlling Dangerous Pathogens The Controlling Dangerous Pathogens Project at the Center for International and Security Studies at Maryland (CISSM) A proposed international biosecurity oversight system

26. Raise awareness on the dual-use issue and to obtain feedback on its ideas through a series of regional workshops Two key questions 1.What types of dual-use biotechnology research pose the greatest potential danger? 2.How can we manage the risks from such research without impeding scientific progress? 25. University of Maryland project on Controlling Dangerous Pathogens

27. Two key elements 26. University of Maryland project on Controlling Dangerous Pathogens Technically qualified Have undertaken biosecurity training Have nothing in their background 1.National licensing or registration of relevant personnel and research facilities 2.Independent peer review of relevant research activities prior to their initiation Any individual interested in conducting research covered by the oversight system would be required to provide information about their proposed project to an independent oversight body for review and approval Consistent with a recommendation from a US National Academy of Sciences expert group, known as the Fink Committee

28. Research about anthrax genome (Read et al., 2003) Research about SARS genome (Marra et al., 2003) Analysis of hemagglutinin crystal of 1918 type Influenza virus (Gamblin et al., 2004; Stevens et al., 2004) Receptor of anthrax toxin (Santelli et al., 2004) Gene synthesis, synthetic biology (Ball, 2004; Breaker, 2004) Reconstitution of 1918 Spanish Flu viruses (Taubenberger et al., 2005; Tumpey et al., 2005) Botulinum toxin food supply (Wein and Liu, 2005) Genetic changes of Listeria, alter the host range of a pathogen (Wollert et al., 2007) 27. Recent papers of typical dual-use life science research Published in popular journals such as Nature, Science, Cell, PNAS, etc. Some research areas are beyond the category of Fink Report

29. 28. Emerging concept of dual-use research Seven categories of Fink and more

30. 29. Core responsibilities of life scientists regarding dual use research of concern Individuals involved in any stage of life sciences research have an ethical obligation to avoid or minimize the risks and harm that could result from malevolent use of research outcomes. Toward that end, scientists should: Assess their own research efforts for dual use potential and report as appropriate; Seek to stay informed of literature, guidance, and requirements related to dual use research; Train others to identify dual use research of concern, manage it appropriately, and communicate it responsibly; Serve as role models of responsible behavior, especially when involved in research that meets the criteria for dual use research of concern; and Be alert to potential misuse of research.

31. NB: the decision-making in question pertains only to dual-use research in the biological sciences identified as potentially problematic by virtue of coming under one of the pre-established headings of Experiments of Concern. By Professor Seumas Roderick Macdonald Miller, Professor of Philosophy (Charles Sturt University and the Australian National University) 30. Decision-making regarding dual-use dilemmas in the biological sciences Government Independent Authority (i)Individual editor (ii)Corporation (iii)Government Research Centre (i)Individual editor (ii)Corporation (iii)Government Research Centre Individual editor Decision-makers regarding Censorship/Constraint of Material Proposed for Dissemination? Yes No Is Personnel Security Regulation Mandatory? Yes No Is Education & Training Mandatory? Yes No Is Licensing Dual-Use Technology Mandatory? Yes No Mandatory Physical Safety & Security Regulation Government Independent Authority (i)Scientists in University (collegial) (ii)Corporation (iii)Government Research Centre (i)Scientists in University (collegial) (ii)Corporation (iii)Government Research Centre Individual researcher Who are the Decision- makers regarding Im/permissible Research? Governmental Control Independent Authority Institutional & Governmental Control Institutional Control Complete Autonomy of Individual Scientist Option 5Option 4Option 3Option 2Option 1 Options Decisions