At the request of the Minister for Health and Aged Care, the National Health and Medical Research Council has undertaken a review of gain-of-function research in Australia.
The Executive Summary from the review report, and a copy of the full report, is available below.
At the request of the Minister for Health and Aged Care, the National Health and Medical Research Council (NHMRC) has undertaken a review of gain-of-function research. The Gain-of-Function Research Review reports on:
- the definition of gain-of-function research, the uses and benefits of such research, as well as how research of this nature could pose a threat to human health
- the framework for the regulation and oversight of research in Australia, with a focus on those aspects of the framework that ensure the safe, responsible and ethical conduct of research, including gain-of-function research
- gain-of-function research that has been funded by the Australian Government, or conducted by a Government agency, over the last 10 years and that could increase the harmfulness of an infectious agent to humans (also called gain-of-function research of concern)
- how the regulatory framework that controls such research in Australia compares internationally, with a focus on the management of biosafety and biosecurity risks.
The terms of reference for the review are outlined at Appendix A. The terms of reference do not include investigating the origin of the SARS-CoV-2 virus responsible for the COVID-19 pandemic.
The review involved consultation with, and collection of information from, Australian Government agencies, including those that fund or conduct life sciences research and that are responsible for the regulation of such research (Appendix B).
What is gain-of-function research?
‘Gain of function’ is a general term. For the purposes of this review, it is used to describe a change to the genome of any biological entity – a living organism such as an animal, insect, plant, virus, bacterium or fungus – through any process so that it acquires a new or enhanced function. Changes to the genome may occur spontaneously in nature or as the result of an experimental manipulation in a laboratory.
Gain-of-function research is a type of research where the manipulation of the genome results in a gain of function. Investigating gain of function is a powerful experimental approach that is routinely used in life sciences research, including genetic, biological and microbiological research. It involves a broad range of experimental techniques that have been used for many decades.
The use of ‘gain of function’ in this report reflects the wide-ranging occurrence of gain of function in nature and an experimental approach used in a broad range of scientific disciplines. Recently, the term has been used to refer to its application in research involving infectious agents and, more specifically, viruses. However, limiting the definition of gain of function to these types of research represents only a part of its application.
Most gain-of-function research is safe and leads to many benefits for human health. Gain-of-function research has led to new knowledge and technologies, including:
- new knowledge about how biological systems work and the processes underlying human and animal health and disease
- new knowledge about how infectious agents spread, infect and cause disease
- new pharmaceuticals and vaccines, precision medicine and gene therapies.
Concerns about some gain-of-function research
Gain-of-function research can be ‘of concern’ if it changes the characteristics of an infectious agent in a way that could increase the risk of harm to humans. Such research is generally performed to study a particular infectious agent and to develop strategies and technologies to prevent, detect or treat human infection by the agent.
This type of research has also been described as ‘gain-of-function research of concern’ and was the focus of this review.
A range of additional characteristics (gain of function) may be conferred on an infectious agent that could increase its harmfulness to humans, such as:
- enhanced production of the infectious agent (e.g. increased replication cycle or growth)
- enhanced morbidity (illness) and mortality (death)
- enhanced transmissibility (how easily it spreads) and host susceptibility
- evasion of existing natural or induced immunity
- resistance to drugs or evasion of other medical countermeasures such as vaccines, therapeutics or diagnostics.
Concerns about gain-of-function research have led to calls to ban such research, especially where it involves infectious agents with pandemic potential. An infectious agent with pandemic potential is one that is highly transmissible and capable of wide and uncontrollable spread in human populations, and highly virulent and likely to cause significant morbidity and/or mortality in humans. In a very small subset of gain-of-function research, characteristics may be conferred on an infectious agent that increase its pandemic potential or cause it to acquire pandemic potential. In the United States of America (USA), this has been called research involving ‘enhanced potential pandemic pathogens’ (enhanced PPP).
This review focused on identifying ‘gain-of-function research that could increase the harmfulness of an infectious agent to humans’, which includes but is broader than enhanced PPP. For the purposes of the review, this broader category is also described as ‘gain-of-function research of concern’.
Australian regulatory framework
Research in Australia is expected to be conducted responsibly and be ethically justified. Biosafety or biosecurity risks must be identified and effectively mitigated and the potential for inadvertent or deliberate misuse of the research must be minimised.
