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Thread: The Potential Lab Origin of COVID-19

  1. #61
    Ludicus's Avatar Vicarius Provinciae
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    Default Re: The Potential Lab Origin of COVID-19

    Another nail in the coffin of coronavirus conspiracy theories.
    Published today, 28 July.
    Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID 19 pandemic. Nature Microbiology (2020) full article

    ABSTRACT
    There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses.
    We find that the sarbecoviruses—the viral subgenus containing SARS-CoV and SARS-CoV-2—undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China.

    SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination.

    To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000) and 1982 (95% HPD: 1948–2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades.
    ---
    28 July.
    expert reaction to study looking at the evolutionary origins

    A study, published in Nature Microbiology, looked at he evolutionary origins of the SARS-CoV-2 virus lineage responsible for the COVID-19 pandemic.
    Prof Mark Pagel, Professor of Evolutionary Biology, University of Reading, said:
    Has this study been done well; is it robust?
    “Yes.
    Does the press release accurately reflect the paper?
    “Yes.
    Is this a surprise / is it a significant finding?
    “Less a surprise than a careful analysis of a lingering question.
    Is this the first study to put a specific data on the evolution of Sars-Cov-2 and the divergence from bat viruses?
    “No, but it is probably the best estimate yet.

    The new Nature Microbiology paper is important for providing evidence that the SARS-CoV-2 (hereafter covid-19) jumped directly into humans from the horseshoe bats rather than via an intermediate host, suspected by many to be the pangolins.
    The authors’ analyses, if correct, suggest that coronaviruses capable of infecting humans have been present in bats for perhaps 40 to 70 years but have gone undetected.
    This is significant in pointing to the scale and nature of the problems that zoonotic transmission presents to humans — there may be numerous and as yet undetected viruses capable of infecting humans that reside in animal hosts.

    “Pangolins have been suspected as the possible source of covid-19 because of their prevalence in live animal markets and their use in traditional medicines, but also because a key part of the pangolin coronavirus that is implicated in human infectivity – the variable loop region of the important spike protein – is more closely related to covid-19 than is the variable loop region of the most closely related horseshoe bat coronavirus, known as RaTG13.
    “The spike protein is the region of the covid-19 virus that allows it to gain access to human cells, and is the part of the virus that vaccine developers are targeting. Superficially this new result might suggest that the pangolin is the intermediate host from which the virus jumped to humans.

    But the authors’ analysis shows that the difference between RaTG13 and covid-19 in the critical variable loop region probably arose in RaTG13 after it separated from the common ancestor it shares with covid-19. This then points to the conclusion that there are as yet undetected horseshoe bat viruses that are the likely source of covid-19 — ones that have not been altered like RaTG13 has.
    “To achieve these new results the authors removed regions of the bat, human and pangolin coronavirus sequences that are thought to exchange information with each other when they are found in the same host, a phenomenon known as recombination.
    Previous studies have not done this. Removing these regions leaves a clearer signal of ancestry and improves dating. The authors’ work is robust, but unlikely to be the final word.
    If they are correct, there will be coronaviruses circulating in horseshoe or other closely related bats that will prove to be closer to covid-19 than is RaTG13. In an earlier epidemic – that of the original SARS – researchers searched for over 14 years before finding the probable source, also in horseshoe bats.”
    Last edited by Ludicus; July 28, 2020 at 03:25 PM.
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  2. #62

    Default Re: The Potential Lab Origin of COVID-19

    They estimated the date of divergence between RaTG13 and a hypothesized precursor of SARS-CoV-2 as it hypothetically existed before it acquired RNA from other coronaviruses. Setting aside the fact that no one outside of the Wuhan Institute of Virology has ever examined RaTG13, because they lost it or something, this doesn't address how the RNA of the other viruses got into this hypothesized precursor, nor does it take into account that evolution can be sped up in a lab, nor does it explain how a virus could have appeared suddenly in Wuhan far away from any natural hosts and pre-adapted to humans without anyone having noticed. But if they are correct, the way to prove it is very simple, find the precursor. If this hypothesized precursor is really out there in nature, for reasons of public safety, it is absolutely imperative that it be found.

    Peter Dazsak claimed that RaTG13 was never really studied before because it wasn't of interest, which is an odd thing to say since it was found in 2013 during an investigation of a mine-shaft where six miners contracted SARS-like pneumonia that killed three of them. Dazsak was lying of course, it just wasn't obvious at first because Zheng-li Shi had renamed it before she published its genome January 23rd, 2020 as if it was a new discovery. Here is a rather extensive and well-referenced article on the topic: A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic

    Recently, the lab origin hypothesis was deemed worthy of investigation in a New York Times article, which you can also read here if it's behind a paywall. I guess that means it's not a conspiracy theory anymore. They're the ones who get to decide, right?
    Last edited by sumskilz; July 30, 2020 at 01:44 AM. Reason: fixed RNA/DNA typo
    Quote Originally Posted by Enros View Post
    You don't seem to be familiar with how the burden of proof works in when discussing social justice. It's not like science where it lies on the one making the claim. If someone claims to be oppressed, they don't have to prove it.


  3. #63
    Aexodus's Avatar Persuasion>Coercion
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    Default Re: The Potential Lab Origin of COVID-19

    https://www.independent.co.uk/news/w...14391.html?amp

    It’s quite concerning to me, if prominent health authorities are ruling out a hypothesis this early. Why would they do this?

    Edit: By rule out, I mean to say, not even investigate in the first place.
    Last edited by Aexodus; July 28, 2020 at 06:59 PM.
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  4. #64
    Legio_Italica's Avatar Lost in Limbo
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    Default Re: The Potential Lab Origin of COVID-19

    Of course WHO isn’t gonna do anything in China the Politburo doesn’t want them to do.

  5. #65

    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by Legio_Italica View Post
    Of course WHO isn’t gonna do anything in China the Politburo doesn’t want them to do.
    Yeah...

    Bosses at WHO have also declined to provide details of places its investigators will inspect or the people they will meet ⁠– however, it is understood Chinese authorities will monitor and limit all movements.
    To be fair, the alternative would probably be having no access at all. Although, I'm not sure that would be worse, because there is a danger of this investigation legitimating whatever narrative the Chinese government wants, if the investigators are limited to examining a specially curated set of evidence, some of which may be fraudulent.

    Quoting from the previously linked New York Times article:

    “It is important to address questions about any potential laboratory source of the virus, whether in Wuhan or elsewhere,” Dr. Lucey wrote in his blog post.

    To that end, he urges the W.H.O. investigators to look for any signs of “gain of function” research — the deliberate enhancement of pathogens to make them more dangerous. The technique is highly contentious. Critics question its merits and warn that it could lead to catastrophic lab leaks. Proponents see it as a legitimate way to learn how viruses and other infectious organisms might evolve to infect and kill people, and thus help in devising new protections and precautions...

    “If done well scientifically, then this investigation should allay persistent concerns about the origin of this virus,” he wrote. “It could also help set an improved standard for investigating and stopping the awful viruses, and other pathogens, in the decades ahead.”
    And from the article Aexodus linked:

    Richard Ebright, a molecular biologist at Rutgers University in New Jersey, said: “To have any value, an investigation must address the possibility the virus entered humans through a laboratory accident.”

    He added WHO should also consider if the virus’s ability to infect humans was “enhanced through laboratory manipulation”.
    Ebright added on Twitter, paraphrasing the Wall Street Journal:

    "WHO..must be empowered to explore all relevant questions about..origins of..pandemic..This comprehensive forensic investigation must include..access to all..scientists, biological samples, lab..records and other materials from..Wuhan virology institutes"
    In other words, it really needs to be an independent investigation, but I don't expect that to happen.
    Quote Originally Posted by Enros View Post
    You don't seem to be familiar with how the burden of proof works in when discussing social justice. It's not like science where it lies on the one making the claim. If someone claims to be oppressed, they don't have to prove it.


