This is joint policy guidance from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC).
Introduction
BBSRC and MRC are committed to supporting research of the highest quality to increase understanding of biological systems, improve health and prevent disease. This includes innovative, ambitious and disruptive research that has the potential to deliver beneficial outcomes to society.
Responsible research and innovation and good research practice are essential elements for ensuring that the UK’s people, economy, food system and ecosystems are protected from harm. We have rigorous processes in place for ensuring that the research we fund is scrutinised to demonstrate that it conforms to all relevant ethical, legal and regulatory requirements, and that the research organisations where it takes place have robust policies and processes to support its delivery.
Our approach fits within a broader multilayer oversight system in the UK of complementary governance mechanisms. This includes regulatory and legal requirements to safeguard against the risks of research causing harm (see Appendix).
In this statement, we set out our expectations for the people and organisations we fund for managing research with potential misuse risk. We also outline what we will do as funders to minimise the potential risks of harm arising from the research that we support.
Scope
This statement applies to all research-related activities funded by BBSRC and MRC, regardless of where the research takes place or the funding mechanism by which it is supported. This includes internationally collaborative research, and research tools and technologies where they intersect with the biological and biomedical sciences.
This statement distinguishes between research that poses a risk of misuse and ambitious research that is considered ‘high risk’ due to uncertainty of outcomes.
This statement should be considered alongside resources available from the UKRI Good Research Resource Hub so that a holistic responsible research approach is taken when planning and undertaking research.
Definition of research with potential misuse risk
For the biological and biomedical sciences, we define research with potential misuse risk as research that is undertaken to provide benefits but may have the potential to be used for harmful purposes, cause harm through accidental release, or be targeted for malicious intent. This includes dual-use research of concern (see Terminology and Definitions, Appendix), such as experiments dealing with the threats posed by a pathogen or a toxin.
The following are some examples of research with potential misuse risk.
Harmful agents, including human, animal, and plant pathogens
Examples include:
- research regulated under UK law or regulations, or equivalent international law or frameworks to which the UK is signatory that govern potentially hazardous agents and materials
- research that utilises approaches to increase or alter pathogen host range or tissue or organ tropism, disease severity or resistance to therapeutics, to further our understanding of the pathogen’s biology or pathogenicity (sometimes termed ‘gain of function research of concern’)
- research involving the modulation of host biology that increases disease susceptibility, severity, or transmissibility, or evasion of detection methods
- studies on pathogen dispersal dynamics, for example modelling of airborne transmission
- isolation of uncharacterised microorganisms from wild animals that may have potential for zoonotic transmission
- research that may inform the design and synthesis of toxins or inform the efficacy of toxins in the disruption of biological processes
Predictive, computational and synthesis technologies, and novel methodologies
Examples include the:
- use of computational, and predictive technologies in pathogen or toxin-relevant research, such as artificial intelligence (AI), molecular modelling, and protein domains prediction. For example, computational design or redesign of pathogenicity-related genotypes, or AI-driven experimental design without human intervention (in this context convergence of AI with Engineering Biology)
- use of gene synthesis technologies in pathogen or toxin-relevant research, such as genetic sequence synthesis in vitro, and 3D bioprinting. For example, use of gene sequence synthesis technology to confer novel pathogenic properties on microorganisms or towards resurrection of extinct pathogens or their pathogenic traits
- sharing of biological data that pertains to known or anticipated ‘sequences of concern’ (SOCs), as defined under UK government screening guidance (see Appendix)
- unrestricted access to predictive, computational and synthesis technologies that may enable research with potential misuse risk
Engineered organisms
Examples include research:
- introducing pathogenic or toxin-related traits into otherwise benign biological agents
- utilising genetic technologies for gene drive applications
- towards the development of fully synthetic microorganisms that are capable of self-replication or reproduction
- towards the development of organisms with biomolecular chirality reversed from that of naturally occurring life on Earth (‘Mirror Life’ organisms)
Principles
BBSRC and MRC, as part of UKRI, have a responsibility to ensure that the research we fund is aligned with good research practice and creates benefits for society.
Governance and management of research with potential misuse risk should also be guided specifically by the following principles.
Self-governance by individual researchers, their institutions, and research communities
Freedom of scientific inquiry is a fundamental principle that enables the advancement of knowledge for societal benefits. However, individual researchers, their organisations, and the relevant research community, have a responsibility to minimise and mitigate the potential for harm or misuse.
