Did the Wuhan Institute of Virology engage in coronavirus gain-of-function research?

Question

Hannity said on Foxnews:

The Wuhan facility was experimenting with gain of function with coronaviruses

NewsMedical defines the term "gain of function research" as:

Gain-of-function research refers to the serial passaging of microorganisms to increase their transmissibility, virulence, immunogenicity, and host tropism by applying selective pressure to a culture.

Setting aside the question of who knew what at which point in time, is there evidence that the Wuhan Institute of Virology engaged in coronavirus research that "alters the virus in a way that increased its transmissibility, virulence, immunogenicity, and host tropism by applying selective pressure"?

This feels a like a duplicate, but I can't find the original. — Oddthinking, Jun 04 '21 at 18:30
@Oddthinking: it wasn't probably asked as such before, but surely related to https://skeptics.stackexchange.com/questions/45808/was-the-virus-which-causes-covid-19-made-in-a-chinese-lab The problem I have with such questions is that they are often used to validate a wider conspiracy theory by "narrowing" the question to one point in the theory. It's certainly the case that Trump is [doing that](https://www.bbc.com/news/world-us-canada-57352992) now and Fox News is just the accompaniment. — Fizz, Jun 04 '21 at 20:29
@Fizz We are here to answer questions and validate/invalidate claims, not babysit the “proper” opinions of people. — Just Some Old Man, Jun 04 '21 at 20:36
@Fizz So you're upset that circumstantial evidence might support a "conspiracy theory"? I'm afraid that's just the nature of conspiracies (and also truth finding and having to occasionally adjust one's views). *If* the Wuhan lab has done this kind of research, it makes sense to me that a thorough answer [here](https://skeptics.stackexchange.com/questions/45808/was-the-virus-which-causes-covid-19-made-in-a-chinese-lab) would address that. — , Jun 05 '21 at 03:20
@Fizz: I suspect I was thinking of [this question](https://skeptics.stackexchange.com/questions/50561/do-elements-of-the-genetic-code-of-sars-cov-2-provide-evidence-that-sars-cov-2-o) which also uses the clumsy term-of-art "gain of function". — Oddthinking, Jun 05 '21 at 04:38
@KonradRudolph And a thorough answer here can't address that? We've certainly understood for a long time that factual answers to certain questions can actually obscure the truth rather than reveal it, but isn't that a problem with answers? I don't want to get too meta on the comments here, so we can [continue in chat if you like](https://chat.stackexchange.com/rooms/126111/discussion-on-question-by-christian-did-the-wuhan-institute-of-virology-engage-i). — , Jun 05 '21 at 14:13
@fredsbend Honestly, the answer is probably no: without expert knowledge this is simply really hard to explain well. This is seriously complicated stuff, it’s absolutely unreasonable to expect that it’s easy enough to be understandable by a lay audience without causing mistunderstandings. *I* certainly don’t feel up to explaining it, and I’m told that I’m fairly good at breaking complicated things down for non-experts. — Konrad Rudolph, Jun 06 '21 at 17:06
@KonradRudolph You can vtc this question as too broad then... — , Jun 06 '21 at 18:48
I think one potential issue here is that the person posting the question looked up what the phrase means, while Hannity most likely threw it out there as a scary sounding buzz-phrase, with no idea of what it means in any context. — PoloHoleSet, Jun 09 '21 at 17:10

Ben Barden · Accepted Answer · 2021-06-08T00:41:51.267

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With the specific question and definitions provided, and a fairly broad definition of "engaged in"? Yes. We even have a published paper.

https://www.nature.com/articles/nm.3985

A paper published in 9 November 2015. The abstract includes:

Using the SARS-CoV reverse genetics system2, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

One of the authors is Shi Zhengli, who the Wuhan Institute of Virology page lists as "Principal Investigator, Research Group of Emerging Viruses". Another is Ge Xing-Ye, who (like Shi Zhengli) is noted in the paper itself as working for "Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology".

So, based on this alone, we can be pretty certain that at least two of the researchers at the Wuhan Institute of Virology were involved in at least one paper that included gain-of-function research on one or more coronaviruses. It seems reasonably likely that there was more, given the habits of researchers in general, but I can't guarantee that, and I'm not going to be the one to hunt it down.

