The term gain-of-function (GOF) research describes a type of research that modifies a biological agent so that it confers new or enhanced activity to that agent. Some scientists use the term broadly to refer to any such modification. However, not all research described as GOF entails the same level of risk. For example, research that involves the modification of bacteria to allow production of human insulin, or the altering of the genetic program of immune cells in CAR-T cell therapy to treat cancer generally would be considered low risk. The subset of GOF research that is anticipated to enhance the transmissibility and/or virulence of potential pandemic pathogens, which are likely to make them more dangerous to humans, has been the subject of substantial scrutiny and deliberation. Such GOF approaches can sometimes be justified in laboratories with appropriate biosafety and biosecurity controls to help us understand the fundamental nature of human-pathogen interactions, assess the pandemic potential of emerging infectious agents, and inform public health and preparedness efforts, including surveillance and the development of vaccines and medical countermeasures. This research poses biosafety and biosecurity risks, and these risks must be carefully managed. When supported with NIH funds, this subset of GOF research may only be conducted in laboratories with stringent oversight and appropriate biosafety and biosecurity controls(link is external) to help protect researchers from infection and prevent the release of microorganisms into the environment.
U.S. Government Funding Pause
In 2014, the White House Office of Science and Technology Policy (OSTP), in coordination with agencies across the U.S. Government (USG), including the Department of Health and Human Services (HHS) and the National Institutes of Health (NIH), initiated a funding pause (link is external)on GOF research that was reasonably anticipated to confer attributes to influenza, Middle East Respiratory Syndrome (MERS), or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.
The pause allowed the USG, in partnership with the life sciences community and stakeholders, to conduct a public, deliberative process with the explicit goal of developing a new federal policy framework to guide future investments in this area of research. The deliberative process included multiple public meetings and two commissioned independent studies, including a comprehensive risk and benefit assessment of GOF research. As noted above, not all studies that may be considered GOF research pose the same level of risk. The deliberative process identified the subset of research that enhances a pathogen to make it likely highly transmissible and virulent in humans (enhanced PPP) as involving risks that warranted additional oversight.
[NIH, 미국 국립보건원의 2017년 글]