Synthetic Biology - biosafety

regulations and assessing risk

(or………)
Brian Crook, Microbiology Team Leader
Health and Safety Laboratory

www.hsl.gov.uk
www.hsl.gov.uk
Agency
AnAn Agency Health
of theof and Safety
the Health and Executive
Safety Executive
 Either:

• How synthetic biology will save

mankind

OR

• Wicked Frankenstein scientists

playing god …again.

An Agency of the Health and Safety Executive

Health & Safety Laboratory (HSL – who
we are, what we do www.hsl.gov.uk)
Located near Buxton, UK
Britain's leading industrial health and safety
facility - an agency of HSE
450 people covering all main science areas,
e.g. microbiology, immunology, chemistry,
engineering, ventilation, psychology,
metallurgy & materials, minerals & fibres,
ergonomics, computational modelling, fire and
explosives, incident photography
Our services to public and private sectors:
– Research and development
– Incident investigation for HSE
– Environmental and biological monitoring
– Risk Assessment and control evaluation
– Training
– Specialist advice and consultancy
– Drafting of guidance and legislation
– Validation and certification
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 HSL : Where we sit

Central Government

HSE
Health and Safety Executive

HSL
Health and Safety
Laboratory
An Agency of the Health and Safety Executive
Health and Safety Legislation relevant
to biological safety

Duty under the law to assess and manage the risks associated
with biological agents, currently…

HEALTH AND SAFETY AT WORK ACT 1974

CONTROL OF SUBSTANCES MANAGEMENT OF HEALTH

HAZARDOUS TO HEALTH AND SAFETY AT WORK
REGULATIONS 2002 REGULATIONS 1999

GENETICALLY CARRIAGE OF REPORTING OF

MODIFIED DANGEROUS INJURIES DISEASES
ORGANISMS GOODS… AND DANGEROUS
(CONTAINED USE) REGULATIONS 2004 OCCURRENCES
REGULATIONS 2000 REGULATIONS 1995

An Agency of the Health and Safety Executive

 CONTROL MEASURES

• COSHH covers both chemical and biological hazards

Every employer shall ensure that the exposure of his employees to

substances hazardous to health is either prevented or, where this is
not reasonably practicable, adequately controlled

• Hierarchy of principles for controlling exposure:

1. Eliminate the risks

2. Control risks at source

3. Minimise the risks by designing suitable systems of work

An Agency of the Health and Safety Executive

 COSHH HIERARCHY

• Elimination
…if the objectives of the work can be met without using a biological agent
• Substitution
…with a less hazardous biological agent

• Engineering controls
…e.g. containment laboratory, safety cabinets, mechanical ventilation
• Safety procedures
…e.g. hand hygiene policy, waste disposal and decontamination
• PPE and RPE
…lab coats, gloves, goggles, respirators
• Vaccination
…is the very last line of defence. if there is reliance on the protection
afforded by a vaccine then other controls are inadequate

An Agency of the Health and Safety Executive

Current UK Regulatory Position
for biological agents

Control of Substances Hazardous

to Health Regulations
Implements 2000/54/EC (Biological Agents Directive)
Notification; Risk Assessment; Inspection; Enforcement

Specified Animal Pathogens Orders

England; Scotland; Wales; NI (SAPO)
Licence implements 2003/85/EC (FMD Directive)
Inspection - License; Inspection - Re-license

Genetically Modified Organisms

(Contained Use) Regulations
Implements 2009/41/EC (GM Contained Use Directive)
Risk Assessment; Notification; Permissioning; Inspection; Enforcement

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How the Regulations fit together

Control of Substances
Hazardous to Health
Regulations

GM
Human
Pathogens Zoonoses

GM
Zoonoses

Genetically Modified
GM
Organisms (Contained Specified Animal
Animal
Use) Regulations Pathogens Order
Pathogens

An Agency of the Health and Safety Executive

 The future – working towards a
Single Regulatory Framework

COSHH GMO (Contained Specified Animal

Schedule 3 Use) Regulations Pathogens Orders

Biological Agents and Genetically

Modified Organisms (Contained
Use) Regulations 2011
Implements 2000/54/EC (Biological Agents Directive)
Implements 2009/41/EC (GM Contained Use Directive)
Implements “Minimum Standards” in 2003/85/EC (FMD Directive)

