Thank you for the hard work you do Alex. I'm just a lay person trying to understand so I follow along. I admire your due diligence and determination to seek truth.
I don't know the "truth" about the origins. Yet, I read all the "sides" and try to make sense of what I can. I settle on this quote, based upon the behavior of key players regarding this topic, "all the lies people tell just to cover, cover up the truth that reveals itself in the end" Something has always struck me about Alex. He isn't lying. Just a hunch.
Hi Alex, Thanks for explaining this in a Substack article. I found it hard to navigate the blizzard of tweets about it at: https://twitter.com/WashburneAlex/.
However, searching the file I found only "We will analyze all SARSr-CoV- S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential furin cleavage sites" and ref 75.
This is not the same as "inserting" a furin cleavage site.
I recall reading that this DEFUSE grant was later funded by the NIH through Dr Fauci, and then reading that it was not. As far as I know, it was not. Can you clarify this?
It is nonetheless significant in that it shows what the EcoHealth Alliance and its subcontractors Ralph Baric et al. at University of North Carolina (UNC) and the Wuhan Institute of Virology (WiV) might have been working on at that time, to support or at least partially achieve what they were proposing to do.
"In Year 5, we continued with in vivo infection experiments of diverse bat SARSr-CoVs on transgenic mice expressing human ACE2. Mice were infected with 4 strains of SARSr-CoVs with different S protein, including the full-length recombinant virus of SARSr-CoV WIV1 and three chimeric viruses with the backbone of WIV1 and S proteins of SHC014, WIV16 and Rs4231, respectively. Pathogenicity of the 4 SARSr-CoVs was evaluated by recording the survival rate of challenged mice in a 2-week course. All of the 4 SARSr-CoVs caused lethal infection in hACE2 transgenic mice."
This is GoF research, but as Andrew Huff explains in his book, it was not described specifically as "gain of function" research. Somehow, this project was funded by the US government, in violation of the requirements to specifically identify and seek approval for such research. Also, as he points out, the principal investigator organization is required to have a biosafety officer, committee etc. and to take full responsibility for biosafety in all subcontractor operations. Instead, the EcoHealth Alliance had none of this and stated that the WiV took on this role.
All these people and organizations should provide full and truthful records of their work. The fact that they do not leads to us invoking Sherlock Holmes' "dog which didn't bark" reasoning: https://brieflywriting.com/2012/07/25/the-dog-that-didnt-bark-what-we-can-learn-from-sir-arthur-conan-doyle-about-using-the-absence-of-expected-facts/ . It is reasonable to conclude, from the lack of genuine interest and action regarding disclosing all this work, in an effort to understand the likelihood of SARS-CoV-2 having emerged from a lab leak of an engineered virus, that both the Chinese and the United States governments have something to hide. So it reasonably be assumed, until any substantial evidence to the contrary emerges, that both governments were jointly responsible for such reckless research.
Great to hear from you, and I'm glad to hear you found this explainer to be of use.
Regarding insertion of FCS, see page 13 of DEFUSE: "“… we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures.”
NIH didn't exactly fund the DEFUSE grant - they funded related work (the one you mention, "Understanding the Risk of Bat Coronavirus Emergence",). The work NIAID funded includes testing chimeric bat coronaviruses in humanized mice and, while neither the full grant nor the progress reports have been voluntarily disclosed, if you just read the executive summary of DEFUSE, you can see its similarity with the abstract publicly available for the NIH grant. Neither mention inserting an FCS in their abstract or executive summary, but they use very similar language about testing the infectivity of chimeric coronaviruses in cells & mice. While we don't have the full NIH grant available to help us know the exact work proposed (rhetorical question: why don't we have that grant yet?), a FOIA of NIAID communications found emails of progress reports containing evidence that recombinant CoVs created by this project achieved 100x viral titers in mice relative to wild type CoVs. Like the grant itself, the genomes of those CoVs have not been released - we just have a glimpse of emails suggesting NIH knew that the WIV had created CoVs of enhanced transmissibility & virulence.
Hi Alex, Thanks for this explanation. Though, in the presumably unfunded DEFUSE proposal, there is no specific mention of inserting one or more furin cleavage sites into viruses, the text you quote, from PDF page 13, document page 11: "we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures" can be interpreted as referring to "furin cleavage sites", since furin is widely referred to as being specific to humans. However, https://en.wikipedia.org/wiki/Furin states that furin is found in "in humans and other animals", without citing any sources. I couldn't easily find a list of such other species.
This DEFUSE proposal is to create a pilot study for a larger system which would, ideally, prevent or significantly reduce the risk of zoonotic transfer of viruses from bats all over the world, to humans. A secondary goal was to produce an "app" - some software to run on a portable military device - to guide military personnel as to where potentially dangerous (regarding zoonotic transfer) bats might be located in any country in the world.
Here is not the place for a full exploration of the multiple completely unrealistic aspects of such a global plan - or of a subset of it in, for instance, China, or "Asia" (whatever that might mean). I just want to note that there are numerous elements of this DEFUSE proposal which are completely nuts. EcoHealth Alliance surely knew this, but it did not stop them from writing up a storm and trying to get funding for their project. They have no real concern about human health or anything other than getting funding. There are large amounts of potentially impressive sounding words in this proposal. Many people respond to this by thinking "If I don't understand it, it must be profound." I look at this stuff and think that if I can't imagine how it could be practical - and it looks wildly impractical in multiple ways - then it is most likely bullshit.
Their long-running, NIH funded, ""Understanding the Risk of Bat Coronavirus Emergence" seems to have been written in a similar spirit. I guess the funders weren't particular fussy about the outlandish claims of these proposals, which encouraged the EcoHealth Alliance to generate more of the same in the hope of getting further funding - in this case by responding to DARPA's PREEMPT request with their DEFUSE proposal..
