Wuhan, Wuhan-U, and Woohoo!

OK, this came from a threaded discussion I'm having off line. It sent me down a rabbit hole. The initial question is whether or not Anthony Fauci lied to Congress about gain of function research being done at the Wuhan Institute of Virology. I wanted to make use of the formatting here because there are a lot of quotes.

My reply: 

OK, I can see how you get to where you are.

Obama paused certain types of gain of function research for the right reasons. It was for an ethical review and risk-benefit evaluation that led to enhanced safety procedures for gain for function research into transmissibility. Then, with those protections in place, it was back to the science; the pause of gain of function research was lifted given special protections. In the case of the research we're gonna be looking at, it was done in a biosafety level 3 lab. 

Research on coronavirus was done in Wuhan by EcoHealth, who was studying coronavirus in bats, to see if: "spike proteins from naturally occurring bat coronaviruses circulating in China were capable of binding to the human ACE2 receptor in a mouse model." This sounds to me that researchers know 1) where there is a risk of emergence and 2) likely routes of infection--because both were true in the case of SARS-CoV-2. SCIENCE! But it also establishes the fact that there is a very good reason for the outbreak to start where the lab was, not because of an escape but because prior probability suggested that Wuhan was a likely point of origin for the next coronavirus spillover. So, there's a real relationship, but it's not a causal one, but a correlational one.   

So, EcoHealth's funding was provided by the NIH, and EcoHealth picked its own collaborators including WIV. Gain of function research was not covered by the grant (although I'll point out that the strains of mice with human ACE2 receptors are the product of gain of function research, which isn't always "let's make diseases worse," as so many people seem to think). It looks like when some of the mice were infected with naturally occurring virus (the subject of the study), and there was a control that was infected with a modified virus that... I think it was the control--it was a comparable, very similar non-infectious agent. The modified virus was the same virus with a spike that had never infected people (or, more specifically, bound to the human ACE2 receptor before). It was, then, apparently not something designed to make it more virulent, which people seem to assume. Surprisingly, the mice who got the altered virus got sicker than the ones exposed to the wild virus. EcoHealth did not report this to the NIH, though they were required to by the terms of the grant, as pointed out by a director in a letter he sent to Congress, referenced here in the only link I will ever have to the NY Post.

This points, to my mind, to the possibility Fauci and others at NIH were not fully informed at the time about this unexpected result. 

This is the study in question, done by UNC and Wuhan: https://pmc.ncbi.nlm.nih.gov/articles/PMC4797993/  

From the abstract, which clarifies (ha!) how the viruses were used in the research, actually one of the papers that came out of this larger research project:

Therefore, to examine the emergence potential (that is, the potential to infect humans) of circulating bat CoVs, we built a chimeric virus encoding a novel, zoonotic CoV spike protein—from the RsSHC014-CoV sequence that was isolated from Chinese horseshoe bats1—in the context of the SARS-CoV mouse-adapted backbone. The hybrid virus allowed us to evaluate the ability of the novel spike protein to cause disease independently of other necessary adaptive mutations in its natural backbone. Using this approach, we characterized CoV infection mediated by the SHC014 spike protein in primary human airway cells and in vivo, and tested the efficacy of available immune therapeutics against SHC014-CoV. Together, the strategy translates metagenomics data to help predict and prepare for future emergent viruses.

I also looked for the original grant proposal, to see what was proposed.

