An ongoing controversy over what constitutes virology research that is too dangerous to conduct—and whether the U.S government funded studies in China that violated a policy barring funding for such risky research—has taken a new turn. While denying once again it had helped create the virus that sparked the COVID-19 pandemic, the U.S. National Institutes of Health (NIH) revealed in a letter sent yesterday to Republicans in Congress that experiments it funded through a U.S.-based nonprofit in 2018 and 2019 at the Wuhan Institute of Virology (WIV) in China had the “unexpected result” of creating a coronavirus that was more infectious in mice.
NIH says the organization holding the parent grant, the EcoHealth Alliance, failed to immediately report this result to the agency, as required. A newly released progress report on that grant also shows that EcoHealth and WIV conducted experiments changing the virus that causes Middle East respiratory syndrome (MERS), which is raising additional questions.
NIH noted in its letter that when the agency reviewed the original EcoHealth grant proposal, it determined the proposed experiments—designed to determine whether certain bat coronaviruses might infect humans—did not meet its definition of so-called gain-of-function (GOF) experiments that can make pathogens more dangerous to humans.
The letter is giving fuel to critics of NIH who say agency leaders have not been upfront with Congress about the work NIH was supporting in China, many of whom believe WIV could have created SARS-CoV-2, the virus behind the current pandemic. At the same time, NIH emphasized in a newly released analysis that any viruses being studied at WIV under the grant were too evolutionarily distant from SARS-CoV-2 to have been transformed into it.
NIH sent the 20 October letter to Representative James Comer (R–KY), ranking member of the House of Representatives oversight committee, along with a final progress report about the EcoHealth Alliance grant that NIH had funded and later canceled at then-President Donald Trump’s behest. (It was later reinstated but with conditions EcoHealth said it could not comply with.) The report describes studies conducted at WIV between June 2018 and June 2019 on recently collected bat coronaviruses circulating in the wild in China. Some examined whether their spike proteins, which the viruses use to attach to and infect cells, could when expressed in a previously known bat coronavirus called WIV1, bind to the human angiotensin-converting enzyme 2 cell receptor in a mouse model.
In a “limited experiment,” mice infected with one of these chimeras, SHC014 WIV1, “became sicker than those infected with the WIV1 bat coronavirus. As sometimes occurs in science, this was an unexpected result … as opposed to something that the researchers set out to do,” states the letter from NIH Principal Deputy Director Lawrence Tabak.
Before the chimera work was funded, NIH had determined it was not GOF research involving what NIH calls “enhanced pathogens of pandemic potential,” because neither the new bat coronaviruses nor WIV1 were known to infect humans, the letter says. But the letter says the terms of the grant stated that if the virus experiments produced certain results, such as “a one log increase in [virus] growth,” EcoHealth should inform NIH “immediately” and that NIH would do a “secondary review” of the research, to see whether it should be re-evaluated or new biosafety measures imposed.
But “Ecohealth failed to report this finding right away, as was required by the terms of the grant,” the letter states. It says EcoHealth now has 5 days to submit all unpublished data from the project.
EcoHealth embraced NIH’s backing that it had not created SARS-CoV-2, but also challenged the agency’s letter in a statement: “As the NIH states, the science is clear: none of the coronaviruses EcoHealth Alliance researched bear a close enough resemblance to the virus that causes COVID-19 to have played any role in its emergence. EcoHealth Alliance is working with the NIH to promptly address what we believe to be a misconception about the grant’s reporting requirements and what the data from our research showed. These data were reported as soon as we were made aware, in our year 4 report in April 2018. NIH reviewed those data and did not indicate that secondary review of our research was required, in fact year 5 funding was allowed to progress without delay. We are also working to answer any questions NIH has about the research on this R01 grant, which is not currently ongoing.”
Critics of NIH who claim the agency has lied about the work it funded at WIV pounced on the letter. Rutgers University, Piscataway, microbiologist Richard Ebright, a prominent critic of GOF research, commented in a tweet: “NIH corrects untruthful assertions by NIH Director [Francis] Collins and NIAID [National Institute of Allergy and Infectious Diseases] Director [Anthony] Fauci that NIH had not funded gain-of-function research in Wuhan.”
Virologists who have reviewed the EcoHealth grant disagree on whether the chimera experiments fit the U.S. definition of GOF research of concern, according to a story last month in The Intercept. That media organization, which had sued under public records laws to force NIH to release the final progress report, today noted the report also detailed chimeric virus experiments with the MERS virus, which infects humans; the EcoHealth report describes changing the binding properties of the spike protein of the MERS virus. One virologist told The Intercept the experiment was “sort of crazy” and “definitely gain of function” research.
Along with its letter to Congress, NIH appended and also posted online a new analysis asserting that the viruses studied at WIV under the grant share no more than 96% to 97% of the SARS-CoV-2 sequence, which puts the viruses “decades” of evolution apart.
“The naturally occurring bat coronaviruses studied under the NIH grant are genetically far distant from SARS-CoV-2 and could not possibly have caused the COVID-19 pandemic. Any claims to the contrary are demonstrably false,” the agency said in a statement.