Researchers’ tests of lab-made version of the Covid virus come under scrutiny

RResearch at Boston University testing a lab-created hybrid version of the SARS-CoV-2 virus is generating heated headlines claiming the scientists involved may have unleashed a new pathogen.

There is no evidence that the work performed under Biosafety Level 3 precautions at the BU’s National Emerging Infectious Diseases Laboratories was performed improperly or unsafely. It was even approved by an internal biosafety review committee and Boston’s Public Health Commission, the university said Monday night.

But it has become clear that the research team has not approved work with the National Institute of Allergy and Infectious Diseases, which was one of the project’s funders. The agency said it is looking for answers to why it first learned of the work through media reports.

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Emily Erbelding, director of the NIAID’s division of microbiology and infectious diseases, said the BU team’s original grant applications did not specify that the scientists wanted to do this precise work. Also, in the progress reports it provided to NIAID, the group did not make it clear to the group that it was conducting experiments that involved boosting a pathogen with pandemic potential.

“I think we’re going to have conversations in the next few days,” Erbelding told STAT in an interview.

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When asked whether the investigative team should have informed NIAID of its intention to do the job, Erbelding said, “We wish they had, yes.”

The research has been posted online as a preprint, which means that it has not yet been peer-reviewed. The senior author is Mohsan Saeed, of the BU’s National Emerging Infectious Diseases Laboratories. STAT contacted Saeed on Monday, but had not received a response at the time this article was published.

In email comments, the university later disputed some media outlets’ claims that the work had created a more dangerous virus.

The email, from Rachel Lapal Cavallario, associate vice president for public relations and social media, said the work was not, as alleged, a job gain study, a term that refers to manipulation of pathogens to make them more dangerous. “In fact, this research created the virus [replication] less dangerous,” the email said, adding that other research groups have conducted similar work.

In the paper, Saeed and colleagues reported on research they conducted that created a hybrid or chimeric virus — fusing the spike protein from an Omicron version of SARS-2 with a virus from the Wuhan strain, the original version that came from China. in 2020. Omicron viruses first emerged in late 2021 and have since fragmented into multiple different sub-variants.

The aim of the study was to determine whether the mutations in the Omicron spike protein were responsible for this variant’s increased ability to evade the SARS-2 immunity that humans have built up, and whether the changes led to the lower severity of Omicron.

However, the tests showed that the chimeric virus was more deadly to a species of lab mice than Omicron itself, killing 80% of the infected mice. Importantly, the original Wuhan strain killed 100% of the mice in which it was tested.

The study concludes that mutations in the spike protein of the Omicron variant are responsible for the strain’s ability to evade immunity that humans have built up through vaccination, infections, or both, but they are not responsible for the apparent decline. of the severity of the Omicron viruses.

“Consistent with studies published by others, this work demonstrates that it is not the spike protein that causes the pathogenicity of Omicron, but other viral proteins. Determination of those proteins will lead to better diagnostics and disease management strategies,” Saeed said in a commentary distributed by the university.

Research that has the potential to make pathogens more dangerous has been a hot-button issue for years. About a decade ago, a high-profile debate about whether it was safe to publish controversial studies on a dangerous bird flu virus, H5N1, led to a rewrite of the rules surrounding this type of work. Another policy review is currently underway, led by the National Science Advisory Board for Biosecurity.

The controversy surrounding research into pathogens with pandemic potential has been gaining ground since the onset of the Covid-19 pandemic, which some scientists and others believe is an accidental or deliberate result of research on bat coronaviruses at the Wuhan Institute of Virology in the United States. Chinese city where the pandemic is believed to have started. (There is a lot of evidence pointing to the virus spreading from a wet market in the city, not from the Wuhan lab. But proving that nothing happened three years later is a challenge that may be impossible to meet. .)

Under NIAID policy, proposals to conduct federally funded research that could produce so-called enhanced pathogens with pandemic potential must be referred to a committee that would assess the risks and benefits of the work. The policy is known as the P3CO framework.

Erbelding said the NIAID probably would have convened such a committee in this case had it known that Saeed’s team planned to develop a chimeric virus.

“What we would have wanted to do is talk in advance about what exactly they wanted to do, and if it fit what the P3CO framework defines as an enhanced pathogen of pandemic potential, ePPP, we could have submitted a package for review by the committee convened by HHS, the Office of the Assistant Secretary for Preparedness and Response. That’s what the framework says and that’s what we would have done,” she said.

However, Erbelding noted that some of the media coverage of the study overestimates the risk the work may pose. “That 80% death rate, that headline doesn’t tell the whole story,” she said. “Because Wuhan” – the original species – “killed all mice.”

The death rate in this strain of mice when infected with these viruses raises questions about how good they are for what happens when humans are infected with SARS-2. The Wuhan tribe killed less than 1% of those infected.

Virologist Angela Rasmussen, who was not involved in the study, had some sympathy for the BU scientists and said there is ambiguity in the rules as they are currently written.

“Because so much of the definition of ePPP involves ‘reasonable anticipation’ of outcomes in humans (and animal models aren’t always good proxies of this), it’s very difficult for researchers to say ‘Oh yeah, this is ePPP,’ he wrote. Rasmussen in response to questions from STAT.

“When in doubt, I would personally contact NIAID for clarification, but it is often not clear when additional guidance is needed. And because it’s not very transparent, it’s hard to look at other decisions the NIAID has made as examples,” she said.

“I’m tired of people suggesting that virologists and NIAID are reckless or don’t care about biosecurity,” said Rasmussen, a coronavirus expert at the Vaccine and Infectious Disease Organization at the University of Saskatchewan. “That’s not the problem. The problem is that the guidelines and expectations for many experiments are not clear and the process is not transparent.”

— This article has been updated with comments from Boston University and the lead author of the article.

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