  6. #66
    Ludicus's Avatar Vicarius Provinciae
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    Default Re: The Potential Lab Origin of COVID-19

    I came to the conclusion that this pseudoscientific (political) nonsense is viral.

    The team found that the SARS-CoV-2 diverged from RaTG13 a relatively long time ago, sometime in 1969. The spike's ability to attach to ACE2, appears to be an ancestral trait, rather than one gained from recombination. The authors found that the SARS CoV-2 is not the product of genetic "shuffling"; there is no evidence that SARS-CoV-2 is a recombinant of known viruses, SARS-CoV-2 is a perfectly normal coronavirus without recombination.

    According to the authors, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.
    David L. Robertson, one of the authors, says, "no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins".

    Resquiat in peace, conspiracy theories. The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.
    And that's it.

    Quote Originally Posted by Legio_Italica View Post
    Of course WHO isn’t gonna do anything in China the Politburo doesn’t want them to do.
    Trump will get your vote? Don't vote for Biden.Coronavirus: Biden vows to reverse Trump WHO withdrawal ...

    Il y a quelque chose de pire que d'avoir une âme perverse. C’est d'avoir une âme habituée
    Charles Péguy

    Every human society must justify its inequalities: reasons must be found because, without them, the whole political and social edifice is in danger of collapsing”.
    Thomas Piketty

  7. #67

    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by Ludicus View Post
    The spike's ability to attach to ACE2, appears to be an ancestral trait
    Wrong, they did not make this claim. They specifically referred to "the SARS-CoV-2 lineage’s acquisition of residues in its Spike (S) protein’s receptor-binding domain (RBD) permitting the use of human ACE2".

    Quote Originally Posted by Ludicus View Post
    The authors found that the SARS CoV-2 is not the product of genetic "shuffling"; there is no evidence that SARS-CoV-2 is a recombinant of known viruses, SARS-CoV-2 is a perfectly normal coronavirus without recombination.
    Wrong, they identified "some individual recombination events..., esp including two bat (R. sinucus) sequences from Zhejiang province (2015,2017), as well as a short region in the receptor binding domain of SARS-CoV-2's Spike protein". What you have claimed here is so opposite of what they said throughout the paper, that I can only assume that you didn't read it. One of the main objectives of their study was to identify those regions which were most likely the result of recombination in order to remove them from any analysis of the virus's phylogeny.

    They did however speculate without evidence that "the human ACE2-compatible RBD was very likely to have been present in a bat sarbecovirus lineage that ultimately led to SARS-CoV-2". It's possible that the RBD of a this hypothesized precursor strain could have been compatible with infecting hACE2, but it could not have been highly adapted to do so in bats, since bat ACE2 receptors are not particularly similar to those in humans. This is one of the reasons pangolins as an intermediate host were suggested.

    Their paper is fine for what it is, a speculative modeling paper, but it doesn't say what you claim it says and it doesn't address most of the issues relevant to this thread.

    For example, they note:

    Furthermore, the other key feature thought to be instrumental in the ability of SARS-CoV-2 to infect humans—a polybasic cleavage site insertion in the S protein—has not yet been seen in another close bat relative of the SARS-CoV-2 virus.
    In fact, it has not been seen anywhere in nature, and is not the only other feature. As previously cited references have outlined, SARS-CoV-2 was highly adapted to infecting humans when it first appeared.
    Quote Originally Posted by Enros View Post
    You don't seem to be familiar with how the burden of proof works in when discussing social justice. It's not like science where it lies on the one making the claim. If someone claims to be oppressed, they don't have to prove it.


  8. #68

    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by sumskilz View Post
    Wrong, they did not make this claim.
    ...
    Wrong, they identified...
    What you have claimed here is so opposite of what they said throughout the paper, that I can only assume that you didn't read it.
    ...
    ...it doesn't say what you claim it says and it doesn't address most of the issues relevant to this thread.
    Why am I not surprised...

  9. #69
    Ludicus's Avatar Vicarius Provinciae
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    Default Re: The Potential Lab Origin of COVID-19

    Originally Posted by Ludicus
    there is no evidence that SARS-CoV-2 is a recombinant of known viruses,
    Quote Originally Posted by sumskilz View Post
    They specifically referred to "the SARS-CoV-2 lineage’s acquisition of residues in its Spike (S) protein’s receptor-binding domain (RBD) permitting the use of human ACE2"... they identified "some individual recombination events...
    Read again, attentively. Again- I said: "there is no evidence that SARS-CoV-2 is a recombinant of known viruses."
    I quote, ipsis verbis, from the paper,
    " SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date".
    And,
    "Despite the SARS-CoV-2 lineage’s acquisition of residues in its Spike (S) protein’s receptor-binding domain (RBD) permitting the use of human ACE2 (ref. 27) receptors and its RBD being genetically closer to a pangolin virus than to RaTG13 (refs. 11,12,13,22,28)—a signal that suggests recombination—the divergence patterns in the S protein do not show evidence of recombination between the lineage leading to SARS-CoV-2 and known sarbecoviruses"
    ------
    The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the RBD located on the Spike protein. Regarding that fact that the SARS-CoV-2's RBD sequence has so far only been found in a few pangolin viruses, and the polybasic cleavage site insertion in the S protein has not yet been seen in another close bat relative of the SARS-CoV-2 virus, Robertson added, "Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans"
    ------
    Regarding the theory that the virus escaped from a lab: The Telegraph - Coronaviruses linked to Sars-Cov-2 have been circulating

    "The finding not only has significant implications for preventing future pandemics, but adds to mounting evidence discrediting conspiracy theories that suggest Sars-Cov-2 was bioengineered or escaped from a laboratory... Prof Robertson...added that the study confirms that “these viruses are circulating naturally in bats” and there is “no evidence that this was human made or anyone manipulated viruses
    --------
    Let's go back in time.
    In the earlier epidemic of the original SARS, researchers searched for over 14 years before finding the probable source, also in horseshoe bats.It was only as later as 14 years after the beginning of the outbreak that in late 2017, that Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling to horseshoe bats in Yunnan. In 2004, the reservoir was unknown: Epidemiologic Clues to SARS Origin in China - NCBI

    On March 12, 2003, the World Health Organization (WHO) issued a global alert about cases of atypical pneumonia in Guangdong Province and Hong Kong Special Administrative Region, China, and in Vietnam (1). The disease, now known as severe acute respiratory syndrome (SARS), is caused by coronavirus infection (2,3) and subsequently spread rapidly worldwide. The earliest identified cases of the disease occurred in Guangdong Province in late 2002.
    Since the SARS epidemic began in Guangdong, we have sought epidemiologic clues about the origin of the disease. Approximately 75% of emerging infectious diseases are zoonotic (12), and evidence is accumulating that an animal origin for SARS is probable.
    However, phylogenetic analysis and sequence comparisons of the coronavirus that causes SARS (SARS-CoV) indicate that the virus is not closely related to any of the previously characterized human or animal coronaviruses (13). The reservoir is still unknown.
    -----
    Quote Originally Posted by sumskilz View Post
    In other words, it really needs to be an independent investigation, but I don't expect that to happen.
    So, how many years will pass before the end of this opportunistic, pseudoscientific lab escape theory? more 14 years? meanwhile, many more conspiracies will fill the void.
    ----
    Some Americans (not all of them, of course, e.g. the left and the centre of the political spectrum) are constantly blaming others for their own failures: China, the WHO, the UN., and God knows what else.
    Germany shuns Trump's claims Covid-19 outbreak was causes by Chinese lab leak
    Internal report "classifies the American claims as a calculated attempt to distract" from Washington's own failings
    (On a side note, Germany is a delinquent (sic) country, according to your beloved President)
    ---------------
    Blame the government and blame yourselves.
    In an article published several months ago, Zeynep Tufekci, a professor of information science who specializes in the social effects of technology, associate Professor at the UNC School of Information and Library Science (SILS), explains that the COVID-19 crisis in the US is not only a failure of Trump's leadership, but also the result of a systemic thinking that allowed organizations, including the media, and individuals to underestimate the threat. Here,
    Zeynep Tufekci: “It Wasn't Just Trump Who Got It Wrong” The Atlantic

    America’s coronavirus response failed because we didn’t understand the complexity of the problem. We faltered because of our failure to consider risk in its full context, especially when dealing with coupled risk—when multiple things can go wrong together. We were hampered by our inability to think about second- and third-order effects and by our susceptibility to scientism—the false comfort of assuming that numbers and percentages give us a solid empirical basis.

