Biological Weapons Convention 2019 Meeting of Experts: MX2 ...ver4_MX2+presentation+(2019)_Shino… · Francisella tularensis strain that produces b-endorphin (1993) Expression of

Biological Weapons Convention

2019 Meeting of Experts: MX2

31 July and 2 August, 2019

@ Geneva

Biological risk assessment of leading-edge

life science and its management

Nariyoshi Shinomiya, MD, PhDNational Defense Medical College Research Institute

Japan

Dual Use Nature in Life Science

Life Science Technology

• Development of biological weapons

• Bioterrorism

• Destruction of environment

• Malign purposes

• Unintentional misuse

• Promotion of biotech enterprise

• New therapeutic methods

• Improvement of social welfare

• Initial purpose

• Healthy applications

Dual Use Research of Concern (DURC)

Leading-edge life science technology and DURC

2. Reverse geneticsReconstruction of 1918 Spanish flu virus (2005)

Airborne transmission of H5N1 influenza virus (2012)

3. Synthetic biologyChemical synthesis of poliovirus (2002)

Complete chemical synthesis of bacterial genome (2008)

Creation of a bacterial cell controlled by synthetic genome (2010)

Design and synthesis of minimal bacteria (2016)

Construction of an infectious horsepox virus (2017)

1. Recombinant DNA technologyFrancisella tularensis strain that produces b-endorphin (1993)Expression of hemolysin gene in Bacillus anthracis vaccine strain

Genetic modulation of mousepox virus (2001) (1997)

Fink report (2004)

1. Would demonstrate how to render a vaccine ineffective.

2. Would confer resistance to therapeutically useful antibiotics or

antiviral agents.

3. Would enhance the virulence of a pathogen or render a

nonpathogen virulent.

4. Would increase transmissibility of a pathogen.

5. Would alter the host range of a pathogen.

6. Would enable the evasion of diagnostic/detection modalities.

7. Would enable the weaponization of a biological agent or toxin.

Seven classes of experiments

= All these are related to the aggravation of biological weapons

New framework for influenza

GOF research (2013)US government DURC policy

(2015)

Year

Nu

mb

er

ofp

ub

lish

ed

pa

pe

rs / y

ea

r

Genome editing

Synthetic biology

Pathogenicity

modulation

High throughput

sequencing

Based on PubMed

Trends in emerging life science technologies (1)

NGS

2000DNA synthesizer

1986

Cost reduction

2006

CRISPR/Cas9

2012

2000

Deep learning

Neural network

1980

Expert system

Trends in emerging life science technologies (2)

1956

0

1000

2000

3000

4000

5000

6000

7000

8000

2018

2016

2014

2012

2010

2008

2006

2004

2002

2000

1998

1996

1994

1992

1990

1988

1986

1984

1982

1980

1978

1976

1974

1972

1970

1968

1966

1964

1962

1960

artificial intelligenceArtificial intelligenceN

um

be

ro

fp

ub

lish

ed

pa

pe

rs / y

ea

r

Advanced Biological Agents

Genetically Modified Traditional Agents/

Biochemical Agents

Traditional Agents

Pre-Genomic Era

1999 20202003

Thre

at

Genomic Era

Modified from:Petro, J. B., Plasse, T. R., and McNulty, J. A.: Biotechnology: Impact on Biological Warfare and Biodefense.

BioSecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 1(3): 161-168, 2003.

(http://www.liebertonline.com/doi/abs/10.1089/153871303769201815)

Development of life science technology and

timeline of biological warfare threat

Human Genome

Sequenced (Draft)Human Genome

Sequencing (Completed)

1970’s

1990’s

After 2000 • Synthetic biology

• Genome editing

Dual use problems about

pathogens research

Science Council of Japan

(January 23, 2014)

Section meeting on pathogens research

Proposal for DURC issues in Japan

2012

STRATEGIC PROPOSALPreparedness Framework and Its

Governance of Dual Use Research of

Concern for Promising Progress of

life Science

CRDSCenter for Research and Development Strategy,

Japan Science and Technology Agency

Issues related to biological threat and the relationship

among biosafety/ethics, infection control, and biosecurity

Genome

editing

How to implement effective governance in dealing with dual use

issues among different R&D levels and different stakeholders

“Dual-use issues and the role of life scientists”

