New Lab-Made Covid-19 Coronavirus At Boston University Raises Questions

This was one of those should-have-seen-it-coming moments. On October 14, a team of researchers posted on bioRxiv a preprint that described how they had created a new hybrid version of the Covid-19 coronavirus in their lab at Boston University and used this lab-created virus to infect mice, which ended up killing 80% of the mice. These days, if you think that posting something that talks about a lab-created virus killing mice wouldn’t create a commotion, then in the words of the heavy metal band Judas Priest, you’ve got another thing coming.

Yep, it wasn’t too long before GOF claims about this research began on social media, with GOF in this case meaning “gain of function” rather than “go on friend.” For example, Senator Roger Marshall, MD, (R-Kansas) tweeted, “This research must stop immediately. It is unconscionable that NIH sponsors this lethal gain of function virus research through Boston University and EcoHealth Alliance in densely populated areas, creating potential to kill more people than any singular nuclear weapon.” Then there headlines like the following from Fox News: “Boston University researchers claim to have developed new, more lethal COVID strain in lab.” And The Daily Mail ran an article with the following rather lengthy headline: “EXCLUSIVE: ‘This is playing with fire – it could spark a lab-generated pandemic’: Experts slam Boston lab where scientists have created a new deadly Covid strain with an 80% kill rate.” In a word, yikes. In two words, umm yikes. Were such chatter and headlines justified?

Well, such talk and headlines prompted Boston University (BU) to issue the following statement that Rick Sobey quoted in an article for the Boston Herald: “This research is not gain-of-function research, meaning it did not amplify the Washington state SARS-COV-2 virus strain (original virus from 2020) or make it more dangerous.” The BU statement also added that “In fact, this research made the virus replicate less dangerous.” Presumably, they meant “less dangerous” or “in a less dangerous manner,” since you don’t tend to say things like “I shower less dangerous because the toaster was no longer in the tub.” Additionally, Sobey quoted Boston University as saying, “Ultimately, this research will provide a public benefit by leading to better, targeted therapeutic interventions to help fight against future pandemics.” The preprint did include a line that said, “All procedures were performed in a biosafety level 3 (BSL3) facility at the National Emerging Infectious Diseases Laboratories of the Boston University using biosafety protocols approved by the institutional biosafety committee (IBC).”

So what’s the truth? Was this truly gain-of-function research where an even more deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was created? Or was this perhaps loss-of-function research that was indeed of public benefit that could lead to better therapeutic interventions? Or was it something in between? And should the team led by Mohsan Saeed, PhD, an Assistant Professor of Biochemistry at Boston University, have taken more precautions before conducting the research and posting the preprint.

Well, let’s take a look at the preprint. The preprint described how the team had started with the original SARS-CoV-2 that spread in early 2020. This was the virus that started the pandemic before a fraternity and sorority of Greek alphabet-named variants and subvariants subsequently emerged. The research team then used a recombinant technique to introduce a different type of spike protein, the ones that stud the surface of the BA.1 Omicron subvariant, on to the surface of this original SARS-CoV-2. Next they infected sets of mice in the laboratory with three different versions of the SARS-CoV-2: the original virus, the Omicron variant, and this new lab-made hybrid. Each mice got only one version of the virus. The lab-created hybrid virus ended up being not very mice for 80% of them who received it, killing 80% of the squeakers. This was indeed more than the 0% of mice who died after being infected with the Omicron variant of the SARS-CoV-2. However, it was still less than the 100% of mice who died after being infected with the original SARS-CoV-2.

So if adding the Omicron spike protein to the original SARS-CoV-2 made it kill 20% fewer mice, was creating the hybrid virus technically gain-of-function research? The phrase gain-of-function research does include the word “gain” rather than “loss” or “no change.” This implies that the organism that’s being genetically altered has to actually gain in ability as a result. For example, giving a virus the ability to infect a species of animal that it wasn’t previously able to infect would qualify as gain-of-function research. So would helping a virus become more transmissible or more likely to cause worse disease. Therefore, technically, the experiments described by the pre-print may have actually been more like loss-of-function research or reduce-the-function-a-bit research.

