BIOLOGICAL
knowledge & facilities
Dual-Use Management of Biosecurity Threats
dr Stef Stienstra
Active Technology Transfer Europe
Chem / Bio
OPCW
Toxicology
Industrial agents
Direct effect / lag time
Chemical detection
Environment
BTWC
Disease
‘Natural’ spreading
‘lag time’
Bio/Chem detection
Environment
What is clean after decontamination?
The threat of biological agents……
Fear in the
mind
=
Degradation
Toxicity of several compounds
• compound LD50 (µg/kg)
• Kitchen salt 3.700.000
• Mustard 3.000
• Strychnine 500
• Sarin 20
• Tedrodo toxin 5
• Ricin 0,02
• Tetanus toxin 0,0001
• Botulinum toxin 0,00003
Botox first bacterial toxin FDA
approved for injection Botox approved to treat:
* Cross-eyes
* Uncontrollable blinking
* Cervical dystonia (a neurological
disorder that causes severe neck and
shoulder contractions)
* Moderate to severe frown lines
between eyebrows
.
Botox being studied to treat:
Excessive sweating; Spasticity after a stroke; Back spasms
Headaches
Source: Allergan Inc
July 18 2001 FBI report
>100 bioterror threats a year
June 22&23, 2001 Andrews Air Force Base
The Netherlands: Minister Borst June 14, 2001
“Gezondheidsraad”
Bioterrorism after 11 Sept. 2001
11 September 2001: Terror attack on the World Trade
Center, New York
5 October 2001: Anthrax attacks, Boca Raton, Florida;
afterwards Trenton, New Jersey; Washington DC; New York
Consequences:
17 confirmed anthrax cases
5 suspected cases
10 pulmonary cases
7 cutaneous cases
4 deaths
> 30.000 prophylactic antibiotic treatments,
decontamination of numerous public
buildings
Gave a change towards Security
Media attention overwhelming
9
Research
A Large Outbreak of Legionnaires' Disease at a Flower
Show, the Netherlands, 1999 Jeroen W. Den Boer,*† Ed P.F. Yzerman,‡ Joop Schellekens,* Kamilla D. Lettinga,§ Hendriek C. Boshuizen,* Jim E. Van
Steenbergen,¶ Arnold Bosman,* Susan Van den Hof,* Hans A. Van Vliet,* Marcel F. Peeters,# Ruud J. Van Ketel,§ Peter
Speelman,§ Jacob L. Kool,* and Marina A.E. Conyn-Van Spaendonck*
*National Institute of Public Health and the Environment, Bilthoven, the Netherlands;
In 1999, an outbreak of Legionnaires' disease affected many visitors to a
flower show in the Netherlands. To identify the source of the outbreak, we
performed an environmental investigation, as well as a case-control study
among visitors and a serologic cohort study among exhibitors to measure
exposure to possible sources. Of 77,061 visitors, 188 became ill (133
confirmed and 55 probable cases), for an attack rate of 0.23% for visitors
and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the
exhibition and a sprinkler in hall 8 were culture positive for Legionella
pneumophila. One of three genotypes found in both whirlpool spas was
identical to the isolates from 28 of 29 culture-positive patients. Persons
who paused at the whirlpool spa in hall 3 were at increased risk for
becoming ill. This study illustrates that whirlpool spas may be an
important health hazard if disinfection fails.
Focus on Category A, B, and C
priority pathogens
Focus on:
• Anthrax
• Botulism
• Plague
• Smallpox
• Tularemia
• Viral hemorrhagic fevers
It is not new to use biological
substances as weapon 1754-1763 French and Indian War
Smallpox or chicken pox in blankets
First World War – Anthrax and strengles made horses incapable in moving canons
New lists ‘select agents’in
biosecurity
US – 15
Europe – 96 (list 428/2009)
‘Experiments of concern’ – US = 7
Bioterrorism Agents
Potentially hundreds
Features of most likely agents
Availability
Ease of production
Lethality
Stability
Infectivity
Bioagents
bacteria viruses
prions
bioregulators GMO
animals plants
Humans
toxins
Animals Plants
300 genes are enough
Celera Genomics – Graig Venter
•Living bacterium with only 300 genes
•Perfect for biotech protein
production/identification
•Project stopped due to threat of misuse
•Similar project GM of mouse smallpox in
Australia
Venter’s disease
In PNAS (dec 2003) Craig Venter and Hamilton Smith explain how they have build a perfect virus with standard commercial available DNA-oligonucleotides within 14 days.
