An excellent review of the scientific evidence concerning the origins of SARS-CoV-2. I believe it is open access. I encourage everyone to download and read it.
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@Giltil, any comments? Does this review clarify the matter of the origins of SARS-CoV-2 for you? Anything in the review you may wish to discuss?
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No, the review is far from convincing IMO, especially because it doesnât take the lab origin theory seriously.
For those who donât want to fall prey to Holmesâ easy way out, the piece below by Alex Washburne is a formidable antidote.
There is no lab origin theory. Itâs ad-hoc rationalization, and often carried by lying about or ignoring the facts. Such as the idea that virus was âfine tunedâ to infect human cells and didnât undergo any adaptation at the beginning of the pandemic. This is directly refuted by Edward Holmes in his review.
From your supposed âformidable antidoteâ article:
Additionally, our finding of the âBsaI/BsmBIâ map of SARS-CoV-2 being anomalous among wild coronaviruses
Contrary to demonstrable fact, as every known restriction site in SARS-Cov-2 is found in natural coronaviruses. We both saw the figure on this very forum. Your poor memory seems to need monthly refreshers?
Lab-leakers also never deal with the fact that the supposedly frankensteinian and â1 in 50 billlion probability of being seen in natureâ, âfirst-everâ(ROFL) furin cleavage site is an out-of-frame insert in a recombination hotspot, exactly where other more distantly related coronaviruses have furin cleavage sites.
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In your opinion. The opinion of someone who is ignorant of much of modern science, thinks the Turin Shroud is real, swallows and regurgitates pseudoscientific nonsense and quote-mining, cites sources they havenât read, and who claims to have evidence they canât produce for things they donât understand.
It takes it seriously enough to point out why it doesnât work.
So you prefer a bunch of evidence-free hand-waving conspiracy theories and suppositions about work that would have been done on a different continent if it had been funded.
You donât seem to have learnt anything from the previous occasions where Wasburneâs work was dismantled.
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The first cautious step forward is for everyone to acquaint themselves with the current front-lines of lab origin theory, find impartial scientists who can provide testimony about the probable lab origin of SARS-CoV-2
Those would include Edward C. Holmes and Michael Worobey, both of which did not initially rule out a lab leak, but after thorough investigation, concluded that the evidence decisively supported a zoonotic transmission from the Wuhan wet market.
There is now a large body of peer-reviewed scientific research consistent with a zoonotic origin of this pandemic. However, there is no credible, peer-reviewed research pointing to a lab leak. Had the evidence gone in the other direction, Iâd be reporting that. But it hasnât.
âŚI remain open to any and all evidence supporting a laboratory origin of the pandemic. So far, we have no such evidence.
Worobey - Dissecting the early COVID-19 cases in Wuhan
Holmes - The origins of SARS-CoV-2: A critical review
There is currently no evidence that SARS-CoV-2 has a laboratory origin. There is no evidence that any early cases had any connection to the WIV, in contrast to the clear epidemiological links to animal markets in Wuhan, nor evidence that the WIV possessed or worked on a progenitor of SARS-CoV-2 prior to the pandemic. The suspicion that SARS-CoV-2 might have a laboratory origin stems from the coincidence that it was first detected in a city that houses a major virological laboratory that studies coronaviruses. Wuhan is the largest city in central China with multiple animal markets and is a major hub for travel and commerce, well connected to other areas both within China and internationally. The link to Wuhan therefore more likely reflects the fact that pathogens often require heavily populated areas to become established.
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I prefer Washburneâs piece because I read it carefully, which you obviously didnât because then you wouldnât have used this argument, which now falls flat.
The real question is not âhow could covid have started from a wet marketâ, but rather âwhy did it take so longâ? Virologists have been warning for decades that zoonotic transmission was, in some way, shape, or form, bound to happen. There were prior SARS virus transmissions. We should not be surprised when the expected materializes.
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Hmm⌠So, @Giltil, what in any of Washburneâs essays discusses the data - the actual facts, summarized nicely in Figs. 1 and 2 of the review by Holmes - that pretty clearly refute the arguments (if one can call them that) raised by Washburne. Please be specific. If Washburne cannot be bothered with data (and, just so we are clear, Washburneâs suspicions regarding a restriction enzyme site pattern is not data), why should anyone lend him any credence?