    We failed to understand that complex systems defy simplistic reductionism. Widespread asystemic thinking may have cost America the entire month of February, and much of what we’d normally consider credible media were part of that failure.

    (...) Thus from the end of January through most of February, a soothing message got widespread traction, not just with Donald Trump and his audience, but among traditional media in the United States, which exhorted us to worry about the flu instead, and warned us against overreaction.

    It seemed sensible, grown-up, and responsible. “Get a Grippe, America,” read the headline of one piece that made fun of those worried about this pandemic with a play on grippe (French for “flu,” how clever.) The title said that the flu was a much bigger threat “for now.”

    There was a New York Times op-ed with a nice alliteration, telling us to “Beware of the Pandemic Panic,” again comparing the coronavirus to the flu, and warning us that overreaction would be worse than the pandemic. (The author wrote a follow-up admitting he was wrong, but claiming that this was a “black swan” event, something unpredictable, rather than what it was: predictable and predicted, a gray rhino)

    Another New York Times op-ed, on February 5, provocatively titled “Who Says It’s Not Safe to Travel to China?” and written by a tourism-industry reporter, claimed travel bans were unjust and ineffective, and were racist especially because they weren’t issued for flu—and, astonishingly, went on to reassure readers that most coronavirus victims recovered.

    Other media followed suit, in framing the initial response as an overreaction. BuzzFeed News ran a piece telling people to worry about the flu instead of the coronavirus. (It has since wisely changed its headline, though that doesn’t erase the damage.) Recode published an article titled “The Tech Industry Is Terrified of the Virus,” emphasizing that “public officials in the area say the virus is contained”—and even mentioning the eccentric doomsday scenarios of tech billionaires.

    These pieces were neither exceptional nor exceptionally bad. In fact, they were routine examples of the common sentiment among mainstream media
    This complacency went on until about early March, when the severity of the crisis finally sunk in, seemingly only after Italy started suffering the same kind of crisis that had hit Wuhan months earlier.

    Let’s then go back to what we knew as of January 29 and think about it from a complex-systems perspective. A novel coronavirus (the same family as SARS and MERS) had been observed in Wuhan in early December 2019. The NEJM paper informed us that unlike SARS, this coronavirus included hard-to-detect cases.

    Without using systemic thinking, in isolation, the case-fatality rate may not have seemed that alarming, especially because the virus seemed to disproportionately affect the elderly. But viewed through a systemic lens, even a small fatality rate foretold a disaster. It is true that the flu kills tens of thousands annually, but the choice here wasn’t between worrying about this coronavirus or seasonal influenza. It was about assessing what adding a COVID-19 pandemic on top of a flu season would mean—and how it would overwhelm health-care systems.

    If the flu kills about 40,000 people annually in the U.S., and car accidents kill another 40,000 people annually, their combined impact is pretty much just that. They are both predictable events for which we have built infrastructure and expectations; our system anticipates both. But adding one more flu-like illness (as COVID-19 was presented) isn’t a linear event. Tipping points, phase transitions (water boiling or freezing), and cascades and avalanches (when a few small changes end up triggering massive shifts) are all examples of nonlinear dynamics in which the event doesn’t follow simple addition in its impacts—that’s why this coronavirus was never just about its R0 or CFR.

    ..Hospitals in wealthy nations have some slack built in for surge capacity, but not that much. As a result, they can treat only so many people at once, and they have particular bottlenecks for their most expensive parts, such as ventilators and ICUs. The flu season may be tragic for its victims; however, an additional, unexpected viral illness in the same season isn’t merely twice as tragic as the flu, even if it has a similar R0 or CFR: It is potentially catastrophic.

    Worse, COVID-19 wasn’t even just another flu-like illness. By January 29, it was clear that COVID-19 caused severe primary pneumonia in its victims, unlike the flu, which tends to leave patients susceptible to opportunistic, secondary pneumonia. That’s like the difference between a disease that drops you in the dangerous part of town late at night and one that does the mugging itself. COVID-19’s characteristics made it clear that the patients would need a lot of intensive, expensive resources, as severe pneumonia patients do: ICU beds, ventilators, negative-pressure rooms, critical-care nurses.

    This is why the case-fatality rate for COVID-19 was never a sufficient indicator of its threat. If emergency rooms and ICUs are overloaded from COVID-19, we will see more deaths from everything else: from traffic accidents, heart attacks, infections, seasonal influenza, falls and traumas—basically anything that requires an emergency-room response to survive.
    If COVID-19 causes a shortage of masks for emergency-room workers, hospitals will stop everything that looks “elective” or nonurgent to fight that fire, but that means people will then suffer and die from things that those surgeries were intended to treat or improve.An angioplasty may not be urgent that week, but it is still a lifesaving intervention without which more people will die. This is true for even seemingly optional health interventions: If people can’t get knee-replacement surgeries, for example, they will be less active, which will increase their health risks.

    None of this erases the administration’s failures, which are grave, but the painful truth is that we could have tried to do a lot at the local level that would have helped. Not everything had to wait for the government. Hong Kong, too, had a largely unresponsive government, but great popular pressure and people’s own actions—immediate adoption of social distancing in January, universal mask wearing, calling for closures and cancellations even when the government dragged its feet—have meant that the city had a very low rate of infection until late March, despite its nearness to China and its status as one of the most densely populated places in the world.

    (...)In the United States and Europe, the die is mostly cast for the immediate future. But understanding our failures leading up to this moment isn’t an abstract exercise. Maybe we will muddle through the next few months, at great cost.
    --------
    Four months after the publication of this article, the pandemic is getting worse and worse. And, on the top that, zealots and imbeciles win again: "Don't strip away our civil rights!"

    Spoiler Alert, click show to read: 



    What's more, for several months we have been hearing from the retarded Presidents of the US and Brazil that chloroquine is the magic potion that protects civil rights. Those idiots fail to understand that there are times when national governments must temporary curtail individual freedoms to protect the public health.

    Stop constantly blaming others for things that you are not willing to prevent, and get the job done.
    Last edited by Ludicus; July 31, 2020 at 07:47 PM.
    Il y a quelque chose de pire que d'avoir une âme perverse. C’est d'avoir une âme habituée
    Charles Péguy

    Every human society must justify its inequalities: reasons must be found because, without them, the whole political and social edifice is in danger of collapsing”.
    Thomas Piketty

  10. #70

    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by Ludicus View Post
    Read again, attentively. Again- I said: "there is no evidence that SARS-CoV-2 is a recombinant of known viruses."
    I quote, ipsis verbis, from the paper,
    " SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date".
    And,
    "Despite the SARS-CoV-2 lineage’s acquisition of residues in its Spike (S) protein’s receptor-binding domain (RBD) permitting the use of human ACE2 (ref. 27) receptors and its RBD being genetically closer to a pangolin virus than to RaTG13 (refs. 11,12,13,22,28)—a signal that suggests recombination—the divergence patterns in the S protein do not show evidence of recombination between the lineage leading to SARS-CoV-2 and known sarbecoviruses"
    I get that you think that their somewhat speculative model suggesting that the specific regions they analyzed don't show evidence of recent recombination with any known sarbecoviruses means that SARS-CoV-2 isn't a recombinant. If it's not obvious by the underlined words in my previous sentence, I'm not going to bother to explain your misunderstanding further, because it's not relevant. Although to be fair, if they had written their argument in their abstract as they had written it in their key points summery, it would have been less misleading for those who didn't read the whole paper:

    The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date.
    That is SARS-CoV-2 didn't require recombination to deviate from this hypothesized precursor their model predicts. Like I said before, if this hypothesized precursor is out there in nature, then it should be found.