This includes the:
- decision on whether to go ahead with the research
- undertaking of pilot studies to collect preliminary data
- development, implementation, and oversight of best practice approaches for the research area
Careful consideration must be given to ethical issues, potential unintended consequences, balanced against the risk of not realising benefits if the research is not carried out.
Compliance with UK legislation and strategic frameworks
The UK has domestic legislation and international commitments to ensure biosecurity in biological research. Researchers must be aware of relevant pieces of UK legislation and plan how they will ensure compliance during the project concept stage. Researchers should also consider how the UK’s international commitments (see Appendix) relate to their research.
A proportionate, risk-aware research culture
A risk-benefit analysis must be undertaken at project concept stage to ensure that the anticipated benefits significantly outweigh the risks of proceeding with the research, for example balancing the risks and benefits of research to counteract a clear and present biological threat. Risk management approaches must align with the regulatory requirements for the protection of people and the environment from biological agents.
Risk analysis should also consider the choice of location for conducting the research, which must take into account biological security and trusted research considerations for international collaborations. Consideration must also be given to which populations and groups will benefit from the expected research outcomes.
Where the research goes ahead, resources and efforts for risk management should be proportionate to the risk level identified. Risk management must also include provision for identifying any new risks that arise as the research progresses. Appropriate control measures must be put in place where a risk cannot be avoided.
Alternative approaches
Consideration must be given as to whether a research approach with potential misuse risk is the only route by which to answer a research question or produce the desired knowledge. When designing and undertaking a study, alternative lower-risk experimental strategies must be considered and explored first, where feasible, before progressing with higher risk elements of the project where these cannot be avoided. For example, in virology research, tropism changes or entry mechanisms can be explored using pseudoviruses or in conditional viruses that can only replicate in the lab.
Responsible sharing of research findings
Open research is fundamental to maximising the public benefits of science. It embodies the timely and open sharing of research findings, to open participation in, and access to, the research lifecycle. It also helps to ensure that researchers are given due recognition for their work.
In the context of research with potential misuse risk, the sharing of knowledge, research findings, data, and biological materials must be done in a responsible way, to ensure that national security and biological security, including all legal requirements, are considered before knowledge-sharing or publication.
Internationally collaborative research and research taking place outside the UK
Global research and collaborations increase innovation, impact and research quality, but could also introduce security, ethical, reputational and legal compliance risks, including misappropriation or use of UK-generated outcomes and knowledge by third-party actors overseas.
International research and collaborations we fund must take place in line with the UK’s current national security and biological security requirements and follow UKRI’s principles for trusted research and innovation. Research conducted overseas, either through collaboration or direct funding of the overseas research, and the organisations we fund hosting such research, must meet UK standards and requirements. It must also follow the equivalent local regulations for biological security, biosafety and good research practice, adhering to the stricter of these standards where regulations differ.
Public trust and engagement
Opportunities should be considered for undertaking public engagement and dialogue before or during research with potential misuse risk to:
- build trust
- inform decision-making
- enhance research relevance
- promote understanding
- engage with society on ethical considerations
Public engagement may be included as a costed and justified element of a research grant application.
Roles and responsibilities
Researchers including peer reviewers, and research organisations
Planning the research
Researchers and their organisations must ensure that research with potential misuse risk is conducted responsibly and complies with all legal and regulatory requirements, in line with the principles of this statement. All necessary approvals must be in place before commencing.
When designing research, consideration must first be given to alternative approaches to avoid unnecessary risks.
Organisations must be able to provide evidence that their internal research governance processes enable robust measures to safeguard against the misuse of research. This includes providing:
- a secure research environment
- appropriate facilities to manage the risks arising from the research
- a risk management approach, which should be scaled appropriately to the risk level and potential risk impact, and meet any regulatory requirements
A formal internal, project-specific risk assessment and management approach should be applied from the outset of research planning and include active monitoring for new or additional risks arising during the work. All risks must be mitigated appropriately.
Before beginning any research with potential misuse risk, researchers and their organisations are encouraged to seek independent expert advice and independent oversight of their risk management approach (for example, through membership in their local safety committees).
The risk management approach may also be linked to the departmental or organisational risk register, where appropriate.
Applying for grant funding
Applicants must ensure that they consider and identify any potential risks of misuse or unintentional or accidental harm arising from the proposed research. In line with our processes, applicants should demonstrate this in answering questions relevant to good research practice in the UKRI grant application process.
Throughout the research project
Researchers must consider seeking re-approval for their research from the relevant authority where novel biological properties are bestowed on experimental biological agents during a study with potential misuse risk. This must be considered particularly where unanticipated phenotypes with an increased risk profile are generated during the research.
