Irresponsible Gain of Function Research

Scientists at Boston University have grafted the new Omicron spike protein onto the old SARS-Cov-2 virus creating a new and deadlier version of Omicron.

bioRXiv: 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. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes3,8. 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 receptor49 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.

Some of the headlines (here, here, here and here) aren’t making clear that the newly created chimeric virus is deadlier than Omicron (in mice) but less deadly than the ancestral strain. Nevertheless, in my view, this is gain of function research that should have come under extra scrutiny. The authors, however, did not go through P3CO review, a rule requiring agencies under HHS to review grant applications for any research on “a credible source of a potential future human pandemic.” More specifically:

The HHS Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO Framework)(link is external) was established in 2017 to guide funding decisions on proposed research that is reasonably anticipated to create, transfer or use potential pandemic pathogens resulting from the enhancement of a pathogen’s transmissibility and/or virulence in humans, called ePPP research.

I think this research qualifies. Frankly, the authors of the study were irresponsible. Boston University also failed terribly in its oversight. I also put some blame on Anthony Fauci for evading and obfuscating earlier gain of function research in a way that suggested very little falls under this category. (Rand Paul was right about this). Note, I am not taking a position on whether this research should have passed P3CO review but it should have been subject to review. I am also well aware that BSL-3 labs are heavily regulated, greatly increasing the cost of useful research. Overregulation is a real cost than can make us less safe and secure.

Nevertheless, if there is even a 5% chance that the SARS-CoV-II pandemic started with a lab leak–and don’t trust anyone who tells you the probability is less than 5%–then we need more care and scrutiny of research on potential pandemic pathogens. Furthermore, the United States must lead if we are to have any influence at all on what happens elsewhere in the world.

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