A bit of backstory: I was on a DARPA PREEMPT grant that got funded. I wrote a section for phylodynamic analyses of bat henipaviruses, and from this perspective I see most of what EHA is writing is tailored to what was specifically asked for in the PREEMPT call ("jump-capable quasispecies", wildlife vaccines to preempt spillover, etc.). After all, DARPA invented the internet, so there was a desire to go bold with preempting spillover (but not GoF bold, as DEFUSE was not funded).
The virological interest in FCS' is a bit of a niche issue as well, benefiting from a backstory of other literature on furin activity in respiratory syncytial virus, MERS-CoV, Ebola, anthrax, cancer, and more. Molecular studies pre-COVID revealed that FCS's existing in other viruses can improve cell-entry and syncytia formation, providing a means to avoid the typical receptor-binding barriers to host entry. The ubiquity of this chaperone and conserved nature of its recognition sequence suggest it could be a gateway to broad host range (I believe it's also in zebrafish? Such chaperones like heat-shock proteins are often highly conserved in animals). Consequently, the DEFUSE PI's were drawing from a literature that was less about pangolins or other mammals or really any ecological reason for suspecting furin cleavage sites are commonly recombined (that is, unless they had secretly found, and not reported, a bat SARS CoV with an FCS). They were proposing a highly specific - and highly unusual - scenario. While other viruses and in fact many pathogens had FCS's, it seems to me they were taking the scariest spillover virus without an FCS and imagining a scenario in which it obtained one (e.g. even henipaviruses already have a cleavage site, albeit one targeted by a different protease that cleaves the F protein in endosomes).
Part of the reason I believe so strongly SARS-CoV-2 originated in a lab origin is because I was immersed in this community pre-COVID and was drinking all this punch about receptor-binding, protease-mediated cell entry, wildlife virology, reservoir biogeography, and more. This gives me a particularly niche view of the improbability of EHA's FCS-in-SARS-CoV relative to the higher probability that this was the lowest-hanging doomsday GoF scenario broadening host range & tissue tropism of the scariest virus that lacked an FCS and had not yet caused a pandemic.
"claimed that because SARS-CoV-2 is not like any other published virus"
And they cite a 2014 review article to make their point. Of course, in that review most of the cited papers were published prior to 2013, which means they probably submitted them sometime around 2012 and did the work in 2011 or 2012. So KA et al. are basically saying LL is "implausible" in part because SC2 doesn't look like any virus sequence that we could find that people had worked on before 2012. That is some mighty thin gruel.
Very helpful explanation, in a very well-written piece!
You are kinda doing that thing, again, where you neglect to include the other Americans listed on the DARPA DEFUSE proposal. Especially the Americans with coronavirus expertise and labs, like those who have the know how to insert a furin cleavage site. Suppose you have your reasons…we are left to speculate about all the secrets and the secret keepers.
Hi there! My intention in limiting the set of authors is based on the limited set of people who were on both DEFUSE and the NIAID grant and papers publishing CoV infectious clones in Wuhan (e.g. Baric was not listed in the rWIV1 paper, and I don't have any evidence that he was involved in the funded NIAID grant). Other names that commonly comes up in all of these contexts are Jonathan Epstein & Kevin Olival (COI: I published a paper once with Kevin). As someone who got to know this field a bit pre-COVID, I don't list these two because (1) they're contained under the umbrella of EcoHealth Alliance and (2) their research activities were primarily bat-catching in SE Asia (with Epstein involved in some more hands-on public health efforts related to Nipah, far form Wuhan), and data analyses from their offices in NY. Meanwhile, Daszak was spearheading the org, co-authoring papers with Zhengli making recombinant coronaviruses, allocating subawards for GoF work, publishing articles claiming lab origin theories are "conspiracy theories", discussing the results from GoF work with NIAID during GoF pauses/moratoria, and more.
I hope this transparency about my position helps clarify! I think we will benefit from transparency from all parties close to this. If it turns out Baric was involved in the NIAID grant, or if we have any additional evidence pointing to other US or European groups closest to the epicenter (e.g. Danielle Anderson is very close a major suspect, especially given her being in the WIV during the period of interest), I'll be sure to add their names to the discourse. Just trying to focus on the innermost concentric circle of researchers whose truths would be the most valuable in helping us understand CoV research in Wuhan :-)
This sort of research was employed, also, to create the vaccines against these viruses, and it has been found out that not only do these vaccines neither prevent infection nor stop transmission, they have dangerous effects on various organ systems - and the immune system. And every lab in the US doing this kind of research - and the lab at the Wuhan Institute of Virology - have a long history of viral pathogens escaping the controlled environment of the lab. And it is well known that people have suffered severe illness and death from these released pathogens, and yet the researchers and their funders exhibit reckless indifference to the easily predictable outcomes of their acts - and that’s the definition of second-degree murder…
And hiding evidence of criminal activity is in itself a crime, and conspiring to do so is yet another crime. It’s time for a grand jury to have a look into this - a real grand jury, convened by a real prosecutor in a court of law, with the power to compel testimony.
Sadly, it's the way the world is going to go. I don't think there is any stopping any of them now. It's that, and of course, it's a new Eldorado. A terrible one, with terrible consequences.
The word ‘and’ appears to be missing after ‘Zhengli’ in this sentence:
“While this bat coronavirus is not technically a SARS coronavirus, it is part of another clade that, like SARS-CoVs, has been extensively studied by Daszak and Zhengli is of interest for anyone looking to recombine furin cleavage sites.”
Thanks for posting this. It's clear and helpful. A couple comments:
- MERS has a 34% human fatality rate over the last decade. Why the hell are they creating chimeric MERS viruses? The cost/benefit ratio of such experiments is astronomical.
- Doesn't the discovery of this unpublished infectious clone put a nail through the heart of the "Proximal Origin" paper? Didn't they argue that sars-cov-2 must be from a natural origin because there were no published viruses that could be used as the backbone? And here we have an unpublished backbone serving as a template for creating chimeric MERS viruses.
