Rand Paul to Fauci: You perjured yourself by claiming you didn't fund gain of function research in Wuhan

I’d love to tell you who’s right in this dispute but the study Paul references is so highly technical that it reads almost like hieroglyphics to me. Combine that with a running dispute about what constitutes “gain of function” research and it’s hard for a layman to draw a conclusion.

On the merits, I mean. Politically this will split into the familiar pro-Fauci and anti-Fauci camps.

Paul confronted with him a simple question during testimony today. In May Fauci told the Senate that NIH had never funded gain of function research at the Wuhan Institute of Virology. But the 2017 study “Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus” credits NIH with funding and describes something that sounds a lot like gain of function research. Did Fauci perjure himself?

I’ve never seen him so angry in response. First, everyone who’s looked at this paper says it didn’t involve GOF research, he retorts. Second, Paul clearly means to insinuate that the viruses described in the 2017 study somehow led to SARS-CoV-2, which would mean Fauci and NIH are indirectly responsible the pandemic. Paul denies that that’s what he’s doing, but let’s just say I don’t think he’d be all broken up if that’s the conclusion Republican viewers take away from this. Watch, then read on.

Fauci was allowed to finish up:

Let’s try to decipher some hieroglyphics. From the study in question:

Abstract

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Again, I’m 50 miles out of my depth here but that reads to me as suggesting that viruses similar to the original SARS — and potentially SARS-CoV-2, a.k.a. COVID-19 — are found in nature, including ones that might naturally evolve to bind to the same ACE2 receptors in humans that COVID exploits. Ironically, in other words, the abstract bolsters the zoonotic theory of the virus’s origins. You don’t need a “Frankenstein virus made in the lab” scenario to imagine how it might have jumped to humans. Apparently there are a lot of different bat viruses out there in nature and some of them are surprisingly well-suited to mess with people.

The study goes on to discuss how the scientists tinkered with the viral genomes:

Our previous studies demonstrated the capacity of both WIV1 and WIV16 to use ACE2 orthologs for cell entry and to efficiently replicate in human cells [17,18]. In this study, we confirmed the use of human ACE2 as receptor of two novel SARSr-CoVs by using chimeric viruses with the WIV1 backbone replaced with the S gene of the newly identified SARSr-CoVs. Rs7327’s S protein varied from that of WIV1 and WIV16 at three aa residues in the receptor-binding motif, including one contact residue (aa 484) with human ACE2. This difference did not seem to affect its entry and replication efficiency in human ACE2-expressing cells. A previous study using the SARS-CoV infectious clone showed that the RsSHC014 S protein could efficiently utilize human ACE2 [33], despite being distinct from SARS-CoV and WIV1 in the RBD (S1 Fig). We examined the infectivity of Rs4231, which shared similar RBD sequence with RsSHC014 but had a distinct NTD sequence, and found the chimeric virus WIV1-Rs4231S also readily replicated in HeLa cells expressing human ACE2 molecule. The novel live SARSr-CoV we isolated in the current study (Rs4874) has an S gene almost identical to that of WIV16. As expected, it is also capable of utilizing human ACE2. These results indicate that diverse variants of SARSr-CoV S protein without deletions in their RBD are able to use human ACE2.

My best guess at what that means is that, as Paul says, they spliced features of two different viruses together to make a germ that looked more like some of the new SARS viruses they had found in bats in the wild. Then they tested the spliced chimera virus on ACE2 receptors in animals to see if it would bind. It did. (Which, again, suggests that viruses in the wild might be able to make the jump to humans without any help in a lab.) That does sound like GOF to me, but what do I know? Then again, it sounded like GOF research to molecular biologist Richard Ebright too:

Maybe the fact that the new virus was able to bind to the receptors wasn’t enough in and of itself to make it dangerous to humans. Factcheck.org noted that this is how HHS defined GOF research when the moratorium on funding such research was lifted in late 2017:

The framework defined a “potential pandemic pathogen” as one that was both “likely highly transmissible and likely capable of wide and uncontrollable spread in human populations” and “likely highly virulent and likely to cause significant morbidity and/or mortality in humans.” And an enhanced PPP was a PPP “resulting from the enhancement of the transmissibility and/or virulence of a pathogen.”

The framework said enhanced PPPs don’t include “naturally occurring pathogens that are circulating in or have been recovered from nature.”

Was there some other feature of the spliced chimera virus that made it not highly transmissible to humans and therefore distinct in some meaningful way from SARS-CoV-2? Fauci suggests so in his answer to Paul when he says that it would be molecularly impossible for the viruses described in this study to have evolved into the coronavirus that causes COVID-19 but he doesn’t elaborate.

Anyway, he’s not going to be charged with perjury. In lieu of an exit question, read this intriguing Daily Mail piece from last week about a mystery woman who visited a hospital in November 2019 complaining of flu-like symptoms and left a skin sample that showed traces of coronavirus when it was tested months later. The Wuhan epidemic didn’t explode until December 2019. The hospital that treated the woman wasn’t in Wuhan, though. It was in Milan.