Expert recommendations on gain-of-function research aim to boost safety, transparency

CDC

The American Society of Microbiology (AMS) today released consensus recommendations on gain-of-function research into infectious agents with pandemic potential. The recommendations include internationally accepted definitions of terminology, greater transparency with the public, and stronger biorisk-management systems and oversight.

The recommendations were based on a workshop of top scientists who reviewed the benefits and risks of gain-of-function research of concern (GOFROC) in May 2023.

Biosafety, biosecurity risks

GOFROC involves modifying a pathogen's genetic sequence to create models of human infection to see how it enters cells and behaves in the body. The result may be a more transmissible or viral pathogen. The goal is to predict how the pathogen could evolve over time and inform the development of diagnostic tests, surveillance methods, vaccines, and treatments should it emerge in the environment.

Research on enhanced potential pandemic pathogens (ePPPs), which makes up a small fraction of work with infectious pathogens, has raised concerns about the biosafety and biosecurity risks it poses to public health, as well as its necessity and relatively high expense.

For example, in the early 2000s, researchers completed GOFROC on the influenza A/H5N1 virus, discovering that key genetic mutations made the resulting strain more transmissible in ferrets. But the US National Science Advisory Board for Biosecurity raised concerns that publication of these data could lead to bioterrorism or accidental release of the virus, and after publication, scientists decided to put a 1-year pause on this type of research.

"Science can provide key insights and critical countermeasures in the effort to protect ourselves against and respond to pandemics," workshop participant David Relman, MD, of Stanford University, said in an AMS news release. "At the same time, we need to ensure that science itself does not give rise to the next pandemic."

Workshop participants included those from the World Health Organization (WHO) and from institutions in the United States, Canada, England, and the Netherlands.

3 high-level recommendations

The reported noted that, in the United States, the Department of Health and Human Services and the US Department of Agriculture oversee federal regulations on human, other animal, and plant research.

Science can provide key insights and critical countermeasures in the effort to protect ourselves against and respond to pandemics. At the same time, we need to ensure that science itself does not give rise to the next pandemic.

David Relman, MD

"While not statutory, there are policies and guidance in place for recombinant DNA research, research with ePPPs, and dual-use research of concern, though some have raised concerns about their application and the risk of conflict of interest when these rules are being applied and adjudicated by the funding agencies," the report authors wrote. "There are fewer, if any, policies and guidelines for non-government-funded research."

While lab-acquired infections, mostly involving a few people, have occurred all over the world, none are known to have involved an ePPP, the experts wrote. "Continuous monitoring, frequent data sharing, research on the effectiveness of biosafety measures, and periodic updating of these measures are needed to ensure the scientific community is informed and safety conducts these experiments," the report said.

The scientists recommend:

Agreement on universally accepted standardized research terminology, biorisk-management practices, mentoring, training, and reporting to enable scientists to better understand the pros and cons of proposed experiments. "The world lacks an international standard for regulating research on infectious agents in general, much less for ePPP research," the authors wrote. "Each country develops its own review and regulatory process, adding to the lack of clarity."
Better engagement and transparency with policymakers and the public, including candid explanations that justify why GOFROC is needed to answer research questions and the steps that will be taken to safely conduct the experiments. For its part, the public should advocate for evidence-informed policies, support biosafety research funding, and participate in science cafes to stay informed and participate in the dialog. "This includes communicating the difference between short-term and long-term benefits as well as acknowledging that some benefits or concerns will not be known until well after the experiment is over," the report said.
Stronger biorisk-management systems. Discussions should include the risk-benefit considerations for experimenting with ePPP, funding for research on biosafety, biorisk-management training, occupational medical services, enhanced buildings and procedures, and personal protective equipment. "Current administrative responses to accidents are often viewed as punitive rather than constructive," the report said. "This can lead to reticence in reporting laboratory accidents to institutions."

Some lawmakers already looking at GOFROC bans

The group didn't specify which kinds of GOFROC are justified or those that shouldn't be performed, and none suggested a halt to all such studies. They said that each situation is unique and requires thoughtful consideration.

The experts said the scientific community should review current pathogen-oversight frameworks to determine which types of decisions should be made at the institutional level, which should be raised to a higher level, and who is most qualified to make those decisions.

Although the workshop did not discuss exactly what oversight is needed, it highlighted helpful recommendations for the scientific community and society to consider going forward.

Such discussions are timely, as this type of research is already in danger. "Currently in the US, lawmakers at both the federal and state levels are considering (and, in Florida, have already passed legislation to prohibit or pause some gain of function research on 'potential pandemic pathogens or related risk research with potentially dangerous pathogens,' " the authors wrote.

The report acknowledges that future pandemics of natural origin are inevitable. "Science is a key defense mechanism to protect us against and respond to pandemics," it concluded. "In the end, although the workshop did not discuss exactly what oversight is needed, it highlighted helpful recommendations for the scientific community and society to consider going forward."