    It is largely Daszak's team and the Wuhan Institute of Virology who have promoted the argument that SARS-CoV-2 acquired its RBD sequence via recombination with a pangolin coronavirus. This paper you linked argues against that.

    The rational proponents of the lab escape hypothesis argue that SARS-CoV-2, or at least its backbone, is a passaged lineage of RaTG13 or related virus found in the same cave which infected the six miners. This paper you linked argues that most of SARS-CoV-2 derives from a shared lineage with RaTG13.

    In summery, this paper you linked is much more consistent with current iterations of the lab escape hypothesis than with the hypothesis forwarded by EcoHealth and the WIV.

    In more detail (from proponents of a somewhat middle ground hypothesis):

    The Mojiang mine and the Master’s thesis

    In our own search to resolve the COVID-19 origin question we chose to focus on the provenance of the coronavirus genome sequences BtCoV/4991 and RaTG13, since these are the most closely related sequences to SARS-CoV-2 (98.7% and 96.2% identical respectively). See FIG 1. (reproduced from P. Zhou et al., 2020).

    For comparison, the next closest virus to SARS-CoV-2 is RmYN02 (not shown in Fig 1.) (H. Zhou et al., 2020). RmYN02 has an overall similarity to SARS-CoV-2 of 93.2%, making its evolutionary distance from SARS-CoV-2 almost twice as great.

    BtCoV/4991 was first described in 2016. It is a 370 nucleotide virus fragment collected from the Mojiang mine in 2013 by the lab of Zeng-li Shi at the WIV (Ge et al., 2016). BtCoV/4991 is 100% identical in sequence to one segment of RaTG13. RaTG13 is a complete viral genome sequence (almost 30,000 nucleotides) that was only published in 2020, after the pandemic began (P. Zhou et al., 2020).

    Despite the confusion created by their different names, in a letter obtained by us Zheng-li Shi confirmed to a virology database that BtCoV/4991 and RaTG13 are both from the same bat faecal sample and the same mine. They are thus sequences from the same virus. In the discussion below we will refer primarily to RaTG13 and specify BtCoV/4991 only as necessary.

    These specifics are important because it is these samples and their provenance that we believe are ultimately key to unravelling the mystery of the origins of COVID-19.

    The story begins in April 2012 when six workers in that same Mojiang mine fell ill from a mystery illness while removing bat faeces. Three of the six subsequently died.

    In a March 2020 interview with Scientific American Zeng-li Shi dismissed the significance of these deaths, claiming the miners died of fungal infections. Indeed, no miners or deaths are mentioned in the paper published by the Shi lab documenting the collection of RaTG13 (Ge et al., 2016).

    But Shi’s assessment does not tally with any other contemporaneous accounts of the miners and their illness (Rahalkar and Bahulikar, 2020). As these authors have pointed out, Science magazine wrote up part of the incident in 2014 as A New Killer Virus in China?. Science was citing a different team of virologists who found a paramyxovirus in rats from the mine. These virologists told Science they found “no direct relationship between human infection” and their virus. This expedition was later published as the discovery of a new virus called MojV after Mojiang, the locality of the mine (Wu et al., 2014).

    What this episode suggests though is that these researchers were looking for a potentially lethal virus and not a lethal fungus. Also searching the Mojiang mine for a virus at around the same time was Canping Huang, the author of a PhD thesis carried out under the supervision of George Gao, the head of the Chinese CDC.

    All of this begs the question of why the Shi lab, which has no interest in fungi but a great interest in SARS-like bat coronaviruses, also searched the Mojiang mine for bat viruses on four separate occasions between August 2012 and July 2013, even though the mine is a 1,000 Km from Wuhan (Ge et al., 2016). These collecting trips began while some of the miners were still hospitalised.

    Fortunately, a detailed account of the miner’s diagnoses and treatments exists. It is found in a Master’s thesis written in Chinese in May 2013. Its suggestive English title is “The Analysis of 6 Patients with Severe Pneumonia Caused by Unknown viruses“.

    The original English version of the abstract implicates a SARS-like coronavirus as the probable causative agent and that the mine “had a lot of bats and bats’ feces”.

    The findings of the Master’s thesis

    To learn more, especially about the reasonableness of this diagnosis, we arranged to have the whole Master’s thesis translated into English and are here making the translation available. To read it in full see the embedded document below (or download it here).

    The six ill miners were admitted to the No. 1. School of Clinical Medicine, Kunming Medical University, in short succession in late April and early May 2012. Kunming is the capital of Yunnan province and 250 Km from Mojiang.

    Of the descriptions of the miners and their treatments, which include radiographs and numerous CAT scans, several features stand out:

    1) From their admission to the hospital their doctors informed the “medical office” of a potential “outburst of disease” i.e. a potential epidemic outbreak. Thus, the miners were treated for infections and not as if they had inhaled noxious gases or other toxins.

    2) The symptoms (on admission) of the six miners were: a) dry cough, b) sputum, c) high fevers, especially shortly before death d) difficulty breathing, e) myalgia (sore limbs). Some patients had hiccoughs and headaches. (See Table 1).

    3) Clinical work established that patients 1-4 had low blood oxygen “for sure it was ARDS” (Acute Respiratory Distress Syndrome) and immune damage considered indicative of viral infection. Additionally, a tendency for thrombosis was noted in patients 2 and 4. Symptom severity and mortality were age-related (though from a sample of 6 this must be considered anecdotal).

    4) Potential common and rare causes of their symptoms were tested for and mostly eliminated. For patients 3 and 4 these included tests for HIV, Cytomegalovirus, Epstein-Barr Virus (EBV), Japanese encephalitis, haemorrhagic fever, Dengue, Hepatitis B, SARS, and influenza. Of these, only patient 2 tested positive for Hepatitis and EBV.

    5) Treatment of the six patients included ventilation (patients 2-4), steroids (all patients), antivirals (all except patient 5), and blood thinners (patients 2 and 4). Antibiotics and antifungal medications were administered to counter what were considered secondary (but significant) co-infections.

    6) A small number of remote meetings were held with researchers at other universities. One was with Zhong Nanshan at Sun Yat-Sen University, Guangdong. Zhong is the Chinese hero of the SARS epidemic, a virologist, and arguably the most famous scientist in China.

    7) Samples from the miners were later sent to the WIV in Wuhan and to Zhong Nanshan, further confirming that viral disease was strongly suspected. Some miners did test positive for coronavirus (the thesis is unclear on how many).

    8) The source of infection was concluded to be Rhinolophus sinicus, a horseshoe bat and the ultimate conclusion of the thesis reads “the unknown virus lead to severe pneumonia could be: The SARS-like-CoV from the Chinese rufous horseshoe bat.” Thus the miners had a coronavirus but it apparently was not SARS itself.

    The significance of the Master’s thesis

    These findings of the thesis are significant in several ways.

    First, in the light of the current coronavirus pandemic it is evident the miners’ symptoms very closely resemble those of COVID-19 (Huang et al, 2020; Tay et al., 2020; M. Zhou et al., 2020). Anyone presenting with them today would immediately be assumed to have COVID-19. Likewise, many of the treatments given to the miners have become standard for COVID-19 (Tay et al., 2020).

    Second, the remote meeting with Zhong Nanshan is significant. It implies that the illnesses of the six miners were of high concern and, second, that a SARS-like coronavirus was considered a likely cause.

    Third, the abstract, the conclusions, and the general inferences to be made from the Master’s thesis contradict Zheng-li Shi’s assertion that the miners died from a fungal infection. Fungal infection as a potential primary cause was raised but largely discarded.

