Scientists at Boston University came under fire this week for an experiment in which they tinkered with the Covid virus. Breathless headlines claimed they had created a deadly new strain, and the National Institutes of Health rebuked the university for not seeking the government’s permission.As it turned out, the experiments, performed on mice, were not what the inflammatory media coverage suggested. The manipulated virus strain was actually less lethal than the original.But the uproar highlighted shortcomings in how the U.S. government regulates research on pathogens that pose a risk, however small, of setting off a pandemic. It revealed loopholes that allow experiments to go unnoticed, a lack of transparency about how the risk of experiments is judged and a seemingly haphazard pattern in the federal government’s oversight policy, known as the P3CO framework.Even as the government publicly reprimanded Boston University, it raised no red flags publicly about several other experiments it funded in which researchers manipulated coronaviruses in similar ways. One of them was carried out by the government’s own scientists.The Boston episode “certainly tells us the P3CO framework needs to be overhauled pretty dramatically,” said Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Canada. “The whole process is kind of a black box that makes it really difficult for researchers.”The N.I.H. said that every study it considers for funding is vetted for safety concerns by agency experts, who decide whether to escalate it to a higher-level dangerous pathogen committee.Some experiments, though, either because they are conceived later on or because they do not rely directly on federal funds, end up falling outside the scope of that process, leading to confusion, biosafety experts said. And the rules could be overhauled soon. After months of meetings, a committee of government advisers is expected to deliver updated recommendations for such research by December or January, the agency said.Evolving RulesThe government’s policy for such experiments is the Potential Pandemic Pathogen Care and Oversight, or P3CO framework. It was established five years ago in response to a set of contentious experiments in which researchers set out to transform an influenza virus that infected birds into one that could infect mammals.Under the policy, the N.I.H. and other agencies are supposed to flag grant applications for experiments that could potentially produce a new pandemic. Risky research may not be funded or may require extra safety measures.Critics of P3CO have complained that this evaluation happens largely in secret and ignores projects that aren’t funded by the U.S. government. In January of 2020, the government’s advisory panel, the National Science Advisory Board for Biosecurity, held a public meeting to discuss reforms. But subsequent meetings were canceled, ironically enough, because of Covid’s arrival.In the months that followed, Republican politicians attacked the N.I.H. for supporting past research on coronaviruses at the Wuhan Institute of Virology, suggesting that a lab leak there might have been responsible for the pandemic. (In July, Dr. Rasmussen and other scientists published studies pointing instead to a market in Wuhan as the origin.)Security personnel in February outside the Wuhan Institute of Virology in China during the visit by the World Health Organization team tasked with investigating the origins of Covid.Thomas Peter/ReutersUnder this growing scrutiny, the N.I.H.’s advisory board met in February, worked on new recommendations over the summer and released a draft last month. It proposed expanding the scope of pathogens that can prompt a review beyond those that have a high fatality rate. Unlike smallpox or Ebola, Covid has a low fatality rate but is so contagious that it still wreaked global devastation.In its ongoing discussions, the board has also considered the risk posed by computer software, such as programs that could figure out how to make a pathogen spread faster.Read More on the Coronavirus PandemicUpdated Boosters for Kids: The Food and Drug Administration broadened access to updated Covid booster shots to include children as young as 5.Long Covid: A study of tens of thousands of people in Scotland found that one in 20 who had been sick with Covid reported not recovering at all, and another four in 10 said they had not fully recovered many months later.A Persistent Variant: Ten months have passed since Omicron’s debut. Since then it has displayed a remarkable capacity to evolve new tricks.‘Anti-Vax’ Capital No More: Vaccine skeptics once found a home in Marin County, Calif. Now, the pandemic has made them unwelcome, as Covid vaccine rates soar there.Researchers had mixed reactions to the new guidelines.“The first draft makes some important advances and leaves a lot of things unaddressed,” said Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health who has been pushing for tighter rules since the bird flu experiments more than a decade ago.In comments submitted to the advisory board last month, Dr. Lipsitch and his colleagues said that proposed experiments must be justified by real, practical benefits rather than unsupported claims.Other scientists, while welcoming clearer guidance, worried about onerous regulations that would bog down commonplace and innocuous experiments.