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A worker in a biosafety level 3 lab.

A worker in a biosafety level 3 lab.

Maggie Bartlett/NHGRI

U.S. advisers sign off on plan for reviewing risky virus studies

A board of advisers this week signed off on a proposal for how the U.S. government should go about deciding whether to fund certain studies that could potentially create dangerous human pathogens. The plan now goes to government officials, who say they hope to put out a policy by the end of year. Still unclear, however, is exactly when they will lift an 19-month-old ban that has halted a handful of virology studies.

The report from the National Science Advisory Board for Biosecurity (NSABB) is meant to guide decisions about so-called gain-of-function (GOF) studies—experiments that modify a pathogen in ways that could make it more transmissible and more pathogenic in humans. Such studies can help experts prepare for pandemics, but they also pose risks if the altered pathogen should escape the lab. In 2011, two GOF studies with the deadly H5N1 avian influenza virus sparked a lengthy NSABB discussion over whether the work should even be published. (Ultimately, the NSABB said it should be.) The studies also led to a new oversight policy for certain H5N1 experiments.

Then in 2014, more papers on risky flu viruses, along with some mishaps at federal labs, convinced U.S. officials that existing policies weren’t enough. In October 2014, the White House announced a “pause” on new funding for 18 GOF studies of influenza, SARS, and MERS viruses (although several projects were later exempted). Officials then asked a revived NSABB to come up with a process for overseeing risky GOF studies.

New process recommended

Now, after six meetings, two National Academy of Sciences workshops, and a 1000-page risk assessment by a contractor, the NSABB on 24 May approved a final proposal. Their latest report is similar to an earlier draft that found that only a “small subset” of studies are of concern. But this time, the board provides examples—for instance, GOF studies to develop seasonal flu vaccines are not worrisome. The board has also modified its definition of what it now calls Gain of Function Research of Concern (GOFROC). An earlier definition, for instance, covered experiments that generated a pathogen that is highly transmissible, highly virulent, and “resistant to public health control measures.” The new definition, however, drops the “resistant” wording, because not all nations might be able to deploy antiviral drugs or other countermeasures.

Like the previous draft, the new plan lays out a process for reviewing studies: The investigator and his or her institution will determine if a proposed study is potentially GOFROC. If it passes peer review, the funding department—such as the Department of Health and Human Services (HHS)—will then evaluate the experiment using eight criteria. For example, it will look at whether the investigators’ lab has sufficient safety measures in place and the benefits outweigh the risks to society.

The final report also calls for creating a new federal advisory board (something like the NSABB) to publicly review GOFROC policies (but not specific experiments). It suggests GOFROC oversight should extend to privately funded studies, which now are not reviewed by government bodies unless they involve regulated pathogens. And it urges officials to create a system for tracking lab accidents—a suggestion other experts have made. In their meeting, advisers also recommended a system for sharing the experiences of institutional review boards with GOFROC proposals.

The report has new wording that is apparently aimed at critics who have argued that the HHS should not review studies it funds, because that would represent a conflict of interest. The report says the HHS review “should be structured to avoid real or apparent conflicts of interest,” but doesn’t specify how that can be done. Harvard University epidemiologist Marc Lipsitch, one of the critics, says the review group should “have wide representation from well beyond the agencies with vested interest.”

The new review process should ensure that risky GOF research is evaluated early, before it is funded, said NSABB chair Samuel Stanley of Stony Brook University in New York. “We can start to avoid situations where [GOFROC] is only first identified at the publication stage,” as happened with the H5N1 papers, he said.

How hard to implement?

Agencies shouldn’t have trouble implementing the GOFROC policy because it’s similar to the review process for so-called Dual Use Research of Concern, an overlapping category of studies on agents potentially used as bioweapons, said Dennis Dixon of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, which funds GOF research. “We’ve done it before,” Dixon said.

Implementation will require “from light to heavy lifts,” Gerald Epstein of the White House Office of Science and Technology Policy told the NSABB. For example, although  HHS can easily set up new review processes, new rules for university investigators receiving federal grants may have to go through a formal rulemaking process. And oversight of nonfederally funded may require action by Congress. But Epstein promised to “get something done” in the next few months that will “supersede the existing funding pause … It is certainly something I don’t think anybody wants to permit to go into the next administration,” he said.

Stanley urged officials to “move as quickly as possible.” The pause may have only stopped a few studies, he said, but he’s worried that is has “had a broader effect on the infectious disease research community” by creating “uncertainty” that has convinced some young scientists to “rethink careers in certain areas.”