We expect researchers and their organisations to undertake regular review of their project-specific risk assessments (for example, as part of annual review or more frequently if needed). Grant holders must notify BBSRC and MRC, and any relevant authorities, of any significant changes to their project, including the increase in the level or scale of a misuse risk, or any new risks arising during the research project not anticipated at the outset.
Researchers who have concerns about potential misuse risks in ongoing or planned research undertaken by others are encouraged to raise concerns through appropriate institutional channels. Research organisations should offer channels by which such concerns can be raised, in line with UKRI expectations.
Reporting research outcomes and sharing with others
For research with potential misuse risk, researchers must take a responsible approach to consider the risk of materials, sensitive data and know-how being shared unintentionally, or without consent, with third parties that could use the knowledge to cause harm or threaten national security. This also aligns with our expectations for trusted research and innovation, when collaborating internationally. Beyond these considerations, we expect researchers to follow our open research policies. In some circumstances, such as public health emergencies, we may require that sharing of publishable findings is expedited.
Expert reviewers, including members of funding committees
When asked to review research with potential misuse risk, reviewers must consider whether the research is justified and whether alternative approaches, risks and ethics have been considered adequately. Reviewers must raise any concerns in their reviews, or when making funding recommendations.
BBSRC and MRC
We aim to ensure that our grant application and review processes and funding terms and conditions enable thorough consideration of research with potential misuse risk. This includes provisions to ensure that risks of research misuse or accidental harm arising have been identified and will be managed appropriately. We take a proportional approach that avoids over-management of low-risk scenarios and does not unduly impede higher risk research, for example when addressing a clear and present biological threat. This prevents unnecessary bureaucracy while ensuring that each proposal receives adequate scrutiny and includes the following.
Application process questions
Questions on ethics and responsible research and innovation, which seek evidence of the applicants having considered the potential risks of their research and draw out good research practice aspects in the proposed research.
Applicant guidance
Ensuring applicants know what is expected of them and how to write applications that involve research with a potential misuse risk.
Expert reviewers’ and funding committees’ guidance
To request reviewers to consider and comment on potential harms, or ethical aspects during the expert review of research with potential misuse risk, raise any concerns and identify, where relevant, any outstanding issues related to risk or ethics.
Approving research funding
In approving funding, BBSRC and MRC will consider any research misuse concerns raised by reviewers or our funding panels. Where necessary, we will work with grant assessors, ethics experts and grant recipients to address these before awarding the funding. This may include:
- seeking additional expert opinion on biological security and ethical issues
- requiring that a formal risk assessment of the project recommended for funding be undertaken before commencing research
- seeking assurance from the researcher or research organisation about specific risk management approaches that will be taken for the research
- enabling our funding committees to consider conditional recommendations of funding
- making funding contingent on it being reviewed by the local safety committee or another appropriate body
Terms and conditions
UKRI’s standard terms and conditions of funding set out our general expectations for responsible research and innovation, including biosafety. For research with potential misuse risk, we may also add specific conditions of award to gain additional assurance on ethical or biological security aspects, including the right to follow up on risk management with researchers and their organisations during the project lifetime, according to the scale of risk.
Ask a question about this statement
Questions and comments on this statement can be emailed to:
We aim to respond within 10 working days.
Appendix
Terminology and definitions
Biological security
Biological security refers to measures that prevent the misuse (whether deliberate or accidental) of biological materials, data, or technologies in ways that could harm human, animal, or environmental health.
Biosafety
Biosafety is the safe working practices associated with handling of biological materials, particularly infectious agents. It addresses containment principles, technologies and practices that are implemented to prevent the unintentional exposure to pathogens and toxins, or their accidental release. Responsible laboratory practices, including protection, control and accountability for valuable biological materials will help prevent their unauthorised access, loss, theft, misuse, diversion, or intentional release. WHO definition of biosafety.
Dual-use research of concern
Dual-use research of concern describes research that is intended to provide a clear benefit, but which could easily be misapplied to do harm. It encompasses everything from information to specific products that have the potential to create negative consequences for health and safety, agriculture, the environment, or national security. WHO definition of dual-use research of concern.
Gain of function
This describes research that changes the genome of an organism to enhance certain biological functions. Research using gain of function approaches in pathogens (sometimes termed ‘gain of function research of concern’) can contribute towards combating diseases, through improving our understanding of pathogenesis, but also has inherent public health and environmental risks via misuse or accidental release.