How might you refute the results and conclusions that are so plain in these figures, @Giltil?
Then there is this extended excerpt:
Obvious evidence against the laboratory leak allegation is that the first documented cases of COVID-19 were not linked to the WIV nor in the same geographical region ofWuhan (44). The WIV laboratory of Prof. Zhengli Shi, who has been the subject of abundant accusations because of her work on bat coronaviruses (10, 11, 13), is located more than 30 km from the Huanan market epicenter. Clearly, if the virus first emerged at the WIV, then that location should be the site of at least some of the earliest cases or linked to those cases. It is not.
The closest known bat virus relative of SARS-CoV-2 housed by the WIV is RaTG13 (initially called RaBtCoV/4991 or Ra4991), sampled from an abandoned mineshaft in Yunnan province, China, in July 2013 (11, 75). However, as this virus has more than 1,000 nucleotide differences with SARS-CoV-2, it is demonstrably not the proximal ancestor and too distant to be genetically manipulated into SARS-CoV-2 (42). The lab escape allegation therefore posits that the WIV must maintain a larger collection of unpublished viruses and virus sequences, including the direct ancestor of SARS-CoV-2 (Figure 3). There is, however, no evidence for any such virus, neither from the scientific literature nor in any unpublished material.
An important illustration of the lack of evidence for a SARS-CoV-2 progenitor at the WIV comes from an unpublished (rejected and withdrawn) paper from 2018 of which I was a coau- thor (E.C. Holmes, personal communication). This paper described the sequences of 60 new bat betacoronaviruses sampled by the WIV with the aim of understanding the phylogeography of SARS-CoV-like viruses in bats, particularly phylogenetic links between the viruses collected in Yunnan and those from Guangdong province, where the first cases of SARS-CoV were identi- fied in late 2002. In keeping with the focus of Prof. Shiâs research group (76), the majority of the viruses sequenced were SARS-CoV-like. Of most significance is that the closest relative of SARS-CoV-2 in that paper was RaTG13 (then Ra4991), for which only sequences of the RNA- dependent RNA polymerase (RdRp) and ORF8 were obtained at the time of paper submission despite the virus being sampled in 2013. The full genome was obtained later in the year. As Prof. Shi states, âIn 2018, as the [next-generation] sequencing technology and capability in our lab was improved, we did further sequencing of the virus using our remaining samples, and obtained the full-length genome sequence of RaTG13 except the 15 nucleotides at the 5Ⲡendâ (77). She also noted, âI would like to emphasize that we have only the genome sequence and didnât isolate this virusâ (77). Hence, this unpublished paper strongly suggests that RaTG13 is the closest relative of SARS-CoV-2 studied by the WIV. There would have been no reason to hide a more closely related virus from the public prior to the pandemic, and it does not appear logical to conduct secret work on a divergent bat virus that seemingly had no relation to any human disease. Similarly, there is no evidence that the WIV isolated or cultured a virus closely related to SARS-CoV-2 (12, 42). Rather, all cultured virusesâdenoted WIV1, WIV16, and Rs4874âare related to SARS-CoV. Finally, although self-reported, all staff in Prof. Shiâs laboratory lacked antibodies to SARS-CoV-2 (77). If true, this excludes Prof. Shiâs laboratory staff from being responsible for the COVID-19 pandemic and undermines attempts to pin the unfortunate title of patient zero on any of the WIV lab workers (78).
Another argument presented as evidence of the theory of experimental manipulation in a laboratory as the origin of SARS-CoV-2 is that the virus did not undergo extensive adaptive evolution during its early spread, as might be expected for a virus that has newly emerged in humans (79). Such a lack of adaptation is suggested to indicate that the virus was laboratory-adapted to humans, perhaps following the insertion of the furin cleavage site (see the next section) and subsequent pas- sage in humanized mice. However, these experimental procedures would not have produced a virus optimally adapted for human-to-human transmission in nature, and SARS-CoV-2 has experienced extensive adaptive evolution during spread through the human population. The virus circulating in humans now is far more transmissible than the virus that first emerged in Wuhan (80). The first major adaptive mutation in human SARS-CoV-2 was spike D614G, leading to a global selec- tive sweep that greatly increased transmissibility (81, 82). Although D614G was initially thought to have appeared in Italy in late February 2020 (81), another unpublished (rejected) paper (of which I coauthored some versions) shows it was present in patients fromWuhan sampled in early January 2020 (E.C. Holmes, personal communication). Hence, there was early selection pressure on SARS-CoV-2 to fix mutations that would improve transmissibility, a process that has continued unabated (83). This paper also shows that there were no intermediate sequences between the A and B lineages in earlyWuhan patients, contrary to some claims (84).
