The Lab-Leak Theory: Inside the Fight to Uncover COVID-19’s Origins

[Smoove_B]

Well, other than the core reason for argument. I'm firmly in the camp that SARS-CoV-2 is a naturally occurring virus that jumped from some unknown animal to humans. I believe this because people way smarter than I am have supported this theory and because I know of countless examples of zoonotic diseases emerging as described. It's a thing.

To be clear, it's entirely possible that they were studying this existing but widely unknown virus in the Wuhan lab prior to January of 2020 and they don't want to admit it. That doesn't mean they were engineering it and/or that it was released (accidentally or intentionally).

That really seems to be the fundamental issue here - the disbelief that zoonotic illness is a thing and given everything we know, the most likely cause. I still think people are putting equal weight on the other possibilities (or like Nate Silver, coming up with absurd percentages).

I honestly don't know of a single reputable person that is against trying to figure out how this all happened - that's a core element of emerging disease epidemiology. Where things seem to get...dicey is when there's a push to pin this on the Chinese.

[Anonymous Bosch]

Well, other than the core reason for argument. I'm firmly in the camp that SARS-CoV-2 is a naturally occurring virus that jumped from some unknown animal to humans. I believe this because people way smarter than I am have supported this theory and because I know of countless examples of zoonotic diseases emerging as described. It's a thing.

To be clear, it's entirely possible that they were studying this existing but widely unknown virus in the Wuhan lab prior to January of 2020 and they don't want to admit it. That doesn't mean they were engineering it and/or that it was released (accidentally or intentionally).

That really seems to be the fundamental issue here - the disbelief that zoonotic illness is a thing and given everything we know, the most likely cause. I still think people are putting equal weight on the other possibilities (or like Nate Silver, coming up with absurd percentages).

I honestly don't know of a single reputable person that is against trying to figure out how this all happened - that's a core element of emerging disease epidemiology. Where things seem to get...dicey is when there's a push to pin this on the Chinese.

You dodged my question; Jamie Metzl, who sits on the World Health Organization expert advisory committee on human genome editing and served under Senator Joe Biden and in the Clinton administration as the NSC’s director for multilateral affairs, presents a divergent hypothesis from the "trustworthy voices" you cited. Does that make him an untrustworthy, disreputable voice, and if so, why? Is there anything beyond your own agreement that necessarily makes their hypothesis more trustworthy than his? Because this doesn't certainly suggest to me he's necessarily advocating disbelief in the possibility of zoonotic illness "as a thing":

Let me be clear. While I do believe that a lab incident is the most likely origin of the pandemic, this is only a hypothesis. That this pandemic might stem from a zoonotic jump in the wild is also a hypothesis, even though very little evidence supporting that hypothesis has so far emerged. When comparing the evidence for each possibility, the case for a lab incident origin seems significantly stronger to me. Additional evidence could always change that. That’s why my essential argument is that we need a full and unrestricted international scientific and forensic investigation into all COVID-19 origin hypotheses with full access to all relevant records, samples, and key personnel. It is an affront to all of us that this no such investigation has been carried out or is currently planned. We owe everyone who has died from COVID-19, all the people who have lost their loved ones and livelihoods, and future generations a thorough, unbiased, and unrestricted investigation of how the tragedy began and has unfolded.

…

Although it is certainly possible that the SARS-CoV-2 virus had small edits (such as for its furin cleavage site, as suggested by Nobel laureate virologist and former CalTech president David Baltimore), the lab incident hypotheses does not require any genome editing to be valid. The virus or a precursor to it could have easily been collected, isolated, and cultured in one of the Wuhan labs. If the latter, serial passage and so-called “gain of function” research could have pushed the “natural” evolution of the virus toward greater pathogenicity without any genome editing. Again, this is only highly informed inference based on publicly available information and my application of Occam’s razor (and mathematical probabilities). I have no definitive way of proving this thesis but the evidence is, in my view, extremely convincing. If forced to place odds on the confidence of my hypothesis, I would say there’s an 85% chance the pandemic started with an accidental leak from the Wuhan Institute of Virology (or Wuhan CDC) and a 15% chance it began in some other way (in fairness, here is an article making the case for a zoonotic jump “in the wild”). If China keeps preventing a full and unrestricted international forensic investigation into the origins of the pandemic, I believe it is fair to deny Beijing the benefit of the doubt. Should we find a virus in the wild that is clearly a SARS-CoV-2 precursor virus, perhaps with 99.9% genetic similarity, that would be a strong argument for the zoonosis in the wild hypothesis.

…

• Although nothing can be fully conclusive in light of Chinese obfuscation, the continued absence of any meaningful evidence of a zoonotic chain of transmission and mutation in the wild and the accretion of other evidence is pointing increasingly, in my view, toward an accidental lab leak as the most likely origin of COVID-19. Given the extent to which China would benefit from discovering evidence of a transmission in the wild, we can assume Chinese authorities are doing all they can to find this kind of evidence without success. This failure would explain why Chinese officials have recently begun, with little credible evidence, asserting that the outbreak started outside of China.
• This Quantitative Biology paper by Nikolai Petrovsky et al makes the very strong case that that the SARS-CoV-2 virus was already pre-adapted to humans by the time it appeared in late 2020.
• Similarly, Sirotkin and Sirotkin assert in their Wiley essay: “Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual‐use gain‐of‐function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS‐CoV‐2’s distinctive spike‐protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus’s origins and a re‐examination of the risks and rewards of dual‐use gain‐of‐function research.

[Smoove_B]

You dodged my question;

Wasn't intentional. I'm not sure I'd say he's disreputable or untrustworthy, no. But I'm not going to lie - I am highly suspicious of anyone with (1) current or former political ties (any) that is (2) pushing a narrative that ties this to the Chinese in any way. The academics that I lump in the "trusted voices" bucket are all just that - researchers that have decades of experience and haven't been connected to any political element. They all seem to be saying the same thing - most likely a natural occurrence, but we can't completely rule out the significantly smaller chance a lab-leak was involved. We should look into this to figure out how to deal with the disease (and future diseases), not to pin blame or fuel a political agenda.

So again, it's not that I don't trust him; I question his motivations. So much of this stuff (the genomics, the evolutionary analysis, the morphology) is so far beyond what I can process; I don't know how John Q. Public can process it. Not that people are stupid, it just information that requires an insane level of knowledge to process. So ultimately what are people going to believe? That this just "randomly appeared in nature" (which I know happens all the damn time because of my professional training and knowledge) or that a "Chinese lab was hard at work 'researching' the virus when it escaped" (which makes for much more interesting news pieces and pundits to discuss on their nightly garbage TV show).

When people hear "lab leak" there's apparently a supposition that nefarious forces were at work. It really could have been a leak involving legitimate research and poor lab controls. If so, what then? Or has the narrative already been carefully sculpted at that point to justify whatever is coming next?

I want to reiterate that there's overwhelming interest in figuring out why/how this happened. I'm firmly in the camp that we need to do it for the science - we need to understand the etiology. I am highly suspect of those uninterested in the disease and instead trying to pin this on state actors.

[Anonymous Bosch]

You dodged my question;

Wasn't intentional. I'm not sure I'd say he's disreputable or untrustworthy, no. But I'm not going to lie - I am highly suspicious of anyone with (1) current or former political ties (any) that is (2) pushing a narrative that ties this to the Chinese in any way.

I understand, but realistically, one cannot simply ignore the fact we're specifically referring to and dealing with the type of totalitarian nation that routinely tortures and abuses millions of Uyghurs and members of other Turkic Muslim minorities in modern-day slavery 're-education camps'. They and their politics are an undeniably relevant factor in all of this. For an illustration of how and why, I would strongly encourage you to watch the terrific HBO miniseries, Chernobyl. Because there's a good reason why, as the WSJ observed, a quote from that miniseries went viral on the Chinese messaging app WeChat during the pandemic:

As Chinese authorities botched their response to the coronavirus outbreak in Wuhan, a quote from the HBO miniseries “Chernobyl” went viral on the Chinese messaging app WeChat: “What is the cost of lies? It’s not that we’ll mistake them for the truth. The real danger is that if we hear enough lies, then we no longer recognize the truth at all.”

The analogy between the 1986 nuclear accident and the 2020 pandemic—Communist regimes trying to cover up the truth of a disaster and thereby worsening it—may seem a little pat. It may also seem wishful: After all, the Chinese Communist Party, unlike the Soviet one, emerged from the unrest of 1989 with a tighter grip on power. Edward Luttwak doesn’t exactly agree with the analogy, but he takes it seriously.