Side Event to the 7th Review Conference of the

Biological and Toxin Weapons Convention

December 12th, 2011 Palais des Nations, Geneva

Survey of Universities’ Education for DURC in Japan (2016)

Bachelor course Master/Doctor course

School Fink report BWC,CWCIAP statement

on biosecurityFink report BWC,CWC

IAP statement on

biosecurity

School of

Medicine 26.2% 14.3% 42.9% 23.8% 19.0% 52.4%

School of

Biotechnology 22.0% 19.5% 36.6% 17.1% 19.5% 36.6%

Medicine +

Biotechnology24.1% 16.9% 39.8% 20.5% 19.3% 44.6%

2. Make reference to "Dual use" in current education: Rates

Biosafety (%) Biosecurity (%) Dual use (%)

76.2% 64.3% 50.0%

85.4% 73.2% 43.9%

80.7% 68.7% 47.0%

SchoolSchool of

MedicineSchool of

BiotechnologyMedicine +

Biotechnology

1. Problem recognition by school staff

Total number

80

72

152

SchoolSchool of

MedicineSchool of

BiotechnologyMedicine +

Biotechnology

According to a journalist of “The Guardian” James Randerson, all it took was an invented company name, a mobile phone number, a free email address and a house in north London to receive the order of variola virus DNA by post. The investigation makes clear that anyone, without attempting to prove a link to a legitimate research organisation, can order DNA sequences from any potential pathogen without fear of extensive questioning.In this case the provider company did not realise it was supplying part of the smallpox genome, but many scientists argue that it is the responsibility of companies selling custom-made pieces of DNA to check their orders for potentially dangerous sequences.

Custom DNA synthesis is very easy to order

(June, 2006)

From vaccinia virus to horsepox virus

• Possibility of saving other virus genomes using artificial chromosome

• Possibility of making virulent virus particles from the construct

（2002）

（2018）

After 15 years, horsepox virus was artificially synthesized

Creation of variola virus

has been technically

cleared!

Evaluation item Outline / Policy

1. Gene sequence

screening

• Screen the complete DNA sequence of every synthetic gene order

• Use a common Regulated Pathogen Database (RPD), and the international

sequence reference databanks (i.e., NCBI/GenBank, EBI/EMBL, or DDBJ)

• Screen against all pathogen and toxin genes (the US Select Agents and Toxins

List, the US Commerce Control List, and the EU list of dual-use items)

2. Customer

screening

• Identify data from all potential customers, including at a minimum a shipping

address, institution name, country, telephone number, and email address

3. Record keeping • Retain records of every gene synthesized and delivered for a minimum of 8

years after shipping

4. Order refusal &

reporting

• Reserve the right to refuse to fill any order and to notify other IGSC members

and/or authorities upon identifying potentially problematic orders

• Establish relationships with local and national law enforcement and intelligence

authorities

5. Regulatory

compliance

• Comply with all applicable laws and regulations governing the synthesis,

possession, transport, export, and import of gene synthesis and other products

• Will not synthesize gene sequences unique to Variola virus DNA

6. Consortium

collaborative

activities

• Update annually the IGSC Regulated Pathogen Database

• Include all gene sequences identified as potentially hazardous by authoritative

groups such as the CDC, the Australia Group, and the U.S. and European

governments

Harmonized Screening Protocol© v2.0Gene Sequence & Customer Screening to Promote BiosecurityBy International Gene Synthesis Consortium (19 November 2017)

https://genesynthesisconsortium.org/* The ICGS companies together represent approximately 80% of commercial gene synthesis

capacity world-wide.

1. To properly manage biological risks, timely evaluation of trends

in emerging life science technologies related to this convention

is essential.

2. Construction of a suitable framework for biological risk

assessment and management at the national science council

level as well as at academic conference levels is needed.

3. Recognition of dual use risks in emerging life science fields at

university education levels has been improved in Japan during

these several years.

4. To support healthy development of life science, construction of a

more appropriate biosecurity screening system at service

providing company/consortium levels is required.

5. For increased transparency, information exchange about the

activities related to synthetic biology among different countries

is important.

Conclusions / Recommendations

Thank you very much for your attention!