In response to White House concerns about allegedly risky research on viruses, bacteria, and other pathogens, the National Institutes of Health (NIH) has begun a crackdown on dozens of studies it was funding, Science has learned.
Citing President Donald Trump’s executive order promising greater oversight of “gain-of-function” (GOF) research that’s potentially dangerous, the agency has demanded the scientists leading those studies suspend part or all of their work and propose modifications to their experiments that would limit any risk of creating more deadly or transmissible pathogens.
“NIH has identified 40 projects that may meet the definition of dangerous gain-of-function research. … Erring on the side of caution, all projects potentially meeting the definition are being suspended,” Matt Memoli, NIH’s deputy director, wrote in a 3 July draft letter to the White House describing NIH’s “interim response” to the executive order. The letter, obtained by Science, indicates an additional 172 projects have been flagged for potential suspension or termination.
Most of the suspended projects are taking place at U.S. universities, but nine are being conducted by NIH’s in-house scientists, according to a spreadsheet listing the 40 projects. That document also notes that those intramural investigators have already agreed to either stop or modify their research.
A dozen of the academic scientists on NIH’s suspensions list confirmed to Science that they had received notices from the agency but most did not want to comment on the matter. NIH’s selections have puzzled many infectious disease scientists and dismayed others. Nearly half involve tuberculosis (TB); studies on the mycobacterium that causes the disease have not traditionally sparked GOF concerns because an estimated one-fourth of the human population is infected with it and suffers no harm, the pathogen depends on prolonged exposure to spread, and TB is curable in most cases.
The studies targeted by NIH include both relatively low-risk, routine work and higher risk experimentation that is essential for developing new drugs and vaccines, several researchers told Science. JoAnne Flynn, a TB researcher at the University of Pittsburgh who is a co–principal investigator of one of the suspended grants, reviewed NIH’s list and called it “crazy” and “ridiculous.” Flynn’s own project involved using standard techniques to create mutants of Mycobacterium tuberculosis (Mtb) that are resistant to antibiotics. But she stresses that her work is not using any compounds that are currently recommended for TB treatment so she sees no risk of creating a dangerous strain capable of undermining those therapies. “This will really impede our understanding of Mtb infection,” Flynn says.
University of Wisconsin–Madison toxicologist Sabine Pellett similarly was dismayed and mystified by the suspension her grant received, though she well recognizes the risks posed by her lab’s work with Clostridium botulinum, a bacterium that produces a deadly neurotoxin. “My project is already done under high security conditions and already has undergone review following the processes by NIH,” Pellett says. “My lab is the only academic lab in the U.S. that can do what I do. There’s no safer place to work with the agent I work with.” Not only will the suspension impede a better understanding of the bacterium that causes various forms of botulism, she says it will also slow development of new therapeutics for the neurotoxin.
When shown the NIH spreadsheet of flagged projects, the American Society for Microbiology (ASM) also expressed concern. “ASM encourages NIH to reconsider its approach so that it is more transparent, fair, and aligned with the stated objectives of the policy,” said Allen Segal, an ASM spokesperson. “For some of the grants it’s hard to see the justification for the pause unless you interpret the executive order very broadly. Other grants are already subjected to a higher level of scrutiny. This is all compounded by the lack of an appeals process.”
Concern about GOF research came to the fore in 2011 when two labs modified the deadly H5N1 bird flu virus to determine which mutations might allow it to better transmit between mammals. Federal officials in 2014 paused 18 projects before releasing 2017 guidelines that allowed work to move forward. But the debate flared again during the COVID-19 pandemic, when some scientists and Republican politicians, including Trump, alleged that the coronavirus responsible came from GOF work at a lab in Wuhan, China, that had received NIH funding.
Former President Joe Biden’s administration later revamped the U.S. government’s GOF policy, but Trump officials jettisoned that work with its executive order on 5 May. Some researchers criticized Trump’s order as vague and potentially so broad that it could derail relatively low-risk, promising research. NIH provided some follow-up guidance, but until now many infectious disease scientists were uncertain what work would be stopped by the agency.
NIH began to send out suspension notices last week and more were being issued this week, according to Memoli’s letter. NIH staff reviewed more than 71,000 projects, he said.
In the NIH spreadsheet, there is a column noting the rationale for each grant’s selection. For 17 projects, that rationale included the phrase “suspended out of an abundance of caution.” One such study involves examining protective antibodies to two deadly viruses, but the work does not involve the actual pathogens, raising questions about why the work sparked GOF concerns. Typically, potential GOF experiments modify a pathogen in a way that could enhance its pathogenicity or ability to spread between humans.
Richard Chaisson, a TB researcher at the Johns Hopkins University Bloomberg School of Public Health, notes that one of NIH’s suspended projects studied a loss of function to Mtb. Other suspended studies involve viruses that cause COVID-19, influenza, dengue, and Zika. Work on more obscure alphaviruses, bunyaviruses, and phleboviruses is also on the list. NIH has also suspended a project to modify a flu virus to treat cancer.
Virologist Andrew Pekosz of Johns Hopkins notes that NIH doesn’t provide any detailed explanation for its decisions. “There doesn’t seem to be a risk-benefit analysis or understanding that things like this are going on in the real world,” Pekosz says.
Debates about what constitutes a GOF experiment that is too risky have raged for years, with many arguments revolving around whether the modifications to the pathogens being studied have the potential to trigger a pandemic or worsen the harm they already cause to humans. David Relman, a microbiologist at Stanford University who has pushed for stronger GOF regulations, reviewed the NIH list and said it was difficult to determine why many of these projects were selected. He worries the ambiguity could lead some principal investigators (PIs) to stop doing work that does not present high risks to the public. “Ill-considered self-censorship by PIs and the effects of intimidation on PIs might be some of the most damaging and (both figuratively and literally) sickening effects of the current circumstances,” wrote Relman in an email.
Harvard University epidemiologist Marc Lipsitch, who has publicly called for stronger U.S. regulations on high-risk lab work that might accidentally trigger a pandemic, also questioned why NIH had suspended most of these projects. “Only a handful plausibly meet the standard in the executive order that they ‘could result in significant societal consequences,’” Lipsitch says. “While there are a few studies where I would want to learn more about the risks and benefits, I would predict that ending this list of studies, as a whole, will be detrimental to health security and public health.”
Paul Friedrichs, who headed the White House Office of Pandemic Preparedness and Response Policy during the Biden administration, says he hopes the government will better explain how it decided to single out these specific projects. “Ambiguous criteria which are applied unilaterally may paradoxically actually increase, not decrease, our vulnerabilities to future biological threats,” says Friedrichs, a retired major general who worked at the Pentagon before serving in the White House.
Some of the affected scientists say the way NIH has communicated the suspensions has further confused the situation. Volker Briken, who studies Mtb at the University of Maryland, says he received the agency’s letter on 27 June “completely out of the blue” and responded within 2 days, as requested. He told NIH his group would not perform the specific experiment it had flagged, which called for studying mutations that help Mtb dodge immune attack. “I have not received a response, not even an acknowledgement of our response,” says Briken, noting that he also didn’t receive a 1 June funding installment for the now-suspended grant.
“I have no idea what is going on,” Briken says. “We find ourselves at the mercy of whatever direction the current administration chooses to take. Who knows what will happen next.”
Update, 14 July, 1:35 p.m.: This story has been updated.