Ironically, the point of the paper was to warn people of the possibility of a coronavirus-like outbreak.

Edit: As a point of clarification, the above is an accurate answer to the rather broad question asked. In particular, the above paper is on gain-of-function research with respect to mice. We do not currently have any evidence indicating that the Wuhan Institute of Virology was performing gain-of-function research with respect to humans, and we do have some fairly strong evidence suggesting that medical researchers in general draw a significant distinction between gain-of-function research with respect to those two species.

I have made certain adjustments to my answer accordingly, as it has been noted (fairly) that the original formation was unnecessarily easy to interpret as meaning more than it did.

edited Jun 08 '21 at 00:41

answered Jun 04 '21 at 17:58

Ben Barden

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I don't know if "ironic" is the word to use. The typical purpose of these papers and the research more generally is exactly that: people trying to figure out the risk of pandemic disease from existing viruses or potential combinations of the genetic diversity that's out there. – Bryan Krause Jun 04 '21 at 18:17
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@BryanKrause the irony is that either their efforts to protect us were what led to the epidemic (if it was their fault) or their efforts to protect us are leading to their being demonized for something that isn't their fault. Irony either way. – Ben Barden Jun 04 '21 at 18:19
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I take it back, I see your point. – Bryan Krause Jun 04 '21 at 18:20
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It is probably worth mentioning that the strains and methods used in this paper cannot be the source of SARS-CoV-2. – Jack Aidley Jun 05 '21 at 06:20
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@JackAidley I would suspect that this was not the only such paper produced. As such, the fact that the strains and methods of this *particular* paper (from 2015) can't have been the source seems like it's not particularly pertinent. I mean, this one was published in 2015. Of *course* it wasn't the source of the outbreak. Whatever experiments caused the outbreak (if that's how it happened) would probably have been being carried out in 2019, and are pretty much guaranteed to never see publication at all. – Ben Barden Jun 05 '21 at 19:05
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As Fizz's answer states, the mouse studies described in the linked paper were performed in the United States, not in the Wuhan facility: "All mouse studies were performed at the University of North Carolina". If you can't be bothered to hunt down a paper that actually confirms the existence of gain of function research that was carried out at the Wuhan facility, it seems this answer would be better if it were edited to remove the "Simply put? Yes" and replace it with a more detailed description. – paradisi Jun 06 '21 at 08:16
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You can "suspect" what you like but what you've actually find evidence for is what matters. Particularly as it turns out this experiment was done in the US and doesn't meet the questions definition of "gain of function" anyway. – Jack Aidley Jun 06 '21 at 15:22
@purposefulporpoise fair point. After a bit of further investigation, I have made some clarifying edits. Does this cover your concerns? – Ben Barden Jun 07 '21 at 03:30
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Thanks for the edits, and sorry for the unnecessarily antagonistic tone of my first comment. The remaining concern that I would have left is clarifying that the Wuhan facility does not seem to have been the physical location of the mouse-involved research activities reported in the referenced study; this seems pretty relevant to the implications of the initial claim. – paradisi Jun 07 '21 at 04:53
@purposefulporpoise I believe that the line talking about the fairly broad definition of "engaged in" that is required should be sufficient to cover that. Honestly, I resent the tendency on this site for people to insist that every question or answer that implies anything they don't like *must* include every scrap of counterargument they can come up with. I have literally had someone stop trying to argue about the acceptability of one of my questions because I revealed my personal opinion of a political figure. *It gets old*. – Ben Barden Jun 07 '21 at 17:09
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@BenBarden it could be even more ironic than that. NIH funded research to stabilize the spike protein to develop a vaccine for SARS well before the breakout. It could be the very research into the vaccine in the first place is what caused the outbreak. See timestamp at 22 minutes in their video documenting the vaccine development. https://videocast.nih.gov/watch=41289 – yters Jun 07 '21 at 22:00
The "clear distinction" between mice & humans isn't as clear as this A wants it to be. Evident from the cited paper itself ("To extend these findings, primary human airway epithelial (HAE) cultures were infected and showed robust replication of both viruses"), as well as eg https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30302-4 Consider the timeline necessary for when these humanized lung-cell mice used must have been created… – LangLаngС Jun 07 '21 at 23:09
@LangLаngС Properly interpreting that line (as to whether or not the modifications made would result in increased transmissibility to humans) would require reading and understanding the preceding couple of paragraphs. I attempted that, and failed. If you can actually understand that kind of text well enough to actually understand what they're saying and the implications thereof, then please, write up an answer for us yourself. I'd love to read it. – Ben Barden Jun 08 '21 at 00:39

