BIOLOGICAL

knowledge & facilities

Dual-Use Management of Biosecurity Threats

dr Stef Stienstra

Active Technology Transfer Europe

Stef.Stienstra@inter.nl.net

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.