Draft Lecture No 14

By

Malcolm Dando

I. Outline

• The concept of dual-use• Slides 2 - 6

• The Fink Committee Report– A. Objective and structure of the report

• Slides 7 - 10

– B. Recommendations of the report• Slides 11 - 14

– C. Experiments of concern• Slides 15 - 20

2. Dual-Use (i)

• Traditionally the concept of ‘dual-use’ described technologies developed by the military that came to have civil uses. The internet is an example of a military technology which was used in this way.

• Now, in regard to the life sciences, the concept refers to materials, technologies and knowledge developed for benign civil purposes that might be misused by others for hostile purposes.

3 Dual-Use (ii)

• Newsweek 2007– “…Just as physics shocked the world in the 20th

century, it is now clear that the life sciences will shake up the world in the 21st. In a handful of years, your doctor may be able to run a computer analysis of your personal genome to get a detailed profile of your health prospects….A new technology called RNA interference may also allow your doctor to control how your DNA is ‘expressed’, helping you circumvent potential health risks…”

4. Dual-Use (iii)

• Bioregulators as instruments of terror– “…Bioregulators are structurally diverse

compounds that are capable of regulating a wide range of physiologic activities, such as bronchial and vascular tone, muscle contraction, blood pressure, heart rate, temperature, and immune responses. These substances can be harmful, however, in large concentrations or if modifications to them bring about changes in the nature or duration of their action…”

5. Dual-Use (iv)

• Some examples of bioregulators that could be misused– Cytokines

• E.g. IL-1, IL-6

– Eicosanoids• E.g. PGD2, LTC4

– Neurotransmitters and hormones• E.g. Catecholamines, Neuropeptides, Insulin

– Plasma proteases• Kallikrein, bradykinin

6. Dual-Use (v)

• Advantages of Bioregulators to attackers– Readily available– Clinical effects are nonspecific– Rapid onset of action– Not on standard list of threat agents– No vaccines available– Potential for widespread dissemination

7. The Fink Committee Report (Ai)

• Biotechnology Research in an Age of Terrorism– “Although the National Academies have had many

reports on national security, this is the first to deal specifically with national security and the life sciences….much has happened to justify an examination of the life sciences in this contest - the discovery of nations with clandestine research programs dedicated to the creation of biological weapons, the anthrax attacks of 2001, the rapid pace of progress in biotechnology, and the accessibility of these new technologies…”

8. The Fink Committee Report (Aii)

• The committee’s view of the dual-use problem– “…Our committee addressed one important part of

this spectrum…of possible misuse: the capacity for advanced biological research activities to cause disruption or harm... Broadly stated, that capacity consists of two elements:

• (1) the risk that dangerous agents that are the subject of research are stolen or diverted for malevolent purposes; and (2) the risk that the research results,knowledge, or techniques could facilitate the creation of ‘novel’ pathogens with unique properties or create entirely new classes of threat agents…”

9. The Fink Committee Report (Aiii)

• The international dimension– “Although the focus of the report is on the

United States, this country is only one of many pursuing biotechnology research at the highest level….It is entirely appropriate for the United States to develop a system to provide oversight of research activities domestically, but the effort will ultimately afford little protection if not adopted internationally…”

10.The Fink Committee Report (Aiv)

• The Structure of the report– 1. Introduction– 2. The evolving regulatory environment for

life sciences research in the 21st century– 3. Information restrictions and control

regimes– 4. Conclusions and recommendations

11. The Fink Committee Report (Bi)

• Recommendations of the report– “1. Educating the Scientific Community

• We recommend that national and international professional societies and related organizations and institutions create programs to educate scientists about the nature of the dual-use dilemma in biotechnology and their responsibilities to mitigate its risks.”

12. The Fink Committee Report (Bii)

• “2. Review of Plans for Experiments– We recommend that the Department of Health and

Human Services (DHHS) augment the already established system of review of experiments involving recombinant DNA conducted by the National Institutes of Health to create a review system for seven classes of experiments (the Experiments of Concern) involving microbial agents that raise concerns about their potential for misuse.”

13. The Fink Committee Report (Biii)

• 3. Review at the Publication Stage– “We recommend relying on self-governance by

scientists and scientific journals to review publications for their potential national security risks.

• ….publication of research results provides the vehicle for the widest dissemination, including to those who would misuse them. It is thus appropriate to consider what sort of review procedures can be put in place at the stage of publication to provide another layer of protection…”

14. The Fink Committee Report (Biv)

• “4. Creation of a National Science Advisory Board for Biodefense– We recommend that the Department of

Health and Human Services create a National Science Advisory Board for Biodefense (NSABB) to provide advice, guidance and leadership for the system of review and oversight we are proposing.”

15. The Fink Committee Report (Ci)

• “The committee identified seven classes of experiments that it believes illustrate the types of endeavors or discoveries that will require review and discussion by informed members of the scientific and medical community before they are undertaken or, if carried out, before they are published in full detail…”

16. The Fink Committee Report (Cii)

• “The seven areas of concern listed here only address potential microbial threats….Over time, however, the Committee believes that it will be necessary…to expand the areas of concern to cover a significantly wider range of potential threats to humans, animals or crops…”

17. The Fink Committee Report (Ciii)

• Experiments of concern would be those that– 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 into this class.”

18. The Fink Committee Report (Civ)

• “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 the 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.”

19. The Fink Committee Report (Cv)

• “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 aviod detection by established molecular methods.”

20. The Fink Committee Report (Cvi)

• “7. Would enable the weaponization of a biological agent or toxin. This would include environmental stabilization of pathogens.”

• The report notes that– “All of the experiments that fall within the seven

areas of concern should currently require review by an Institutional Biosafety Committee (IBC)…We thus recommend relying on the system of IBCs as the first review tier for experiments of concern..”