Why the hell indeed. Many scientists were arguing pre-COVID that the rewards didn’t come close to exceeding the risks of gain of function research, but Anthony Fauci & Francis Collins oversaw the expiration of a moratorium on GoF research without resolving these questions. It was an undemocratic and IMO reckless move that led to US taxpayers funding research with the potential to kill 1 million Americans or more.
As for the Proximal Origin paper, that already had many nails through its heart the day it was published, most notably their erroneous alignments leading to an improper inference that the FCS was inserted “out of frame”, their hollow reasoning that “suboptimal” ACE2 binding implies this wasn’t a lab leak (a straw man of lab origin scenarios, which includes GoF research on bat COVs unlikely to produce optimal binding in early phases), and more. All that said, this does greatly undermine the argument that SARS-CoV-2 can’t be an infectious clone because there’s no backbone, as the authors have found a DNA backbone of a CoV with an FCS in Wuhan, unpublished. This was obvious to many of us for the past three years, but Jones et al have provided hard proof of the existence of undisclosed CoV infectious clones in Wuhan, giving us good reason to believe there are others, such as the progenitor to SARS-CoV-2.
Do you know what point Robert Redfield was going to make about the Ebola virus when he was cut off? I'm referring to when Congresswoman Malliotakis was questioning him about 1 hour, 24 minutes into the hearing. He started to say that you can't compare Ebola virus to a coronavirus. I think that earlier in the hearing, Dr. Auwaerter had said that the progenitor virus for Ebola has not yet been found. And Dr. Redfield was going to explain why you can't compare the 2. Do you know what point he was going to make? Thanks!
I don't know exactly what point he was going to make, but, like Dr. Redfield, I disagree with Dr. Auwaerter's claim for many reasons. The question likely came up regarding the discovery of a reservoir (finding Ebola progenitor in wildlife)
- Ebola emerged in Sub-Saharan Africa, a region of the world with very little surveillance capacity in people, let alone wildlife, and it emerged prior to the sequencing era. The time it took to find Ebola in a wild bat is not comparable to the time it should take to find a CoV in a reservoir because we for SARS-COV-2 we have better technology, better human + animal surveillance capacity in Wuhan, and a better prior understanding of reservoir hosts. It took just 3 months to find SARS-CoV's progenitor in animals in animal trade networks back in 2002. Since then, we've greatly increased our knowledge of where to find CoVs and how to surveil animal populations for them - it should've been far easier to find SARS-CoV-2's progenitor. What's more, we've had wildlife CoV surveillance across SE Asia for over a decade thanks to EcoHealth Alliance, and EHA president Peter Daszak boasted of having hundreds of unreported SARS CoVs in a database in Wuhan - that database would probably have the progenitor, even it if were a natural origin, and the fact that they refuse to release the database is completely damning IMO.
Thank you! I appreciate your response. What you write makes sense.
FWIW, I thought Dr. Redfield's testimony was very compelling. He made his points clearly and candidly. Prior to his testimony, I hadn't given much thought to how he was frozen out of COVID high-level discussions. Keep up the good work. I enjoy reading your posts.
Thanks! And I agree - Dr. Redfield is a scientist's scientist. His language is measured, he is aware of many pieces of evidence pointing in different directions, and he makes assessments that draw on the entirety of evidence as well as some critical biological intuition he's gained from 20 years doing virology. He's a hero, and I hope we can train more scientists to be more like him.
Your article "Science Is Not to Be Trusted" is excellent. You write beautifully.
As I was reading what you wrote about tobacco companies and oil companies muddying the scientific waters, I thought of Dr. Fauci saying just a few days ago (if you missed it, here's the clip, about 11 mins in https://www.foxnews.com/video/6322236885112), that the annual flu vaccine uses gain-of-function work. To me, it seems like Dr. Fauci is trying to confuse the issue, and argue that he only supported the most benevolent and widely accepted use for gain-of-function research, like the annual flu vaccine, rather than other more high-risk ventures. And I'm not even sure that the annual flu vaccine uses "gain-of-function" work. Do you think Dr. Fauci is trying to muddy the water here? Or do you think he has a legitimate point? (or somewhere in between).
Thanks for your thoughts. I appreciate your comments.
In short, WIV still hasn't been shown to insert FCS into CoVs, only Baric did this (hidden behind the "and colleagues" in your article). So this preprint actually adds evidence against a WIV origin.
The molecular techniques required to go from a coronavirus in a BAC clone to a coronavirus in a BAC clone with an FCS could be replicated by an undergrad. There’s not some special sauce that Baric had which is indicated in this work, other than efficient reverse genetic systems and infectious clone technology, and the rWIV1 article showed Daszak & Zhengli were capable of implementing those protocols without any involvement from Baric.
Again, WIV has never been shown to have done it. WIV, Duke and Daszak all confirmed FCS was Baric's task in DEFUSE. This new paper adds further evidence WIV wasn't doing it even in 2019. Baric was doing it all the time. Priors strongly favor Baric.
You’re correct about DEFUSE, but there’s no evidence (yet) that Baric was a PI on the NIH grant or other work. In fact, the EcoHealth progress report documenting gain of function in bat COVs seems to have involved WIV as the primary lab, and the failure of WIV to comply with NIH requests on that grant led to the termination of their subaward. Happy to entertain Baric, especially if there becomes any evidence of his involvement in funded proposals or related work, but until then most evidence we have, from NIAID progress reports to the location of emergence, points to the WIV.
The EHA progress report makes no mention of FCS insertion at WIV, either. NIH termination of the EHA/WIV grant in August 2022 was politically motivated. WIV didn't provide "laboratory notebooks and original electronic files", but Baric wasn't even asked to provide his files and notes.