[Smoove_B]

I think I've made it clear that I have no doubts China hasn't been completely honest with us from day one - particularly in how it all unfolded originally (numbers, timing) and how it progressed (total illnesses, deaths) - that's kinda their thing. I am also confident they're going to do it again (because even after being caught lying, they have continued to do it).

I also make no apologies for their horrible human-rights violations and generally how they conduct themselves in the global market.

But all that is a far cry away from suggesting they were genetically engineering a virus that was either intentionally or accidentally released from their labs. Then can be awful actors for all those other reasons and still be completely innocent of a "lab leak", as being proposed.

[Anonymous Bosch]

I think I've made it clear that I have no doubts China hasn't been completely honest with us from day one - particularly in how it all unfolded originally (numbers, timing) and how it progressed (total illnesses, deaths) - that's kinda their thing. I am also confident they're going to do it again (because even after being caught lying, they have continued to do it).

I also make no apologies for their horrible human-rights violations and generally how they conduct themselves in the global market.

But all that is a far cry away from suggesting they were genetically engineering a virus that was either intentionally or accidentally released from their labs.

We seem to be talking past one another here, because if you read what I cited above from Jamie Metzl, that's clearly not what he, and others like him, are hypothesizing at all. Granted, there are fringe elements (like Steve Bannon and Guo Wengui) fuelling claims that China had engineered the disease as a bioweapon and purposefully unleashed it upon the world. But it's incredibly unfair and disingenuous to conflate that sort of flapdoodle with what Jamie Metzl et al are hypothesizing.

Then can be awful actors for all those other reasons and still be completely innocent of a "lab leak", as being proposed.

Sure, they could be completely innocent. But for the reasons Scott Gottlieb clearly elucidated:

China could provide evidence that would be exculpatory here. They could provide the blood samples from those who worked in the lab in Wuhan. They've refused to do that. They could provide the source strain, some of the original strains. They've refused to do that. They can provide access to some of the early samples that we could sequence. They could provide an inventory of what was in the lab, the Institute of Virology, the lab that has been implicated in a potential lab leak. They have refused to do that. And we know that that lab was poorly constructed, had poor controls. That was reported at the time that it was first opened. We know the lab was engaging in very high-risk research, including infecting transgenic animals, animals with fully human immune systems. We know they were working with SARS-like viruses that have never been disclosed before. And now we have new evidence that some lab workers became infected right at the time that this virus was believed to be first introduced. That's been publicly reported. So that side of the ledger has expanded.

I would echo Metzl's remark above:

If China keeps preventing a full and unrestricted international forensic investigation into the origins of the pandemic, I believe it is fair to deny Beijing the benefit of the doubt.

[Smoove_B]

We seem to be talking past one another here, because if you read what I cited above from Jamie Metzl, that's clearly not what he, and others like him, are hypothesizing at all. Granted, there are fringe elements (like Steve Bannon and Guo Wengui) fuelling claims that China had engineered the disease as a bioweapon and purposefully unleashed it upon the world. But it's incredibly unfair and disingenuous to conflate that sort of flapdoodle with what Jamie Metzl et al are hypothesizing.

Maybe. My sense is that there's a group of people all gunning for China in some capacity. The true wackjobs (Steve Bannon) are proposing malicious manipulation of genetic material. Adjacent are those (apparently) like Metzl that believe they were researching things (though I'm not clear if he's stated why he believes they were researching things - to what end?) and somehow the virus got out. He's just asking questions.

I'm not lumping them in the same box (though I can see where it might seem like I am), it's just that anyone claiming China is directly involved in COVID-19 (by accident, intentional) is going to be be closer in their argument than people like me waaaaaaaaaay on the other side of the spectrum in my belief that this emerged from a natural source.

For Gottlieb and Metzl's commentary, this isn't something new. China has without question withheld outbreak related information in the past. And as Trump, the GOP and now a-holes like Rand Paul are whipping everyone up into a frenzy over "gain of function", is it any wonder the Chinese aren't being forthcoming? Just like auditing the ballots in AZ, I'm confident they know after all the evidence is provided they'll be told it doesn't clear them and now new investigations need to be conducted. They know this because since Day 1, Trump and the MAGA goons started with the "China Virus" nonsense. I'm not sure we're ever going to figure this out with their help because it became a political cudgel from the get go - and people continue to call it the "China Virus" and perpetrate hatred towards Asians all over America because of it.

[Anonymous Bosch]

Adjacent are those (apparently) like Metzl that believe they were researching things (though I'm not clear if he's stated why he believes they were researching things - to what end?) and somehow the virus got out.

To quote Metzl: "It is my view that Chinese researchers at these institutes were studying these viruses with the best intentions of developing surveillance systems, treatments, and vaccines for the good of humanity. Countries make mistakes, even terrible and deadly ones. I was in the White House when the US bombed the Chinese embassy in Belgrade. We believed it was an accident but many Chinese people thought it was a deliberate act. I understood why."

As someone with sincere scientific interest in this virus, I highly recommend you read what he has posted in its entirety. You may not agree with everything he says, but it's an incredibly sober, coherent, and rational non-partisan hypothesis that's well worth reading.

I'm not lumping them in the same box (though I can see where it might seem like I am), it's just that anyone claiming China is directly involved in COVID-19 (by accident, intentional) is going to be be closer in their argument than people like me waaaaaaaaaay on the other side of the spectrum in my belief that this emerged from a natural source.

For Gottlieb and Metzl's commentary, this isn't something new. China has without question withheld outbreak related information in the past. And as Trump, the GOP and now a-holes like Rand Paul are whipping everyone up into a frenzy over "gain of function", is it any wonder the Chinese aren't being forthcoming? Just like auditing the ballots in AZ, I'm confident they know after all the evidence is provided they'll be told it doesn't clear them and now new investigations need to be conducted. They know this because since Day 1, Trump and the MAGA goons started with the "China Virus" nonsense. I'm not sure we're ever going to figure this out with their help because it became a political cudgel from the get go - and people continue to call it the "China Virus" and perpetrate hatred towards Asians all over America because of it.

Whether or not politicians like Rand Paul happen to mention gain-of-function research in the rhetoric for their own particular benefit is beside the point, because serial passage gain-of-function research is a hugely relevant factor to the lab leak vs. zoonotic hypothesis, for the reasons Jamie Metzl clearly elucidates below:

• Although nothing can be fully conclusive in light of Chinese obfuscation, the continued absence of any meaningful evidence of a zoonotic chain of transmission and mutation in the wild and the accretion of other evidence is pointing increasingly, in my view, toward an accidental lab leak as the most likely origin of COVID-19. Given the extent to which China would benefit from discovering evidence of a transmission in the wild, we can assume Chinese authorities are doing all they can to find this kind of evidence without success. This failure would explain why Chinese officials have recently begun, with little credible evidence, asserting that the outbreak started outside of China.
• This Quantitative Biology paper by Nikolai Petrovsky et al makes the very strong case that that the SARS-CoV-2 virus was already pre-adapted to humans by the time it appeared in late 2020.
• Similarly, Sirotkin and Sirotkin assert in their Wiley essay: “Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual‐use gain‐of‐function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS‐CoV‐2’s distinctive spike‐protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus’s origins and a re‐examination of the risks and rewards of dual‐use gain‐of‐function research.
• The two known coronaviruses genetically closest to SARS-CoV-2, RaTG13 and RmYN02, were discovered in bats in Yunnan, China. The genome of RaTG13 is 96.2% similar to SARS-CoV-2. That of RmYN02 is 93.3 % similar. Given that the SARS-CoV-2 genome is made up of 30,000 nucleotides (aka letters), the genetic distance between RaTG13 and SARS-CoV-2 is a significant 1,200 nucleotides. Under normal circumstances in the wild, this would suggest that the two viruses diverged decades ago. But an essential question is whether gain of function research could have massively sped up this evolutionary rate, including by inducing the development of chimeric viruses well adapted to human cells. This type of research could have been done using the tools of genome editing (which I believe is highly unlikely in this case) or by exposing different viruses to human cells or humanized mouse or other animal cells in a laboratory.
• Stanford’s David Relman states: “SARS-CoV-2 is a betacoronavirus whose apparent closest relatives, RaTG13 and RmYN02, are reported to have been collected from bats in 2013 and 2019, respectively, in Yunnan Province, China. COVID-19 was first reported in December 2019 more than 1,000 miles away in Wuhan City, Hubei Province, China. Beyond these facts, the “origin story” is missing many key details, including a plausible and suitably detailed recent evolutionary history of the virus, the identity and provenance of its most recent ancestors, and surprisingly, the place, time, and mechanism of transmission of the first human infection… Some have argued that a deliberate engineering scenario is unlikely because one would not have had the insight a priori to design the current pandemic virus. This argument fails to acknowledge the possibility that two or more as yet undisclosed ancestors (i.e., more proximal ancestors than RaTG13 and RmYN02) had already been discovered and were being studied in a laboratory—for example, one with the SARS-CoV-2 backbone and spike protein receptor binding domain, and the other with the SARS-CoV-2 polybasic furin cleavage site. It would have been a logical next step to wonder about the properties of a recombinant virus and then create it in the laboratory… there is probably more than one recent ancestral lineage that contributes to SARSCoV-2 because its genome shows evidence of recombination between different parental viruses. In nature, recombination is common among coronaviruses. But it’s also common in some research laboratories where recombinant engineering is used to study those viruses.”
• The Brufsky et al Wiley pre-print letter lays out the underlying science which seems to explain why the gain of function research at the WIV is the most likely origin of the pandemic. To be fair, the conclusion these authors draw is extremely cautious: “These unique features of SARS–CoV–2 raise several questions concerning the proximal origin of the virus that require further discussion.” They do not list the question but the implication is clear enough.
• The analysis by Boni, Robertson, and their colleagues made those researchers believe that despite the genetic closeness, RaTG13 and SARS-CoV-2 split up quite a long time ago, possibly in 1969.
• It could also be possible that SARS-CoV-2 might be the result of gain of function research on another virus in the Wuhan Institute of Virology repository. Quoting a private communication from a scientist I trust (who chose to remain anonymous out of personal safety concerns), “the issue is that there is this internal database at the WIV that even other Chinese scientists can’t access. Even the first team to point out the similarity of SARS2 to the 4991 sequence — they had no idea that 4991 aka RaTG13 had been fully genome sequenced. What other viruses are in this database? Was the pangolin CoV RBD also in this database by mid 2019?”
• In an August 12, 2020 BioEssays paper, Sirotkin and Sirotkin assert that the WIV is sitting on somewhere in the neighborhood of 2,000 undisclosed wild viruses, and Dr. Shi herself disclosed that 9 previously undisclosed betacoronaviruses had been held in a WIV lab repository. The database issues are further explored in this thread as well as in this thread.)
• Sirotkin and Sirotkin also state: “Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual‐use gain‐of‐function research practice of viral serial passage should be considered a viable route by which the novel coronavirus arose.”
• “The long‐standing practice of serial passage is a form of gain‐of‐function research that forces zoonosis between species, and requires the same molecular adaptations necessary for a natural zoonotic jump to occur within a laboratory, leaving the same genetic signatures behind as a natural jump but occurring in a much shorter period of time… serial passage through a live animal host simply forces the same molecular processes that occur in nature to happen during a zoonotic jump, and in vitro passage through cell culture mimics many elements of this process—and neither necessarily leaves any distinguishing genetic traces.”

[Zarathud]

Those quotes talk about possible links, assumptions and anonymous sources. Not data, speculation.

[Little Raven]

Those quotes talk about possible links, assumptions and anonymous sources. Not data, speculation.

You say this as if one side has data and the other has speculation. Is there any actual DATA on either side of the argument?

[Anonymous Bosch]

Those quotes talk about possible links, assumptions and anonymous sources. Not data, speculation.

Of course, but broadly speaking, the same is true of the zoonotic origin hypothesis (although until very recently, there was far less controversy and risk involved in hypothesizing a zoonotic origin, hence also less anonymity). And only a haplessly naive simpleton would believe the CCP hasn't by now almost certainly destroyed any potential data and hard evidence that the virus leaked from the WIV.

[Smoove_B]

You say this as if one side has data and the other has speculation. Is there any actual DATA on either side of the argument?

There is in the genomic analysis of SARS-CoV-2 - its code and physical appearance. The evidence is that nothing supports anything other than a naturally occurring virus.

However, to AB's points above the way to get more definitive answers is to get literal boots on the ground in China and start collecting local samples - truly begin the hunt for the animal reservoir - as has been done for any number of other viruses (including Ebola). In addition, an examination of the lab and their protocols, etc.. would be in order. However, given the highly politicized nature of COVID-19 internationally (again, Trump), here's where we need to hope they agree to let a team of international scientists and researchers inside to continue the investigation.

Until they do it'll be round and round in circles we go. And given the prior administration's openly hostile position over it, I can't imagine they're looking to open their doors and give access to the international community any time soon. Given the initial hostility and the current beating of the war drums by member of the GOP and their proxies, it also makes it highly unlikely they're going to be inclined to share anything any time soon (if ever).

And while it's true that maybe they never would have shared anything to begin with, we certainly didn't need to give them the pretense to refuse to cooperate in any way by immediately accusing them of a coverup.

[malchior]

Until they do it'll be round and round in circles we go. And given the prior administration's openly hostile position over it, I can't imagine they're looking to open their doors and give access to the international community any time soon. Given the initial hostility and the current beating of the war drums by member of the GOP and their proxies, it also makes it highly unlikely they're going to be inclined to share anything any time soon (if ever).

And while it's true that maybe they never would have shared anything to begin with, we certainly didn't need to give them the pretense to refuse to cooperate in any way by immediately accusing them of a coverup.

At this point there is no incentive to cooperate for a couple of simple reasons. Our politics give them several outs and they can't prove a negative. Even if evidence is found of a zoonotic origin - it doesn't disprove the lab leak. Both scenarios could be true. All these factors lead to a frankly increasingly pointless discussion if you are seeking hard outcomes. That is why this is great for misinformation purposes. There is not going to be a definitive answer in the short-term and they'll just say it is fraud even if somehow hard evidence was found. Meanwhile they play in the sea of nefarious possibilities. This isn't really an honest discussion like many politicized topics in the United States.

[Anonymous Bosch]

You say this as if one side has data and the other has speculation. Is there any actual DATA on either side of the argument?

There is in the genomic analysis of SARS-CoV-2 - its code and physical appearance. The evidence is that nothing supports anything other than a naturally occurring virus.

However, to AB's points above the way to get more definitive answers is to get literal boots on the ground in China and start collecting local samples - truly begin the hunt for the animal reservoir - as has been done for any number of other viruses (including Ebola). In addition, an examination of the lab and their protocols, etc.. would be in order.

The SARS1 and MERS viruses seem more analogous to SARS-CoV-2 than Ebola, and as science writer Nicholas Wade observed:

Natural emergence was the media’s preferred theory until around February 2021 and the visit by a World Health Organization commission to China. The commission’s composition and access were heavily controlled by the Chinese authorities. Its members, who included the ubiquitous Dr. Daszak, kept asserting before, during and after their visit that lab escape was extremely unlikely. But this was not quite the propaganda victory the Chinese authorities may have been hoping for. What became clear was that the Chinese had no evidence to offer the commission in support of the natural emergence theory.

This was surprising because both the SARS1 and MERS viruses had left copious traces in the environment. The intermediary host species of SARS1 was identified within four months of the epidemic’s outbreak, and the host of MERS within nine months. Yet some 15 months after the SARS2 pandemic began, and a presumably intensive search, Chinese researchers had failed to find either the original bat population, or the intermediate species to which SARS2 might have jumped, or any serological evidence that any Chinese population, including that of Wuhan, had ever been exposed to the virus prior to December 2019. Natural emergence remained a conjecture which, however plausible to begin with, had gained not a shred of supporting evidence in over a year.

And as long as that remains the case, it’s logical to pay serious attention to the alternative conjecture, that SARS2 escaped from a lab.

However, given the highly politicized nature of COVID-19 internationally (again, Trump), here's where we need to hope they agree to let a team of international scientists and researchers inside to continue the investigation.

Until they do it'll be round and round in circles we go. And given the prior administration's openly hostile position over it, I can't imagine they're looking to open their doors and give access to the international community any time soon. Given the initial hostility and the current beating of the war drums by member of the GOP and their proxies, it also makes it highly unlikely they're going to be inclined to share anything any time soon (if ever).

And while it's true that maybe they never would have shared anything to begin with, we certainly didn't need to give them the pretense to refuse to cooperate in any way by immediately accusing them of a coverup.

Right, because butter wouldn't melt in the mouths of the very same CCP that routinely tortures and abuses millions of Uyghurs and members of other Turkic Muslim minorities in modern-day slavery 're-education camps,' and they totally would've opened their doors and granted access to a fully transparent international community investigation into the origins of the virus but for mean comments from members of the GOP.

[malchior]

Nicholas Wade you say?