“Tell us what paperwork we need to fill out so we can do our jobs, which is to help the public respond to these types of things when they come at us,” said Robert F. Garry, Jr., a virologist at Tulane University.Boston ExperimentsThe ambiguity of the government’s policy was laid bare this week when the news hit about the experiments at Boston University.Mohsan Saeed, a virologist at the school, and his colleagues posted a report online aiming to understand the differences between Omicron and other variants. The researchers made a new virus that was identical to the original version but carried an Omicron spike. They then put the modified virus into a strain of mice that is very sensitive to Covid and widely used to study the disease.Previous research had found that the original strain of Covid killed 100 percent of the mice. The new study found that the modified virus was less deadly, killing 80 percent.Colored scanning electron micrograph of the highly transmissible SARS-CoV-2 Omicron variant.Steve Gschmeissner/Science SourceLast Sunday, a story ran in The Daily Mail with a headline claiming that “scientists have created a new deadly Covid strain with an 80 percent kill rate.” The following day, an N.I.H. official, Emily Erbelding, told the news site Stat that Boston University should have discussed the experiments with the agency ahead of time.But, some researchers pointed out, the federal guidance is vague on what disclosures are required after a research proposal is approved. Science often takes unexpected turns, and officials do not generally apply the guidance to experiments that are conceived after funding has been granted.“The government should be providing the guidance to help people figure this out,” said Gregory Koblentz, a biodefense specialist at George Mason University.In a statement to The New York Times, Boston University said that the experiments were approved by its own safety committee as well as the Boston Public Health Commission.The university also said its scientists were not obligated to notify the N.I.H. because, although they had received government funding for related research, they used university funds to pay for the experiments in question. The agency said it is reviewing the matter.The highly publicized dispute over technical laboratory protocols sent mixed messages to the scientific community and the public, said Syra Madad, an infectious disease epidemiologist at NYC Health and Hospitals.“It seems like an epic communication failure,” said Dr. Madad, who is also on the National Science Advisory Board for Biosecurity. “This is why we’re revisiting the policy — to make sure that it’s clear, it’s transparent, it makes sense and it is operationally feasible.”Dr. Madad and other experts agreed that the proposal for the Boston University experiments should have gone through a more rigorous evaluation. “​​In my opinion, that certainly looks like it meets the criteria for P3CO review,” she said.But even if the study had gone through that process, some scientists said, it would have likely been given the green light.Boston University said that the experiments were approved by its own safety committee as well as the Boston Public Health Commission.Cydney Scott for Boston UniversityJesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center, noted that the coronavirus is already rampant among humans and has evolved far beyond the variants used in the experiment. The hybrid lab virus would be unlikely to cause a serious threat if it escaped.“I understand why it worries people because you are making a virus for which you can’t totally predict the properties,” Dr. Bloom said. “But this does not seem to me to be a particularly high risk.”Similar StudiesThe N.I.H.’s stern public statements about Boston University’s research raised questions about the way it and other health agencies had assessed such experiments in the past. Last month, scientists with the Food and Drug Administration published a study in which they, like the Boston team, injected mice with coronaviruses engineered to carry an Omicron spike.The F.D.A. is required to follow the P3CO rules. But the agency said in a statement that the hybrid virus created as part of its study did not amount to “a new version of the virus.” The study did not fall under the dangerous pathogen guidelines, the statement said, because “we set out to understand how the virus works, not identify new ways to make it more potent.”Some independent experts said the agency’s rationale did not explain why the study passed muster: An experiment cannot bypass the approval process simply because the researchers did not intend to make a more dangerous virus.“If it’s research that could be anticipated to possibly result in the enhancement of a potential pandemic pathogen — a more transmissible and/or virulent strain than exists in nature — it needs to be reviewed. Period,” Dr. Tom Inglesby, the director of the Johns Hopkins Center for Health Security at the Bloomberg School of Public Health, said in an email.The F.D.A. researchers are not the only American scientists to tinker with coronaviruses in this manner. At the University of Texas Medical Branch in Galveston, scientists have relied partly on federal funding for studies on whether vaccines generate protection against coronaviruses altered to carry Omicron spikes.Those techniques can save scientists months of waiting for samples of Omicron viruses from human patients, allowing them to study the dangers of new variants and anticipate the need for booster shots. Outside experts said the Texas experiments were even less risky than the Boston study because they generally infected cells, not live animals, with the viruses.While proposals from the Texas team would have been reviewed by the N.I.H., they were not escalated to the dangerous pathogen committee. The agency did not say why. (Since 2017, only three studies that the N.I.H. proposed to fund were reviewed by that committee, it has said.)