Research misuse
Some research involves materials, methods or technologies or generates knowledge or applications that could be misused. Although such research is carried out with benign intentions, it has the potential to harm humans, animals or the environment and may have substantial negative impacts on the security of individuals, groups or states. European Commission, 2021 Guidance Note – Potential misuse of research (PDF 212 KB).
Trusted research and innovation
Trusted research and innovation is a term that denotes protecting the UK’s intellectual property, sensitive research, people and infrastructure from potential theft, manipulation, and exploitation, including as a result of interference by hostile actors.
UK legislation
This section provides an overview of some key relevant legislation. It is not an exhaustive list. Researchers should check whether other UK legislation applies to their research.
Anti-Terrorism, Crime and Security Act 2001 (ATCSA)
Part 7 regulates the ability of sites including universities and science research laboratories to obtain, store and work with certain pathogens and toxins. Section 58 notes the pathogens and toxins that could be used in an act of terrorism to endanger life or cause serious harm to health.
Anti-Terrorism, Crime and Security Act 2001 (ATCSA)
Control of Substances Hazardous to Health Regulations 2002 (COSHH)
Requires employers to prevent or control exposure to substances that are hazardous to health, including the protection of workers from risks related to exposure to hazardous biological agents at work. This requires the UK to classify biological agents that are or may be a hazard to human health. The Approved List of biological agents provides the classification of biological agents as referred to in COSHH.
Control of Substances Hazardous to Health Regulations 2002 (COSHH)
Genetically Modified Organisms (Contained Use) Regulations 2014
Ensures the safety of people doing biological research and the environment. Those undertaking research on certain pathogens must notify the Health and Safety Executive, undertake a risk assessment and study specific organisms in a laboratory with a biosafety containment level that corresponds to the potential risks associated with that research.
Genetically Modified Organisms (Contained Use) Regulations 2014
Specified Animal Pathogens Order 2008 (SAPO)
Regulates animal pathogens that are not endemic to the UK. SAPO prohibits any person from having in their possession any specified animal pathogen listed in Part 1 of Schedule 1 of SAPO without a licence. Those who wish to possess or work with a specified animal pathogen or a carrier in England, Scotland or Wales need to complete an application for a SAPO license. SAPO licenses are issued by the Health and Safety Executive on behalf on Defra and the devolved administrations.
Specified Animal Pathogens Order 2008 (SAPO)
Biological Weapons Act 1974
Prohibits the development, production, stockpiling, acquisition or retention of any biological agent or toxin of a type and in a quantity that has no justification for prophylactic, protective or other peaceful purposes or any weapon, equipment or means of delivery designed to use biological agents or toxins for hostile purposes or in an armed conflict.
National Security and Investment Act 2021
The National Security and Investment Act gives the government powers to scrutinise and intervene in business transactions, such as takeovers, to protect national security, while providing businesses and investors with the certainty and transparency they need to do business in the UK.
International commitments
The UK also plays an active role in promoting biosecurity through international commitments (not an exhaustive list).
The Biological and Toxins Weapons Convention
The Biological and Toxins weapons convention (BTWC), also known as the Biological Weapons Convention, came into force in 1975 and effectively prohibits the development, production, acquisition, transfer, stockpiling and use of biological and toxin weapons which could threaten human, other animal, and plant health. The UK was one of the originators of the BTWC and since entry into force, has been an active participant and recognised global leader on the BTWC. The UK is also one of three Depositary States for the Convention.
The Australia Group
A co-operative and voluntary group of 42 member states and the EU, which through the harmonisation of export controls, seeks to ensure that exports do not contribute to the development or acquisition of chemical and biological weapons. The Australia Group Common Control Lists include the pathogens and toxins subject to export controls.
Further UK government oversight
UK screening guidance on synthetic nucleic acids for users and providers
This gene synthesis guidance from the Department for Science, Innovation and Technology (DSIT) sets baseline expectations for all individuals and organisations involved in the provision, use, and transfer of synthetic nucleic acids and benchtop equipment that synthesises nucleic acids in the UK. The guidance points to areas for further work and welcomes input from academia, industry and think tanks to shape future interventions.
Engineering Biology Regulators Network
The UK’s Engineering Biology Regulators Network seeks to enable a joined-up system to support technology from discovery research to market. It brings together regulators, agencies and policy teams, from across government, to share best practice on pro-innovation regulation, identify common challenges and collaborate on solutions. The network will enable a joined-up system to support technology from discovery research to market.