DESCRIPTION (provided by applicant): This project will examine the risk of future coronavirus (CoV) emergence from wildlife using in-depth field investigations across the human-wildlife interface in China, molecular characterization of novel CoVs and host receptor binding domain genes, mathematical models of transmission and evolution, and in vitro and in vivo laboratory studies of host range. Zoonotic CoVs are a significant threat to global health, as demonstrated with the emergence of pandemic severe acute respiratory syndrome coronavirus (SARS-CoV) in China in 2002, and the recent and ongoing emergence of Middle East Respiratory Syndrome (MERS-CoV). Bats appear to be the natural reservoir of these viruses, and hundreds of novel bat-CoVs have been discovered in the last two decades. Bats, and other wildlife species, are hunted, traded, butchered and consumed across Asia, creating a large scale human-wildlife interface, and high risk of future emergence of novel CoVs. This project aims to understand what factors increase the risk of the next CoV emerging in people by studying CoV diversity in a critical zoonotic reservoir (bats), at sites of high risk for emergence (wildlife markets) in an emerging disease hotspot (China). The three specific aims of this project are to: 1. Assess CoV spillover potential at high risk human-wildlife interfaces in China. This will include quantifying the nature and frequency of contact people have with bats and other wildlife; serological and molecular screening of people working in wet markets and highly exposed to wildlife; screening wild-caught and market sampled bats from 30+ species for CoVs using molecular assays; and genomic characterization and isolation of novel CoVs. 2. Develop predictive models of bat CoV emergence risk and host range. A combined modeling approach will include phylogenetic analyses of host receptors and novel CoV genes (including functional receptor binding domains); a fused ecological and evolutionary model to predict host-range and viral sharing; and mathematical matrix models to examine evolutionary and transmission dynamics. 3. Test predictions of CoV inter-species transmission. Predictive models of host range (i.e. emergence potential) will be tested experimentally using reverse genetics, pseudovirus and receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice.

Very important: I don't see gain-of-function mentioned in this proposal. I have learned that these R01 research grants can lead to follow up studies and can be renewed and ammended. Eventually it may have mentioned GoF (it looks like the last version of the updated proposal has something that sounds like it). But what's really important is that the Internet Archive captured this version of the page on April 16, 2020, two and a half months after an early email discussion (Feb 1) between Fauci and and Francis Collins and other important muckety mucks, where he relayed a conversation about a rumor floated by an Indian team that the virus was manufactured, and he said: "The suspicion was heightened by the fact that scientists in Wuhan University are known to have been working on gain-of-function experiments to determine the molecular mechanisms associated with bat viruses adapting to human infecton, and the outbreak originated in Wuhan."

OK, a few things, 1) the Wuhan Institute of Virology does not appear to be a subdivision of Wuhan University, but an independent entity. 2) The research looks very similar to what's going on in the research above, so perhaps he misspeaks here, but that suggests, 3) he's not familiar enough with the research institution to speak about it or what goes on there authoritatively. This is important if you are seeking to establish whether or not he lied to Congress--what he knows and intends are abolutely relevant, if not determinative. He can be legitimately wrong and think he is right. That's not perjury, that's sloppy. But I suspect, maybe, because his initial contact with the idea came from people who were positing a rather out-there theory that his experts generally dismissed, he dismissed the idea that that research was being done there in the first place. Possibly. That's speculation. However, it's consistent with the idea, a guiding principle I apply to accusations of malevolence, that you should usually suspect run of the mill error ahead of malevolence. I suspect that most people who have spent their professional lives testifying in front of Congress, like Fauci, don't go into those meetings intending to perjure themselves to such a hostile audience on something that is so checkable. He can be wrong.  

So, what's the takeaway, since I need to go to bed? 1) It's complicated. 2) Most of this does not speak to what Fauci knew or didn't know and therefore shouldn't be used as primary evidence of his knowingly perjuring himself to Congress. I strongly suspect that Fauci was too high up on the totem pole to be signing off on piddling research grants worth mere hundreds of thousands of dollars, and that he is at best tangentially related to this research. 3) The research seems legit and interesting and done with appropriate safety procedures, but that of course doesn't push the pudding pop one way or the other, to coin a new phrase. 4) It's not enough to establish guilt by noting that he benefitted from the outcomes of his actions; and in this case, I'm not entirely sure that he did benefit from his misstatement, since his statement has provided endless confirmation for the eager to believe that he did do something sinister. 

That's what I have for now, gents. I'm pooped.