    Fourth, if a SARS-like coronavirus was the source of their illness the implication is that it could directly infect human cells. This would be unusual for a bat coronavirus (Ge et al., 2013). People do sometimes get ill from bat faeces but the standard explanation is histoplasmosis, a fungal infection and not a virus (McKinsey and McKinsey, 2011; Pan et al., 2013).

    Fifth, the sampling by the Shi lab found that bat coronaviruses were unusually abundant in the mine (Ge at al., 2016). Among their findings were two betacoronaviruses, one of which was RaTG13 (then known as BtCoV/4991). In the coronavirus world betacoronaviruses are special in that both SARS and MERS, the most deadly of all coronaviruses, are both betacoronaviruses. Thus they are considered to have special pandemic potential, as the concluding sentence of the Shi lab publication which found RaTG13 implied: “special attention should particularly be paid to these lineages of coronaviruses” (Ge at al., 2016). In fact, the Shi and other labs have for years been predicting that bat betacoronaviruses like RaTG13 would go pandemic; so to find RaTG13 where the miners fell ill was a scenario in perfect alignment with their expectations.

    The Mojiang miners passaging proposal

    How does the Master’s thesis inform the search for a plausible origin of the pandemic?

    In our previous article we briefly discussed how the pandemic might have been caused either by a virus collection accident, or through viral passaging, or through genetic engineering and a subsequent lab escape. The genetic engineering possibility deserves attention and is extensively assessed in an important preprint (Segreto and Deigin, 2020).

    We do not definitively rule out these possibilities. Indeed it now seems that the Shi lab at the WIV did not forget about RaTG13 but were sequencing its genome in 2017 and 2018. However, we believe that the Master’s thesis indicates a much simpler explanation.

    We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2*, that escaped from the WIV in 2019.

    We refer to this COVID-19 origin hypothesis as the Mojiang Miners Passage (MMP) hypothesis.

    Passaging is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host’s immune system vanquishes the ill-adapted virus. But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique (called “serial passaging” or just “passaging”) intensively selects for viruses adapted to the new host or cell type (Herfst et al., 2012).

    At first glance RaTG13 is unlikely to have evolved into SARS-CoV-2 since RaTG13 is approximately 1,200 nucleotides (3.8%) different from SARS-CoV-2. Although RaTG13 is the most closely related virus to SARS-CoV-2, this sequence difference still represents a considerable gap. In a media statement evolutionary virologist Edward Holmes has suggested this gap represents 20-50 years of evolution and others have suggested similar figures.

    We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalised miners favoured a very high rate of evolution inside them.

    i) When viruses infect new species they typically undergo a period of very rapid evolution because the selection pressure on the invading pathogen is high. The phenomenon of rapid evolution in new hosts is well attested among corona- and other viruses (Makino et al., 1986; Baric et al., 1997; Dudas and Rambaut 2016; Forni et al., 2017).

    ii) Judging by their clinical symptoms such as the CT scans, all the miner’s infections were primarily of the lungs. This localisation likely occurred initially because the miners were exerting themselves and therefore inhaling the disturbed bat guano deeply. As miners, they may already have had damaged lung tissues (patient 3 had suspected pneumoconiosis) and/or particulate matter was present that irritated the tissues and may have facilitated initial viral entry.

    In contrast, standard coronavirus infections are confined to the throat and upper respiratory tract. They do not normally reach the lungs (Perlman and Netland, 2009). Lungs are far larger tissues by weight (kilos vs grammes) than the upper respiratory tract. There was therefore likely a much larger quantity of virus inside the miners than would be the case in an ordinary coronavirus infection.

    Comparing a typical coronavirus respiratory tract infection with the extent of infected lungs in the miners from a purely mathematical point of view indicates the potential scale of this quantitative difference. The human aerodigestive tract is approximately 20cm in length and 5cm in circumference, i.e. approximately 100 cm2 in surface area. The surface area of a human lung ranges from 260,000-680,000 cm2 (Hasleton, 1972). The amount of potentially infected tissue in an average lung is therefore approximately 4500-fold greater than that available to a normal coronavirus infection. The amount of virus present in the infected miners, sufficient to hospitalise all of them and kill half of them, was thus proportionately very large.

    Evolutionary change is in large part a function of the population size. The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.

    Furthermore, according to the Master’s thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus.

    iii) The length of infection experienced by the miners (especially patients 2, 3 and 4) far exceeded that of an ordinary coronavirus infection. From first becoming too sick to work in the mine, patient 2 survived 57 days until he died. Patient 3 survived 120 days after stopping work. Patient 4 survived 117 days and then was discharged as cured. Each had been exposed in the mine for 14 days prior to the onset of severe symptoms; thus each presumably had nascent infections for some time before calling in sick (See Table 2 of the thesis).

    In contrast, in ordinary coronavirus infections the viral infection is cleared within about ten to fourteen days after being acquired (Tay et al., 2020). Thus, unlike most sufferers from coronavirus infection, the hospitalised miners had very long-term bouts of disease characterised by a continuous high load of virus. In the cases of patients 3 and 4 their illnesses lasted over 4 months.

    iv) Coronaviruses are well known to recombine at very high rates: 10% of all progeny in a cell can be recombinants (Makino et al., 1986; Banner and Lai, 1991; Dudas and Rambaut, 2016). In normal virus evolution the mutation rate and the selection pressure are the main foci of attention. But in the case of a coronavirus adapting to a new host where many mutations distributed all over the genome are required to fully adapt to the new host, the recombination rate is likely to be highly influential in determining the overall speed of adaptation by the virus population (Baric et al., 1997).

    Inside the miners a large tissue was simultaneously infected by a population of poorly-adapted viruses, with each therefore under pressure to adapt. Even if the starting population of virus lacked any diversity, many individual viruses would have acquired mutations independently but only recombination would have allowed these mutations to unite in the same genome. To recombine, viruses must be present in the same cell. In such a situation the particularities of lung tissues become potentially important because the existence of airways (bronchial tubes, etc.) allows partially-adapted viruses from independent viral populations to travel to distal parts of the lung (or even the other lung) and encounter other such partially-adapted viruses and populations. This movement around the lungs would likely have resulted in what amounted to a passaging effect without the need for a researcher to infect new tissues. Indeed, in the Master’s thesis the observation is several times made that areas of the lungs of a specific patient would appear to heal even while other parts of the lungs would become infected.

    v) There were also a number of unusual things about the bat coronaviruses in the mine. They were abnormally abundant but also there were many different kinds, often causing co-infections of the bats (Ge et al., 2016). Viral co-infections are often more infectious or more pathogenic (Latham and Wilson, 2007).

    As the WIV researchers remarked about the bats in the mine:

    “we observed a high rate of co-infection with two coronavirus species and interspecies infection with the same coronavirus species within or across bat families. These phenomena may be owing to the diversity and high density of bat populations in the same cave, facilitating coronavirus intra- and interspecies transmissions, which may result in recombination and acceleration of coronavirus evolution.” (Ge et al., 2016).

    The diversity of coronaviruses in the mine suggests that the miners were similarly exposed and that their illness may potentially have begun as co-infections.

    Combining these observations, we propose that the miners’ lungs offered an unprecedented opportunity for accelerated evolution of a highly bat-adapted coronavirus into a highly human-adapted coronavirus and that decades of ordinary coronavirus evolution could easily have been condensed into months. However, we acknowledge that these conditions were unique. They and their scale have no exact scientific precedent we can refer to and they would be hard to replicate in a lab; thus it is important to emphasize that our proposal is fully consistent with the underlying principles of viral evolution as understood today.

    In support of the MMP theory we also know something about the samples taken from the miners. According to the Master’s thesis, samples were taken from patients for “scientific research” and blood samples (at least) were sent to the WIV.