In the delayed NIH/EHA grant report, both Baric/UNC and WIV/Shi are listed. Experiments in the UNC BSL3 lab are mentioned. FCS insertion isn't mentioned, but if it was done, rational to assume Baric did it, as described in DEFUSE.
"location of emergence" doesn't tell you who designed this virus. There are many ways how a virus designed by Baric may end up in Wuhan.
If it was designed by Baric, then we should be able to uncover this by getting oligos from oligo printers that Baric used, and other communications that haven’t yet been shared. If it turns out Baric did make SARS-CoV-2, then Dr. Fauci’s February 2020 in-person meeting with Baric, and his later claim under oath doubting to have ever met him, would start to look more suspicious.
I’m honestly shocked that the public hasn’t yet received all the information from this NIH/NIAID grant, from the entire grant document to all communications from all parties listed on the grant.
Fauci's claim under oath doubting to have ever met Baric already looks rather suspicious anyway, doesn't it.. :)
And UNC fiercly resisted releasing Baric emails. If I remember correctly, Baric even used his private email address to avoid FOIA.
At any rate I think both Defuse and the NIH/EHA grant point towards UNC not WIV. Maybe WIV was doing such work in secret but I haven't yet seen any evidence of it.
A WIV leak of a Baric virus is still possible, but other ways are possible too. Baric may also have had access to Banal-like CoVs via USAID rather than EHA/WIV.
Alex, I just re-read the EHA/NIH grant reports (FOIAed by the Intercept). The evidence pointing towards Baric is even stronger than I had remembered. You have to search for "Barie" not "Baric" to find his name in the document.
Initially Baric was an external collaborator of the EHA/WIV/Shanghai consortium. Already at that time, Baric was to do the most delicate work: "humanized mouse experiments if viruses are identified of significant human infection potential".
Later Baric became a co-investigator of the consortium. All the delicate work was to be done by his lab, just as in DEFUSE: "Small animal models of viral pathogenesis, primary human cell cultures, CoV reverse genetics, reconstruction of zoonotic CoV "
WIV/Shi was assigned the following tasks: "CoV screening and serology of non-human samples, viral pathogenesis, serological testing protocol development, host receptor binding, S protein sequencing, in vitro and in vivo virus characterization"
So the EHA/NIH grant reports provide further strong evidence that SARS-2 was designed in the US, not in Wuhan. There is simply no evidence WIV ever did such work.
Except your unreported CoV infectious clone was in fact reported. From the EHA progress report to May 2019 :
“We constructed the full-length infectious clone of MERS-CoV, and replaced the RBD of MERS-CoV with the RBDs of various strains of HKU4-related coronaviruses previously identified in bats from different provinces in southern China,”
What the authors seem to be saying is they believe the inverse was also happening: ie the MERS RBD was being also put into an HKU4-related coronavirus backbone.
Had either of these resulted in a pandemic we would immediately known these were chimeric viruses because a) the MERS backbone is well known and not from China and b) the HKU sequences had already been claimed and uploaded by the WIV.
I can't speak for the Proximal Origin authors, but I do wish they could come to the table and discuss these issues calmly with us. As for being easy to fool, I find that I'm usually my own worst critic. This slows down my progress and limits how much I publish, but does have the benefit of compressing conceptual coal into better diamonds of insight.
I'm not sure. The divide in this field of science is quite extreme, with both sides lobbing serious charges. However, this is a bit asymmetric as it is inevitable that if we are entertaining a lab origin of this virus, we must entertain serious charges. If this did come from a lab, it means not only is there a researcher who created a virus that killed millions, but that we're currently playing a game of werewolf as these researchers amongst us would be withholding their knowledge of the lab origin of this virus.
For those of us entertaining a lab origin, we need transparency - disclosure of grants, genomes, and even lab notebooks so we can rule out the involvement of various funding agencies, labs, and researchers in the origin of the pandemic. Should we ever in the world have research being conducted that is capable of killing millions yet unaccountable or uninvestigable in the event of an accident at their doorsteps?
The proximal origin authors are closely connected to the funders, and the funders like Anthony Fauci historically supported gain of function research. A pandemic caused by gain of function research, especially by an organization funded by the agencies Fauci & Collins oversaw, would define their legacy next to the scientist who invented mustard gas, except with many more deaths caused by this research and no clear evidence of lives saved. It's hard to find higher stakes than that, and so the mere mention of a possible lab origin is enough to convert the funders & those closely connected to them into a defensive phalanx.
Literally all we're asking for is transparency that would help us rule out a lab origin. The single best evidence to disprove a lab origin is in the hands of labs and researchers who insist there was not a lab origin. Why aren't they releasing that evidence?
As I point out in my other articles, the reason they're not releasing that evidence is because it's overwhelmingly likely this virus came from a lab. That's why the extreme accusations - of 18 million deaths, of scientific misconduct, and more - are so potent, and that's why it seems impossible to get a conference. I'm personally okay with a conference, because I know for a fact that I have nothing to lose except my ignorance if my theory is disproven. If the proximal origin theorists' theory is disproven, however, they risk losing their funding, their careers, their reputations, and some of them may risk losing their freedoms in a criminal case.
Hard to be jolly over bagels and coffee & goofy PowerPoint jokes with stakes like that.
Thank you for the hard work you do Alex. I'm just a lay person trying to understand so I follow along. I admire your due diligence and determination to seek truth.
I don't know the "truth" about the origins. Yet, I read all the "sides" and try to make sense of what I can. I settle on this quote, based upon the behavior of key players regarding this topic, "all the lies people tell just to cover, cover up the truth that reveals itself in the end" Something has always struck me about Alex. He isn't lying. Just a hunch.
Hi Alex, Thanks for explaining this in a Substack article. I found it hard to navigate the blizzard of tweets about it at: https://twitter.com/WashburneAlex/.
