NIH gain-of-function regulations are vague and secretive, advisers say

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Cells infected with SARS-CoV-2. (Photo credit: NIAID)

The National Institutes of Health should improve how it regulates lab generated viruses that could pose a national security risk, according to its biosecurity advisers.

The National Science Advisory Board for Biosecurity highlighted wide gaps in the oversight of controversial projects that create “enhanced pandemic potential pathogens” in preliminary recommendations to the NIH. The report comes ahead of a public meeting to finalize recommendations this week.

Privately funded research that risks causing a pandemic occurs largely in the shadows, the group found. Meanwhile, NIH-funded research with pandemic risks is falling through the cracks of the agency’s vague internal processes.

On paper, NIH-funded projects that could pose a pandemic risk are subject to an extra layer of regulatory review by the enhanced pandemic potential pathogens committee, or “P3CO.”

In practice, the NIH refers few research projects for closer scrutiny, the NSABB says, echoing the concerns of nonpartisan experts.

In rare instances where projects are referred for review by the P3CO, the deliberation occurs in secret. The composition of the P3CO is unknown to anyone outside of the process except for the NSABB and a few members of Congress.

The biosecurity advisers say that regulation should be expanded beyond “a small fraction of the life sciences research enterprise” and recommend more transparency to build public trust.

The group also recommends tougher rules for determining whether safer approaches like pseudotyping or in silico experiments could answer the same scientific questions, and evaluating whether the project has a potential payoff for public health.

The group also recommended broadening the definition of an “enhanced pandemic potential pathogen” to include any engineered virus with the potential to overwhelm the health care system. Though not stated explicitly in its report, COVID-19 has demonstrated the capacity of a virus with low virulence but high transmissibility to kill millions and upend hundreds of millions of lives.

The group also recommended expanding oversight of a related field of research: “dual use research of concern.” DURC refers to research with scientific aims but which could also be used to generate a bioweapon.

NSABB recommended expanding the definition of DURC to include viruses that pose a national security risk if accidentally released, not just research that could be intentionally weaponized.

The group also recommended subjecting foreign labs using U.S. funds and performing high-risk experiments to U.S. regulations. Last August the NIH terminated a subgrant to the Wuhan Institute of Virology, a lab at the COVID-19 pandemic’s epicenter, for failing to meet U.S. regulations.

The draft recommendations have been three years in the making.

The advisory committee first met to consider changes to regulations in January 2020. The group met unmasked, unaware that the novel coronavirus emerging out of Wuhan, China, would significantly raise the temperature of the debate.

In the intervening years, COVID-19 has moved pandemics out of the realm of abstract threats.

The debate about gain-of-function virology once generated little interest outside the infectious diseases community, with virologists concerned about censorship on one side and epidemiologists and microbiologists concerned about lab escape on the other. It has since moved into the mainstream.

Laboratory-made viruses have drawn unprecedented public concern.

But the issue was placed on the backburner as the advisers responded to more urgent public health needs in the pandemic’s chaotic early months. In 2022, HHS reconvened the NSABB and held public meetings.

Experts have sought to clarify the conflation of gain-of-function research and the creation of more dangerous viruses.

Tweaking flu strains to grow well in eggs in order to generate annual flu vaccines may be considered “gain-of-function” research, for example. But the benefits of creating more dangerous strains of viruses in the lab have not been well articulated.

The NSABB describes the benefits of enhanced pandemic potential research in terms of what may be possible in the future, stating that “the existence of these technological capabilities creates a moral obligation” to explore its possibilities.

But the NSABB also underlines the need to consider the risks.

Government Accountability Office highlights lack of accountability

Scientists and members of the public have in particular flagged the gain-of-function research undertaken in Wuhan under low biosafety standards with SARS-like viruses. The scientific collaborations undertaken in Wuhan included scientists with a stated interest in polybasic cleavage sites in coronaviruses, much like the furin cleavage site found in SARS-CoV-2, which some scientists believe could be engineered.

Those concerns have been met with an often caustic rebuttal by prominent virologists, who have cast these worries as fringe and conspiratorial.

However, nonpartisan government watchdogs released a report Wednesday flagging chronic lapses in the oversight of pandemic potential pathogen research.

Scientists advising the Government Accountability Office confirmed that research on pandemic potential pathogens has gone unregulated in several respects.

The National Institutes of Health — and specifically the NIH’s infectious diseases institute, the NIAID — has underwritten nearly every publicly funded enhanced pandemic pathogen research project.

NIAID flags research that can be “reasonably anticipated” to create a new pandemic potential virus. However the nonpartisan experts found that there’s no clear standard for what “reasonably anticipated” means.

Only three research projects have been referred by NIAID for extra scrutiny by the committee in its five year lifespan, suggesting that NIH is not referring enough projects for review.

“Only three [research projects] have been forwarded for review,” said Mary Denigan-Macauley, who directs the oversight of public health programs at GAO. “We want to make sure there is a good, strong, consistent definition so that all of the projects are reviewed with the same amount of scrutiny, otherwise we don’t have assurance that they’re seeing all of them.”

Though not cited by the report, a controversial experiment undertaken at the Wuhan Institute of Virology with a NIAID subgrant has generated concerns about whether controversial projects are slipping the agency’s notice or receiving carveouts.

The experiment generated a SARS-like virus with 10,000 times its initial viral load, but was not subject to the proper oversight. NIH said it was because the result was unexpected. The lapse in oversight has been criticized by members of Congress and biosecurity experts. NIH requested complete lab notes related to the experiment from the Wuhan Institute of Virology but has been rebuffed.

Private research on pandemic potential pathogens is unregulated unless it involves a select agent.

For example, a privately funded lab voluntarily informed the Centers for Disease Control and Prevention that it would generate a virus unlikely to arise in nature: a hybrid virus splicing together the original SARS virus and SARS-CoV-2. GAO acknowledged that without the voluntary disclosure, the project would have proceeded under the radar of the U.S. government.

The P3CO was also criticized by the GAO for a lack of transparency.

The names of its members have not even been provided to the GAO.

Chris Hassell, chair of the committee, said that NIH staff had received threats in response to perceived involvement in gain-of-function research.

“There are concerns about the safety of those involved,” said Denigan-Macauley. “We asked [for the names] several times.”

Those threats were not provided to the GAO.

Denigan-Macauley did however cite Fauci’s testimony to Sen. Rand Paul, R-Ky., last year that he had received death threats.

Hassell initially would not even provide the names to the Congressional committee overseeing HHS. Eventually Hassell provided some of the names confidentially.

“Whether or not the U.S. government played any role—directly or indirectly—in the creation of COVID-19, our committee’s investigation is uncovering a host of issues that require more attention,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers, R-Wash., in a statement. “We will continue pushing for more accountability and oversight to start rebuilding public trust in these research agencies.”

The GAO recommended that the public at least receive more information about the P3CO’s makeup.

Another key policy recommendation from the GAO was first made by experts over a decade ago.

A new governmental body should be empowered to regulate all high biocontainment labs, public and private, GAO recommends.

The GAO first made this recommendation in 2009 in a report titled: “High Containment Laboratories: National Strategy for Oversight Is Needed.”

But national security staff at the White House stalled on the recommendation for years, then told GAO that they disagreed.

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