Dual-Use Examples

Lecture No. 15
Applied Version

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 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 Dangero
us Pathogens’
– Slides 24-26
• Emerging concept of dual-use research
– Slides 27-30
 2. The meaning of dual-use today
The term “dual-use technologies,” primarily applied to tech
nologies with both military utility and viable commercial ap
plications, has acquired a second meaning in the context
of potential weapons development: the tools, skills, equip
ment, and knowledge critical to conducting legitimate rese
arch and development that could be subverted to maliciou
s use. Rapid advances in biology, chemistry, and the infor
mation 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

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 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?
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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
8. Toxins and other bioactive molecules Useful in protecting against disease and BW
9. Detection and identification technologies
10. Human infectious disease patterns
11. Smallpox destruction
12. Drug resistance
13. Disease in agriculture Many were seen as causes of concern
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 Further Inf.
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 pr
otection 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) -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 vacc
inal 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

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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.

Genetically-manipulated • Unexpected toxi

Analysis of the mechanism city
mouse virus
• Inefficacy of pre
sent vaccine pro
gramme
If similar technique were used,
Dual-use research? Human smallpox it stimulates the development
virus 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 g
ene 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 m
anipulating the gene that directly involves in immune response. (The pos
sibility of making new pathogenic viruses using similar concept)
3. The recombinant virus exerted strong immunosuppressive effect to the h
ost that already has acquired immunity to the same virus strain. (Warnin
g to the vaccine programme)
4. Novel vaccine research regarding cancers and other diseases may produ
ce unexpected products such as killer viruses. (Similar research may pro
duce 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

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 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 hum
ans, animals, or crops. Introduction of ciprofloxacin resistance in Bacillus anthracis wo
uld 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 to
xin 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 v
iruses 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 alt
eration 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 …

• 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)

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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

Work conducted in
Dual-use research of
accordance with
concern identified
risk management

No dual use
potential identified
 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 Reg
ulation of Research into Biological Disease Agents, 2008. Israel.)

• Charles Sturt University and the Australian National University recent

ly passed legislation enforcing mandatory training.

• Most recently, the report of the Commission on the Prevention of We

apons of Mass Destruction Proliferation and Terrorism (WMD Commi
ssion), entitled World at Risk, calls for mandatory education of life sci
entists about dual use research. The Report of the Commission on th
e Prevention of WMD Proliferation and Terrorism (World at Risk) wa
s 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

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 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 Option 2 Option 3 Option 4 Option 5
Options
Decisions Complete Autonomy Institutional & Independent Governmental
Institutional Control
of Individual Scientist Governmental Control Authority Control
(i) Scientists in (i) Scientists in
Who are the Decision- University (collegial) University (collegial)
Independent
makers regarding Im/pe Individual researcher (ii) Corporation (ii) Corporation Government
Authority
rmissible Research? (iii) Government (iii) Government
Research Centre Research Centre
Mandatory Physical
Safety & Security No Yes Yes Yes Yes
Regulation
Is Licensing Dual-Use
Technology No No Yes Yes Yes
Mandatory?

Is Education & Training

No No Yes Yes Yes
Mandatory?
Is Personnel Security
No No Yes Yes Yes
Regulation Mandatory?
Decision-makers
(i) Individual editor (i) Individual editor
regarding
(ii) Corporation (ii) Corporation Independent
Censorship/Constraint Individual editor Government
(iii) Government (iii) Government Authority
of Material Proposed
Research Centre Research Centre
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.
References

References