Edit: The author of the linked article is about as credentialed on the subject matter as Mr. Wade. However, I don't give a rat's ass about the rest of the piece unless an expert tells me it's right. I'm just focused on the fact the guy has credibility issues.

For many years, virologists, disease ecologists, and many other medical and biological researchers had been predicting that it was only a matter of time before the next pandemic arrived, including details such as how it would arise and what the most effective strategies for combating it would be. Despite the enormous scientific knowledge humanity has gained, however, an unfounded conspiracy theory about the virus’s origin has gained a lot of traction: that it was genetically engineered with the purpose of infecting humans, that it was leaked from the Wuhan Institute of Virology, and that’s where it came from. Most recently, disgraced journalist Nicholas Wade has penned an error-filled, misleading piece promoting this nonsense, but the science tells a different story.

[Anonymous Bosch]

Nicholas Wade you say?

Edit: The author of the linked article is about as credentialed on the subject matter as Mr. Wade. However, I don't give a rat's ass about the rest of the piece unless an expert tells me it's right. I'm just focused on the fact the guy has credibility issues.

Of course, rather than addressing the substance of what he wrote above, you resort to attacking Nicholas Wade's character. How surprising.

[malchior]

Nicholas Wade you say?

Edit: The author of the linked article is about as credentialed on the subject matter as Mr. Wade. However, I don't give a rat's ass about the rest of the piece unless an expert tells me it's right. I'm just focused on the fact the guy has credibility issues.

Of course, rather than addressing the substance of what he wrote above, you resort to attacking Nicholas Wade's character. How surprising.

He was widely criticized for the quality of his analysis in genetics. It is entirely relevant when you are pointing at his argument as having weight. But also this is a pretty silly comment as I linked to someone who refuted his argument.

[Anonymous Bosch]

He was widely criticized for the quality of his analysis in genetics.

So what? Be specific. How is that relevant to the specific substance of what I quoted from him above? Nicholas Wade has been criticized for the quality of his analysis in genetics, so the SARS1 and MERS viruses did not leave copious traces in the environment? He's been criticized for the quality of his analysis in genetics, so the intermediary host species of SARS1 was not identified within four months of the epidemic’s outbreak, and the host of MERS was not identified within nine months?

But also this is a pretty silly comment as I linked to someone who refuted his argument.

If he specifically refuted what I was quoting above, by all means elucidate.

[Smoove_B]

so the intermediary host species of SARS1 was not identified within four months of the epidemic’s outbreak

No, it wasn't confirmed until 2017 - 15 years after it emerged. Note the date on the article and the following:

The killer strain could easily have arisen from such a bat population, the researchers report in PLoS Pathogens1 on 30 November. They warn that the ingredients are in place for a similar disease to emerge again.

Creepy, right?

and the host of MERS was not identified within nine months?

We still don't know for sure where MERS hangs out or where it originally came from. Camels are suspected, but it was never proven. Research is ongoing (index case of MERS in humans was first identified in ~2012.

I'm not sure if you're being fast and loose with your terminology but host doesn't mean reservoir. Host is just an organism that can uhh...host the pathogen and allow it to reproduce. In doing so, it will typically (though not always) experience symptoms. A reservoir is where the virus hangs out, typically without causing a problem for the organism. What we'd be looking for is interactions between humans and these animal reservoirs to see if there's a chance the virus makes the "jump" from one to the other.

My point with this is that humans (for both SARS and MERS) became hosts. The mystery was trying to figure out where the reservoirs were. That's also why I mentioned Ebola earlier. For decades it's been a mystery as to how any why it cycles in the environment, seemingly randomly appearing in human populations. Trying to figure out where the index cases were and what animals they could have been interacting with has been the challenge in identifying where Ebola hides.

So the fact that we still don't now where SARS-CoV-2 originated from isn't all that surprising; it's typical.

[malchior]

He was widely criticized for the quality of his analysis in genetics.

So what? Be specific.

So what? Are you seriously going to argue that there is no consequence that the man's opinion on the broad subject
brought him widespread criticism? Really? I'm not saying he is wrong but his credibility is compromised. That's just basic accountability.

How is that relevant to the specific substance of what I quoted from him above? Nicholas Wade has been criticized for the quality of his analysis in genetics, so the SARS1 and MERS viruses did not leave copious traces in the environment? He's been criticized for the quality of his analysis in genetics, so the intermediary host species of SARS1 was not identified within four months of the epidemic’s outbreak, and the host of MERS was not identified within nine months?

[scoff]I have no idea if this is meaningful. I also strongly suspect you don't either. There is no point debating the specific substance when very few people here have any expertise in the subject matter. I have no idea why SARS1 and MERS left copious traces in the environment or *if that even happened*. It might be all bullshit. It might be irrelevant. It might be bad analysis (again). This is why his credibility matters (at least to me).

If he specifically refuted what I was quoting above, by all means elucidate.

The whole thing is a refutation.

[Anonymous Bosch]

so the intermediary host species of SARS1 was not identified within four months of the epidemic’s outbreak

No, it wasn't confirmed until 2017 - 15 years after it emerged. Note the date on the article and the following:

The killer strain could easily have arisen from such a bat population, the researchers report in PLoS Pathogens1 on 30 November. They warn that the ingredients are in place for a similar disease to emerge again.

Creepy, right?

and the host of MERS was not identified within nine months?

We still don't know for sure where MERS hangs out or where it originally came from. Camels are suspected, but it was never proven. Research is ongoing (index case of MERS in humans was first identified in ~2012.

I'm not sure if you're being fast and loose with your terminology but host doesn't mean reservoir. Host is just an organism that can uhh...host the pathogen and allow it to reproduce. In doing so, it will typically (though not always) experience symptoms. A reservoir is where the virus hangs out, typically without causing a problem for the organism. What we'd be looking for is interactions between humans and these animal reservoirs to see if there's a chance the virus makes the "jump" from one to the other.

My point with this is that humans (for both SARS and MERS) became hosts. The mystery was trying to figure out where the reservoirs were. That's also why I mentioned Ebola earlier. For decades it's been a mystery as to how any why it cycles in the environment, seemingly randomly appearing in human populations. Trying to figure out where the index cases were and what animals they could have been interacting with has been the challenge in identifying where Ebola hides.

So the fact that we still don't now where SARS-CoV-2 originated from isn't all that surprising; it's typical.

Quoting from the Bayesian analysis Wade linked to:

For two prior human coronavirus epidemics, an intermediate or proximate host was identified. For SARS-CoV-1 in 2003-4 it was the civet cat while for Middle Eastern Respiratory Syndrome (MERS) in 2012-4 it was the camel. In both of these human epidemics, the intermediate host was identified within four to ten months of the first clinically identified human infection. With CoV-2 we are at 12 months since the pandemic began and still waiting for evidence of, despite a much larger effort inside China to find, an intermediate host. For both of these previous pandemics, a bat species reservoir host was also identified, but not in the case of SARS-CoV-2.

Based on the genome sequence of CoV-2, Drs. Shi and Daszak have proposed that the reservoir host for CoV-2 is the intermediate horseshoe bat (Rhinolophus affinis), which is found in Yunnan Province. Yunnan Province is in southern, rural China and about 1900 km from the north central province of Hubei, where the 11 million people of Wuhan live. In the US this would be equivalent in distance, climate change, and human population density difference to going from the Everglades in Florida to Manhattan, in New York City. The intermediate horseshoe bat isn’t found at all in Hubei province, making a direct bat-to-human transmission improbable. Experiments in three independent laboratories also demonstrate that CoV-2 has changed genetically so much that it can no longer infect any bat species cell culture tested. So, while the leading US coronavirus expert, Dr. Ralph Baric of The University of North Carolina suggested in early 2020 that CoV-2 may have jumped into the human population directly from bats without an intermediate host, this hypothesis seems to no longer be viable.

For the zoonosis hypothesis to be advanced, it is now necessary to find an intermediate host. In January 2020 a theory was proposed that CoV-2 arose in the Huanan Seafood Market, a traditional Chinese “wet market” where live animals are butchered and sold for food. The market theory was based on the observation that about 40% of early patients worked or shopped there. This was reminiscent of the wet market sources for civet cats infected with SARS-CoV-1 or the camel markets for the MERS coronavirus. The Chinese authorities closed the market on December 31, 2019 after performing extensive environmental sampling and sanitation.

But by May 2020 Dr. Gao Fu, Director of the Chinese CDC, announced that the market was not the source of CoV-2, as all of the animal specimens tested negative for CoV-2. And while SARS-CoV-1 was found in 100% of local farmed civets when tested, CoV-2 was different. In July 2020 Dr. Shi reported that extensive testing of farmed animals throughout Hubei Province failed to find CoV-2 in any animals.