score 38 · Answer 2 · edited Jun 08 '21 at 02:38

Actually, the main/corresponding author (Ralph Baric) of the paper cited in Barden's answer as evidence for "yes" argued in press statements quoted in the Washington Post that the answer is "no".

In a lengthy statement to The Fact Checker, Baric — who signed the letter calling for a new investigation — also pushed back against Paul’s assertions at the [Senate] hearing.

“The Baric laboratory has never investigated strategies to create super viruses,” he said. “Studies focused on understanding the cross-species transmission potential of bat coronaviruses like SHC014 have been reviewed by the NIH and by the UNC Institutional Biosafety Committee for potential of gain-of-function research and were deemed not to be gain of function.”

“We never introduced mutations into the SHC014 [horseshoe bat coronavirus] spike to enhance growth in human cells, though the work demonstrated that bat SARS-like viruses were intrinsically poised to emerge in the future,” he added. “These recombinant clones and viruses were never sent to China. Importantly, independent studies carried out by Italian scientists and others from around the world have confirmed that none of the bat SARS-like viruses studied at UNC were related to SARS-CoV-2, the cause of the COVID-19 pandemic.”

[...]

Update, May 19: The National Institutes of Health issued a statement to The Fact Checker which in part said: “NIH has never approved any grant to support 'gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans. The research proposed in the EcoHealth Alliance, Inc. grant application sought to understand how bat coronaviruses evolve naturally in the environment to become transmissible to the human population.” When gain-of-function research was paused, “this grant was reviewed again and determined by experts to fall outside the scope of the funding pause.”

The argument is basically around what constitutes "gain of function". The [Rand] Paul side disagrees:

“Despite Dr. Fauci’s denials, there is ample evidence that the NIH and the NIAID, under his direction, funded gain of function research at the Wuhan Institute of Virology,” said Paul spokeswoman Kelsey Cooper.

Besides the disagreement on the definition of GoF, it seems the actual research on those those engineered/chimera viruses was carried out at UNC (Baric's lab) in the US. It's a bit less clear what the contribution of the VIW co-authors (Shi) was to that paper. I'll update this answer if I find more clear info on this. (As the original/unmodified SHC014 was collected in China I suspect that's reason why Shi is a co-author to that paper.)

As the accepted answer draws its own conclusions, I'll draw mine: just based on that co-authoring of that paper, this claim is even more silly than claiming that iPhones are developed in China because they polish the aluminum for the cases there. In this case, the modified/"GoF" virus never left the US... if the claims of the papers' authors are correct. (iPhones at least are assembled in China, but the modified SHC014 was "made in USA" for any definition of "made"... in both intellectual and physical senses.) I can equally claim that "Stack Exchange has been engaged in validating Fox News stories" (for some definition[s] of "engaged" and "validating").

I upvoted your answer for the informative first part, which puts Ben's answer into more perspective, and _despite_ your rant in the last paragraph. You should consider deleting or rephrasing it. — Dubu, Jun 07 '21 at 13:23
I'm not sure if being corresponding author on this paper makes his (Ralph Baric) statement authoritative or extremely biased. — noslenkwah, Jun 07 '21 at 19:01
This answer would could be improved by describing which aspects of the research were performed in which facilities. I'm getting that there was at least one virologist from Wuhan on the author list. What did he/she do? Where were the actual experiments done? — Dave, Jun 07 '21 at 21:03

Did the Wuhan Institute of Virology engage in coronavirus gain-of-function research?

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