“There is really no one in charge of scanning the medical literature, and it can be random events that bring these particular experiments to public attention,” Dr. Inglesby said. “And it shouldn’t be that way.”Others raised a different problem: Research that isn’t funded by the government does not have to follow the government’s rules.“I think that ultimately we would all agree that publishing a policy that would be broadly applicable would be ideal,” said Karmella Haynes, a biomedical engineer at Emory University and a member of the National Science Advisory Board for Biosecurity. “Now how to actually enforce that, I think, is beyond our charge.”One possibility might be to come up with a policy modeled on the Federal Select Agent Program, which requires anyone seeking to work with certain dangerous substances, such as anthrax, to register with the government.“Any recommendation that does not include codifying the requirements in regulations with the force of law will not add up to anything,” said Richard Ebright, a molecular biologist at Rutgers University.Federal officials, he added, may be under pressure to strengthen oversight next year if Republican proponents of a crackdown win power in the midterm elections in November.On the other hand, a politically fractious debate could put better regulations even further out of reach, some said.“I worry about inhibiting our ability to understand these viruses that have killed millions of people,” said Gigi Gronvall, a biosafety specialist at the Johns Hopkins Bloomberg School of Public Health.

A report out of South Africa offered a first glimpse at how vaccinated people might fare against the fast-spreading Omicron variant of the coronavirus.Laboratory experiments found that Omicron seems to dull the power of the Pfizer-BioNTech vaccine, but also hinted that people who have received a booster shot might be better protected.The study, published online on Tuesday, found that antibodies produced by vaccinated people were much less successful at keeping the Omicron variant from infecting cells than other forms of the coronavirus.Scientists said the results were somewhat worrisome, but no cause for panic. The data suggests that vaccinated people might be vulnerable to breakthrough infections with Omicron, which is spreading rapidly in South Africa and has appeared in dozens of countries around the world.But vaccines stimulate a wide-ranging immune response that involves more than just antibodies. So these experiments offer an incomplete picture of how well the vaccine protects against hospitalization or death from Omicron.“While I think there’s going to be a lot of infection, I’m not sure this is going to translate into systems collapsing,” Alex Sigal, a virologist at the Africa Health Research Institute in Durban, South Africa, who led the research, said in an interview. “My guess is that it’ll be under control.”Dr. Sigal and his colleagues worked at breakneck speed over the past two weeks to grow the virus and then test antibodies against it. “If I don’t die from the virus, I’ll die of exhaustion,” he said.Originally, Dr. Sigal feared that vaccines might not provide any protection at all. It was possible that the Omicron variant had evolved a new way of entering cells, which would have rendered antibodies from vaccines useless. “Then all our efforts would be trash,” he said.Fortunately, that proved not to be the case.Dr. Sigal and his colleagues used antibodies from six people who received the Pfizer vaccine without ever having had Covid-19. They also analyzed antibodies from six other people who had been infected before getting the Pfizer vaccine.The researchers found that the antibodies from all of the volunteers performed worse against Omicron than they did against an earlier version of the coronavirus. Overall, their antibodies’ potency against Omicron dropped dramatically, to about one-fortieth of the level seen when tested with an earlier version of the virus. That low level of antibodies may not protect against breakthrough Omicron infections.Theodora Hatziioannou, a virologist at Rockefeller University who was not involved in the research, said that number was not surprising. “It’s more or less what we expected,” she said.The results could help explain some high-profile superspreading events caused by Omicron. At an office Christmas party in Norway, the virus seems to have infected at least half of 120 vaccinated attendees.Dr. Sigal announced the results on Twitter Tuesday afternoon.His team found a distinct difference between the two sets of volunteers. The antibodies from the six uninfected vaccinated people were very weak against Omicron. But among the volunteers who had Covid-19 before vaccination, five out of six still produced fairly potent responses.The Coronavirus Pandemic: Key Things to KnowCard 1 of 4The Omicron variant.

