US health officials should broaden their oversight of federally funded research that modifies deadly viruses to include some less risky types of pathogens, a panel of experts has concluded. Their preliminary report, released today, also recommends that funding agencies share more information about decisions to approve such work.
The recommendations are good news for scientists, policymakers and others concerned that the SARS-CoV-2 pandemic has revealed gaps in the rules for so-called gain-of-function (GOF) research. The report recommends “significant policy improvements,” says Stanford University microbiologist David Relman, a critic of US oversight of the GOF studies, which are funded by the National Institutes of Health (NIH).
The group’s recommendations, from a National Science Advisory Board for Biosafety (NSABB) working group, may also bring some relief to virologists who were concerned that surveillance would extend to common pathogens that rarely cause serious disease. such as cold viruses. But some experts say the proposed definition of risky research still leaves too much for interpretation and could eliminate routine studies important to public health.
Concerns about the GOF studies exploded 12 years ago when two researchers reported that they had modified H5N1 avian influenza so that the virus spread more easily between ferrets, a model for human transmission. Although the work was intended to help prepare for pandemics, some experts worried that such an improved virus could escape the lab or be released deliberately, potentially triggering a pandemic.
The concerns led to a 3-year moratorium on certain GOF studies on avian influenza, Middle East respiratory syndrome, and severe acute respiratory syndrome, as well as a 2017 Department of Health and Human Services (HHS) policy. that governs future work. The policy, known as the Potential Pandemic Pathogens Surveillance and Care (P3CO) Framework, requires the NIH to submit for review by an HHS committee studies that are “reasonably anticipated” to generate a “improved” version of a human pathogen that is likely to be both highly transmissible and highly virulent.
The P3CO policy came under new scrutiny 3 years ago after the COVID-19 pandemic broke out in China. A lab in Wuhan had NIH funding to create hybrids of existing bat coronaviruses to study whether such viruses could evolve to infect people. Some argued that this work, or similar studies, could have created SARS-CoV-2 and that the NIH had incorrectly exempted the studies from P3CO’s review. Critics have also suggested that other risky studies are escaping P3CO’s review, such as a proposal to combine two mpox virus strains.
Today’s NSABB report calls for expanding the definition of a “potential pandemic pathogen” to agents that are “probably moderately or highly virulent” but not necessarily rapidly spreading, such as the Ebola virus. It would also include any pathogens that are “likely to be moderately or highly communicable” and capable of spreading widely in humans, such as SARS-CoV-2. Similar changes were included in a draft published in September 2022. But the new version also adds a condition limiting reviews to work that could lead to pathogens “likely to pose a serious threat” to public health or national security.
The apparent logic of that language is to exempt the GOF’s routine research on viruses that generally do not cause serious illness, such as herpes viruses and cold viruses. But it’s not clear whether other standard studies, such as tweaking seasonal flu viruses to find out if new mutations are helping them spread, might now require a P3CO review, says Andrew Pekosz, a flu researcher at Johns Hopkins University. . “I still have a lot of worries,” he says.
The report also says that GOF studies conducted for surveillance or vaccine development, which are now exempt from the P3CO policy, must undergo expedited review. That policy could apply, for example, to work adding parts of the Omicron strain of SARS-CoV-2 to a different strain to try to understand why Omicron causes milder symptoms. Such a study at Boston University caused a stir last fall.
A summary of the HHS committee’s reviews of the P3CO investigation should be made public, the report says, a step many observers have called for. HHS should also issue clearer P3CO guidelines for NIH-funded institutions and researchers, and strengthen oversight of NIH-funded studies abroad. And the P3CO policy should be expanded to apply to privately funded studies, the report says.
While generally satisfied with the recommendations, Relman and Johns Hopkins biosecurity expert Tom Inglesby say limiting reviews to pathogens that are “likely to pose a serious threat” is problematic because that assessment would be done by the NIH, not the P3CO committee. . “It doesn’t make sense… to [an NIH official] make a judgment before the proposal enters the [review] process,” says Inglesby.
Johns Hopkins biosecurity expert Gigi Kwik Gronvall is concerned that the phrase “reasonably anticipated” remains part of P3CO’s definition. She points out that a government watchdog group this week concluded that without a “standard” to explain that phrase, the agencies’ interpretation will be subjective.
The full NSABB will vote on whether to accept the report at a meeting on January 27. If the group approves it, NIH and HHS will decide whether to revise the P3CO policy.