    “In the later stage we worked with Dr. Zhong Nan Shan and did some sampling. The patient* tested positive for serum IgM by the WuHan Institute of Virology. It suggested the existence of virus infection” (p62 in the section “Comprehensive Analysis”.)

    (*The original does not specify the number of patients tested.)

    The Master’s thesis also states its regret that no samples for research were taken from patients 1 and 2, implying that samples were taken from all the others.

    We further know that, on June 27th, 2012, the doctors performed an unexplained thymectomy on patient 4. The thymus is an immune organ that can potentially be removed without greatly harming the patient and it could have contained large quantities of virus. Beyond this the Master’s thesis is unfortunately unclear on the specifics of what sampling was done, for what purpose, and where each particular sample went.

    Given the interests of the Shi lab in zoonotic origins of human disease, once such a sample was sent to them, it would have been obvious and straightforward for them to investigate how a virus from bats had managed to infect these miners. Any viruses recoverable from the miners would likely have been viewed by them as a unique natural experiment in human passaging offering unprecedented and otherwise-impossible-to-obtain insights into how bat coronaviruses can adapt to humans.

    The logical course of such research would be to sequence viral RNA extracted directly from unfrozen tissue or blood samples and/or to generate live infectious clones for which it would be useful (if not imperative) to amplify the virus by placing it in human cell culture. Either technique could have led to accidental infection of a lab researcher.

    Our supposition as to why there was a time lag between sample collection (in 2012/2013) and the COVID-19 outbreak is that the researchers were awaiting BSL-4 lab construction and certification, which was underway in 2013 but delayed until 2018.

    We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.

    Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic. In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic.

    Evidence in favour of the MMP proposal

    Our proposal is consistent with all the principal undisputed facts concerning SARS-CoV-2 and its origin. The MMP proposal has the additional benefit of reconciling many observations concerning SARS-CoV-2 that have proven difficult to reconcile with any natural zoonotic hypothesis.

    For instance, using different approaches, numerous researchers have concluded that the SARS-CoV-2 spike protein has a very high affinity for the human ACE2 receptor (Walls et al., 2020; Piplani et al., 2020; Shang and Ye et al., 2020; Wrapp et al., 2020). Such exceptional affinities, ten to twenty times as great as that of the original SARS virus, do not arise at random, making it very hard to explain in any other way than for the virus to have been strongly selected in the presence of a human ACE2 receptor (Piplani et al., 2020).

    In addition to this, a recent report found that the spike of RaTG13 binds the human ACE2 receptor (Shang and Ye et al., 2020). We proposed above that the virus in the mine directly infected humans lung cells. The main determinant of cell infection and species specificity of coronaviruses is initial receptor binding (Perlman and Netland, 2009). Thus RaTG13, unlike most bat coronaviruses, probably can enter and infect human cells, providing biological plausibility to the idea that the miners became infected with a coronavirus resembling RaTG13.

    Moreover, the receptor binding domain (RBD) of SARS-CoV-2, which is the region of the spike that physically contacts the human ACE2 receptor, has recently been crystallised to reveal its spatial structure (Shang and Ye et al., 2020). These authors found close structural similarities between the spikes of SARS-CoV-2 and RaTG13 in how they bound the human ACE2 receptor:

    “Second, as with SARS-CoV-2, bat RaTG13 RBM [a region of the RBD] contains a similar four-residue motif in the ACE2 binding ridge, supporting the notion that SARS-CoV-2 may have evolved from RaTG13 or a RaTG13-related bat coronavirus (Extended Data Table 3 and Extended Data Fig. 7). Third, the L486F, Y493Q and D501N residue changes from RaTG13 to SARS CoV-2 enhance ACE2 recognition and may have facilitated the bat-to-human transmission of SARS-CoV-2 (Extended Data Table 3 and Extended Data Fig. 7). A lysine-to-asparagine mutation at the 479 position in the SARS-CoV-2 RBD (corresponding to the 493 position in the SARS-CoV-2 RBD) enabled SARS-CoV to infect humans. Fourth, Leu455 contributes favourably to ACE2 recognition, and it is conserved between RaTG13 and SARS CoV-2; its presence in the SARS CoV-2 RBM may be important for the bat-to-human transmission of SARS-CoV-2″ (Shang and Ye et al., 2020). (italics added)

    The significance of this molecular similarity is very great. Coronaviruses have evolved a diverse set of molecular solutions to solve the problem of binding ACE2 (Perlman and Netland, 2009; Forni et al., 2017). The fact that RaTG13 and SARS CoV-2 share the same solution makes RaTG13 a highly likely direct ancestor of Sars-CoV-2.

    A further widely noted feature of SARS-CoV-2 is its furin site (Coutard et al., 2020). This site is absent from RaTG13 and other closely related coronaviruses. The most closely related virus with such a site is the highly lethal MERS (which broke out in 2012). Possession of a furin site enables SARS-CoV-2 (like MERS) to infect lungs and many other body tissues (such as the gastrointestinal tract and neurons), explaining much of its lethality (Hoffman et al., 2020; Lamers et al., 2020). However, no convincing explanation for how SARS-CoV-2 acquired this site has yet been offered. Our suggestion is that it arose due to the high selection pressure which existed in the miner’s lungs and which in general worked to ensure that the virus became highly adapted to the lungs. This explanation, which encompasses how SARS-CoV-2 came to target lung tissues in general, is an important aspect of our proposal.

    The implication is therefore that the furin site was not acquired by recombination with another coronavirus and simply represents convergent evolution (as suggested by Andersen et al., 2020).

    An intriguing alternative possibility is that SARS-CoV-2 acquired its furin site directly from the miner’s lungs. Humans possess an epithelial sodium channel protein called ENaC-a whose furin cleavage site is identical over eight amino acids to SARS-CoV-2 (Anand et al., 2020). ENaC-a protein is present in the same airway epithelial and lung tissues infected by SARS-CoV-2. It is known from plants that positive-stranded RNA viruses recombine readily with host mRNAs (Greene and Allison, 1994; Greene and Allison, 1996; Lommel and Xiong, 1991; Borja et al., 2007). The same evidence base is not available for positive-stranded animal RNA viruses, (though see Gorbalenya, 1992) but if plant viruses are a guide then acquisition of its furin site via recombination with the mRNA which encodes ENaC-a by SARS-CoV-2 is a strong possibility.

    A further feature of SARS-CoV-2 has been the very limited adaptive evolution of its genome since the pandemic began (Zhan et al., 2020; van Dorp et al., 2020; Starr et al., 2020). It is a well-established principle that viruses that jump species undergo accelerated evolutionary change in their new host (e.g. Baric et al., 1997). Thus, SARS and MERS (both coronaviruses) underwent rapid and readily detectable adaptation to their new human hosts (Forni et al., 2017; Dudas and Rambaut, 2016). Such an adaptation period has not been observed for SARS-CoV-2 even though it has now infected many more individuals than SARS or MERS did. This has even led to suggestions that the SARS-CoV-2 virus had a period of cryptic circulation in humans infections that predated the pandemic (Chaw et al., 2020). The sole mutation consistently observed to accumulate across multiple studies is a D614G substitution in the spike protein (e.g. Korber et al., 2020). The numerically largest analysis of SARS-CoV-2 genomes, however, found no evidence at all for adaptive evolution, even for D614G (van Dorp et al., 2020).

    The general observation is therefore that Sars-CoV-2 has remained functionally unchanged or virtually so (except for inconsequential genetic changes) since the pandemic began. This is a very important observation. It implies that SARS-CoV-2 is highly adapted across its whole set of component proteins and not just at the spike (Zhan et al., 2020). That is to say, its evolutionary leap to humans was completed before the 2019 pandemic began.

    It is hard to imagine an explanation for this high adaptiveness other than some kind of passaging in a human body (Zhan et al., 2020). Not even passaging in human cells could have achieved such an outcome.

