A recent COVID-19 research paper generated outrage on Twitter dot com.
To be precise, the Twitter rage was about the research article, “Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 2 Omicron.” In the article, researchers at Boston University School of Medicine report engineering a mutant SARS-CoV-2 Omicron virus that has an 80% fatality rate in mice. You can see the survival data in the chart below. The engineered Omicron is labeled Omi-S.
You might also notice the regular Omicron version has a 100% survival rate, while the original, wild-type (WT) version had a 100% fatality rate.
The researchers made Omi-S by splicing the Omicron spike protein’s receptor binding motif (RBM) into the original SARS-CoV-2 genome.
This experiment was done because the Omicron RBM has greater affinity than WT virus to the human ACE2 receptor. But the WT virus is better able to infect cells in the lungs.
In theory this means Omi-S is better able to 1) bind to human cells and 2) damage the lungs than other known variants.
While Omi-S’ 80% fatality rate is cause for concern, it should be noted the mice in the study did not have natural immunity and were not vaccinated. Compare that to the US population where 85%-95% of people have pre-existing immunity from vaccination and/or natural immunity. Suffice to say, the mouse study’s 80% fatality rate occurred in experimental conditions absent in the real world.
For a period of time, a variant similar to Omi-S did exist in the real world. The variant was named XD, and was present back in March 2022. Variant XD had the Omicron spike protein and the rest of the Delta genome (see image below). However that variant failed to get a foothold and isn’t spreading today.
The issues raised on Twitter were more about viral gain-of-function (GoF) research than this specific study, though. Adding to the concern, the Boston University researchers appear to have performed the research without approval by the US government. Since XD variant already existed in the wild, it is unclear to what degree Boston Uuniversity’s GoF research violated regulations.
It should be noted, variant XD’s existence prior to the Omi-S publication demonstrates nature’s superior performance for testing the boundaries of viral evolution.
Regardless, concerns expressed on Twitter are justified after the emergence of SARS-CoV-2. To date it is unclear how the virus emerged, and there is reasonable suspicion it was created in a lab in China.
While GoF research has risks, from an virology and immunology perspective there are reasons to engage in the research.
Here are some questions GoF research could address:
To what degree is the virus capable of genetic drift and amino acid substitutions?
How do genetic drift and amino acid substitutions affect vaccine or natural immunity?
Is the virus capable of recombining with other variants or viruses?
What virus or variant is most likely to recombine with a current virus?
Which human cells are most susceptible to infection after viral recombination?
Does viral recombination change the route of transmission?
How pathogenic are the probable recombined viruses?
Can you create a vaccine, monoclonal antibodies or anti-viral medications that protect against current and probable future variants?
Which types of viruses are most concerning, and deserve more research focus?
Can you train machine learning models to better predict future variants?
Homeland defense is another reason to engage in GoF research. We cannot control everything that happens in the world, nor can we expect adversaries to live up to our moral standard. If CCP China did create SARS-CoV-2, then what would stop them from engineering another deadly virus? GoF research can help us prepare in case that happens.
At the same time, there are elements and people within the US Government who lack trust. Some of these people may even have had a hand in funding and/or engineering SARS-CoV-2.
The counter argument to GoF research for defense, is that Safetyism has been used by the US government to do a lot of shady stuff. So it is fair to ask, to what degree does our own government deserves trust in this domain?
Should we, or shouldn’t we engage in GoF research? Your opinion is as good as mine. There is a lot to be gained, and a lot to be lost. Humans are corruptible, morality is subjective, and humans can rationalize anything.
It seems with GoF research, we are damned if we do and damned if we don’t.