BU lab wasn’t required to clear potentially controversial study with NIH, director says

The director of a Boston University laboratory that conducted potentially controversial research on the viruses that cause Covid-19 said his institution didn’t clear the work with the National Institutes of Health because it wasn’t funded by the federal agency.

Ronald Corley said the research, which was designed to explore what makes some SARS-CoV-2 viruses more pathogenic than others, was paid for with money from the university itself. The work was approved by the institutional biosafety committee of BU’s National Emerging Infectious Diseases Laboratories, and by Boston’s Public Health Commission.

Scientists from the BU facility posted results from their work in a preprint, a study that has yet to go through peer review. The British tabloid The Daily Mail published an explosive article about the work on Monday, suggesting the group had fabricated a more dangerous version of the SARS-2 Omicron variant.

In response to questioning from STAT, the National Institute of Allergy and Infectious Diseases, which had awarded two grants to the research group, said on Monday that it should have been informed about the nature of the work beforehand, in order for a review to be conducted.

Emily Erbelding, director of NIAID’s division of microbiology and infectious diseases, said that is the policy set out in what’s known as the P3CO framework, which lays out the rules for work that could lead to enhancement of dangerous pathogens.

“What we would have wanted to do is to talk about exactly what they wanted to do in advance, and if it met what the P3CO framework defines as enhanced pathogen of pandemic potential, ePPP, we could have put a package forward for review by the committee that’s convened by HHS, the office of the assistant secretary for preparedness and response. That’s what the framework lays out and that’s what we would have done,” she said.

But the policy only applies to work of this type that is funded by the federal government. And NIAID money was not used for this research, Corley said.

Some funding from NIAID went towards work that might be considered foundational to the questioned research. Corley said the team used some of the federal funds to develop a system for making plasmids it would need to do the later work.

He acknowledged it can be difficult to see where lines are drawn, when research groups are using different pots of money to fund their work.

“It is a murky world, but in our view because the funding was not supporting the work that was supported in this paper, that it wasn’t necessary to report it to NIH,” he said.

STAT asked the NIAID if it was satisfied with Boston University’s response. The agency’s response, received by email on Tuesday evening, did not directly answer the question, though it indicated the situation is still being investigated.

“NIH is examining the matter to determine whether the research conducted was subject to the NIH Grants Policy Statement or met the criteria for review under the HHS Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO framework),” the statement said.

Corley also challenged the notion that the work done by scientist Mohsan Saeed and colleagues was what is known as “gain of function” research. The group created a hybrid or chimeric virus — in which the spike protein of an Omicron version of SARS-2 was fused to a virus of the Wuhan strain, the original version that emerged from China in 2020. Omicron viruses first emerged in late 2021 and have since splintered into multiple different subvariants.

The purpose of the work was to see if the mutations in the Omicron spike protein were responsible for the lower rate of severity caused by Omicron viruses.

The testing actually showed, though, that the chimeric virus was more lethal to a type of lab mice than Omicron itself, killing 80% of the mice infected. But the original Wuhan strain killed 100% of mice it was tested in. That suggests that the spike protein itself is not responsible for the pathogenicity of SARS-2 viruses, Corley said.

He noted that because the chimeric virus was less dangerous in mice than the original strain, this work could not be characterized as gain of function research. That is unlikely to assuage critics of the work, who may argue that the Wuhan strain is not the right benchmark to use as a comparison, given that it no longer circulates. The chimeric virus was more pathogenic than the currently circulating SARS-2 viruses, which are Omicron variants.

But it is important to note that the severity in the species of mice used in the experiment is not reflective of what happens in people. All of the mice exposed to the original SARS-2 viruses died. Less than 1% of people who contracted those viruses died.

Corley said that BU safety protocols require that if researchers produce a pathogen that is more virulent than the Wuhan strains, they must immediately report it to the Institutional Biosafety Committee. Saeed’s study protocol further stipulated that if such an event occurred, he would immediately stop the work and destroy the viruses, Corley noted.

STAT approached Saeed for an interview but he did not respond to the request.

Corley said the principal investigators of the study — Saeed is one of two — spoke Tuesday with their program managers at the NIH.

“They support the work that we’re doing and we certainly want to make sure that we are on comfortable ground,” Corley said.

— This article has been updated with a comment from the National Institute of Allergy and Infectious Diseases.

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