New lab-made Covid-19 coronavirus at Boston University raises questions

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It was one of those moments that should have seen it coming. On October 14, a team of researchers posted on bioRxiv a preprint describing 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 posting something about a lab-created virus killing mice wouldn’t create a stir, then in the words of heavy metal band Judas Priest, you have something else to come.

Yes, it wasn’t long before GOF claims about this research started on social media, GOF in this case meaning “gain of function” rather than “carry on friend”. For instance, Sen. Roger Marshall, MD, (R-Kansas) tweeted, “This search must stop immediately. It is unconscionable that the NIH is sponsoring this deadly gain in functional virus research through Boston University and the EcoHealth Alliance in densely populated areas, creating the potential to kill more people than any what a nuclear weapon. Then there are titles like this from FoxNews: “Researchers at Boston University claim to have developed a new, deadlier COVID strain in the lab.” And the Daily Mail published an article with the rather lengthy headline: “EXCLUSIVE: ‘It’s playing with fire – it could spark a lab-generated pandemic’: Experts slam the Boston lab where scientists created a deadly new strain of Covid with an 80% death rate.” In a word, yuck. In two words, uh yuck. Were such chatter and headlines justified?

Well, such speeches and headlines prompted Boston University (BU) to issue the following statement which Rick Sobey quoted in an article for the Boston Herald: “This research is not gain-of-function research, which means it did not amplify or amplify the Washington State SARS-COV-2 virus strain (2020 original virus) ‘made it more dangerous.” BU’s statement also added that “In fact, this research has made replicating the virus less dangerous.” Presumably they meant “less dangerous” or “in a less dangerous way”, since you don’t tend to say things like “I’m taking a less dangerous shower because the toaster wasn’t in the tub anymore “. Additionally, Sobey quoted Boston University as saying, “Ultimately, this research will provide public benefit by leading to better targeted therapeutic interventions to help combat future pandemics.” The preprint included a line that read, “All procedures were performed in a Biosafety Level 3 (BSL3) facility at the National Emerging Infectious Diseases Laboratories, Boston University using biosafety protocols approved by the Institutional Board of biosafety (IBC).

So what is the truth? Was this really gain-of-function research where an even deadlier severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was created? Or was it perhaps loss-of-function research that was indeed of public interest and could lead to better therapeutic interventions? Or was it something in between? And the team led by Mohsan Saeed, PhD, assistant professor of biochemistry at Boston University, should have taken more care before conducting the research and publishing the preprint.

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

So if adding the Omicron spike protein to the original SARS-CoV-2 caused it to kill 20% fewer mice, was creating the hybrid virus technically gain-of-function research? The search phrase on gain of function includes the word “gain” rather than “loss” or “no change”. This implies that the organism that is genetically modified must actually gain capacity as a result. For example, giving a virus the ability to infect an animal species that it was previously unable to infect would be considered gain-of-function research. So would helping a virus become more transmissible or more likely to cause more severe disease. Therefore, technically, the experiments described by the pre-print may actually look more like loss-of-function research or research on reducing a bit of function.

Now, some may argue that even though the virus weakened a bit in this case, who’s to say the opposite couldn’t have happened instead. They can counter that when you play with the genetic makeup of a virus, how can you know for sure if the virus can get weaker or stronger? Could it be a bit like stepping into plastic surgery where the surgeon says, “let’s see what happens” and maybe you’ll become more Instagramable or maybe you’ll end up on the show “Botched?” What if there is a not-so-pleasant surprise result?

Of note, according to Helen Branswell writing for STAT, this preprint seemed to take the National Institute of Allergy and Infectious Diseases (NIAID) by surprise. The preprint credited NIAID, which is led by Anthony Fauci, MD, as one of the funders of this research. From what Emily Erbelding, MD, MPH, director of NIAID’s Division of Microbiology and Infectious Diseases, told Branswell, the Boston University team did not specify in advance to the NIAID that she was actually going to conduct experiments that could be perceived as gain of function research. For example, according to Branswell, the team’s grant proposal did not outline this specific type of research.

Of course, when researchers receive NIH grants, they don’t necessarily have to tell the NIH about everything they plan to do. After all, research isn’t like making a casserole of green beans. Researchers don’t just follow an established recipe. Instead, they often explore and try different things to see what can happen. Of course, there are restrictions. For example, you don’t want a lab funded to study a particular set of viruses to suddenly spring up and use its funding to study whether teddy bears can drive cars. But NIH grantees generally have some leeway to change course as long as established precautions are followed and the research falls reasonably within the scope of what the proposal had indicated.

However, things can be a little different when it comes to modifying dangerous pathogens, especially those that have already been shown to be able to trigger a pandemic. And 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 claim that the Covid-19 pandemic began when a lab-created SARS-CoV-2 was released. Of course, they have yet to produce any real scientific evidence to back up such claims. But nowadays, who needs real proof before claiming something, right? There have also been allegations that the NIH, particularly Fauci, has supported and funded gain-of-function research, although Fauci and others have vehemently denied these claims. Again, none of these claims have been proven.

Given this current environment of pretending whatever you want, perhaps the Boston University-based research team would have done better to give NIAID a little warning before dropping the preprint like a bar in a swimming pool. You know the saying: “If a tree falls in a forest and no one is there to hear it, does it make a sound?” Well, what about when a tree falls in bedrooms, bathrooms, or wherever they read their social media feeds? When conducting research that can be interpreted and misinterpreted in all sorts of ways, it is best to communicate the potential implications of the research in advance, perhaps even before the experiments are conducted. It remains to be seen what really happened with the search and the events leading up to it. Branswell quoted Erbelding as saying, “I think we’re going to be having conversations over the next few days.”

Remember that a preprint is not the same as a peer-reviewed publication in a respectable scientific journal. Anyone with internet access and opposable thumbs can in theory easily publish a preprint on the internet. The Covid-19 pandemic has made it even more common for researchers to do such a thing. The rationale was that this information is immediately useful to society and that the peer review and journal acceptance process takes far too long. For example, preprints have allowed scientists to more quickly communicate information about the transmissibility of SARS-CoV-2 and the effectiveness of vaccines and treatments. However, this practice had its drawbacks. This has allowed a fair amount of poor quality studies and misinformation to attract unwarranted attention.

This preprint may not contain everything you need to know to evaluate this research, its safety and its potential implications. So it remains to be seen what will come out of the discussions between the research team and NIAID. During the Covid-19 pandemic, it has become clear that there needs to be clearer communications about what needs to be communicated when research on dangerous pathogens is being conducted. It should be made clear to researchers working with dangerous pathogens what they can and must not do. When it comes to researching dangerous pathogens, it’s not just about the released pathogens that you have to worry about. Publishing a preprint that can be easily misinterpreted in different ways could also be a problem.

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