The federal agency told a G.O.P. House member that it had notified EcoHealth Alliance, a group criticized for its U.S.-funded work with Wuhan scientists, to file data within five days.The National Institutes of Health said on Wednesday that a nonprofit group under fire from some Congressional Republicans for its research collaborations in China had failed to promptly report findings from studies on how well bat coronaviruses grow in mice.In a letter to Representative James Comer, Republican of Kentucky, the N.I.H. said that the group, EcoHealth Alliance, had five days to submit all unpublished data from work conducted under a multiyear grant it was given in 2014 for the research. The organization’s grant was canceled in 2020 under President Trump’s administration during his feud with China over the origins of the coronavirus.In recent months, N.I.H. officials have rejected claims — sometimes in heated exchanges with Congressional Republicans — that coronaviruses studied with federal funding might have produced the pandemic. Dr. Francis Collins, the director of the N.I.H., released a statement Wednesday night reiterating that rebuttal.“Naturally occurring bat coronaviruses studied under the N.I.H. grant are genetically far distant from SARS-CoV-2 and could not possibly have caused the Covid-19 pandemic,” he said in the statement. “Any claims to the contrary are demonstrably false.”EcoHealth Alliance has come under scrutiny because of its collaboration on coronavirus research with researchers at the Wuhan Institute of Virology, which is situated in the city where the pandemic began. The group did not immediately respond to phone and email messages on Thursday.Some scientists have argued that it’s possible SARS-CoV-2 was the result of genetic engineering experiments or simply escaped from a lab in an accident. But direct evidence for those theories has yet to emerge. Others have deemed those scenarios unlikely, pointing instead to many lines of evidence suggesting that people acquired the coronavirus in a natural spillover from bats or an intermediate mammal host.The controversy has drawn scrutiny to the experiments that EcoHealth Alliance and the Wuhan Institute of Virology carried out with funding from the N.I.H.EcoHealth Alliance’s collaboration with the Wuhan Institute of Virology, funded by grant money from the N.I.H., was often the target of Congressional Republicans over the origins of the pandemic.Ng Han Guan/Associated PressLast month, The Intercept, an online publication, posted 900 pages of materials related to the N.I.H. grants to EcoHealth Alliance for the research. The materials provided details about experiments designed to provide new insights into the risk that bat coronaviruses have for sparking new pandemics.In some of their experiments, the researchers isolated genes from bat coronaviruses that encode a surface protein, called spike. Coronaviruses use the spike protein to bind to host cells, the first step to an infection. The spike protein latches onto a cell-surface protein called ACE2.According to the materials published, the researchers then engineered another bat virus, called WIV1, to carry spike proteins from other bat coronaviruses. They then conducted experiments to see if the engineered WIV1 viruses became better at attaching to ACE2 on cells.Such experiments reignited a debate that has been going on for years about what sort of research is simply too dangerous to carry out, regardless of the insights it may provide. Experiments that can endow viruses with new abilities — sometimes called “gain of function” — have caused particular concern.N.I.H. Letter on EcoHealth Alliance’s Late Study FilingsRead Document 2 pagesIn 2019, the National Institutes of Health rolled out the “P3CO framework” for research on “enhanced potential pandemic pathogens.” Dr. Lawrence Tabak, the principal deputy director of the N.I.H., wrote in the letter to Representative Comer that the agency determined that the research proposed by EcoHealth Alliance did not meet the criteria for additional review under that framework “because these bat coronaviruses had not been shown to infect humans.”But, “out of an abundance of caution,” Dr. Tabak wrote, the agency had added requirements for EcoHealth Alliance to notify it of certain results of the experiments.Representative James Comer, Republican of Kentucky, held hearings criticizing the use of federal funds for research related to bat coronaviruses in China.  