The inconvenient truth is that the original Wuhan variant of SARS-CoV-2 was merely good enough to spread in the dense, well-connected human population that characterized Wuhan in November/December 2019. A virus with the capacity to transmit between hosts will thrive in such an environment, with the mass of susceptible hosts providing the fuel for natural selection to rapidly optimize a virus for efficient human spread. Emergence inWuhan is what made SARS- CoV-2 a pandemic virus. If SARS-CoV-2 had first emerged in a small rural community, there would have been more opportunities for stochastic processes to have influenced virus evolution and for transmission to cease. The selective milieu in Wuhan was different. Any virus emerging in such an environment would have a good chance of spreading worldwide. And far from being a specifically human-optimized virus, one of the defining characteristics of SARS-CoV-2 is its capacity to infect so many animal species (see the section titled Transmission of SARS-CoV-2 to the Animal Hosts). SARS-CoV-2 is a host generalist virus, with humans serving as just one of the hosts in question (85).
The bottom line - only if one ignores ALL of the actual data can one even begin to entertain the delusion that SARS-CoV-2 was a deliberate, or even an accidental, product of research at the WIV.
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A scientific disagreement would focus on evidence. Youâre not taking evidence seriously.
I see your avoidance of evidence as the âeasy way outâ here.
I donât see anything formidable about it, but then Iâve done actual virology.
Once again, nothing to do with the evidence.
Weâve read it carefully. We note the lack of evidence. People who donât have evidence pretend that science is about arguing and pretending that something that is a thoroughly disproven hypothesis has somehow been elevated to a âtheory.â
My question too. Please stop with the pretense that others arenât reading and deal with the actual evidence.
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What, then, is your response to the clearly duplicitous claim by Washburne:
âThereâs more science on the lab origin of SARS-CoV-2, such as the lack of zoonotic evidence we ought to have obtained by nowâŚâ
Holmes spells things out clearly, and in fact there is good evidence for a zoonotic origin of SARS-CoV-2. He also makes it plain that there is in fact no evidence, and especially ZERO evidence of the sort demanded by Washburne, that the virus originated in the WIV.
@Giltil, have you ever communicated with Washburne and asked him why he is not willing to hold himself to the same standards of evidence he is demanding of others? Do you think this is proper scientific discourse? A good way to examine data, evidence?
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You prefer Washburneâs piece because you like itâs conclusions.
No it doesnât. The grant wasnât funded. No other funding has been confirmed. There are no details of any work that was being done. This is what Washburne writes:
Many argued that âDEFUSE wasnât fundedâ under the assumption that if one agency doesnât fund work then every other agency will follow suit. However, the DEFUSE PIâs, who had never all published a paper together prior to DEFUSE, were all together in 2019 on an NIAID call - and grant - studying bat SARS-related coronaviruses in Wuhan. In other words, after their 2018 grant the authors were all together doing work in 2019 as predicted by lab origin theory, and itâs reasonable to suspect NIAID may have funded this work. In 2023, when the DNI released its unclassified assessment on the origins of COVID-19, lab origin theory still had some predictions up its sleeve that could only be corroborated or refuted by opening up lab notebooks of researchers involved in this DEFUSE-related program, and all signs pointed towards NIAID. Admittedly, prior work along this research program wasnât funded exclusively by NIAID but also had support from the Chinese Academy of Sciences and the Chinese Academy of Medical Sciences, but the Chinese government is run by an oppressive authoritarian regime that has refused to be transparent, doesnât provide people the same freedoms, and doesnât have the same checks and balances our government does, so we have to capitalize on the rights and powers of our liberal democracy to try to get information from NIAID, knowing that even if the check was split 50:50 we all can still be a little more grateful for a country like the US, and a little more upset at China for its lax biosafety standards, complete lack of transparency, and jailing of citizens or doctors who tried to speak up.