Australia’s framework for the regulation and oversight of research is comprehensive and aims to ensure the safe, responsible and ethical conduct of research. The framework includes a combination of Commonwealth and state/territory legislation, national standards and guidance, as well as local institutional governance and practices.
Controls applied to all life sciences research also apply to research that involves infectious agents, including potential gain-of-function research. These controls include ethics and safety approvals (including biosafety and biosecurity) from government bodies and/or institutional committees that encompass consideration of the risks and benefits of the research. There are additional controls for, and oversight of, research involving infectious agents and research involving genetically modified organisms (GMOs) including Commonwealth, and corresponding state and territory, biosecurity legislation and gene technology legislation.
Relevant approvals must be obtained before research commences. Monitoring and reporting requirements ensure that research is conducted in accordance with relevant licences and approvals. Monitoring and reporting also ensure that any issues that arise during the conduct of the research are detected and adequately addressed.
Gain-of-function research in Australia
Over the last 10 years, the Australian Government has funded or conducted 17 research projects that were identified in this review as gain-of-function research that could increase the harmfulness of an infectious agent to humans (also described as ‘gain-of-function research of concern’). These projects comprise less than 0.3% of the more than 6000 infectious disease research projects that were funded or conducted by Australian Government agencies in the same period.
Of the 17 research projects identified, 10 were funded by NHMRC and 8 were conducted by the Commonwealth Scientific and Industrial Research Organisation (CSIRO); one project was both funded by NHMRC and conducted by CSIRO. Information about the projects is presented in general terms and, where appropriate, aggregated form. This approach is necessary to protect researchers from potentially serious threats to their personal and professional lives, as has been experienced by scientists around the world in the context of COVID-19.
Of the 17 research projects, 13 involved virological studies and 4 involved bacteriological studies. The research projects aimed to achieve benefits for human health including better understanding of viral and bacterial infections and how to detect, prevent and treat these infections. In all cases, the controls required under Australia’s regulatory framework for the safe and ethical conduct of research, including biosecurity and biosafety, were in place. All projects were conducted in appropriate physical containment facilities with the required approvals or licences. The projects were monitored appropriately and there were no reported incidents involving infectious agents or GMOs during the conduct of the projects.
Australia’s framework for the regulation and oversight of life sciences research is comprehensive and comparable to frameworks in other relevant countries. The comparability of Australia’s framework with relevant international benchmarks is in part because of the adoption and harmonisation of international standards in many areas (e.g. research involving animals or human biospecimens, export controls and dual-use research).
In other areas, Australia’s regulatory framework is more extensive than other countries. For example, unlike Canada and the USA, Australia has specific legislation for laboratory-based research with GMOs and the Gene Technology Regulator certifies facilities undertaking such research.
Australia’s approach to health security has also been recognised internationally for its capabilities to prevent, detect and prepare for biosecurity and biosafety risks. Aspects of Australia’s approach to biosecurity have also been used as the model for other countries and our biosafety requirements are recognised as establishing an organisational culture of safety in Australian laboratories.
The review report notes the many uses of gain-of-function research that have resulted in significant medical innovations and benefits to human health, and outlines the strong regulatory controls in Australia that ensure research is conducted safely, ethically and responsibly.
The Australian Government has funded and/or conducted a large volume of research on infectious agents that could cause disease in humans (including potential zoonotic animal diseases) over the last decade, contributing to Australia’s considerable strengths in this field. The review found that the Government has funded through NHMRC, or conducted at CSIRO, gain-of-function research that could be categorised as ‘of concern’ because it involved modifying a virus or bacterium in a way that may make it more dangerous to humans. This research aimed to increase understanding and improve the detection, prevention and treatment of a range of viral and bacterial infections.
Gain-of-function research in Australia is subject to best-practice biosafety and biosecurity controls that protect both the scientists undertaking the research and the Australian community. For example, Australia has a strong regulatory framework for the use of GMOs, which includes specific national legislation for laboratory-based research with GMOs and certification of facilities undertaking such research by the Gene Technology Regulator. Australia also has world-class physical containment facilities, including CSIRO’s Australian Centre for Disease Preparedness (ACDP), which is a physical containment level 4 facility designed to allow scientific research on the most dangerous infectious agents to be performed safely. Australia’s depth of expertise in infectious disease research and the availability of high-quality biosafety containment facilities enables the safe conduct of important research to prevent, detect and protect the Australian community from the threat of infectious diseases.