You wrote that the DEFUSE grant proposal https://www.documentcloud.org/documents/21066966-defuse-proposal from the EcoHealth Alliance (in response to DARPA's PREEMPT request, which DARPA did not fund: https://www.projectveritas.com/news/military-documents-about-gain-of-function-contradict-fauci-testimony-under/) proposed "to insert furin cleavage sites inside bat coronavirus infectious clones at Wuhan".
However, searching the file I found only "We will analyze all SARSr-CoV- S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential furin cleavage sites" and ref 75.
This is not the same as "inserting" a furin cleavage site.
I recall reading that this DEFUSE grant was later funded by the NIH through Dr Fauci, and then reading that it was not. As far as I know, it was not. Can you clarify this?
It is nonetheless significant in that it shows what the EcoHealth Alliance and its subcontractors Ralph Baric et al. at University of North Carolina (UNC) and the Wuhan Institute of Virology (WiV) might have been working on at that time, to support or at least partially achieve what they were proposing to do.
The EcoHealth Alliance was already working as the Principal Investigator on bat coronaviruses with UNC and WiV as subcrontractors for years before, including when Andrew Huff worked at the EcoHealth Alliance, under the project "Understanding the Risk of Bat Coronavirus Emergence" https://reporter.nih.gov/search/xQW6UJmWfUuOV01ntGvLwQ/project-details/9491676 . I have not yet figured out how to navigate all the documents listed there, but one related PDF is https://www.nih.gov/sites/default/files/institutes/foia/20211020-risk-of-bat-emergence.pdf .This includes, on page 15:
"In Year 5, we continued with in vivo infection experiments of diverse bat SARSr-CoVs on transgenic mice expressing human ACE2. Mice were infected with 4 strains of SARSr-CoVs with different S protein, including the full-length recombinant virus of SARSr-CoV WIV1 and three chimeric viruses with the backbone of WIV1 and S proteins of SHC014, WIV16 and Rs4231, respectively. Pathogenicity of the 4 SARSr-CoVs was evaluated by recording the survival rate of challenged mice in a 2-week course. All of the 4 SARSr-CoVs caused lethal infection in hACE2 transgenic mice."
This is GoF research, but as Andrew Huff explains in his book, it was not described specifically as "gain of function" research. Somehow, this project was funded by the US government, in violation of the requirements to specifically identify and seek approval for such research. Also, as he points out, the principal investigator organization is required to have a biosafety officer, committee etc. and to take full responsibility for biosafety in all subcontractor operations. Instead, the EcoHealth Alliance had none of this and stated that the WiV took on this role.
All these people and organizations should provide full and truthful records of their work. The fact that they do not leads to us invoking Sherlock Holmes' "dog which didn't bark" reasoning: https://brieflywriting.com/2012/07/25/the-dog-that-didnt-bark-what-we-can-learn-from-sir-arthur-conan-doyle-about-using-the-absence-of-expected-facts/ . It is reasonable to conclude, from the lack of genuine interest and action regarding disclosing all this work, in an effort to understand the likelihood of SARS-CoV-2 having emerged from a lab leak of an engineered virus, that both the Chinese and the United States governments have something to hide. So it reasonably be assumed, until any substantial evidence to the contrary emerges, that both governments were jointly responsible for such reckless research.
Hi Robin!
Great to hear from you, and I'm glad to hear you found this explainer to be of use.
Regarding insertion of FCS, see page 13 of DEFUSE: "“… we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures.”
NIH didn't exactly fund the DEFUSE grant - they funded related work (the one you mention, "Understanding the Risk of Bat Coronavirus Emergence",). The work NIAID funded includes testing chimeric bat coronaviruses in humanized mice and, while neither the full grant nor the progress reports have been voluntarily disclosed, if you just read the executive summary of DEFUSE, you can see its similarity with the abstract publicly available for the NIH grant. Neither mention inserting an FCS in their abstract or executive summary, but they use very similar language about testing the infectivity of chimeric coronaviruses in cells & mice. While we don't have the full NIH grant available to help us know the exact work proposed (rhetorical question: why don't we have that grant yet?), a FOIA of NIAID communications found emails of progress reports containing evidence that recombinant CoVs created by this project achieved 100x viral titers in mice relative to wild type CoVs. Like the grant itself, the genomes of those CoVs have not been released - we just have a glimpse of emails suggesting NIH knew that the WIV had created CoVs of enhanced transmissibility & virulence.
Hope this helps!
Hi Alex, Thanks for this explanation. Though, in the presumably unfunded DEFUSE proposal, there is no specific mention of inserting one or more furin cleavage sites into viruses, the text you quote, from PDF page 13, document page 11: "we will introduce appropriate human specific cleavage sites and evaluate growth potential in Vero and HAE (Human Airway Epithelial) cell cultures" can be interpreted as referring to "furin cleavage sites", since furin is widely referred to as being specific to humans. However, https://en.wikipedia.org/wiki/Furin states that furin is found in "in humans and other animals", without citing any sources. I couldn't easily find a list of such other species.
This DEFUSE proposal is to create a pilot study for a larger system which would, ideally, prevent or significantly reduce the risk of zoonotic transfer of viruses from bats all over the world, to humans. A secondary goal was to produce an "app" - some software to run on a portable military device - to guide military personnel as to where potentially dangerous (regarding zoonotic transfer) bats might be located in any country in the world.
Here is not the place for a full exploration of the multiple completely unrealistic aspects of such a global plan - or of a subset of it in, for instance, China, or "Asia" (whatever that might mean). I just want to note that there are numerous elements of this DEFUSE proposal which are completely nuts. EcoHealth Alliance surely knew this, but it did not stop them from writing up a storm and trying to get funding for their project. They have no real concern about human health or anything other than getting funding. There are large amounts of potentially impressive sounding words in this proposal. Many people respond to this by thinking "If I don't understand it, it must be profound." I look at this stuff and think that if I can't imagine how it could be practical - and it looks wildly impractical in multiple ways - then it is most likely bullshit.
