There is no indication that the work, carried out under biosafety level 3 precautions at BU’s National Laboratories for Emerging Infectious Diseases, was conducted in an inappropriate or unsafe manner. In fact, it was approved by an internal biosafety review board and the Boston Public Health Commission, the university said Monday night. However, it has become apparent that the research team did not clear the job with the National Institute of Allergy and Infectious Diseases, which was one of the funders of the project. The agency said it is seeking some answers about why it first learned about the project through media reports. advertising 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 expensive work. Nor did the team make clear that it was doing experiments that could involve enhancing a potential pandemic pathogen in the progress reports it provided to NIAID. “I think we will have conversations in the next few days,” Erbelding said in an interview with STAT. advertising Asked if the research team should have informed NIAID of its intention to do the work, Erbelding said, “We wish they had, yes.” The research has been posted online as a preprint, meaning it has not yet been peer-reviewed. The senior author is Mohsan Saeed, of BU’s National Laboratories for Emerging Infectious Diseases. STAT reached out to Saeed on Monday, but had not heard back by the time this article was published. In emailed comments, the university later disputed claims 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 project was not, as it claimed, profiteering from operations research, a term that refers to the 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 his colleagues reported research they conducted that involved creating a hybrid or chimeric virus — in which the spike protein of an Omicron version of SARS-2 was fused to a Wuhan strain virus, the original version that emerged from the China in 2020. The Omicron viruses first appeared in late 2021 and have since split into many different sub-variants. 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 a lower Omicron severity rate. The test showed, however, that the chimeric virus was more lethal to a strain of lab mice than the Omicron itself, killing 80% of the infected mice. Importantly, the original Wuhan strain 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 built up by humans through vaccination, infection, or both, but are not responsible for the apparent reduction in the severity of the virus Omicron. “Consistent with studies published by others, this work shows that it is not the spike protein that drives the pathogenicity of Omicron, but instead other viral proteins. Identifying these proteins will lead to better diagnostics and disease management strategies,” Saeed said in a commentary released by the university. Research into the potential to make pathogens more dangerous has been a topic of concern for many years. About a decade ago, a high-profile debate over whether it was safe to publish controversial studies done on a dangerous bird flu virus, H5N1, led to a rewriting of the rules around this kind of work. Another review of the policy is currently underway, led by the National Biosafety Science Advisory Board. UPCOMING EVENT
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We host events nationwide (and virtually) to address the biggest issues in health and medicine. Browse our upcoming events to see what’s on the horizon. Controversy surrounding research into potentially pandemic pathogens 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 research on bat coronaviruses at the Wuhan Institute of Virology in China. city where the pandemic is believed to have started. (There’s plenty of evidence that the virus spread 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.) According to NIAID policy, proposals for federally funded research that could produce so-called enhanced pathogens of pandemic potential must be referred to a committee that will evaluate the risks and benefits of the work. The policy is known as the P3CO framework. Erbelding said that NIAID likely would have convened such a committee in this case if it had known that Said’s group was planning to develop a chimeric virus. “What we would like to do is talk about exactly what they wanted to do up front, and if it met what the P3CO framework defines as enhanced pandemic potential pathogen, the ePPP, we could have submitted a package for consideration by the committee convened by HHS, Office of the Assistant Secretary for Preparedness and Response. That sets the framework and that’s what we would do,” he said. Erbelding noted, however, that some media coverage of the study overstated the risk the work may have had. “That 80% death rate, that headline doesn’t tell the whole story,” he 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 a model it is for what happens when humans are infected with SARS-2. The Wuhan strain killed less than 1% of people infected. Virologist Angela Rasmussen, who was not involved in the research, had some sympathy for the BU scientists, saying there is ambiguity in the rules as they are currently written. “Because so much of the definition of ePPP relates to the ‘reasonable expectation’ of results in humans (and animal models are not always good proxies for that), it’s very difficult for researchers to say, ‘Oh yeah, that’s ePPP.’ , Rasmussen wrote. answering questions from STAT. “I personally would seek clarification from NIAID when in doubt, but it is often not obvious when additional guidance is needed. And because it’s not very transparent, it’s hard to see, for example, other decisions that NIAID has made,” he said. “I’m very tired of people suggesting that virologists and NIAID are reckless or don’t care about biosecurity,” said Rasmussen, a coronavirus expert at the University of Saskatchewan’s Institute of 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.” — This article has been updated to include comments from Boston University and the paper’s senior author. Get your daily dose of health and medicine every day with STAT’s free Morning Rounds newsletter. Register here.