Stefani Reynolds for The New York TimesDr. Tabak noted that in one line of research, the researchers produced mice genetically engineered to produce the human version of the ACE2 protein on their cells. Infecting these animals with coronaviruses could potentially provide a more realistic sense of the risk that the viruses have of infecting humans than just using dishes of cells.The N.I.H. required that EcoHealth Alliance notify the agency if the engineered viruses turned out to grow 10 times faster or more than WIV1 would without their new spike proteins.In some experiments, it turns out, that viruses did grow quickly.“EcoHealth failed to report this finding right away, as required by the terms of the grant,” Dr. Tabak wrote.The N.I.H. also sent Representative Comer a final progress report that EcoHealth Alliance submitted to the agency in August.In the report, the researchers describe finding that WIV1 coronaviruses engineered to carry spike proteins were more virulent. They killed infected mice at higher rates than did the WIV1 virus without spikes from the other coronaviruses. The filing had been submitted late, the N.I.H. said, nearly two years beyond the grant-specified deadline of 120 days from completion of the work. “Delayed reporting is a violation of the terms and condition of N.I.H. grant award,” Renate Myles, a spokeswoman for the agency, said.Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center who has called for more research into the origins of the pandemic, said the revelations raised serious questions about the risks of investigating viruses originating from animals, known as zoonotic viruses.“In my view, some of this research on potential pandemic pathogens poses unacceptable risks,” he said. “In addition to asking if EcoHealth adhered to current regulations, we need to honestly ask what research should be done in the future to best minimize both zoonotic and lab-associated pandemic risks.”Some Congressional Republicans have pushed for more information for months, suggesting the research was the source of the pandemic. In a statement, Representative Comer claimed that “thanks to the hard work of the Oversight Committee Republicans, we now know that American taxpayer dollars funded gain-of-function research at the Wuhan lab.”Dr. Tabak’s letter did not include any mention of “gain-of-function” research.EcoHealth Alliance researchers collecting samples from bats in the field in Guandong Province in China in 2019.EcoHealth AllianceRepresentative Comer also accused Dr. Collins and Dr. Anthony Fauci, the head of the National Institutes for Allergies and Infectious Diseases, of potentially misleading the committee, vowing that the G.O.P. panel “will leave no stone unturned as we seek the truth for the American people about how their taxpayer dollars may have been associated with the start of this pandemic.”Ms. Myles dismissed the claim that EcoHealth’s experiments constituted gain-of-function research. She acknowledged that the findings in mice were “somewhat unexpected.” But Ms. Myles said the agency had reviewed the research described in EcoHealth’s progress report, and said it would not have triggered a review under the stricter protocols for P3CO studies.“The bat coronaviruses used in this research have not been shown to infect humans, and the experiments were not reasonably expected to increase transmissibility or virulence in humans,” she said.On a webpage posted Wednesday night, the National Institutes of Health provided additional details about the viruses that were studied in the experiments, demonstrating that they were not closely related to SARS-CoV-2.Bats harbor thousands of species coronaviruses, and since the start of the pandemic, researchers have searched for the closest relatives of SARS-CoV-2 that infect the animals. They have found several coronaviruses that are much more closely related to SARS-CoV-2 than WIV1.The analysis, Dr. Tabak wrote in his letter, “confirms that the bat coronaviruses studied under the EcoHealth Alliance grant could not have been the source of SARS-CoV-2 and the Covid-19 pandemic.”.