Their long-running, NIH funded, ""Understanding the Risk of Bat Coronavirus Emergence" seems to have been written in a similar spirit. I guess the funders weren't particular fussy about the outlandish claims of these proposals, which encouraged the EcoHealth Alliance to generate more of the same in the hope of getting further funding - in this case by responding to DARPA's PREEMPT request with their DEFUSE proposal..
A bit of backstory: I was on a DARPA PREEMPT grant that got funded. I wrote a section for phylodynamic analyses of bat henipaviruses, and from this perspective I see most of what EHA is writing is tailored to what was specifically asked for in the PREEMPT call ("jump-capable quasispecies", wildlife vaccines to preempt spillover, etc.). After all, DARPA invented the internet, so there was a desire to go bold with preempting spillover (but not GoF bold, as DEFUSE was not funded).
The virological interest in FCS' is a bit of a niche issue as well, benefiting from a backstory of other literature on furin activity in respiratory syncytial virus, MERS-CoV, Ebola, anthrax, cancer, and more. Molecular studies pre-COVID revealed that FCS's existing in other viruses can improve cell-entry and syncytia formation, providing a means to avoid the typical receptor-binding barriers to host entry. The ubiquity of this chaperone and conserved nature of its recognition sequence suggest it could be a gateway to broad host range (I believe it's also in zebrafish? Such chaperones like heat-shock proteins are often highly conserved in animals). Consequently, the DEFUSE PI's were drawing from a literature that was less about pangolins or other mammals or really any ecological reason for suspecting furin cleavage sites are commonly recombined (that is, unless they had secretly found, and not reported, a bat SARS CoV with an FCS). They were proposing a highly specific - and highly unusual - scenario. While other viruses and in fact many pathogens had FCS's, it seems to me they were taking the scariest spillover virus without an FCS and imagining a scenario in which it obtained one (e.g. even henipaviruses already have a cleavage site, albeit one targeted by a different protease that cleaves the F protein in endosomes).
Part of the reason I believe so strongly SARS-CoV-2 originated in a lab origin is because I was immersed in this community pre-COVID and was drinking all this punch about receptor-binding, protease-mediated cell entry, wildlife virology, reservoir biogeography, and more. This gives me a particularly niche view of the improbability of EHA's FCS-in-SARS-CoV relative to the higher probability that this was the lowest-hanging doomsday GoF scenario broadening host range & tissue tropism of the scariest virus that lacked an FCS and had not yet caused a pandemic.
"claimed that because SARS-CoV-2 is not like any other published virus"
And they cite a 2014 review article to make their point. Of course, in that review most of the cited papers were published prior to 2013, which means they probably submitted them sometime around 2012 and did the work in 2011 or 2012. So KA et al. are basically saying LL is "implausible" in part because SC2 doesn't look like any virus sequence that we could find that people had worked on before 2012. That is some mighty thin gruel.
Very helpful explanation, in a very well-written piece!
You are kinda doing that thing, again, where you neglect to include the other Americans listed on the DARPA DEFUSE proposal. Especially the Americans with coronavirus expertise and labs, like those who have the know how to insert a furin cleavage site. Suppose you have your reasons…we are left to speculate about all the secrets and the secret keepers.
Hi there! My intention in limiting the set of authors is based on the limited set of people who were on both DEFUSE and the NIAID grant and papers publishing CoV infectious clones in Wuhan (e.g. Baric was not listed in the rWIV1 paper, and I don't have any evidence that he was involved in the funded NIAID grant). Other names that commonly comes up in all of these contexts are Jonathan Epstein & Kevin Olival (COI: I published a paper once with Kevin). As someone who got to know this field a bit pre-COVID, I don't list these two because (1) they're contained under the umbrella of EcoHealth Alliance and (2) their research activities were primarily bat-catching in SE Asia (with Epstein involved in some more hands-on public health efforts related to Nipah, far form Wuhan), and data analyses from their offices in NY. Meanwhile, Daszak was spearheading the org, co-authoring papers with Zhengli making recombinant coronaviruses, allocating subawards for GoF work, publishing articles claiming lab origin theories are "conspiracy theories", discussing the results from GoF work with NIAID during GoF pauses/moratoria, and more.
I hope this transparency about my position helps clarify! I think we will benefit from transparency from all parties close to this. If it turns out Baric was involved in the NIAID grant, or if we have any additional evidence pointing to other US or European groups closest to the epicenter (e.g. Danielle Anderson is very close a major suspect, especially given her being in the WIV during the period of interest), I'll be sure to add their names to the discourse. Just trying to focus on the innermost concentric circle of researchers whose truths would be the most valuable in helping us understand CoV research in Wuhan :-)
This sort of research was employed, also, to create the vaccines against these viruses, and it has been found out that not only do these vaccines neither prevent infection nor stop transmission, they have dangerous effects on various organ systems - and the immune system. And every lab in the US doing this kind of research - and the lab at the Wuhan Institute of Virology - have a long history of viral pathogens escaping the controlled environment of the lab. And it is well known that people have suffered severe illness and death from these released pathogens, and yet the researchers and their funders exhibit reckless indifference to the easily predictable outcomes of their acts - and that’s the definition of second-degree murder…
And hiding evidence of criminal activity is in itself a crime, and conspiring to do so is yet another crime. It’s time for a grand jury to have a look into this - a real grand jury, convened by a real prosecutor in a court of law, with the power to compel testimony.
Sadly, it's the way the world is going to go. I don't think there is any stopping any of them now. It's that, and of course, it's a new Eldorado. A terrible one, with terrible consequences.
Question is whether the media will report on any of this. Not holding my breath given their track record.
The word ‘and’ appears to be missing after ‘Zhengli’ in this sentence:
“While this bat coronavirus is not technically a SARS coronavirus, it is part of another clade that, like SARS-CoVs, has been extensively studied by Daszak and Zhengli is of interest for anyone looking to recombine furin cleavage sites.”