For about six months, the pangolin, a scaly anteater, was suspected to be the intermediate host but finally Dr. Daszak reported that CoV-2 was not found in pangolins in the wild or from the (illegal) market trade. Domestic and feral cats also were ruled out as a possible source. A comprehensive computer-based screen of 410 different animals reported the remarkable finding that the best ACE2 receptor matches to CoV-2 were human and other primates (or primate cells in the laboratory), including the favorite laboratory coronavirus host, the VERO monkey cell culture, and that all bat species were the worst host. At the time of this writing, there is not even a working hypothesis for the species of an intermediate host.

A typical zoonosis has a number of characteristic properties that can allow identification of a zoonotic infection, even in the absence of identifying an intermediate host. None of these properties are found for CoV-2.

All zoonotic infections have in common the principle that when a virus in nature uses evolution to move from, for example, a bat host to a camel host and then to a human host, it is a hit and miss, slow process. After all, evolution is the result of random genetic changes, mutations, and then enrichment of the ones that are helpful by amplification during reproduction. With both SARS-CoV-1 and MERS, the coronavirus spent months and years jumping from the intermediate host into humans, not having all of the necessary mutations needed to be aggressive, grow, and then spread, but spending enough time in humans to cause an infection and leaving behind a corresponding immune response.

The hallmark evidence of this ‘practice’ in abortive host jumping is in stored, archived human blood specimens taken from before the epidemic, where one can find evidence of pre-epidemic, usually sub-clinical, community spread from the antibodies to the eventual epidemic virus. For SARS-CoV-1 and MERS, about 0.6% of people in the region where the epidemic began showed signs of an infection in archived blood. With CoV-2, this seroconversion, as it is called, has never been observed, including in 540 specimens collected from ‘fever clinics’ in Wuhan between October 2019 and January 2020, reported by the WHO. Because this is such a potent signal of a zoonosis, and because I believe that China has over 100,000 stored specimens from Wuhan taken in the fall of 2019, the lack of reports of seroconversion, the silence from China on this evidence, speaks volumes.

Another hallmark of a slow, natural zoonosis can be found in the virus. In SARS-CoV-1 and MERS, the coronavirus spent years in the intermediate host, passing back and forth among populations of hosts, the civets or camels, that were living in close proximity. During this time, they would accumulate a background of genetic mistakes, i.e., mutations- usually about one mistake every two weeks. When the final chip falls, and a mutation(s) happens allowing the jump into humans, the virus with that new mutation(s) also jumps around within the intermediate host population. The consequence of this latter behavior for a true zoonosis is that the genome sequences found in humans don’t all descend from a single jump into a single human but show jumps from viruses that are only cousins of each other, not direct lineal descendants.

In a true zoonosis, the family tree of virus genome sequences doesn’t pass back through the first patient but instead tracks all the way back to an ancestor months or years earlier. This is called posterior diversity, and it is an easy genetic test to perform. With CoV-2, every one of the more than 294,000 virus genomes sequenced can be traced back to the first genomic cluster and in the first patient in that cluster, a 39-year-old man who was seen at the People’s Liberation Army (PLA) Hospital about one mile from the Wuhan Institute of Virology. The CoV-2 pandemic has the phylogenetic signature of one pure virus sequence infecting one human, with human-to-human spread thereafter; there is just the one and only jump into the human population ever seen. This lack of posterior diversity has been alluded to by Dr. Shi, by the WHO, and by other prominent virologists; they just never take that critical piece of the evidence to the next the proper inference.

The virus in a true zoonosis also contains the signature record of the gradual changes and adaptions it made in the protein key, the Spike Protein, it uses to unlock human cells and cause infection. With SARS-CoV-1 the Spike Protein had fewer than one-third of all the changes it would later develop by the time it became an epidemic. With CoV-2 the Spike Protein was almost perfectly adapted to the human lock, using 99.5% of the best amino acids possible.

Since with CoV-2 we have no evidence from stored blood that it was quietly practicing on humans in the community of Wuhan, it is surprising that when it finds its first patient, it has perfected to 99.5% the spike protein amino acid sequence, its ability to attack and infect humans. If this adaption couldn’t have happened in the community, the only place it could have happened is in a laboratory, by what is called serial passage, a common laboratory process that repeatedly gives the virus a chance to practice on humanized mice or VERO monkey cells. A related study showing human adaption right from the start of the pandemic looked at which of the dozens of protein manufacturing tools that CoV-2 uses (called tRNAs). It showed the same uncanny adaptation to the human tools with no evidence that the tools from other potential intermediate hosts would be suitable.

This evidence presented makes a strong case that CoV-2 did not come from nature. But is there affirmative evidence that it could have come from a laboratory? The answer is yes.

(And you'll have to forgive me for any fast and loose terminology, because I make no claims to be anything more than a layman here).

[Anonymous Bosch]

I'm not saying he is wrong but his credibility is compromised.

Right, so instead of addressing the substance of what Wade wrote and I specifically quoted, your only interest here was in attacking the person making the argument, as I suspected. Wade had sufficient credibility to serve as science writer and editor for the journals Nature, from 1967 to 1971, Science, from 1972 to 1982, and as an editor of the science section for The New York Times from 1982 until 2012. So as far as bona fides go, I think that's plenty sufficient not to dismiss him as some sort of crackpot pariah merely because he dared to post a divergent hypothesis on the origins of COVID-19.

That's just basic accountability.

Or fallacious reasoning. Toh-may-toe, toh-mah-toe.

I have no idea if this is meaningful. I also strongly suspect you don't either.

Suspect whatever you like. From what I've read, I got the distinct impression that the SARS1 and MERS viruses seemed more analogous to SARS-CoV-2 than Ebola, which was why I said as much and quoted Nicholas Wade's comment in my conversation with Smoove. Sure, it's a complex subject, but I am making a good faith effort as a layperson to sincerely grok and understand it as best I can. But I don't believe further dialogue between the two of us on this subject is going anywhere productive or respectful, so I am done trying to converse with you about this.

[malchior]

I'm not saying he is wrong but his credibility is compromised.

Right, so instead of addressing the substance of what Wade wrote and I specifically quoted, your only interest here was in attacking the person making the argument, as I suspected.

Am I going crazy here? (Anyone feel free to chime in here) There was nothing to suspect. I said it directly.

That's just basic accountability.

Or fallacious reasoning. Toh-may-toe, toh-mah-toe.

More power to you if you think that considering the credibility of information sources leads to 'fallacious reasoning'.

I have no idea if this is meaningful. I also strongly suspect you don't either.

Suspect whatever you like. From what I've read, I got the distinct impression that the SARS1 and MERS viruses seemed more analogous to SARS-CoV-2 than Ebola, which was why I said as much and quoted Nicholas Wade's comment in my conversation with Smoove.

I wouldn't say I suspect it. I have about 90% confidence that there is little chance you could defend what you are quoting in sufficient detail. My basis of that guess is the nearest thing to an expert here says some of it is beyond him.

Sure, it's a complex subject, but I am making a good faith effort as a layperson to sincerely grok and understand it as best I can.

Yeah, yeah...you're just asking questions.

[Anonymous Bosch]

I'm not saying he is wrong but his credibility is compromised.

Right, so instead of addressing the substance of what Wade wrote and I specifically quoted, your only interest here was in attacking the person making the argument, as I suspected.

Am I going crazy here? (Anyone feel free to chime in here) There was nothing to suspect. I said it directly.

That's just basic accountability.

Or fallacious reasoning. Toh-may-toe, toh-mah-toe.

More power to you if you think that considering the credibility of information sources leads to 'fallacious reasoning'.

Attacking the character of a person making an argument instead of addressing the substance of their argument or position is logically fallacious. Anyone else feel free not to chime in here, because as I previously explained, my attempts at conversation with malchior are going nowhere productive or respectful, so I think it best we simply agree to differ and leave it at that.

[malchior]

I'm not saying he is wrong but his credibility is compromised.

Right, so instead of addressing the substance of what Wade wrote and I specifically quoted, your only interest here was in attacking the person making the argument, as I suspected.

Am I going crazy here? (Anyone feel free to chime in here) There was nothing to suspect. I said it directly.

That's just basic accountability.

Or fallacious reasoning. Toh-may-toe, toh-mah-toe.

More power to you if you think that considering the credibility of information sources leads to 'fallacious reasoning'.

Attacking the character of a person making an argument instead of addressing their argument or position is fallacious.

Oh. That clears it up. With that folderol out of the way, how does credibility not matter? BTW this is the point where I seriously question your interest in a good faith discussion.

[Anonymous Bosch]

I'm not saying he is wrong but his credibility is compromised.

Right, so instead of addressing the substance of what Wade wrote and I specifically quoted, your only interest here was in attacking the person making the argument, as I suspected.

Am I going crazy here? (Anyone feel free to chime in here) There was nothing to suspect. I said it directly.

That's just basic accountability.

Or fallacious reasoning. Toh-may-toe, toh-mah-toe.

More power to you if you think that considering the credibility of information sources leads to 'fallacious reasoning'.

Attacking the character of a person making an argument instead of addressing their argument or position is fallacious.

Oh. That clears it up. With that folderol out of the way, how does credibility not matter? BTW this is the point where I seriously question your interest in a good faith discussion.

As I said above, Nicholas Wade had sufficient credibility to serve as science writer and editor for the journals Nature, from 1967 to 1971, Science, from 1972 to 1982, and as an editor of the science section for The New York Times from 1982 until 2012, which is a good deal more than the theoretical astrophysicist blogger you quoted. As far as bona fides go, I think that's plenty sufficient not to completely dismiss him or the substance of what he says as if he's some sort of crackpot pariah merely because he dared to post a divergent hypothesis on the origins of COVID-19 or stirred up political controversy with one of his books. You disagree. You are not going to convince me, and I have no interest in any further attempts to convince you, so let's simply agree to differ and leave it at that.

[malchior]

As I said above, Nicholas Wade had sufficient credibility to serve as science writer and editor for the journals Nature, from 1967 to 1971, Science, from 1972 to 1982, and as an editor of the science section for The New York Times from 1982 until 2012, which is a good deal more than the astrophysicist you quoted.

Cool. So how does that speak to his current credibility issues which arose in 2014? Or as I said earlier make either of them experts on emerging diseases?

As far as bona fides go, I think that's plenty sufficient not to completely dismiss him or anything he says like he's some sort of crackpot pariah merely because he dared to post a divergent hypothesis on the origins of COVID-19 or stirred up political controversy with one of his books. You disagree.

That's the problem. I never said to dismiss it. I simply was implying that we as non-experts had to be more than cautious about using him as a source because he had previous been discredited for issues with the quality of his analysis. It wasn't just a 'controversy'. And he also happens to be aggregating stories that happen to align with a current political controversy. A major concern here. It's absolutely relevant to consider but you chose to do this fallacious reasoning dance.

You are not going to convince me, and I have no interest in any further attempts to convince you, so let's simply agree to differ and leave it at that.

It doesn't escape me that you keep saying this over and over.

[Formix]

It's not as if the CDC hasn't mishandled a sample or two in their time and tried to hide it. The difference is that if it becomes public knowledge here in the US, there may be a push to tighten protocols, increase transparency, and maybe move the really terrifying strains out of a highly-populated area that is also a major air transport hub. If this investigation into the Wuhan lab would have a similar outcome, then I would say, "great! let's investigate". But it's a fruitless endeavor. China already knows what happened, and if someone did get a little fast and loose with a sample, and got themselves infected, which then spread, then they are already making whatever changes they are going to make. The problem is that most of this is either political theater or media hype sell-some-commercial-time theater. I don't see how this ever comes to any useful conclusion.
It seems like the most likely scenario is (assuming lab-leak is true, which I am NOT conceding) -
1) the lab was studying it, and they got sloppy and the virus spread.
Okay, what exactly should happen next? And how would we in the US respond if it had happened in Atlanta and China was breathing down our necks about it?
Even if you assume that
2) The lab was studying it, created a more virulent strain for whatever reason, then they got sloppy, and the virus spread, again, I ask
What exactly should happen next? And how would we in the US respond if it had happened in Atlanta and China was breathing down our necks about it?

[Anonymous Bosch]

More on the lab leak hypothesis from Dr. Steven Quay and emeritus professor of physics at U.C. Berkeley and former senior scientist at the Lawrence Berkeley National Laboratory, Richard Muller writing for the WSJ:

The Science Suggests a Wuhan Lab Leak

The Covid-19 pathogen has a genetic footprint that has never been observed in a natural coronavirus.

The possibility that the pandemic began with an escape from the Wuhan Institute of Virology is attracting fresh attention. President Biden has asked the national intelligence community to redouble efforts to investigate.

Much of the public discussion has focused on circumstantial evidence: mysterious illnesses in late 2019; the lab’s work intentionally supercharging viruses to increase lethality (known as “gain of function” research). The Chinese Communist Party has been reluctant to release relevant information. Reports based on U.S. intelligence have suggested the lab collaborated on projects with the Chinese military.

But the most compelling reason to favor the lab leak hypothesis is firmly based in science. In particular, consider the genetic fingerprint of CoV-2, the novel coronavirus responsible for the disease Covid-19.

In gain-of-function research, a microbiologist can increase the lethality of a coronavirus enormously by splicing a special sequence into its genome at a prime location. Doing this leaves no trace of manipulation. But it alters the virus spike protein, rendering it easier for the virus to inject genetic material into the victim cell. Since 1992 there have been at least 11 separate experiments adding a special sequence to the same location. The end result has always been supercharged viruses.

A genome is a blueprint for the factory of a cell to make proteins. The language is made up of three-letter “words,” 64 in total, that represent the 20 different amino acids. For example, there are six different words for the amino acid arginine, the one that is often used in supercharging viruses. Every cell has a different preference for which word it likes to use most.

In the case of the gain-of-function supercharge, other sequences could have been spliced into this same site. Instead of a CGG-CGG (known as “double CGG”) that tells the protein factory to make two arginine amino acids in a row, you’ll obtain equal lethality by splicing any one of 35 of the other two-word combinations for double arginine. If the insertion takes place naturally, say through recombination, then one of those 35 other sequences is far more likely to appear; CGG is rarely used in the class of coronaviruses that can recombine with CoV-2.

In fact, in the entire class of coronaviruses that includes CoV-2, the CGG-CGG combination has never been found naturally. That means the common method of viruses picking up new skills, called recombination, cannot operate here. A virus simply cannot pick up a sequence from another virus if that sequence isn’t present in any other virus.

Although the double CGG is suppressed naturally, the opposite is true in laboratory work. The insertion sequence of choice is the double CGG. That’s because it is readily available and convenient, and scientists have a great deal of experience inserting it. An additional advantage of the double CGG sequence compared with the other 35 possible choices: It creates a useful beacon that permits the scientists to track the insertion in the laboratory.

Now the damning fact. It was this exact sequence that appears in CoV-2. Proponents of zoonotic origin must explain why the novel coronavirus, when it mutated or recombined, happened to pick its least favorite combination, the double CGG. Why did it replicate the choice the lab’s gain-of-function researchers would have made?

Yes, it could have happened randomly, through mutations. But do you believe that? At the minimum, this fact—that the coronavirus, with all its random possibilities, took the rare and unnatural combination used by human researchers—implies that the leading theory for the origin of the coronavirus must be laboratory escape.

When the lab’s Shi Zhengli and colleagues published a paper in February 2020 with the virus’s partial genome, they omitted any mention of the special sequence that supercharges the virus or the rare double CGG section. Yet the fingerprint is easily identified in the data that accompanied the paper. Was it omitted in the hope that nobody would notice this evidence of the gain-of-function origin?

But in a matter of weeks virologists Bruno Coutard and colleagues published their discovery of the sequence in CoV-2 and its novel supercharged site. Double CGG is there; you only have to look. They comment in their paper that the protein that held it “may provide a gain-of-function” capability to the virus, “for efficient spreading” to humans.

There is additional scientific evidence that points to CoV-2’s gain-of-function origin. The most compelling is the dramatic differences in the genetic diversity of CoV-2, compared with the coronaviruses responsible for SARS and MERS.

Both of those were confirmed to have a natural origin; the viruses evolved rapidly as they spread through the human population, until the most contagious forms dominated. Covid-19 didn’t work that way. It appeared in humans already adapted into an extremely contagious version. No serious viral “improvement” took place until a minor variation occurred many months later in England.

Such early optimization is unprecedented, and it suggests a long period of adaptation that predated its public spread. Science knows of only one way that could be achieved: simulated natural evolution, growing the virus on human cells until the optimum is achieved. That is precisely what is done in gain-of-function research. Mice that are genetically modified to have the same coronavirus receptor as humans, called “humanized mice,” are repeatedly exposed to the virus to encourage adaptation.

The presence of the double CGG sequence is strong evidence of gene splicing, and the absence of diversity in the public outbreak suggests gain-of-function acceleration. The scientific evidence points to the conclusion that the virus was developed in a laboratory.

[Smoove_B]

Regarding that piece:

I have no idea if this is plausible, and I’m fairly certain the editors of the Wall Street Journal don’t either. Whether it’s correct or not, op-ed pages seem like a pretty obviously horrible place to float technical empirical claims like this. If it’s correct, or at least has a good chance of being correct, it should be reported in the news pages after peer review. If it’s wrong, you’ve leapfrogged that process and given it unwarranted currency. Either way, this is not a useful “opinion”. Which is to say, it does not present an argument that the normal reader (or, really, 99.9% of the readership) has any meaningful capability to evaluate. I’m among that 99.9% and have no idea if this claim holds water, but I do find it bizarre that a couple of scientists would opt to present it in this venue, rather than, you know… to their peers. Obviously lots of op-eds turn at least IN PART on an expert assessment readers have to decide how much weight to give based on credentials, but this is ENTIRELY that. I see no possible benefit to foisting it unmediated on a general audience. Honestly, running a piece like this seems borderline unethical. *At best* you’re very lucky & rushing a true claim around the normal validation process. At worst you’re presenting misinformation to an audience totally unequipped to evaluate it. And you have no idea which. A cursory search shows that one of the authors, Quay, uploaded a paper advancing his argument to an open-access repository in January & then pushed out a YouTube video & press releases touting it. While I am, again, no more qualified to evaluate the substance than the modal Wall Street Journal reader, this is not how reputable science normally operates.

The more I look at this guy’s site the more red flags pop up, and the more appalled I am WSJ decided to run this. Muller is a retired physicist. Quay is what we might charitably call an “aggresively self-promoting” MD & entrepreneur (subscribe to his wellness newsletter, or book him to speak!) whose specialty until about a year ago appears to have been breast cancer. So these are a couple of guys who, while accomplished in other fields, don’t appear to be specialists in virology, given a massive national platform to advance a highly technical thesis without submitting to the peer review proceess that normally filters such claims. Whether or not they’re right—again, I don’t know, and don’t have any particular dog in that fight—this is journalistic malpractice. You’re accountable for scientific claims you present to readers who can’t directly assess them, even if you put them on the “opinion” page. In case anyone else was confused, my claim is not “newspapers should banish any mention of scientific research in opinion essays.” It’s that a mass-readership op-ed page shouldn’t be where nonspecialist researchers go to launder novel assertions that haven’t survived peer review.

I can’t tell whether their claim makes sense, but if it does they should pitch it to the NEJM or the Lancet, where it will be reviewed by people who are equipped to render that judgment. Then if they want to write an op-ed summarizing their published paper, godspeed.

[Smoove_B]

(And you'll have to forgive me for any fast and loose terminology, because I make no claims to be anything more than a layman here).

If you're a layman then I'm Layman, First Class (to borrow from the Lord Bathing Towel). While I have formal education in many of these topics, I would not (and could not) perform critical review of their claims; at some point I have to listen to the chorus of the scientific community.

That being said, "intermediate hosts" are just that - a bridge organism. They are not the place where a virus (or whatever) originates, but a way for the virus (in this case) to get from it's original location (the reservoir) to humans.

If you may recall, early on with SARS-CoV-2, there were some initial reports in the first few months that scientists identified a possible connection to pangolins (similar to SARS). Here, the theory was that pangolin exposure occurred in or as part of the so-called "wet-markets" in and around Wuhan. However, there still hasn't been a definitive answer as to whether or not the pangolin is the reservoir (seems unlikely now) or just an intermediate host. I I haven't been keeping up with this one, but a quick glance suggests the debate continues - and of course more data is needed.

My point with all this is that finding intermediate hosts is helpful, but it's not the complete etiology. To what degree pangolins are involved with COVID-19 is unclear. Are they transmitting it to humans? Are they dead-end hosts?

I think we're both in agreement that more data is needed, and I also fully and completely believe China needs to share more information. However, I think where I step off the train is when people start suggesting malfeasance. Not because China isn't capable, but because I don't believe they're crazy enough to tinker with something that had (and has) the potential to cause all humans harm.

[malchior]

More on the lab leak hypothesis from Dr. Steven Quay and emeritus professor of physics at U.C. Berkeley and former senior scientist at the Lawrence Berkeley National Laboratory, Richard Muller writing for the WSJ:

Here we go again. Another dubious source. As it so happens, I was in the process of writing a long-response about Quay's Bayesian analysis last night when it felt less than useful. However, I'll cut it down to some basics just to expose why there is a decent chance Quay made some fundamental errors. Something I am actually near enough to an expert to critique at the level of the math and analysis process involved as I do have a Graduate Degree in an Applied Statistics field. I can not however critique his decisions about individual variables - that'd need a virologist/epidemiologist type background. I can just suggest his Bayesian methodology he lays out is non-standard and introduces some doubt.

I noticed from the outset that Quay began his analysis with a discussion of competing hypotheses that had a fairly bad assumption. He took what might as well be n=1 samples from two different papers. One about infections related to zoonotic sources discovered which amounted to ~162 over 20 years and calculated to 8.1/year. He also pulled from another paper which showed 'lab originated' illnesses which amounted to 27 over 35 years calculated to 0.8/year. He then summed them come up with a blended rate of 8.9 diseases emerge/year. He then computed a simple ratio that was supposed to be a ballpark guess at the chance any disease emerging that appears in the human population each year has certain origins. In this case a 91% chance of a zoonotic origin and a 9% chance to be lab originated. Smoove_B might be able to chime in here and say this is not a mainstream number but I'll assume it is off by perhaps an order of magnitude if not more. The reason why seems relatively straightforward even to a layman. It assumes we identify every disease that people get every year. It isn't hard to imagine there are probably plenty of circulating diseases that aren't severe, don't merit investigation, or are believed to be something else and aren't in the count.

To be clear he actually was doing that calculation as a paper exercise to show competing hypotheses but it just struck me that his first analysis seemed to have a very basic foundational error. It certainly doesn't lend much credibility to the eventual much more complicated Bayesian analysis which had a lot of his thumb on the scale action (more on this later).

FWIW he did however work towards a much more reasonable (relatively speaking) starting point which is a 1.2% chance of a lab origin for any emerging disease in a given year. This however still seems much, much too high but happy to hear if that is an estimate in the realm of the reasonable.

Anyway, beyond that then his methodology goes a bit downhill from there as he mixed together multiple Bayesian statistical techniques into a single model. He used Naïve Bayes for qualitative data and introduced a Subjective Discount Factor for qualitative data which might as well be called Quay's feelings. Subjective is in the variable name! It's also nothing I've ever seen before. I don't know how much "model" wreckage occurred there alone but it is very, very iffy at best. It isn't that this is necessarily wrong but most of the time what you end up doing with qualitative data is let the model normalize it on its own. That is what Naïve Bayes does as a feature. It assumes that certain statements are right or wrong and works in from there. This notion of a Subjective Discount Factor may have very well badly biased his model.

Another issues is he described a test for variable independence. This is critical to Bayes and again it was pretty much Quay's feelings. There wasn't a clear inclusion/exclusion criteria which is what I usually would see in a paper like this. These are a known challenges and he was absolultely right to address them. However, I have a reasonable belief without deep diving into each decision that his methodology was shaky at best.

To be fair to him, he reasonably treated quantitative data properly. He assumed anything that met p < 0.05 or less was statistically significant which is reasonable and gated it there no matter how certain the p-number was. That is pretty straightforward.

The reason I suspect it's wrong is because in the end he arrived at a 98% chance of a lab origin. That should have informed him that maybe it was off. It's not even close to what actual credentialed experts in that field have calculated (as I've read it at least). This paper I'm speaking to was behind the WSJ article and wasn't peer reviewed. I think the reasons are straightforward. This is a cursory read and there appear to be significant obvious flaws. There is little chance it would have survived any serious scrutiny. I saw issues that would have had led to a peer reviewer asking hard questions of the author. He in the end just splashed out the paper via PR Newswire. Without peer review by experts in that field to level set the assumptions and the math involved...the credibility of the paper is very low in my estimation.

In the end reading this, I personally conclude that these apparent mistakes are genuine mistakes. I believe the errors if they exist were simply lack of expertise with mixed Bayes analyses. My sense without reworking the whole thing is he normalized his data incorrectly.

[Smoove_B]

Another take on the lab leak theory, via Slate:

On the virus:

So how is this no longer a conspiracy theory? Is there new data?

There is currently no direct evidence for either a natural origin or a lab leak. That is, no one has found the smoking gun—the virus hanging out in a lab, or in nature. Genetically, the virus is similar to coronaviruses found in bats and in pangolins, which are a type of anteaterlike mammal. But scientists haven’t found the virus’s exact sequence in an animal.

That seems like good evidence for the lab leak theory!

Not really. It can take years to identify a virus’s source. It’s also not a unique situation—scientists also aren’t exactly sure where Ebola came from, either. Also, almost every vertebrate gets infected by coronaviruses, says Shangxin Yang, assistant medical director of the Clinical Microbiology Laboratory at UCLA Health. It’s really no surprise we haven’t found this one yet.

On the scientists:

OK, but what about that Wall Street Journal article about the researchers who got sick?

In May, the Wall Street Journal reported that in November 2019, three researchers at the Wuhan Institute of Virology were sick enough that they sought hospital treatment for respiratory illness. They had symptoms that were similar to those of COVID-19—but also to those of other illnesses, like the flu.

Although some saw the report as supporting the lab leak theory, Yang notes that there was already some evidence that COVID-19 could have begun spreading in Wuhan as early as October. “I don’t really see that as evidence [of a lab leak],” Yang says, because even if the researchers did have COVID-19, they wouldn’t have had to have gotten it from a lab. “Those three could be only three out of hundreds or thousands of people who already got it.”

This article is too long, what is the point?

OK, so it sounds like the jury is still out.

Most experts still tend to think the virus has a natural origin. Yang explains that a lab leak is theoretically possible but extremely unlikely. So many other infectious diseases have originated from animals, including the MERS and SARS outbreaks caused by coronaviruses. Because humans live increasingly close to animals, diseases that originate from animals have also long been predicted to become more prevalent.

But yes, without more data, it’s impossible to know for sure. Chan thinks scientists shouldn’t be asked to constantly make public judgment on the likelihood of one scenario versus another—if new evidence emerges, they might feel like they can’t change their mind. She also thinks it’s just impossible to really nail down the probability of a lab leak without a transparent understanding of what was happening in the lab. “It would be like trying to guess what’s the likelihood of rolling a six without knowing how many sides of the dice there are,” says Chan.

[malchior]

On the scientists:

OK, but what about that Wall Street Journal article about the researchers who got sick?

In May, the Wall Street Journal reported that in November 2019, three researchers at the Wuhan Institute of Virology were sick enough that they sought hospital treatment for respiratory illness. They had symptoms that were similar to those of COVID-19—but also to those of other illnesses, like the flu.

Although some saw the report as supporting the lab leak theory, Yang notes that there was already some evidence that COVID-19 could have begun spreading in Wuhan as early as October. “I don’t really see that as evidence [of a lab leak],” Yang says, because even if the researchers did have COVID-19, they wouldn’t have had to have gotten it from a lab. “Those three could be only three out of hundreds or thousands of people who already got it.”

This article is too long, what is the point?

OK, so it sounds like the jury is still out.

Most experts still tend to think the virus has a natural origin. Yang explains that a lab leak is theoretically possible but extremely unlikely. So many other infectious diseases have originated from animals, including the MERS and SARS outbreaks caused by coronaviruses. Because humans live increasingly close to animals, diseases that originate from animals have also long been predicted to become more prevalent.

But yes, without more data, it’s impossible to know for sure. Chan thinks scientists shouldn’t be asked to constantly make public judgment on the likelihood of one scenario versus another—if new evidence emerges, they might feel like they can’t change their mind. She also thinks it’s just impossible to really nail down the probability of a lab leak without a transparent understanding of what was happening in the lab. “It would be like trying to guess what’s the likelihood of rolling a six without knowing how many sides of the dice there are,” says Chan.

This is where I figure this is forever going to be controversial. There is no realistic way to convince anyone who thinks China was responsible that it has a natural origin. The best we can hope for is that the origin species is found so the science is straight at least. The people at large? Like many things there isn't much hope there.

[Kurth]

I think we're both in agreement that more data is needed, and I also fully and completely believe China needs to share more information. However, I think where I step off the train is when people start suggesting malfeasance. Not because China isn't capable, but because I don't believe they're crazy enough to tinker with something that had (and has) the potential to cause all humans harm.

Am I wrong to just assume China and Russia and the U.S. and other major world powers are doing all sorts of research on viruses, research that can serve the dual purposes of treating/monitoring but also potentially weaponizing (or other nefarious purposes)?

I’m just not certain what all the furor is about over this question. I understand why we should want to get to the facts behind the COVID-19 outbreak for purposes of future prevention and scientific understanding.

But, in terms of pointing the finger at wrongdoers, who really gives a shit if it accidentally was leaked from a lab in Wuhan or developed in some bats or pangolins?

I mean, unless someone (who is not a certifiable whack-job) is suggesting that China deliberately developed and released COVID-19 to cause a global pandemic, I have a hard time being all that interested.

[malchior]

But, in terms of pointing the finger at wrongdoers, who really gives a shit if it accidentally was leaked from a lab in Wuhan or developed in some bats or pangolins?

Trumpists. The misinformation being pushed at them is pretty high right now. It is one of the three prongs of assault being used to rehabilitate Trump's image. The only real reason to give a shit is the impact on our politics. Especially since the reality is that the discussion is pretty hopelessly mired if you care about actual truth.

[Smoove_B]

I’m just not certain what all the furor is about over this question. I understand why we should want to get to the facts behind the COVID-19 outbreak for purposes of future prevention and scientific understanding.

Right, so as pointed out earlier, only the most fringe elements are suggesting COVID-19 was an intentionally created strain that was released (accidentally or on purpose) to attack America (or whatever). The creation of bioweapons is strictly forbidden and has been for decades

A slight step down from that are the wingnuts that are saying "Gain of function" researchers were tinkering with SARS-CoV-2 "for science" and "accidentally" (wink wink) created a virus that crippled America (and elsewhere). Thanks China virus!

What people aren't getting is that "gain of function" research is how we develop an understanding of disease agents. It's like reading Marvel "What If?" comics - to see what might happen if various elements of the genetic code are tweaked. It's not being done to "weaponize" a virus, but instead to see what's possible or what might happen if various changes occur. And then they add other variables to see how and if they respond to treatments or environmental pressure. In short, the research that's happening in Wuhan (and all over the globe) is how you make predictions and try to anticipate problems.

"Hey, there's this new virus we discovered in bats that if it comes into contact with Goose DNA has the potential to jump to humans."

So to go back to your point, there's clear and directed intention to somehow tie this to China - that they were doing research and somehow unleashed this on the world. And that's why I keep pushing back on this. Is is possible? I guess. Is it more likely (by orders of magnitude) that this is just a naturally occurring event? Yes.

[Kurth]

Smoove, am I way off base to assume that the banning of bio-weapon research hasn’t actually resulted in a complete lack of research into bio-weapons? Have I read too many Tom Clancy and Robert Ludlum books?

Melchior, is the end game for the Trumpists that if China is to blame, then Trump is not? Like, if Trump wasn’t to blame for the initiation of the outbreak in Wuhan, then he’s blameless for his handling of COVID-19 here in the U.S.? I was about to comment on how ridiculously stupid that is, but then, I suppose when compared to some of the other narratives the Trumpaloos have swallowed, it actually makes sense.

[Smoove_B]

Smoove, am I way off base to assume that the banning of bio-weapon research hasn’t actually resulted in a complete lack of research into bio-weapons? Have I read too many Tom Clancy and Robert Ludlum books?

Good question. I'm sure there's a lot of research going on that could be questionable based on the application. But at some point its arguably how information is being applied. In some ways you could argue the use of CRISPR might lend itself to biowarfare. But it's being used to study (and develop treatments for) diseases.

So no, I don't believe anyone is openly doing things like what we saw in days long gone (like Japanese Unit 732 in WW2), but you could make the argument that some of the research could be applied to bioweapon development/use/dispersal.

[malchior]

Melchior, is the end game for the Trumpists that if China is to blame, then Trump is not? Like, if Trump wasn’t to blame for the initiation of the outbreak in Wuhan, then he’s blameless for his handling of COVID-19 here in the U.S.? I was about to comment on how ridiculously stupid that is, but then, I suppose when compared to some of the other narratives the Trumpaloos have swallowed, it actually makes sense.

A few people have been tracking a concerted effort to rehabilitate his image on several fronts. You've got the main sense of it right. One of his big failures is obviously 600K+ dead. If they can shift the cultist to change the story that China lied to us and is responsible then it just shifts blame to an other 'hated adversary'. It's a fairly standard propaganda tactic unfortunately. Even worse is it could work even though it fundamentally makes no sense.