The National Institutes of Health allowed a U.S. nonprofit it funds to police its own controversial research on bat coronaviruses in China, raising new concerns about insufficient oversight at the agency.
Detailed notes on NIH communications obtained by The Intercept show that beginning in May 2016, agency staff had an unusual exchange with Peter Daszak, the head of EcoHealth Alliance, about experiments his group was planning to conduct on coronaviruses under an NIH grant called “Understanding the Risk of Bat Coronavirus Emergence.” The notes were taken by congressional staff who transcribed the emails.
EcoHealth was entering the third year of the five-year, $3.1 million grant that included research with the Wuhan Institute of Virology and other partners. In a 2016 progress report, the group described to NIH its plans to carry out two planned experiments infecting humanized mice with hybrid viruses, known as “chimeras.”
The plans triggered concerns at NIH. Two staff members — Jenny Greer, a grants management specialist, and Erik Stemmy, a program officer handling coronavirus research — wrote to EcoHealth Alliance to say that the experiments “appear to involve research covered under the pause,” referring to a temporary moratorium on funding for gain-of-function research that would be reasonably anticipated to make MERS and SARS viruses more pathogenic or transmissible in mammals. Generally, gain-of-function research involves manipulating viruses to give them new attributes; it becomes of concern to the government when the altered viruses appear likely to cause more severe disease or spread more easily among humans.
One of the experiments proposed by EcoHealth Alliance involved making chimeras from the MERS virus. The other experiment used chimeras developed from bat viruses related to SARS. The researchers went on to infect the genetically engineered mice with the altered viruses.
Initially, NIH staff appeared intent on enforcing the funding pause. The two administrators requested additional information from EcoHealth Alliance within 15 days and noted that the next round of funding would be withheld until the information was received. They also asked the group to provide a detailed description of changes that would allow the researchers to pursue their aims without conducting the dangerous experiments.
Agency staff adopted language that EcoHealth Alliance crafted to govern its own work.
But what happened next sets off alarm bells for biosafety advocates: Agency staff adopted language that EcoHealth Alliance crafted to govern its own work. The agency inserted several sentences into grant materials describing immediate actions the group would take if the viruses they created proved to become more transmissible or disease-causing as the result of the experiments.
Although the experiments demonstrate a lack of oversight and present dangers to public health, according to several scientists contacted by The Intercept, none of the viruses involved in the work are related closely enough to SARS-CoV-2 to have sparked the pandemic.
In December 2017, the funding for some gain-of-function research was resumed under carefully constructed guidelines for “Potential Pandemic Pathogen Care and Oversight,” or P3CO — but the language suggested by Daszak helped the group evade this oversight as well. In July 2018, NIAID program officers decided that the experiments on humanized mice — which had been conducted a few months earlier — would get a pass from these restrictions as long as EcoHealth Alliance immediately notified appropriate agency officials according to the circumstances that the group had laid out.
While it is not unusual for grantees to communicate with their federal program officers, the negotiation of this matter did not appropriately reflect the gravity of the situation, according to Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center. “The discussions reveal that neither party is taking the risks sufficiently seriously,” said Bloom. “MERS-CoV has killed hundreds of people and is thought to pose a pandemic risk, so it’s difficult to see how chimeras of MERS-CoV with other high risk bat coronaviruses shouldn’t also be considered a pandemic risk.”
“The NIH is bending over backward to help people it’s funded.”
“It’s absolutely outrageous,” said Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris. “The NIH is bending over backward to help people it’s funded. It isn’t clear that the NIH is protecting the U.S. taxpayer.”
The NIH did not respond to questions about the communications with Daszak. EcoHealth Alliance did not immediately respond to questions.
In a written response to questions submitted in September and October, an NIH spokesperson told The Intercept that the rule that was supposed to trigger a stop to the research was added “out of an abundance of caution.” Similarly, in a letter sent to the House Committee on Oversight and Reform last month, NIH principal deputy director Lawrence Tabak called the rule “an additional layer of oversight,” implying that the agency had devised the rule itself. But the notes reviewed by The Intercept show that the language was inserted at Daszak’s suggestion and that the NIH and EcoHealth Alliance worked together to evade additional oversight.
Daszak responded to the NIH on June 8, 2016, arguing that, because EcoHealth Alliance’s proposed hybrid viruses were significantly different from the SARS virus, which was already known to infect humans, the experiments were not gain-of-function research and should not be restricted.
Daszak also pointed out that WIV1, the parent of the proposed chimeric SARS-like viruses, “has never been demonstrated to infect humans or cause human disease,” according to the transcribed emails. And he said that previous research “strongly suggests that the chimeric bat spike/bat backbone viruses should not have enhanced pathogenicity in animals.” The NIH would go on to accept these arguments.
But the group’s argument that its viral research did not pose a risk of infection appears to contradict the justification for the work: that these pathogens could potentially cause a pandemic. “The entire rationale of EcoHealth’s grant renewal on SARS-related CoVs is that viruses with spikes substantially (10-25%) diverged from SARS-CoV-1 pose a pandemic risk,” said Bloom. “Given that this is the entire rationale for the work, how can they simultaneously argue these viruses should not be regulated as potential pandemic pathogens?”
The NIH has not made the correspondence public. Instead, the agency arranged for an “in camera” review for select congressional staff. The staffers were allowed to read and take notes on printed copies of the written exchange — an unusual approach for grant communications that are in the public interest. The Intercept reviewed notes taken by congressional staff.
“Given the importance and interest in this topic, it’s important for the NIH to be fully transparent about the research they support and how they make crucial decisions about the regulation of research on potential pandemic pathogens,” said Bloom.
The Escape Clause
Regulating risky research is the NIH’s role. But Daszak gave his group a way out. If the recombinant viruses grew more quickly than the original viruses on which they were based, he suggested, EcoHealth Alliance and its collaborators would immediately stop its research and inform their NIAID program officer. Specifically, he suggested a threshold beyond which his researchers would not go: If the novel SARS or MERS chimeras showed evidence of enhanced virus growth greater than 1 log (or 10 times) over the original viruses and grow more efficiently in human lung cells, the scientist would immediately stop their experiments with the mutant viruses and inform their NIAID program officer.
In a July 7 letter to EcoHealth Alliance, NIH’s Greer and Stemmy formally accepted Daszak’s proposed rule. The chimeric viruses were “not reasonably anticipated” to “have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route,” the administrators concluded, according to the transcribed emails.
The language that the NIH later inserted into the grant was strikingly similar to what Daszak proposed: “Should any of the MERS-like or SARS-like chimeras generated under this grant show evidence of enhanced virus growth greater than 1 log over the parental backbone strain you must stop all experiments with these viruses.”
But when the scientists conducted the experiments in 2018, one of the chimeric viruses grew at a rate that produced a viral load of log 4 — or 10,000 times — greater than the parent virus. Even so, the work was allowed to proceed.
Despite the careful wording meant to assure the agency that the research would be immediately halted if it enhanced the viruses’ pathogenicity or transmissibility, EcoHealth violated its own rule and did not immediately report the concerning results to NIH, according to the letter from NIH’s Tabak.
In a letter sent to NIH on October 26, Daszak insisted EcoHealth Alliance did comply with all the requirements of its NIH grant, pointing out that the group reported the results of its experiment in its year four progress report, which it submitted to the agency in April 2018 — and that no one at the agency responded to the description of the experiment. “At no time did program staff indicate to us that this work required further clarification or secondary review,” he wrote.
Daszak also argued in the letter that the viral growth reported in the year four progress report did not correspond to the viral growth outlined in the rule he himself had devised. “The experiment we reported to NIH actually shows genome copies per gram not viral titer.”
Daszak emphasized that the growth of the chimeric viruses in the genetically engineered mice was enhanced only in the early part of the experiment. “By day 6-8, there was no discernably significant difference among the different viral types,” he wrote.
Yet virologists contacted by The Intercept dismissed both the distinction between viral titer and viral growth and the focus on the latter part of the mouse experiment, when the rate of growth between the viruses had evened out.
“I don’t agree with their interpretation,” said Wain-Hobson, of the Pasteur Institute. He described the EcoHealth Alliance’s response as “hairsplitting” and said that viral growth inevitably peters out. “Every growth of a virus comes to a plateau. This has been known since time immemorial,” said Wain-Hobson. “They have chosen this interpretation because it suits them.”
NIH officials have previously stated unequivocally that the agency did not fund any gain-of-function research in Wuhan. “The NIH has not ever and does not now fund gain-of-function research in the Wuhan Institute of Virology,” said Anthony Fauci, the head of the NIAID, during a Senate hearing in May. Fauci is scheduled to testify before the Senate health committee tomorrow morning.
In its statement to The Intercept, an NIH spokesperson wrote, “the Agency did not support the kind of ‘gain of function’ research warranting the additional and unique P3CO oversight identified by stakeholders during extensive prior policy development. To claim otherwise is incorrect and irresponsible.” And in his letter last month, Tabak reiterated the claim that the research was not gain-of-function.
But the correspondence with Daszak makes clear that at least some at the agency were concerned that EcoHealth Alliance’s proposed experiments met the criteria for gain-of-function research of concern as early as 2016.
According to Richard Ebright, a molecular biologist at Rutgers University who has criticized the lack of federal oversight of gain-of-function research, the fact that the NIH allowed EcoHealth Alliance to write its own rules is further evidence of the NIH’s regulatory failure. “This is like the teacher giving you the opportunity to write your own homework problem and grade your own homework when you turn it in. Then you decide the teacher is so lenient, there’s no need to hand it in,” said Ebright. “The oversight process clearly failed.”
Beyond the question of oversight, others question whether these experiments should be conducted at all.
“In addition to the legalistic questions of whether EcoHealth and NIH were adhering to current guidelines,” said Bloom, “we urgently need a broader discussion about whether it’s a good idea to be making novel chimeras of coronaviruses that are at this point universally acknowledged to pose a pandemic risk to humans.”