Hi @angie_rasmussen, thanks for asking these important questions about risk / benefits of different types of virology experiments. Because you locked your Tweet thread, I can't reply, so will post my thoughts here in a new thread that anyone can reply to. 🧵
https://twitter.com/angie_rasmussen/status/1436360111698726936
This is not about being pro- or anti-chimeric virus, but about risks of specific experiments. As scientists we have this responsibility. My favorite essay is Feynman's The Value of Science (calteches.library.caltech.edu/40/2/Science.p…), which he wrote after his field of physics built nuclear bomb. 
As we all know, experiments that manipulate viruses have yielded important scientific insights & been of tremendous value to human health. This includes smallpox vaccine, oncolytic viruses, gene delivery, etc. Even some vaccines (eg, J&J #SARSCoV2 vaccine) are chimeric viruses!
However, certain uses of viruses can also be dangerous. For instance, 1977 flu pandemic was caused by misguided use of a flu strain (
https://twitter.com/jbloom_lab/status/1385664869949599744). There have been lab accidents w other viruses such as smallpox and SARS-CoV-1 that caused small outbreaks.
So we virologists have to leverage science to benefit human health & knowledge while mitigating risks. My roadmap for thinking about this is following article by @mlipsitch (journals.asm.org/doi/10.1128/mB…). He highlights specific risks of *potential pandemic pathogens*.
Potential pandemic pathogens are viruses that could cause a global pandemic if they somehow escaped from lab. Viruses that pose such risks include ones that caused historical pandemics but are now extinct (smallpox, 1918 flu, H2N2 flu) and...
... new viruses that we think might plausibly have potential to cause a pandemic if they infected humans. Viruses in this class include avian H5N1 and H7N9 flu, and MERS- and SARS-like coronaviruses.
The *explicit goal* of EcoHealth Alliance grant in question (documentcloud.org/documents/2105…) was to collect bat SARS-like coronaviruses thought to pose high risk of being able to spill over to humans, bring them back to Wuhan Institute of Virology & characterize them experimentally.
Some experiments were protein-based or pseudotype assays, which are safe. But others included testing live viruses or chimeras w other SARS-like bat CoVs in cells & humanized mice to try to assess how dangerous they might be to humans (Aim 3 of grant).
In my view, this last part poses unacceptable risks. Why? If premise of grant is correct & these bat CoVs pose pandemic risk, then accident could manifest by human infections with a new SARS-like CoV in Wuhan that could spread globally & potentially kill millions of people.
This doesn't mean we need to limit all (or even most) work w coronaviruses. For instance #SARSCoV2 is no longer potential pandemic pathogen (it's endemic) & studying mutations informs vaccines. Today accident w #SARSCoV2 would not trigger new pandemic, so current safety fine.
Indeed, the vast majority of virology is plenty safe with current rules--and can bring great value to human health. It's just potential pandemic pathogens that worry me.
You also referenced two papers by my group. Let me explain why I don't think either poses potential pandemic pathogen risks.
In this paper (elifesciences.org/articles/03300) we measured effects of all mutations to flu HA on viral growth in culture, & in related papers we have done same for antibody binding. Certainly if we did such experiments w H5N1 or H7N9 or 1918 flu, there would be pandemic risk!
However, the paper you mentioned used the A/WSN/1933 (H1N1) strain, which is a heavily lab-adapted strain that has been passaged in mice and culture for decades, is thought to be unable to infect humans, and is generally considered very safe at BSL-2. Other work...
... we have done in this area uses HAs from human endemic H3N2 or H1N1 strains & all other genes from A/WSN/1933. These are intentional choices to ensure we are *not* working strains that pose any pandemic risk. These experiments are also of value for vaccine strain selection.
The second paper you reference is this one (mdpi.com/1999-4915/12/9…). In that paper, we replace the NA gene of the A/WSN/1933 flu strain with a gene that expresses RBD of #SARSCoV2 to induce neutralizing antibodies against that protein.
The goal is to make a vaccine, and again we use a "safe" flu strain, attenuate it by removing a gene, and simply express RBD as an antigen that confers no functional property on virions. Again, this poses no plausible pandemic pathogen risk.
In fact, a similar flu vectored RBD vaccine developed by another group is in phase 2 clinical trials in humans (chictr.org.cn/showprojen.asp…).
If you disagree with these assessments, I'd of course be happy to hear your specific reasoning as well as those of anyone else. I fully agree it is important to critically assess risks of experiments, and welcome any feedback.
Also, as a practical matter, the public that so generously funds the work of all scientists is increasingly interested in risks and benefits of certain types of virology experiments (washingtonpost.com/nation/interac…).
If we want to keep getting this generous support, we virologists need to honestly and openly discuss risks / benefits so we and public can assess the best ways to leverage power of science for good without creating undue risks.
Finally, for reference here is the excellent article by @fastlernerer @MaraHvistendahl @maiahibbett that @angie_rasmussen refers to in her original Tweet: theintercept.com/2021/09/09/cov…
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