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In totally fine and completely safe experiment, researchers curious about why Omicron is mild create chimeric horror virus that kills 80% of their mice
If they hadn't spliced Omicron spike onto ancestral SARS-2, though, we never would've known that "major determinants of viral pathogenicity reside outside of S," so there's that
The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date1-7 43 . The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.
To be clear: Just three years after Wuhan researchers decided it would be cool to insert a codon-optimised furin cleavage site at the S1/S2 junction of this interesting SARS-related bat virus they found, Boston researchers thought maybe it’d be fun to start mixing and matching different SARS-2 proteins to see if a new chimeric virus might be more exciting than boring old Omicron. The payoff is not any vaccine or treatment, but the mere knowledge that it is not just the spike protein that contributes to the pathogenicity of SARS-2. For extra fun, they did not conduct this research in space or at the bottom of the Marianas Trench, but in a BSL-3 facility at the National Emerging Infectious Diseases Laboratories on Albany Street in the Boston South End.
I doubt the Boston Chimeric Strain would’ve gotten very far outside the lab, because I think there are firm upper limits on the pathogenicity of any widely circulating seasonal respiratory virus that depends upon direct person-to-person contact. Still, though: Biological replicators freak me out. The most successful of them have a way of making all of us part of their extended phenotype and using our services to replicate more efficiently in more hosts. I don’t know how this works, exactly, but I do know that the pandemic has left us with a serious problem, namely legions of eager virologists tinkering with SARS-2 in labs all over the world. These guys were a serious problem before the pandemic, but now there are many more of them and they have never had so much funding. Virus enhancement is not hard, it does not require hypersophisticated equipment, it is within the skillset of literally thousands and thousands of postdocs and lab technicians. These blinkered lunatics are going to leak lab-enhanced viruses multiple times, and we just have to hope to the heavens that whatever they leak isn’t dangerous or doesn’t spread effectively. And the cherry on top of it all – what really makes this perfect – is that none of this research will have any meaningful payoff to compensate for the incredible risk, or any real salutary purpose at all. All of humanity has to live with this Sword of Damocles over their heads, because scientists need publications to secure grant funding and further their careers and SARS-2 is a hot topic right now. That is the only reason.
UPDATE: Berenson is of course right that the Boston Chimeric Strain seems to have been less lethal than the wild-type strains, which killed 100% of the humanised mice in the study. But, I’m just not much comforted by this. Beyond broader concerns with the entire enterprise of enhancing viruses in the lab for shits and giggles: The experimenters improved a slower-moving and more lethal wild-type strain by giving it the more infectious Omicron BA.1 spike. I think there are evolutionary reasons why such a combination is unlikely to arise naturally, and why this kind of research amounts to helping viruses achieve otherwise out-of-reach protein combinations for which our natural defences are ill-equipped.
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