Thanks for posting this. It's clear and helpful. A couple comments:
- MERS has a 34% human fatality rate over the last decade. Why the hell are they creating chimeric MERS viruses? The cost/benefit ratio of such experiments is astronomical.
- Doesn't the discovery of this unpublished infectious clone put a nail through the heart of the "Proximal Origin" paper? Didn't they argue that sars-cov-2 must be from a natural origin because there were no published viruses that could be used as the backbone? And here we have an unpublished backbone serving as a template for creating chimeric MERS viruses.
Keep up the good work.
Why the hell indeed. Many scientists were arguing pre-COVID that the rewards didn’t come close to exceeding the risks of gain of function research, but Anthony Fauci & Francis Collins oversaw the expiration of a moratorium on GoF research without resolving these questions. It was an undemocratic and IMO reckless move that led to US taxpayers funding research with the potential to kill 1 million Americans or more.
As for the Proximal Origin paper, that already had many nails through its heart the day it was published, most notably their erroneous alignments leading to an improper inference that the FCS was inserted “out of frame”, their hollow reasoning that “suboptimal” ACE2 binding implies this wasn’t a lab leak (a straw man of lab origin scenarios, which includes GoF research on bat COVs unlikely to produce optimal binding in early phases), and more. All that said, this does greatly undermine the argument that SARS-CoV-2 can’t be an infectious clone because there’s no backbone, as the authors have found a DNA backbone of a CoV with an FCS in Wuhan, unpublished. This was obvious to many of us for the past three years, but Jones et al have provided hard proof of the existence of undisclosed CoV infectious clones in Wuhan, giving us good reason to believe there are others, such as the progenitor to SARS-CoV-2.
Hi Alex, in case you get notices of comments...
Do you know what point Robert Redfield was going to make about the Ebola virus when he was cut off? I'm referring to when Congresswoman Malliotakis was questioning him about 1 hour, 24 minutes into the hearing. He started to say that you can't compare Ebola virus to a coronavirus. I think that earlier in the hearing, Dr. Auwaerter had said that the progenitor virus for Ebola has not yet been found. And Dr. Redfield was going to explain why you can't compare the 2. Do you know what point he was going to make? Thanks!
I don't know exactly what point he was going to make, but, like Dr. Redfield, I disagree with Dr. Auwaerter's claim for many reasons. The question likely came up regarding the discovery of a reservoir (finding Ebola progenitor in wildlife)
- Ebola emerged in Sub-Saharan Africa, a region of the world with very little surveillance capacity in people, let alone wildlife, and it emerged prior to the sequencing era. The time it took to find Ebola in a wild bat is not comparable to the time it should take to find a CoV in a reservoir because we for SARS-COV-2 we have better technology, better human + animal surveillance capacity in Wuhan, and a better prior understanding of reservoir hosts. It took just 3 months to find SARS-CoV's progenitor in animals in animal trade networks back in 2002. Since then, we've greatly increased our knowledge of where to find CoVs and how to surveil animal populations for them - it should've been far easier to find SARS-CoV-2's progenitor. What's more, we've had wildlife CoV surveillance across SE Asia for over a decade thanks to EcoHealth Alliance, and EHA president Peter Daszak boasted of having hundreds of unreported SARS CoVs in a database in Wuhan - that database would probably have the progenitor, even it if were a natural origin, and the fact that they refuse to release the database is completely damning IMO.
Thank you! I appreciate your response. What you write makes sense.
FWIW, I thought Dr. Redfield's testimony was very compelling. He made his points clearly and candidly. Prior to his testimony, I hadn't given much thought to how he was frozen out of COVID high-level discussions. Keep up the good work. I enjoy reading your posts.
Thanks! And I agree - Dr. Redfield is a scientist's scientist. His language is measured, he is aware of many pieces of evidence pointing in different directions, and he makes assessments that draw on the entirety of evidence as well as some critical biological intuition he's gained from 20 years doing virology. He's a hero, and I hope we can train more scientists to be more like him.
Your article "Science Is Not to Be Trusted" is excellent. You write beautifully.
As I was reading what you wrote about tobacco companies and oil companies muddying the scientific waters, I thought of Dr. Fauci saying just a few days ago (if you missed it, here's the clip, about 11 mins in https://www.foxnews.com/video/6322236885112), that the annual flu vaccine uses gain-of-function work. To me, it seems like Dr. Fauci is trying to confuse the issue, and argue that he only supported the most benevolent and widely accepted use for gain-of-function research, like the annual flu vaccine, rather than other more high-risk ventures. And I'm not even sure that the annual flu vaccine uses "gain-of-function" work. Do you think Dr. Fauci is trying to muddy the water here? Or do you think he has a legitimate point? (or somewhere in between).
Thanks for your thoughts. I appreciate your comments.
David
In short, WIV still hasn't been shown to insert FCS into CoVs, only Baric did this (hidden behind the "and colleagues" in your article). So this preprint actually adds evidence against a WIV origin.
The molecular techniques required to go from a coronavirus in a BAC clone to a coronavirus in a BAC clone with an FCS could be replicated by an undergrad. There’s not some special sauce that Baric had which is indicated in this work, other than efficient reverse genetic systems and infectious clone technology, and the rWIV1 article showed Daszak & Zhengli were capable of implementing those protocols without any involvement from Baric.
Again, WIV has never been shown to have done it. WIV, Duke and Daszak all confirmed FCS was Baric's task in DEFUSE. This new paper adds further evidence WIV wasn't doing it even in 2019. Baric was doing it all the time. Priors strongly favor Baric.
You’re correct about DEFUSE, but there’s no evidence (yet) that Baric was a PI on the NIH grant or other work. In fact, the EcoHealth progress report documenting gain of function in bat COVs seems to have involved WIV as the primary lab, and the failure of WIV to comply with NIH requests on that grant led to the termination of their subaward. Happy to entertain Baric, especially if there becomes any evidence of his involvement in funded proposals or related work, but until then most evidence we have, from NIAID progress reports to the location of emergence, points to the WIV.