    Two examples illustrate this point. In a follow up to Shang and Ye et al., (2020), a similar group of Minnesota researchers identified a distinct strategy by which the spike (S) protein (which contains the receptor bind domain; RBD) of SARS-CoV-2 evades the human immune system (Shang and Wan et al., 2020). This strategy involves more effective hiding of its RBD, but it implies again that the spike and the RBD evolved in tandem and in the presence of the human immune system (i.e. in a human body and not in tissue culture).

    The Andersen authors, in their critique of a possible engineered origin for SARS-CoV-2, also stress the need for passaging in whole humans:

    “Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred during cell-culture passage, as such features suggest the involvement of an immune system” (Andersen et al., 2020).

    The final point that we would like to make is that the principal zoonotic origin thesis is the one proposed by Andersen et al. Apart from being poorly supported this thesis is very complex. It requires two species jumps, at least two recombination events between quite distantly related coronaviruses and the physical transfer of a pangolin (having a coronavirus infection) from outside China (Andersen et al., 2020). Even then it provides no logical explanation of the adaptedness of SARS-CoV-2 across its whole genome or why the virus emerged in Wuhan.

    By contrast, our MMP proposal requires only the one species jump, which is documented in the Master’s thesis. Although we do not rule out a possible role for mixed infections in the lungs of the miners, nor the possibility of recombination between closely related variants in those lungs, nor the potential acquisition of the furin site from a host mRNA, only mutation was needed to derive SARS-CoV-2 from RaTG13. Hence our attention earlier to the figure from P. Zhou et al., 2020 showing that RaTG13 is the most closely related virus to SARS-CoV-2 over its entire length. This extended similarity is perfectly consistent with a mutational origin of SARS-CoV-2 from RaTG13.

    In short, the MMP theory is a plausible and parsimonious explanation of all the key features of the COVID-19 pandemic and its origin. It accounts for the propensity of SARS-CoV-2 infections to target the lungs; the apparent preadapted nature of the virus; and its transmission from bats in Yunnan to humans in Wuhan.

    Further questions

    The hypothesis that SARS-CoV-2 evolved in the Mojiang miner’s lungs potentially resolves many scientific questions about the origin of the pandemic. But it raises others having to do with why this information has not come to light hitherto. The most obvious of these concern the actions of the Shi lab at the WIV.

    Why did the Shi lab not acknowledge the miners’ deaths in any paper describing samples taken from the mine (Ge et al., 2016 and P. Zhou et al., 2020)? Why in the title of the Ge at al. 2016 paper did the Shi lab call it an “abandoned” mine? When they published the sequence of RaTG13 in Feb. 2020, why did the Shi lab provide a new name (RaTG13) for BtCoV/4991 when they had by then cited BtCoV/4991 twice in publications and once in a genome sequence database and when their sequences were from the same sample and 100% identical (P. Zhou et al., 2020)? If it was just a name change, why no acknowledgement of this in their 2020 paper describing RaTG13 (Bengston, 2020)? These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.

    These are not the only questionable actions associated with the provenance of samples from the mine. There were five scientific publications that very early in the pandemic reported whole genome sequences for SARS-CoV-2 (Chan et al., 2020; Chen et al., 2020; Wu et al., 2020; P. Zhou et al., 2020; Zhu et al., 2020). Despite three of them having experienced viral evolutionary biologists as authors (George Gao, Zheng-li Shi and Edward Holmes) only one of these (Chen et al., 2020) succeeded in identifying the most closely related viral sequence by far: BtCoV/4991 a viral sequence in the possession of the Shi lab at the WIV that differed from SARS-CoV-2 by just 5 nucleotides.
    I'd also add that their response to Andersen et al isn't necessary since the predicted O-linked glycans don't exist.

    And since I know not everyone will read all that, I'll reiterate some of the unanswered questions that may be of more general interest:

    • Why did the Wuhan Institute of Virology not acknowledge the miners’ deaths in any of the papers describing samples taken from the mine the miners contracted the mysterious coronavirus in?
    • Why did the Wuhan Institute of Virology refer to the mine as abandoned in their publication when miners were clearly working in it?
    • Why did the Wuhan Institute of Virology and EcoHealth team initially fail to identify BtCoV/4991 as SARS-CoV-2's closest relative despite it being in searchable public databases and in their own lab's possession?
    • Why did Zheng-li Shi change BtCoV/4991's name before publishing its full sequence post COVID-19 outbreak as if it was a new discovery?
    • Why did Zheng-li Shi later claim that the miners had died of fungal infections when they died of a coronavirus, samples of which, her lab would have had in its possession?

    Then the biggest question: Why did the Wuhan Institute of Virology never publish the coronavirus samples taken directly from the miners who died? It has been seven years since they collected them.
    Last edited by sumskilz; August 01, 2020 at 08:29 AM.
    Quote Originally Posted by Enros View Post
    You don't seem to be familiar with how the burden of proof works in when discussing social justice. It's not like science where it lies on the one making the claim. If someone claims to be oppressed, they don't have to prove it.


  11. #71
    Ludicus's Avatar Vicarius Provinciae
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    Default Re: The Potential Lab Origin of COVID-19

    I can't say I don't admire your well intentioned effort.
    ----
    Prof. Mark Pagel says, "the authors’ analysis shows that the difference between RaTG13 and covid-19 in the critical variable loop region probably arose in RaTG13 after it separated from the common ancestor it shares with covid-19. This then points to the conclusion that there are as yet undetected horseshoe bat viruses that are the likely source of covid-19"

    On the contrary, sumskilz,there is zero evidence of a lab origin. Based on the available evidence, the virus likely emerged in bats in the wild and then jumped to humans. "Highly speculative", did you say? Tell me that the existence of God is highly speculative and I agree. In this case it's just a matter of time until bats will be proven as SARS-CoV-2 reservoirs, read below,I just finished reading this new paper (1)

    God gave you Leah- the still unknown reservoir- instead of Rachel - your desired lab theory. Jacob waited 14 years before he could be with Rachel.A bat cave solved the mystery of the SARS virus origin, 14 years after the beginning of the pandemic. Are you following me? Rachel is an illusion, sumskilz.
    No, very much to the contrary, the case is not building that the COVID had a lab origin. Stick with Lia, don't waste your time involuntarily feeding racist narratives.
    -------

    (1) One more nail in the coffin of the lab accident theory.Read the full paper.
    A palindromic RNA sequence as a common breakpoint contributor to copy-choice recombination in SARS-COV-2.
    Published a few hours ago, excerpts,

    Into that ancestral genetic background, several recombination events have since occurred from other divergent bat-derived coronaviruses, resulting in localized discordance between the two. One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion.

    This paper demonstrates by bioinformatic analysis that such recombinational events are facilitated by short oligonucleotide “breakpoint sequences”, similar to CAGAC, that direct recombination naturally to certain positions in the genome at the boundaries between blocks of RNA code and potentially RNA structure. This “breakpoint sequence hypothesis” provides a natural explanation for the biogenesis of SARS-CoV-2 over time and in the wild.

    ....The origin of the furin site RNA sequence has been a complete mystery, even though similar amino acid motifs are found in many coronaviruses.
    A BLAST search for the actual insert sequence, CTCCTCGGCGGG, identifies a sequence derived from bat coronavirus HKU-9, from a region in the S protein downstream of the S1/S2 junction, with identity at the last 10 nucleotides. Looking further at the HKU9 sequence, CAGAC lies directly prior to the identity (Fig. 3b).
    The SARS-CoV-2 and HKU-9 sequences can be aligned as 18 identities in a span of 28 nucleotides of HKU-9, with minimal gaps. While not perfect, this does support the hypothesis that the entire furin insert may have been derived by recombination from an as yet unsampled coronavirus, mediated by the presence of CAGAC as the lead nucleotide in both progenitor viruses, with other palindromic oligonucleotides as contributors.
    ... All of these recombination events, in Orf1a, in the RBD, and the furin site itself, have most likely occurred since SARS-CoV-2 and RaTG13 diverged from their most recent common ancestor (MRCA). As estimated above, this would give a wide range for the time period during which these recombination events may have taken place, from the last half of the 20th century to the present.