Bacteriophage Φ-X174 – 5,386 base pairs
(Eckard Wimmer, synthetic polio virus, 3 years)
To make it secret does not give
Security
The al-Qa`ida Manual “Cookbook”
Same ricin extraction
procedure
RICIN production described in:
• France - United Kingdom (Dec/2002-Mar/2003)
RICIN
Immune response
h
Calcutta, 1997
Immunization/exposure Blood donation
B B
B B
P P
P
P P
. ..
. . . .
.. . . .
Production
B B
B B
B
B Cell expansion
H H
H
H
H
1 2
3
4
5
Immortalization
H 2 P
Gene transfer
In vitro research
Animal research
Clinical Development
Per-c6
Efficacy studies aerosol Single dose IQNPA and IQNLF administered to rabbits
challenged with 100 LD50 spores (aerosol); 24h post-exposure.
Studies performed at Battelle.
Time of
treatment
(hrs)
IQNPA
dosage
(mg/kg)
% Survival
(PA alone)
IQNLF
dosage
(mg/kg)
% Survival
(LF alone)
+24 5 100 15 67
+24 2.5 50 7.5 21
+24 1.25 33 3.75 33
+24 0.625 NA 1.88 NA
+24 0.3125 NA 0.94 NA
+24 0 0 0 0
+24 2.5 50 5 13
+24 2.5 50 2.5 50
+24 2.5 50 1.25 0
+24 2.5 50 0.625 NA
+24 0 0 0 0
% Survival
(Combined)
100
100
67
50
33
0
88
88
63
88
0
Studies performed with suboptimal dosages to be able to demonstrate improvement
Scientific and technological developments in the
fields of microbiology, genetic engineering,
molecular biology and biotechnology
Dual Use Dilemma
Potential for
developing
novel detection toolkits, vaccines, drugs,etc.
Potential for misuse to create novel warfare and BT agents
Rifle launched non lethal cargo dispenser
US patent 6,523,478
(USPTO 2003)
crowd control agents, biological agents, chemical agents..
Who is the owner of the
problem?
One person responsible for threat
management process
How often is the threat/risk assessment
updated?
How would the organisation know if the
risk/threat has changed – what is the
analysis, review and communication
route?
H5N1 in Rotterdam
Suddenly the group of Prof Fouchier was
world news when Prof Ron Fouchier was
offering his manuscript for publication
for publication in Science.
It was about mutations which enabled the
H5N1-virus (bird flu virus) to be
transferable between mammals.
Simultaneously an American group had
the same issue with Nature. And finally
they published two months earlier.
Dual Use
American National Science Advisory Board for
Biosecurity (nsabb). Its description is as
follows: ‘Research that, based on current
understanding, can be reasonably anticipated
to provide knowledge, products or technologies
that could be directly misapplied by others to
pose a threat to public health, agriculture,
plants, animals, the environment or material.’
Dual use research is in the context of
biosecurity is research which:
1. that, based on current information,
utilises or can reasonably be expected to
lead to knowledge, products or
technologies that can be misused
2. that involves an identifiable threat and a
significant risk of misuse
3. that can have serious consequences for
society (health, safety, agriculture, plants,
animals, the environment or property)
Types of code
Type / Name
Aspirational codes
> Code of ethics
Educational/ Advisory codes
> Code of conduct
Enforceable codes
> Code of practice
Main Aims
Alert; set realistic or idealistic standards
Provide guidelines, raise awareness & debate; foster moral agents
Prescribe or proscribe certain acts
A Code of Conduct for Biosecurity
Required by
Biological and Toxin Weapons Convention (btwc), which was ratified in 1972
> Statement on Biosecurity issued
by the Inter Academy Panel (iap) in 2005
68 academies of science signed the iap’s ‘Statement on Biosecurity’.
Aim
The aim of the code of conduct is to prevent life sciences research or its application from directly or indirectly contributing to the development, production or stockpiling of biological weapons, as described in the Biological and Toxin Weapons Convention (btwc), or to any other misuse of biological agents and toxins.
