US health officials should expand oversight of federally funded research that tweaks deadly viruses to include some less risky types of pathogens, an expert panel concluded. Its preliminary report, released today, also recommends that funding agencies share more information about decisions to approve this work.
The recommendations are welcome news for scientists, policymakers and others who worry 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 Biosecurity (NSABB) working group, may also bring some relief to virologists who worried that oversight would extend to common pathogens that rarely cause serious illness, such as cold viruses. . But some experts say the proposed definition of risky research still leaves too much up for interpretation and could overwhelm routine studies important to public health.
Concerns over the GOF studies exploded 12 years ago, when two researchers reported that they had modified the H5N1 avian flu in a way that made the virus more easily spread among ferrets, a model of human transmission. While the work was intended to help prepare for pandemics, some experts feared that such a poisonous virus could escape the lab or be deliberately released, potentially triggering a pandemic.
The concerns led to a 3-year moratorium on certain GOF studies of avian flu, Middle East respiratory syndrome and severe acute respiratory syndrome, as well as a 2017 Department of Health and Human Services (HHS) policy governing future work. The policy, known as Potential Pandemic Pathogen Care and Oversight (P3CO), requires the NIH to submit for review by an HHS committee studies that are “reasonably predicted” to generate an “enhanced” version of a human pathogen that is likely to be highly transmissible. and highly virulent.
P3CO’s policy came under renewed scrutiny 3 years ago, following the onset of the COVID-19 pandemic in China. A laboratory in Wuhan has had funding from the NIH to create hybrids of existing bat coronaviruses in order to study whether these viruses can evolve to infect people. Some have argued that this work – or similar studies – could have created SARS-CoV-2 and that the NIH incorrectly exempted the studies from the P3CO review. Critics have also suggested that other risky studies are escaping P3CO’s review, such as a proposal to combine two strains of the Mpox virus.
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 pathogen that is “probably moderately or highly transmissible” and capable of spreading widely in humans, such as SARS-CoV-2. Similar changes were included in a draft released in September 2022. But the new version also adds a condition limiting revisions to work that could lead to pathogens “likely to pose a serious threat” to public health or national security.
The apparent rationale for this language is to exempt routine GOF research on viruses that generally do not cause serious illness, such as herpes viruses and cold viruses. But it’s unclear whether other standard studies, such as tweaking seasonal flu viruses to find out whether new mutations are helping them spread, might now require P3CO to be revised, says Andrew Pekosz, a flu researcher at Johns Hopkins University. “I still have a lot of concerns,” 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 an accelerated review. This policy could apply, for example, to work that adds 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 analysis of the P3CO research is to be made public, the report says — a step that many observers have called for. HHS should also issue clearer P3CO guidelines for NIH-funded institutions and investigators 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 happy with the recommendations, Relman and Johns Hopkins biosafety expert Tom Inglesby say limiting reviews to pathogens that “likely pose a serious threat” is problematic because such an assessment would be done by the NIH, not the P3CO committee. “Does not make sense… [an NIH official] make a judgment even before the proposal enters the [review] process,” says Inglesby.
Biosecurity expert Gigi Kwik Gronvall of Johns Hopkins is concerned that the phrase “reasonably anticipated” will remain part of the P3CO definition. She notes that a government watchdog group concluded this week that without a “standard” to explain that phrase, agencies’ interpretation will be subjective.
The full NSABB will vote on whether to accept the report at a Jan. 27 meeting. If the group approves, the NIH and HHS will decide whether to revise the P3CO policy.