    (...) I would end with a warning. Karst limestone formations extend widely across southern China, from Yunnan province through Guangxi province and into westernmost Guangdong province. Portions of such wilderness are designated a UNESCO World Heritage Site (https://whc.unesco.org/en/list/1248). The limestone is riddled with caves carved by water flow that are occupied by large colonies of bats. Several colonies of both insectivorous microbats and fruit macrobats can occupy the same caves. Bats and bat viruses of innumerable variety cohabit this ecological environment, providing ample and ongoing opportunities for mixed infection of bats by a variety of bat coronaviruses [10, 11, 31,32,33]. Likewise, bat guano, mined for fertilizer, is a viral soup with many contributing sources. The proximal source of SARS-CoV-2, and particularly of the critical sequences in the RBD or furin-sensitive site, remains to be identified.

    As these recombination processes are endless, natural and ongoing, the possibilities for emergence of pandemic viruses from these natural virological parks of Southeast Asia are also endless. As the emergence of the 1918 pandemic influenza virus from western Kansas [34, 35], hantavirus from the American Southwest [36], Ebola virus from Africa [37], and Zika virus from Africa via South America [38] prove, emergence can occur from every wilderness area on planet Earth. Every human virus represents an emergence from an animal source. In the past, they have occurred only occasionally, but in the 21st century, the emergence of a pandemic virus has just changed the world as we have known it.
    ------
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    Tackling Rumors of a Suspicious Origin of nCoV2019 - nCoV ...
    Last edited by Ludicus; August 02, 2020 at 03:19 PM.
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  12. #72

    Default Re: The Potential Lab Origin of COVID-19

    It's very interesting how much of these viruses originate from China, don't you think? There's never talk about viruses emerging in countries like India and Southeast Asia where people are destroying nature as well. But then the question is whether it's really in China's interest to create biological weapons they can't take control of? And then damage their own economy? It's not looking good. But nobody knows the truth yet.

  13. #73
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    Default Re: The Potential Lab Origin of COVID-19

    Diseases have come from Asia since the bubonic plague in the middle ages, and probably earlier. Must be an ecological factor. There’s been a number of deadly flus from Asia in the last 100 years or so alone.
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    Default Re: The Potential Lab Origin of COVID-19

    Diseases have come from Asia since the bubonic plague in the middle ages, and probably earlier. Must be an ecological factor. There’s been a number of deadly flus from Asia in the last 100 years or so alone.
    Longer history of dense population.

    Think about it Ebola and Aids come from Africa. But until recently Africa did not the the kind of density to support widespread transmission and the repeated opportunity for jumps to humans or other animals until munitions allowed more easy transmission.

    Same goes for the maybe Henta virus that was the English Sweating Sickness

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917436/

    Or really the plague at Athens. Its notable that it seems not to have affected the Arche just one place that suddenly had the density in the Aegean to sustain it.

    I would suspect historically most jumps simply burn out in isolated populations. But when you get the right prolonged and sustained human density you set yourself up for a new virus jump.
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  15. #75
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    Default Re: The Potential Lab Origin of COVID-19

    Why misinformation about COVID-19’s origins keeps going viral
    https://www.nationalgeographic.com/s...act-check-cvd/

    This is about the following study: https://zenodo.org/record/4028830

    Which started some debate:
    https://twitter.com/K_G_Andersen/sta...37072914866178
    https://twitter.com/CT_Bergstrom/sta...43494913245184
    Open Access Defenders Step Up to Save ‘Pirate Bay of Science’
    https://nerdist.com/article/open-acc...brary-genesis/

  16. #76

    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by Genava View Post
    Why misinformation about COVID-19’s origins keeps going viral
    https://www.nationalgeographic.com/s...act-check-cvd/

    This is about the following study: https://zenodo.org/record/4028830

    Which started some debate:
    https://twitter.com/K_G_Andersen/sta...37072914866178
    https://twitter.com/CT_Bergstrom/sta...43494913245184
    Andersen is correct that Yan et al's hypothesis is pointlessly convoluted, since Chinese scientists could have simply synthesized the virus in any configuration they like using this methodology, the result of which would be undetectable. Respect to him for linking that article and making the connection, although I linked the preprint of that same study when I critiqued his correspondence to Nature back in March. Was he really not aware of the technology at the time?

    Not that I think that's actually what happened.

    I also respect Andersen for calling out Peter Daszak for his BS on Twitter and elsewhere:

    “I feel the claim they are making that you can prevent the next pandemic by doing this type of work is preposterous,” Andersen said. “If you could, given they worked in Wuhan for so long specifically, you would have thought they could have prevented the current pandemic, and they didn’t.”
    I have been following this story much less since I last posted, to some extent because I simply don't have the time, but more so because it's an exercise in futility. Scientists working on the issue are all relying on information provided by the Wuhan Institute of Virology without independent verification, most notably the sequence of RaTG13 published after the virus was already major news, taken from a sample WIV claims no longer exists, and whose origins WIV scientists lied about and otherwise tried to obscure (I assume under pressure from above). Whatever the origin of SARS-CoV-2, information will likely be slow to emerge. As I recall, it took seven years before the origin of SARS-CoV-1 was well understood. On the other hand, when a virus escaped from a lab in 1977 causing a global pandemic, it was more than 30 years before the fact quietly gained mainstream acceptance.

    Alina Chan on Twitter:

    Journalists, scientists, and people interested in SARS2 origins, you've been barking up the wrong Zenodo article. This is the more interesting one albeit it requires serious journalistic fact-checking. Released same day as the Yan report. Viewed 259 times.
    Referring to this: Proposed SARS-CoV-2 Spillover During 2019 Review of Samples from a Mineshaft in Mojiang, Yunnan Province, China

    And now here's something too ridiculous to be true (yet it is):

    An international team of scientists will examine the possibility Sars-Cov-2 leaked from a laboratory as part of a comprehensive investigation into the origins of the virus.

    The team is being set up as part of the Lancet COVID-19 Commission, a body established in July to “offer practical solutions” to the pandemic and make recommendations on how the next one can be avoided or better defended against.

    The team looking at the origins of the virus will be led by Dr Peter Daszak, a British zoologist and leading authority on zoonotic spillover events.
    That's right, the man chosen to lead the team is specifically the man who has the most to lose personally, professionally and financially if the lab leak hypothesis turns out to be true. The Lancet could not have chosen anyone with a greater conflict of interest, because literally no scientist with a greater conflict of interest exists.

    Whatever the truth of the matter is, there could hardly be a more obscene lack of scientific integrity. The fact that the issue is being handled this way points to a much bigger problem than whether or not the virus escaped from a lab.
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  17. #77
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    Default Re: The Potential Lab Origin of COVID-19

    Quote Originally Posted by sumskilz View Post
    That's right, the man chosen to lead the team is specifically the man who has the most to lose personally, professionally and financially if the lab leak hypothesis turns out to be true. The Lancet could not have chosen anyone with a greater conflict of interest, because literally no scientist with a greater conflict of interest exists.

    Whatever the truth of the matter is, there could hardly be a more obscene lack of scientific integrity. The fact that the issue is being handled this way points to a much bigger problem than whether or not the virus escaped from a lab.
    There is a lot of pressure on Daszak to release information and grant access to the Wuhan lab to foreign officials. Since he is not directly directing the Wuhan lab (he is only an important partnair), I think he has more to lose if he tries to hide information or to put pressure on other scientists. Furthermore, Jeffrey Sachs will oversee the commision. There is also Richard Horton, a strong defender of free speech in science.
    Open Access Defenders Step Up to Save ‘Pirate Bay of Science’
    https://nerdist.com/article/open-acc...brary-genesis/

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