TARGET GROUP Professionals engaged in the performance of biological,
biomedical, biotechnological and other life sciences research;
Organisations, institutions and companies that conduct life sciences research;
Organisations, institutions and companies that provide education and training in life sciences;
Organisations and institutions that issue permits for life sciences research or which subsidise, facilitate and monitor or evaluate that research;
Scientific organisations, professional associations and organisations of employers and employees in the field of life sciences;
Organisations, institutions and companies where relevant biological materials or toxins are managed, stored, stockpiled or shipped;
Authors, editors and publishers of life sciences publications and administrators of websites dedicated to life sciences.
RAISING AWARENESS
Devote specific attention in the education in life sciences to the risks of misuse of biological, biomedical, biotechnological and other life sciences research and the constraints imposed by the btwc and other regulations in that context.
Devote regular attention to the theme of biosecurity in professional journals and on websites.
ACCOUNTABILITY AND
OVERSIGHT
Report any finding or suspicion of misuse
of dual-use technology directly to the
competent persons or commissions.
Take whistleblowers seriously and ensure
that they do not suffer any adverse effects
from their actions.
INTERNAL AND EXTERNAL
COMMUNICATION
Provide (additional) security for internal
and external e-mails, post, telephone
calls and data storage concerning
information about potential dual-use
research or potential dual-use materials.
ACCESSIBILITY
Carry out (additional)
screening with attention to
biosecurity aspects of staff
and visitors to institutions
and companies where
potential dual-use life
sciences research is
performed or potential
dual-use biological
materials are stored.
USAMRIID Test
Facility
SHIPMENT AND TRANSPORT
Carry out (additional) screening with
attention to biosecurity aspects of
transporters and recipients of potential
dual-use biological materials, in
consultation with the competent
authorities and other parties.
RESEARCH AND
PUBLICATION POLICY
Screen for possible dual-use aspects during the application and assessment procedure and during the execution of research projects.
Weigh the anticipated results against the risks of the research if possible dual-use aspects are identified.
Reduce the risk that the publication of the results of potential dual-use life sciences research in scientific publications will unintentionally contribute to misuse of that knowledge.
ISO Standards
ISO 31000-2009 Risk Management –
Principles and Guidelines
ISO Guide 73-2009 Risk Management –
Vocabulary
ISOIEC 31010-2009 Risk Management –
Risk assessment techniques
Dutch situation after H5N1
publication
Export control on scientific research papers
based on: ‘besluit strategische goederen’.
LOWI – Landelijk Orgaan Wetenschappelijke
Integriteit. – complaints
CCMO - Centrale Commissie Mensgebonden
Onderzoek.
COGEM – Commissie Genetische modificaties.
Adviescommissie Biosecurity bij Onderoek in de
Levenswetenschappen (www.bureaubiosecurity,nl/Missie-Taken )
Gap between Science ad
Security
Code of Conduct was known and
followed
Export licence (H5N1 publication 1rst )
National Biosecurity Centre
Monitoring relevant developments in the field of biosecurity;
Coordinating the publication of information and educational materials,
Including maintaining a website with up-to-date information;
Organising conferences;
Maintaining contacts with relevant actors in the government and civil society;
Consulting experts who can provide advice on whether the results of potential
Dual use life science research should be published;
Performing regular evaluations of awareness of and compliance the with the Biosecurity Code of Conduct.
Five points of attention in the
management of risk and uncertaincy
1. think in the good and bad way
2. incorporate socialpsychological
aspects of potential threat
3. calculate risk comparisions
4. accept uncertaincy
5. organize the management of
uncertaincy risks
Biosecurity, Biosafety, Biorisk
To keep bad bugs from the people
To keep bad people from the bugs
The probability or chance that a
particular adverse event, accidental
infection or unauthorized access, loss,
theft, misuse, diversion or intentional
release, possibly leading to harm, will
occur
Any questions?
Neuroscience
The Royal Society, Neuroscience, Conflict
and Security. RS Policy Document 06/11.
Royal Society,London 2012.
The report states:
Neuroscience should be considered as a focal
topic in the science and technology review
process of the BTWC because of the risks of
misuse for hostile purposes in the form of
incapacitating weapons.