Researchers’ tests of lab-made version of Covid virus draw scrutiny

RResearch at Boston University that involved testing a hybrid lab-made version of the SARS-CoV-2 virus is generating heated headlines alleging that 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 National Emerging Infectious Diseases Laboratories, was performed in an inappropriate or unsafe manner. In fact, it was approved by an internal biosafety review committee and the Boston Public Health Commission, the university said Monday night.

But it has become clear that the research team did not approve of the work with the National Institute of Allergy and Infectious Diseases, which was one of the funders of the project. The agency said it will seek some answers as to why it first found out about the job through media reports.

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Emily Erbelding, director of 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. The group also didn’t make it clear that it was conducting experiments that might involve improving a pathogen with pandemic potential in the progress reports it provided to NIAID.

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

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When asked if the research team should have informed NIAID of their intention to do the work, Erbelding said, “I wish they had, yes.”

The research has been published online as a preliminary version, which means it has not yet been peer-reviewed. The lead author is Mohsan Saeed of the BU National Emerging Infectious Diseases Laboratories. STAT contacted Saeed on Monday, but had not received a response by the time this article was published.

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

The email, from Rachel Lapal Cavallario, associate vice president of public relations and social media, said the work was not, as claimed, gain-of-function research, a term that refers to manipulating pathogens to make them more dangerous. . “In fact, this research made the virus [replication] less dangerous,” the email stated, adding that other research groups have done similar work.

In the article, Saeed and colleagues reported on research they conducted that involved creating a chimeric or hybrid virus, in which the spike protein from an Omicron version of SARS-2 was fused with a virus from the Wuhan strain, the original version that emerged from China. in 2020. Omicron viruses first emerged in late 2021 and have since divided into multiple different subvariants.

The goal of the research was to determine whether mutations in the Omicron spike protein were responsible for this variant’s increased ability to evade immunity to SARS-2 that humans have developed, and whether the changes led to the lower rate of Omicron gravity.

However, tests actually showed that the chimeric virus was more lethal to one class of laboratory mice than Omicron itself, killing 80% of infected mice. Importantly, the original strain from Wuhan killed 100% of the mice it was tested on.

The conclusion of the study is that mutations in the spike protein of the Omicron variant are responsible for the strain’s ability to evade immunity that people have developed through vaccinations, infections or both, but are not responsible for the apparent decrease in the severity of the Omicron Virus.

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

Research that has the potential to make pathogens more dangerous has been a hot topic 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 around this kind of work. Another review of the policy is currently underway, led by the National Scientific Advisory Council for Biosafety.

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Controversy surrounding research on pathogens with pandemic potential has gained ground since the start of the covid-19 pandemic, which some scientists and others believe may have been an accidental or deliberate result of bat coronavirus research in the world. Wuhan Institute of Virology in China. city ​​where the pandemic is believed to have started. (There’s plenty of evidence pointing to the virus spreading from a wet market in the city, not the Wuhan lab. But proving something didn’t happen three years after the fact is a challenge that may be impossible to meet.)

Under the policy, which is administered by the Department of Health and Human Services, proposals to conduct federally funded research that could produce so-called enhanced pathogens with pandemic potential must be referred to an HHS committee that would assess the risks and benefits of the work. . . The policy is known as the P3CO framework.

Erbelding said that if NIAID had known of the BU group’s plans to develop a chimeric virus, it likely would have conducted its own review to see if the matter should be referred to the HHS committee.

“What we would have wanted to do is talk about exactly what they wanted to do ahead of time, and if it met what the P3CO framework defines as enhanced pathogen with 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 sets the framework and that’s what we would have done,” he said.

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

The mortality rate seen in this strain of mice when infected with these viruses raises questions about how good they are as a model for what happens when people become infected with SARS-2. The Wuhan strain killed less than 1% of those infected.

Virologist Angela Rasmussen, who was not involved in the research, sympathized with the BU scientists and said there is ambiguity in the rules as they are currently written.

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

“I would personally seek clarification from NIAID when in doubt, but it is often not obvious when additional guidance is warranted. And because it’s not very transparent, it’s hard to look for examples in other decisions NIAID has made,” she said.

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

— Correction: An earlier version of this article suggested that the federal program for research oversight is administered by the National Institutes of Health. The Department of Health and Human Services administers the program.

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Source: news.google.com