The EHA progress report makes no mention of FCS insertion at WIV, either. NIH termination of the EHA/WIV grant in August 2022 was politically motivated. WIV didn't provide "laboratory notebooks and original electronic files", but Baric wasn't even asked to provide his files and notes.
In the delayed NIH/EHA grant report, both Baric/UNC and WIV/Shi are listed. Experiments in the UNC BSL3 lab are mentioned. FCS insertion isn't mentioned, but if it was done, rational to assume Baric did it, as described in DEFUSE.
"location of emergence" doesn't tell you who designed this virus. There are many ways how a virus designed by Baric may end up in Wuhan.
If it was designed by Baric, then we should be able to uncover this by getting oligos from oligo printers that Baric used, and other communications that haven’t yet been shared. If it turns out Baric did make SARS-CoV-2, then Dr. Fauci’s February 2020 in-person meeting with Baric, and his later claim under oath doubting to have ever met him, would start to look more suspicious.
I’m honestly shocked that the public hasn’t yet received all the information from this NIH/NIAID grant, from the entire grant document to all communications from all parties listed on the grant.
Fauci's claim under oath doubting to have ever met Baric already looks rather suspicious anyway, doesn't it.. :)
And UNC fiercly resisted releasing Baric emails. If I remember correctly, Baric even used his private email address to avoid FOIA.
At any rate I think both Defuse and the NIH/EHA grant point towards UNC not WIV. Maybe WIV was doing such work in secret but I haven't yet seen any evidence of it.
A WIV leak of a Baric virus is still possible, but other ways are possible too. Baric may also have had access to Banal-like CoVs via USAID rather than EHA/WIV.
Alex, I just re-read the EHA/NIH grant reports (FOIAed by the Intercept). The evidence pointing towards Baric is even stronger than I had remembered. You have to search for "Barie" not "Baric" to find his name in the document.
Initially Baric was an external collaborator of the EHA/WIV/Shanghai consortium. Already at that time, Baric was to do the most delicate work: "humanized mouse experiments if viruses are identified of significant human infection potential".
Later Baric became a co-investigator of the consortium. All the delicate work was to be done by his lab, just as in DEFUSE: "Small animal models of viral pathogenesis, primary human cell cultures, CoV reverse genetics, reconstruction of zoonotic CoV "
WIV/Shi was assigned the following tasks: "CoV screening and serology of non-human samples, viral pathogenesis, serological testing protocol development, host receptor binding, S protein sequencing, in vitro and in vivo virus characterization"
So the EHA/NIH grant reports provide further strong evidence that SARS-2 was designed in the US, not in Wuhan. There is simply no evidence WIV ever did such work.
Humanity. Civilization.
#ExtinctionRebellion
Except your unreported CoV infectious clone was in fact reported. From the EHA progress report to May 2019 :
“We constructed the full-length infectious clone of MERS-CoV, and replaced the RBD of MERS-CoV with the RBDs of various strains of HKU4-related coronaviruses previously identified in bats from different provinces in southern China,”
What the authors seem to be saying is they believe the inverse was also happening: ie the MERS RBD was being also put into an HKU4-related coronavirus backbone.
Had either of these resulted in a pandemic we would immediately known these were chimeric viruses because a) the MERS backbone is well known and not from China and b) the HKU sequences had already been claimed and uploaded by the WIV.
Is it known when in 2019 the rice sequences were collected?
I can't speak for the Proximal Origin authors, but I do wish they could come to the table and discuss these issues calmly with us. As for being easy to fool, I find that I'm usually my own worst critic. This slows down my progress and limits how much I publish, but does have the benefit of compressing conceptual coal into better diamonds of insight.
I'm not sure. The divide in this field of science is quite extreme, with both sides lobbing serious charges. However, this is a bit asymmetric as it is inevitable that if we are entertaining a lab origin of this virus, we must entertain serious charges. If this did come from a lab, it means not only is there a researcher who created a virus that killed millions, but that we're currently playing a game of werewolf as these researchers amongst us would be withholding their knowledge of the lab origin of this virus.
For those of us entertaining a lab origin, we need transparency - disclosure of grants, genomes, and even lab notebooks so we can rule out the involvement of various funding agencies, labs, and researchers in the origin of the pandemic. Should we ever in the world have research being conducted that is capable of killing millions yet unaccountable or uninvestigable in the event of an accident at their doorsteps?
The proximal origin authors are closely connected to the funders, and the funders like Anthony Fauci historically supported gain of function research. A pandemic caused by gain of function research, especially by an organization funded by the agencies Fauci & Collins oversaw, would define their legacy next to the scientist who invented mustard gas, except with many more deaths caused by this research and no clear evidence of lives saved. It's hard to find higher stakes than that, and so the mere mention of a possible lab origin is enough to convert the funders & those closely connected to them into a defensive phalanx.
Literally all we're asking for is transparency that would help us rule out a lab origin. The single best evidence to disprove a lab origin is in the hands of labs and researchers who insist there was not a lab origin. Why aren't they releasing that evidence?
As I point out in my other articles, the reason they're not releasing that evidence is because it's overwhelmingly likely this virus came from a lab. That's why the extreme accusations - of 18 million deaths, of scientific misconduct, and more - are so potent, and that's why it seems impossible to get a conference. I'm personally okay with a conference, because I know for a fact that I have nothing to lose except my ignorance if my theory is disproven. If the proximal origin theorists' theory is disproven, however, they risk losing their funding, their careers, their reputations, and some of them may risk losing their freedoms in a criminal case.
Hard to be jolly over bagels and coffee & goofy PowerPoint jokes with stakes like that.
Maybe because they are in on the coverup??