Combined containment tables (Containment levels 1-4 with derogation*)

Risk Assessment; Integrated Notifications; Permissioning (Class 3 and 4); Inspection; Enforcement
An Agency of the Health and Safety Executive
How this will affect the Approach
to Risk Assessment

Determine hazard group of wild-type BA

(using Approved List or assigned by user)

Carry out a risk assessment

Assign risk classification (class 1-4)

using combined containment tables

Identify any unnecessary control measures

Notify HSE (class 2-4)

Apply for Derogation†

†derogations can be requested for work with any GMMs and

specified animal pathogens but only certain wild-type human
pathogens
An Agency of the Health and Safety Executive
 What does all this mean to
synthetic biology?
• Biological materials are “substances hazardous
to health”;
• At present, synthetic biological agents will be
assessed under GMO regulations;
• In future, likely to be assessed under ‘CU2011’
regulations (similar in principle to GM regs.);
• Either way, there is a need to assess risk,
classify, and assign proportionate controls.

An Agency of the Health and Safety Executive

 Assess, classify, assign –
tell me more
This is how it works with GMM (see SACGM
Compendium of Guidance
http://www.hse.gov.uk/biosafety/gmo/acgm/acgmcomp/part2.pdf):
• Knowledge of risk associated with parent organisms
(recipient, insert, vector) - taking into account
disablement or attenuation;
• Potential for modification to alter host organism
pathogenicity, virulence, infectivity, tropism, host
range, susceptibility to prophylaxis;
• Determine necessary controls (human health and
environment)
• Final classification submitted to HSE for approval.

An Agency of the Health and Safety Executive

Craig Venter’s latest - ‘synthetic
bacterium’ or Trojan Horse?
• Synthesis of Mycoplasma
mycoides in a M. capricolum
cell – uses well defined
organisms and properties;
• Risk can be assessed from
known properties of the
agents involved;
• Provides proof of principle,
but closer to GM (‘top down’)
than synthetic biology
(‘bottom up’)?

An Agency of the Health and Safety Executive

 Assessing the risk properties of a
real synthetic organism
The simplistic view:
• The synthetic agent will comprise a number (n) of
synthetic genomes assembled together to create a self
replicating organism;
• Each individual synthetic genome presents zero risk to
human health and the environment;
• Therefore – n x zero = zero.
However:
• In reality the sum is greater than the individual parts;
• Therefore how do you assess the risk?

An Agency of the Health and Safety Executive

 Regulating new technology –
striking the right balance
• In public consultation, effective regulation
and control considered one of the most
important issues; • While the need to control was
important, regulation should
• Scientists “should not be allowed to
also “not stifle development
regulate themselves”;
and progress of synthetic
• In the UK, it was considered that biology”.
safeguards in place would be effective in
controlling current research, but that
“regulations need to keep apace with
scientific developments to remain
adequate”.

An Agency of the Health and Safety Executive

 How HSE plans to regulate
synthetic biology
• Gather knowledge on current and future activities in the
UK and globally;
• Engage with researchers to understand their current
and future work;
• Use current GMO legislative framework as basis for
regulation;
• Possible changes to regulations will follow GMO risk
assessment principles;
• Continue dialogue with UK researchers to develop a
pragmatic legislative framework with practical guidance.

An Agency of the Health and Safety Executive

 Timeframe and future actions

• HSL, on HSE’s behalf, are currently undertaking

knowledge gathering and making contacts with synthetic
biology research networks;
• Final report back to HSE by end of 2010;
• HSE to use information to develop future guidance
(internal guidelines on assessing applications; external
guidance to researchers);
• YOUR INPUT TO THIS IS VITAL – please tell us how
you will assess risks in your projects.

An Agency of the Health and Safety Executive

 Any questions?

Contact:
• Brian Crook, HSL 01298 218421 brian.crook@hsl.gov.uk
• Claire Bailey, HSL 01298 218427 claire.bailey@hsl.gov.uk
• David Brown, HSE 0151 951 3451 david.brown@hse.gsi.gov.uk

An Agency of the Health and Safety Executive