Now, you may argue that while the virus happened to get a little weaker in this case, who’s to say that the opposite couldn’t have resulted instead. You may counter that when you mess with a virus’s genetic make-up, how can you know for sure whether the virus may get weaker versus stronger? Might this be a bit like going into plastic surgery where the surgeon says, “let’s see what happens” and maybe you’ll become more Instagram-able or maybe you’ll end up on the show “Botched?” Florian Krammer, PhD, an Endowed Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai, essentially tweeted about such concerns and uncertainty:

As you can see, Krammer tweeted that “you also need permission from the U.S. government” to perform such experiments.

So did Saeed and his team get such permission from the National Institutes of Health (NIH)? Ummm, according to Helen Branswell writing for STAT, this preprint did appear to catch the National Institute for Allergy and Infectious Disease (NIAID) by surprise. The pre-print credited NIAID, which is led by Anthony Fauci, MD, as one of the funders of this research. Based on what Emily Erbelding, M.D., M.P.H, Director of NIAID’s Division of Microbiology and Infectious Diseases, told Branswell, the Boston University team had not made it clear to NIAID in advance that they were actually going to conduct experiments that could be possibly perceived as gain of function research. For example, per Branswell, the team’s grant proposal had not describe this specific type of research.

Of course, when researchers get grants from the NIH, they don’t necessarily have to give the NIH a heads up about everything that they plan on doing. After all research is not like making a green bean casserole. Researchers don’t simply follow a set recipe. Instead, they often explore and try different things to see what may happen. Sure there are some restrictions. For example, you don’t want a laboratory funded to study a particular set of viruses to then suddenly go off and use their funding to study whether teddy bears can drive cars. But NIH grantees typically have some leeway to change course as long as established precautions are followed and the research is reasonably within the area of what the proposal had indicated

Things may be a bit different when altering dangerous pathogens, though, especially those that have already demonstrated that they can start a pandemic. And the SARS-Cov-2 is a pathogen whose LinkedIn profile should definitely include a line that says “successfully started a pandemic.” A number of politicians and social media accounts have continued to make claims that the Covid-19 pandemic began when a lab-created SARS-CoV-2 was released. Sure they haven’t yet produced any real scientific evidence to support such claims. But these days who needs to actual evidence before claiming something, right? There have also been claims that the NIH, specifically Fauci, has been supporting and funding gain-of-function research, despite Fauci and others vehemently denying such claims. Again, none of these claims have been proven.

Given this current claim-anything-you-want environment, perhaps the Boston University-based research team would have been better off giving the NIAID a little forewarning before dropping the preprint like a barbell in a swimming pool. You know the saying, “If a tree falls in a forest and no one is around to hear it, does it make a sound?” Well, what about when a tree falls in people’s bedrooms, bathrooms, or wherever they happen to be reading their social media feeds? When you conduct research that can be interpreted and misinterpreted in all kinds of ways, it’s better to communicate the potential implications of the research in advance, perhaps even before the experiments are conducted. In his tweet thread, Krammer added that the group got in trouble “because they did not ask for permission” and not because of the experiment itself per se:

Krammer argued that the experiments conducted by the Boston University team weren’t that different from what nature has already done. So might this be a naughty by nature situation? It remains to be seen what actually specifically occurred with the research and the events leading up to it. Branswell quoted Erbelding as saying, “I think we’re going to have conversations over upcoming days.”

Remember a preprint is not the same thing as a peer-reviewed publication in respectable scientific journal. Anyone who has Internet access and opposable thumbs can in theory readily post a preprint on the Internet. The Covid-19 pandemic has made it even more common for researchers to do such a thing. The justification has been that such info is immediately useful for society and that the process of peer-review and journal acceptance takes way too long. For example, preprints have allowed scientists to more quickly communicate information on the transmissibility of the SARS-CoV-2 and the efficacy of vaccines and treatments. However, this practice has had its drawbacks. It’s allowed a fair amount of bad quality studies and misinformation to gain unwarranted attention.

This preprint may not contain everything that one needs to know to assess this research, its safety, and potential implications. So it remains to be seen what will emerge from discussions between the research team and the NIAID. During the Covid-19 pandemic, it’s become clear that there needs to be clearer communications about what needs to be communicated when dangerous pathogen research is being conducted. It has to be clearly communicated to researchers handling dangerous pathogens what they can and shouldn’t do. When it comes to dangerous pathogen research, one shouldn’t just worry about the pathogens being released. The release of a preprint that can be readily misinterpreted in different ways could be a problem as well.