Transcript C14. Dual-Use: The Fink Report

Dual-Use Examples
Lecture No. 15
Applied Version
1. Outline
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The meaning of dual-use today
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Slides 1-7
Typical examples of dual-use research
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Slides 8-11
The Fink Report
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Slides 12-20
The NSABB 2007 Oversight proposals
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Slides 21-22
The 2008 Israeli Report
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Slide 23
University of Maryland project on ‘Controlling
Dangerous Pathogens’
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Slides 24-26
Emerging concept of dual-use research
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Slides 27-30
2. The meaning of dual-use today
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
3. Scientist’s honor and destroyer’s dishonor
（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?
4. Start point of the problems
Good research projects, Excellent results
But …
we cannot exclude the possibility of
hostile misuse
Dual use dilemmas
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 researcher’s 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.
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
.
7. Dual-use concern is not an unrealistic
issue but a real problem
• The UK’s detailed science and technology review covered 23 separate topics
（ Biological and Toxin Weapons Convention; The Fifth Review Conference of 2001-2002）
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
Useful in protecting against disease and BW
8. Toxins and other bioactive molecules
9. Detection and identification technologies
10. Human infectious disease patterns
11. Smallpox destruction
12. Drug resistance
Many were seen as causes of concern
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
8. Sign of dual-use problems in life science research
- Concerns about hostile misuse of bioscience
Examples of dual-use research (Papers in a gray zone)
(1) Genetic manipulation of 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.
The title appears as if “An improvement in anthrax vaccine”
But … the truth was the addition of toxin genes to the anthrax vaccine
(2) b-endorphin production in Francisella tularensis
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.
Combination of biological agent and bioregulator
The possibility of making a new bioweapon?
9. A typical example of dual-use dilemma in scientific research
10. Genetically manipulated new virus showed
unexpectedly strong virulence to kill the mice
• 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.
Analysis of the mechanism
Dual-use research?
Genetically-manipulated
mouse virus
• Unexpected toxicity
• Inefficacy of present
vaccine programme
If similar technique were used,
Human smallpox virus it stimulates the development
of ultimate biological weapon?
Refer to Lecture 13: Dual-Use Example 1: Mousepox
11. Problems in this paper from the viewpoints of
dual-use
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)
12. The Fink Report
13. The Fink Report
• The Committee’s 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.
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.
15. Important points in the report are …
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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
16. National Science Advisory Board for Biosecurity (NSABB)
17. NSABB ex officios
18. NSABB Charge (1)
Recommend:
• 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
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
20. Points To Consider in Assessing the Risks and Benefits of
Communicating Research Information with Dual Use Potential
21. NSABB oversight proposals (1)
Major steps in local oversight of dual use life
science research
Dual-use research of
concern identified
No dual use
potential identified
Work conducted in
accordance with
risk management
22. NSABB oversight proposals (2)
Examples of points of communication of dual use
research during the research process
＊CRISP (Computer Retrieval of Information on Scientific Projects)
23. The 2008 Israeli Report
Mandatory education of life scientists about dual use research
• 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.
Israeli system may prove to be a better model for smaller countries
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
25. University of Maryland project on
‘Controlling Dangerous Pathogens’
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?
Raise awareness on the dual-use issue and to
obtain feedback on its ideas through a series of
regional workshops
26. University of Maryland project on
‘Controlling Dangerous Pathogens’
Two key elements
1. National licensing or registration of relevant personnel
and research facilities
• Technically qualified
• Have undertaken biosecurity training
• Have nothing in their background
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
27. Recent papers of typical dual-use life
science research
① Research about anthrax genome (Read et al., 2003)
② Research about SARS genome (Marra et al., 2003)
③ Analysis of hemagglutinin crystal of 1918 type Influenza virus
(Gamblin et al., 2004; Stevens et al., 2004)
④ Receptor of anthrax toxin (Santelli et al., 2004)
⑤ Gene synthesis, synthetic biology (Ball, 2004; Breaker, 2004)
⑥ Reconstitution of 1918 Spanish Flu viruses
(Taubenberger et al., 2005; Tumpey et al., 2005)
⑦ Botulinum toxin food supply (Wein and Liu, 2005)
⑧ Genetic changes of Listeria, alter the host range of a pathogen (Wollert et al., 2007)
• Published in popular journals such as Nature, Science, Cell, PNAS, etc.
• Some research areas are beyond the category of Fink Report
28. Emerging concept of dual-use research
Seven categories of Fink
and more
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.
30. Decision-making regarding dual-use
dilemmas in the biological sciences
Option 1
Options
Decisions
Complete Autonomy
of Individual Scientist
Option 2
Option 3
Institutional Control
Institutional &
Governmental Control
(i)
(i)
Option 4
Option 5
Independent
Authority
Governmental
Control
Scientists in
University (collegial)
(ii) Corporation
(iii) Government
Research Centre
Independent
Authority
Government
Who are the Decisionmakers regarding
Im/permissible
Research?
Individual researcher
Scientists in
University (collegial)
(ii) Corporation
(iii) Government
Research Centre
Mandatory Physical
Safety & Security
Regulation
No
Yes
Yes
Yes
Yes
Is Licensing Dual-Use
Technology
Mandatory?
No
No
Yes
Yes
Yes
Is Education & Training
Mandatory?
No
No
Yes
Yes
Yes
Is Personnel Security
Regulation Mandatory?
No
No
Yes
Yes
Yes
Individual editor
(i) Individual editor
(ii) Corporation
(iii) Government
Research Centre
(i) Individual editor
(ii) Corporation
(iii) Government
Research Centre
Independent
Authority
Government
Decision-makers
regarding
Censorship/Constraint
of Material Proposed
for Dissemination?
By Professor Seumas Roderick Macdonald Miller, Professor of Philosophy (Charles Sturt University and the Australian National University)
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.