Unfortunately, efforts to FOIA NIAID have fallen short of our democratic ideals, as FOIAs have been obstructed by a remarkable lack of transparency from NIH and the NIAID FOIA office. Now, thanks to congressional subpoenas of David Morensâ gmails, we see how Fauciâs deputy took great measures to delete federal records and try to evade FOIAs, how they had aa FOIA lady who hated FOIAs and helped everyone associated with the DEFUSE PIâs 2019 funding evade embarrassing disclosures (defeating the purpose of FOIAs to ensure our federal officials arenât doing embarrassing things), and how even Tony Fauci, the man at the top who developed this bubble of unaccountability over the course of my entire life, took extreme measures to avoid FOIAs like having David Morens drop off information in-person at Tonyâs house as opposed to just sending him an email.
Early efforts to FOIA these agencies for COVID origins information resulted in hundreds of pages of redactions, followed by lawsuits to provide unredacted versions, followed by unredacted versions that were more embarrassing for NIAID while also revealing the original reasons for redactions were unjustified. For example, NIAID originally redacted Fauciâs emails acknowledging that NIAID funded gain of function research of concern on SARS-related coronaviruses and that researchers informed him that they believed a lab origin was likely, yet the only purpose of this redaction seems to be to protect Fauci from embarrassment and possible perjury charges after he testified under oath that NIAID did not fund gain of function research of concern in Wuhan.
The poor transparency from NIAID has to this day prevented us from learning about the research they were funding in Wuhan in 2019, research connecting the exact authors who wrote the blueprint for SARS-CoV-2 the year before.
All he has is suspicions, conspiracy theories, and claims of perjury. No data. No evidence. No information.
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The first step to stop digging when stuck in a home is to recognize that youâre stick in a holeâŚ
Hi Art
I understand you are pretty convinced by the paper you cited.
Do you really think the ability to bind to human Ace 2 was the result of random change from the animal virus? If not how did this happen?
As usual, you misunderstand the role of ârandomâ.
Are you concluding that God made SARS-CoV-2?
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Humans are a species of animal. As most species present some degree of difference in their cellular receptors, as viruses transfer between hosts they must and do adapt. The traffic is not all one way. Humans infects various other animals all the time, and viruses then mutate to optimize in the other direction. Covid is well established in deer, and displays rapid mutation, which is of concern for spill back.
Evolution, Interspecies Transmission, and Zoonotic Significance of Animal Coronaviruses
CoVs infect various animal species ranging from livestock, poultry, cats, dogs, mice, bats, pangolins, wild felids, and other species of animals such as minks, rabbits, ducks, guinea fowls, gooses, beluga whales, etc.
I am not concluding anything.
I am asking how the virus would transfer from an animal to a human from mutational mechanisms.
Maybe a population genetics model with some experimental data could answer this.
Google is your friend. This has to be one of the most investigated and voluminously published areas of research around. But to start withâŚ
ACE2 binding is an ancestral and evolvable trait of sarbecoviruses
ACE2 binding is highly evolvableâfor many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern12 but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.
Although sufficiently conserved in a huge number of species to support binding of the viral spike with enough affinity to initiate fusion, ACE2 is highly polymorphic both among species and within a species. Here, we provide evidence suggesting that when the viral spike-ACE2 receptor interaction is not optimal, due to host-switching, mutations can be selected to improve the affinity of the spike for the ACE2 expressed by the new host. Notably, SARS-CoV-2 is mutation-prone in the spike receptor binding domain (RBD), allowing a better fit for ACE2 orthologs in animals.
And from back in 2013 - well before the epidemic
Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor
Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV.
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How does it transfer from one host to another, for that matter? All individuals are not identical. Heck, all regions of a single host body are not identical. All cells of a single tissue arenât either. How do some diseases manage to impact even as much as a single multi-celled host, one must wonder, let alone infect the next.