Boston University scientists undertake a gain of function experiment and create a chimeric recombinant SARS-CoV-2 virus with 80% mortality rate in mice.
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.
UPDATE 1 – 20th October 2022 – Scientists weigh-in on this preprint:
Marc Lipsitch: “This is clearly gain of function research. It added the function of evading immunity from the original strain. That does not necessarily imply it is a bad idea, but to deny this is gain of function is to misunderstand the meaning of the term.”
Richard Ebright: “This work constructed a laboratory-generated coronavirus that has the high immune escape properties of Omicron BA.1 and higher lethality than Omicron BA.1. It posed an existential risk, and simply served to confirm what other studies had already proved, which is that the lethality of a coronavirus is not just governed by the spike protein. It should not have gone ahead.”
Alina Chan: “This highlights the lack of oversight for research of this kind. If there is even a small chance that you might get something surprising from these experiments, you would want to have been doing them offshore and at biosafety level four, not a 10-minute drive from downtown Boston.”
UPDATE 2 – 20th October 2022 – Boston University issues a ham-fisted denial that their work is GOF
“We fulfilled all required regulatory obligations and protocols. Following NIAID’s guidelines and protocols, we did not have an obligation to disclose this research for two reasons. The experiments reported in this manuscript were carried out with funds from Boston University. NIAID funding was acknowledged because it was used to help develop the tools and platforms that were used in this research; they did not fund this research directly. NIH funding was also acknowledged for a shared instrumentation grant that helped support the pathology studies. We believe that funding streams for tools do not require an obligation to report.
Secondly, there was no gain of function with this research. If at any point there was evidence that the research was gaining function, under both NIAID and our own protocols we would immediately stop and report. All research at Boston University, whether funded by NIAID or not, follows this same protocol. We are in continued conversation with NIAID leadership and program officers.”
UPDATE 3 – Forbes.com: Who Thought This Was A Good Idea?
Some scientists continue to pursue gain-of-function work. In a new study, just released on the preprint server bioRxiv, a group of virologists at Boston University did the following. They took the Spike protein from the Omicron BA.1 strain of SARS-CoV-2 (that’s the strain that spread throughout the world last winter, often slipping past the protection offered by vaccines) and combined it with an early 2020 strain of the Covid-19 virus.
This experiment gave them a brand-new, never-before-seen strain of Covid-19. Was it more deadly? You bet!
UPDATE 4 – Dr John Campbell has a go at explaining this crazy scientific experiment
UPDATE 5 – Roger Skaer wades into the potential pandemic pathogen debate: