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Tuesday, October 26, 2021

The case for a natural origin of SARS-CoV-2

Lots of people seem to be confused about the origin of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The investigating committee ot the World Health Organization (WHO) concluded last winter that a natural origin is the most likely scenario but there still seems to be a substantial percentage of the population who think that the virus was being studied at the Wuhan Institute of Virology (WIV) and leaked from there to start the pandemic. This belief in a lab leak scenario persists in spite ot the fact that 21 expert scientists have discounted it and concluded that a natural origin is the best hypothesis. The lab leak speculation persists even when the United States intelligence agencies reached the same conclusion as the scientific experts and said that a natural origin was more likely.

I've published several posts on this topic over the past year trying to emphasize four points: (1) the evidence strongly favors a natural origin, (2) there is no scientific evidence to support the claim that the WIV scientists were working on SARS-CoV-2 before the pandemic started, (3) the most knowledgeable science experts agree that a natural origin is the most likely scenario, and (4) the media is misrepresenting the science and treating the two competing explanations as equivalent.

In this post I want to describe the case for a natural origin in as simple a manner as possible so that people can refer to the main lines of evidence and so that opponents of a natural origin can explain why they dismiss that evidence. I also want to briefly explain why we need to listen to the experts instead of arbitrarily dismissing their views as a argument from authority and assuming that our own research trumps the experts.

1. Other infectious coronaviruses have a natural origin

There are seven previously known coronaviruses that infect humans and all of them have a natural origin in either bats or mice. Five of them were most likely transmitted to humans through another animal such as camels, pigs, or cows. This does not prove that SARS-CoV-2 had a natural origin but it does lend strong support to the idea and it make us skeptical of claims that there's something special about SARS-CoV-2 that requires a different explanation.

2. Epidemiology

Most of the first infections in Wuhan were in people who frequented the wet markets suggesting that, at the very least, the market areas were the location of a superspreader event. There is no other location that seems to have been the source of a significant number of early infections. Of the three earliest cases, two were directly linked to the Huanan wet market. SARS-CoV-2 was detected in samples from the Huanan wet market itself although none of the animals that have been tested were positive for SARS-CoV-2.

There were two different SARS-CoV-2 lineages (A and B) in the early cases suggesting two independant events. Lineage B was found in the Huanan market and lineage A is associated with another market and with cases in other parts of China. Lineage B quickly became the dominant lineage worldwide. The data is consistent with a natural origin and spread from animals that were sold in these markets.

3. Sequence data

The first sequence of SARS-CoV-2 was published in early January 2020 and hundreds of other sequences, including all the main variants, have been published since then. Dozens of sequences of related bat viruses have been published including some of the closest relatives that have only been discovered in the past year such as BANAL-52 from bat caves in Laos. The standard reference sequence is 29,903 bp long and it differs from the related bat virus sequences at more than 900 sites.

By looking at the relationship between the full sequences, it is possible to construct phylogenetic trees showing the probable evolution of SARS-CoV-2. The data shows that SARS-CoV-2 clusters with a small group of bat viruses called the betacoronaviruses. This group includes a group of virus sequences recently identified in pangolins and it's quite distinct from the group that includes the original SARS virus that caused the 2002 outbreak.

In terms of the overall backbone sequence, one of the viruses, BANAL-52, isolated just a few months ago, is the closest match to SARS-CoV-2. It is much more closely related than RaTG13, the bat virus isolated from caves in China and sequenced by scientists at WIV. As a recent NIH reports notes,

Although RaTG13 and BANAL-52 are 96-97% identical to SARS-CoV-2 at the nucleotide level (>900 nucleotide differences across the entire genome), the difference actually represents decades of evolutionary divergence from SARS-CoV-2. Experts in evolutionary biology and virology have made it clear that even the closest known relatives of SARS-CoV-2 ... are evolutionarily too distant from SARS-CoV-2 to have been the progenitor of the COVID-19 pandemic (ref, ref). Field studies continue the search for more proximate progenitors.

The data support a natural origin of SARS-CoV-2 from an unknown precursor that may have arisen as the result of a recombination event between two bat viruses. This pattern of evolution is quite common among bat coronaviruses and there's nothing in the sequence data to suggest an unnatural origin.

This is an important point. The sequence of SARS-CoV-2 has all the characteristics of a naturally evolving virus that has shared the same evolutionary history as its closest bat relatives. The data is completely consistent with evolution in a bat host for the past several decades (Deng et al., 2021). This is a pattern based on over 900 mutations that are not present in any of the other bat sequences that have been sequenced. Anyone promoting a non-natural origin has to account for this data.

Here are some links to the life cycle of coronaviruses and the SARS-CoV-2 sequence for those who want more information.

The argument from authority

Very few of us have direct experience in coronavirus evolution. There are hundreds of publications on this topic and many of the studies are well above our pay grade. We have no choice but to trust the word of others with more experience.

Here's the problem. Some scientific publications promote a natural origin of SARS-CoV-2 while others attempt to cast doubt on that scenario. On the surface, it looks like the experts disagree so there's no obvious consensus but appearances can be deceiving. There are far more experts supporting a natural origin but the minority promoting a lab leak hypothesis are getting a lot more press. This leads to a very misleading impression that's often echoed on TV by people like medical doctors who don't have a good grasp of how science works.

The fact that scientists disagree is not unusual.

I used to teach a course on critical thinking and one of the most important lessons was on how to tell which scientists (or science journalists) are likely to be correct. There are several important clues you can use when reading scientific papers or media reports.

  • If the scientists are repeating statments that have aready been refuted then you are right to question their credibility. It suggests that they either have an unscientific agenda or they aren't on top of their subject. For example, if a scientist says that SARS-CoV-2 was highly adapted to humans when it first appeared then you should be skeptical because, in fact, SARS-CoV-2 is a generalist virus that can propagate in a wide variety of mammalian species. The repetition of previously refuted claims is a key indicator of low credibility.

    This also applies to unproven claims that are repeated without mentioning that the claim is disputed. A good example in this debate is the claim that several WIV lab workers were hospitalized with pneumonia-like symptoms in November 2019. So far there is no evidence to back up this claim so a good science writer would mention that.

  • If a claim is only referred to indirectly without fleshing out the actual scenario then you should be cautious. For example, if a scientist claims that SARS-CoV-2 was created in a lab but doesn't spell out how this might have been done other than hand-waving statments about furin cleavage sites then you have to ask yourself why they don't produce a specific scenario that can be examined. It usually means that the writer has not thought through their claim and has not considerd the implications. Those are bad signs.
  • Another bad sign is when a claim is associated with discrediting other scientists rather than just disagreeing with them. There's nothing about the natural origin explanation that requires you to believe that any scientists are lying or trying to mispresent the evidence. However, in order to believe the lab leak explanation you have to also believe that the scientists at WIV are lying about never working with SARS-CoV-2 before the pandemic and that they are now conspiring to cover up their involvement with starting the pandemic. That's possible but, as a general rule, whenever a claim has to invoke a conspiracy in order to believe it then you should see red flags.
  • A favorite trick of the anti-science crowd is to promote irrelevant information dressed up as though it were meaningful. The obvious example in this controversy is the fact that the WIV took down their database of preliminary viral sequence data in September 2019. The data is still available in various caches and most of it was published. We know that there was nothing in that database that pointed to anything but a natural origin of SARS-CoV-2 but that doesn't stop the anti-science crowd from trying to make it look suspicious.

    Sanjay Gupta, a medical doctor not a scientist, on CNN gave us a good example of this in his recent special on the origin of SARS-CoV-2 when he repeatedly brought up this topic without explaining why it was relevant other than to raise suspicions among the uninformed.

    Another exmple of this type of red-herring tactic is the attack on the funding of EcoHealth Alliance by the NIH. The anti-science writers and politicans with an agenda are trying to make it sound as though NIH was funding gain-of-function research at the Wuhan Institute of Virology. It wasn't. The NIH was funding a pefectly normal investigation into the evolution of coronavises in China in an effort to predict, and possibly prevent, a pandemic. The anti-science crowd cleverly raises doubt about the motives of NIH as part of its conspiracy theory and it cleverly doesn't mention the lack of any evidence between what they are suggesting and the origin of SARS-CoV-2. That's another bad sign that critical thinkers will take note of when evaluating credibility.

  • One of the key indicators of reliable authorities is when they present both sides of an argument. For example, if you read a paper that discusses the evidence for a natural origin of SARS-CoV-2 and then goes on to explain the lab leak scenario and why it is less credible then that's a good sign. On the other hand, if a paper only discusses their own baised opinion without mentioning and refuting the contrary evidence then that's a bad sign. I don't know of a single article that promotes the lab leak scenario and also attempts to refute the evidence of a natural origin. I find that troubling because it's typical of many other disputes where that kind of behavior is associated with the losing side. This is one of the problems that Richard Feynman identifies with "cargo-cult science."

    Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can — if you know anything at all wrong, or possibly wrong — to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it.

                                                        Richard Feynman (1985)

The lab leak conspiracy theory has all of the characteristics of other anti-science attacks such as the creationists' attack on evolution and those who deny climate change. We should stop giving them publicity and we should not hesitate to point out their lack of knowledge.

Image Credits: The coronavirus figure is from Alexy Solodovnikov and Wikmedia Commons. The figure illustrating the origins of of coronavirus infections is from a review in Nature Reviews: Microbiology by Zheng-Li Shi of the Wuhan Institute of virology (Cui and Shi, 2019). The review was first published in December 2018 and it's where she warns of future pandemics caused by bat coronaviruses. The figure showing the location of the earliest infections in Wuhan is from Holmes et al. (2021). The phylogentic tree is from Zhou et al. (2021).

Cui, J., Li, F. and Shi, Z.-L. (2019) Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology 17:181-192. [doi: 10.1038/s41579-018-0118-9]

Deng, S., Xing, K. and He, X. (2021) Mutation signatures inform the natural host of SARS-CoV-2. bioRxiv. [doi: 10.1101/2021.07.05.451089]

Holmes, E.C., Goldstein, S.A., Rasmussen, A.L., Robertson, D.L., Crits-Christoph, A., Wertheim, J.O., Anthony, S.J., Barclay, W.S., Boni, M.F., Doherty, P.C., Farrar, J., Geoghegan, J.L., Jiang, X., Leibowitz, J.L., Neil, S.J.D., Skern, T., Weiss, S., R, Worobey, M., Anderson, K.G., Garry, R.F. and Rambaut, A. (2021) The origins of SARS-CoV-2: A critical review. Cell 184:4848-4856. [doi: 10.1016/j.cell.2021.08.017]

Zhou, H., Ji, J., Chen, X., Bi, Y., Li, J., Wang, Q., Hu, T., Song, H., Zhao, R., Chen, Y., Cui, M., Zhang, Y., Hughes, A.C., Holmes, E.C. and Shi, W. (2021) Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. Cell 184:4380-4391. [doi: 10.1101/2021.03.08.434390]


John Harshman said...

I'm unclear on what you think is the relationship between a natural origin and a lab leak. They don't seem mutually exclusive at all. Both could certainly be true, though evidence against a natural origin (presumably this refers to genetic engineering?) woud be evidence in favor of a lab leak. Or do you use "natural origin" to mean something other than absence of manipulation of the virus?

Fré Hoogendoorn said...

Typo alert: 'media is misrepreseting' (misrepresenting); 'mispleading impression' (misleading); and I'm guessing 'betacaronaviruses' should be 'betacoronaviruses'.

Graham Jones said...

A natural origin and a lab leak not mutually exclusive, but evidence that shows SARS-CoV-2 could easily be the result of natural processes that happen all the time changes the prior probabilities. A puddle in a forest is less likely to be the result of human activity than a puddle in a desert.

Given the size of the Chinese wildlife farming industry, we were living a very rainy forest. 14 million people employed, worth $70 billion in 2016. That would be 700 million animals a year at $100 each, or two million animals a day. And they're kept in crowded conditions. And the biosafety level is...?

ERV said...

Graham-- Does that $70b include the fur industry? Im not an economist, but I saw a recent number in some Reuters article that placed it at $50b alone, in China.

John-- 'Both could be true'. I will grant your premise that 'maybe some virologists' were not following guidelines and were technically inept, for the sake of argument. Lets compare the PPE and biosafety protocols at the *best* animal breeding/feed lot or 'processing' facility to that theoretical *worst* lab at the Wuhan institute for Virology. Lets compare how virus is handled in that worst lab, not following rules, to the best SOPs at processing facilities. Lets compare the number of animals/high titer virus these inept researchers interacted with, per day, to the number of animals interacted with/killed/processed at a fur farm.

I mean I understand the Venn Diagram of "people who have worked in a virology lab" and "people who grew up around feed-lots and processing plants" is low, but *think*.

Unknown said...

Another typo alert: 3. Sequence data "The first sequence of SARS-CoV-2 was published in early January 2012..." The year should be 2021.

ERV said...

Larry, Re: Argument from Authority-- The article you cited, "The origins of SARS-CoV-2: A critical review." is basically a 'Whos Who' of scientists we should be listening to. Holmes, Rasmussen, Neil, Rambaut, even Peter freaking Doherty, who has been warning us about the next pandemic for decades now. I dont immediately recognize everyone on the list (sorry *wince*), and Im not sure why they bothered with Worobey (zero independent NIH funding for how long, now?), and there are some names I would have like to have seen, but these are The People who know what theyre talking about.

Compare that to the lab leak crew: Random anons? Microbiologists who dont know anything about basic virology? Alinia Chan, who graduated 4 months after me and is still somehow a post-doc (and I thought I was slow)? Doesnt have time to write grants to actually investigate the claims she is making, has time to play on Twitter literally all day, and write a 'book'? Anyone with even *passing* familiarity with the literature on emerging infectious disease knew this precise event was going to happen. You can find publications 2019, 2018, 2017, 2016, on and on, concluding "This is going to be a problem. We need to address this..." Peter wrote about it in a pop-sci book a decade ago. And yet these folks are simply amazed! Must have been a lab leak! Ridiculous. They have access to PubMed. Maybe they should think about using it.

Graham Jones said...

ERV, I don't know. My figures come from

Graham Jones said...

Whoops, from here:

(The Guardian article has some background info.)

John Harshman said...

I will grant your premise that 'maybe some virologists' were not following guidelines and were technically inept, for the sake of argument.

Not my premise. I merely point out that Larry's makes a false assumption, that a natural origin of the virus is incompatible with a laboratory leak. I doubt that any such thing happened, but that's not the point.

Larry Moran said...


Larry Moran said...


Larry Moran said...

John, I think you're being a bit picky. I'm pretty sure you understood exactly what I was referring to.

I grant you that the scientists at WIV could have isolated a viable SARS-CoV-2 virus from a natural source even though it has previously been shown to be very difficult to isolate intact virus particles. I grant you that those scientists could have grown SARS-CoV-2 in the lab then accidentally allowed it to escape. Assuming that the naturally occurring virus wasn't already spreading in the human population then you could argue that the lab leak is what caused the pandemic. I'm not sure this would still count as a "natural origin" but if you insist on calling it that, for some strange reason, then be my guest.

There's no evidence to support such a scenario so anyone making such a claim would still have to invoke a conspiracy theory and it would still count as a Lab Leak Conspiracy Theory in my mind. And it's still anti-science.

DK said...

I do believe that natural origin is far more likely but the claim that lab leak is completely out of question is not reasonable. Why not "folks in WIV had isolated plenty of viruses they never told the world about and were passaging them on human cells or ferrets"? And then one lucky mutant capable of infecting humans escaped. As we know, S1 in SARS-2 is pretty "universalist" and can bind nearly equally well to ACE2 from many mammals. Evolution in vitro can be very fast.

Larry Moran said...

Please present your evidence that "folks in WIV had isolated plenty of viruses they never told the world about and were passaging them on human cells or ferrets."

Not holding my breath.

jrkrideau said...

I think that should be 2020. I have not gone back to check old notes but I think that the Beijing CDC had published the first sequence of SARS-CoV-2 sometime in the first two weeks of January 2020. Some Australian researchers mentioned this, a lead researcher at either Pfizer or Modern did as did the lead scientist at the The Gamaleya Center in Moscow (Sputnik V)

Larry Moran said...

2020 is correct. Thank-you.

DK said...

Larry, you are missing the point! Which isn't that I have the evidence but that the leak scenario is plausible and does not contradict any well-established facts. So it's just a matter of what probability one assigns to the leak theory: 0% is untenable but anywhere from 1 to 25% seems entirely reasonable - different people assign different weights to the same facts, which is very common in science. FWIW, mine is about 5%. I am just annoyed by people who claim that there is certainty one way or another.

The evidence for the leak, even if it did happen, is practically impossible without the Chinese cooperating. And we know that they are not (if there were no leak, I wouldn't cooperate either because they were treated unacceptably rude from the get go).

Larry Moran said...

Extraordinary claims require extraordinary evidence. In this case, the lab leak conspiracy theory makes an extraordinary claim; namely that the reputable scientists at WIV were secretly working on SARS-CoV-2 before the pandemic started. They make this extraordinary claim in spite of the fact that the scientists deny that they working with that virus.

In order to assign any credibility to that extraordinany claim you need to present some evidence to refute the word of those reputable scientists. Otherwise, the probability of your claim being true is no different than the probability that SARS-CoV-2 escaped from any American lab.

DK said...

Nothing extraordinary about lying government workers working under totalitarian regime that can destroy you and your family at will. Worse lies have been told for less fears.

If the virus were to be first detected around Frederick, MD and the folks at the nearby Ft. Detrick were known to work on it close relatives, I'd similarly have no problem assigning some non-zero probability to the lab leak despite any number of official denials, too.

Larry Moran said...

You are a good example of why conspiracy theories are so popular. Your imagined conspiracy trumps all evidence.

ERV said...

"Why not "folks in WIV had isolated plenty of viruses they never told the world about and were passaging them on human cells or ferrets"? And then one lucky mutant capable of infecting humans escaped."

Because what you just typed is nonsense, and I say this as someone who knows the extraordinary amount of work takes to isolate and construct full-length infectious molecular clones out of a quasispeicies, grow-->propagate that variant in tissue-culture, and actually get what you expect out the other end.

Do you have *any* idea how much work, and failure, and chance, and possible preternatural knowledge it would take to do what you just proposed as casual 'why not...'?

DK said...

"You are a good example of why conspiracy theories are so popular. Your imagined conspiracy trumps all evidence."

LMAO. Can you read? I told you that I am at only 5% probability for a leak (meaning 95% for natural spillover) and you STILL claim that this conspiracy trumps a all evidence for me.

Try to start thinking in probabilistic rather than binary terms - that is much more sciebtific approach because it much more closely reflects how the world works.

DK said...

"Do you have *any* idea how much work, and failure, and chance, and possible preternatural knowledge it would take to do what you just proposed as casual 'why not...'?"

I do. More than you do, in fact. There is no need to make molecular clones if one has isolated live virus. Likewise, MCs are not needed to passage live viruses. And making 30 kbp infectious MC is no big deal these days: I'll do it for you for ~ $10K with Gibson assembly from A to Z in under four weeks.

"and actually get what you expect out the other end"

Nobody said someone expected to get something specific. They may have wanted to study viral adaptive evolution (passaging for this is done all the time). Or they may have gotten truly unlucky to be infected with one of the viruses they isolated. (This happens all the time too: SIV or Herpes B are not normally infectious to humans but occasionally humans get infected with them; inside the labs, too!)

Once again: The evidence is very heavily on the natural origin AND the start of the pandemic. Rational design of SARS-2 can be completely ruled out, of course. But as it stands today, a lab leak scenario cannot be ruled out conclusively. It's that simple.

Larry Moran said...


What is your evidence for assigning a 5% probability to the lab leak conspiracy theory?

And don’t try to get out of answering the question by pretending that it’s not a conspiracy theory because you’ve already admitted that it is.

ERV said...

"... There is no need to make molecular clones if one has isolated live virus..."
That makes absolutely no sense. You cannot do any hypothesis driven research with just 'isolated live virus'.

"...And making 30 kbp infectious MC is no big deal these days..."
The first Sars-cov-2 IMC was published in Cell Host Microbe. You can read how they did it and *some* of the problems they encountered and how they adapted. You have no idea what you are talking about, yet youre annoyed people with actual knowledge and experience are talking about things you dont understand with 'certainty'. *shrug*

DK said...

"What is your evidence for assigning a 5% probability to the lab leak conspiracy theory?"

Wouldn't call it an "evidence" but "considerations": Proximity + known related research program + leaks/infections in the lab happen regularly + alleged links to military (could well be BS) + seemingly lax safety practices at WIV (could also be BS, but, again, I know it happens all the time, so can easily believe it for WIV too).

@ERV. I am well-aware of this paper. I could hardly believe it when I saw it. They did it in the ligation-dependent way. No surprise it was such a mess. It may be cost-effective but, these days, that was idiotic. Gibson assembly is a way to go.

DK said...

And, of course, they should have cloned it into a plasmid before in vitro RNA synthesis - so that no one has to go through the full assembly again (which, IIRC, Baric lab did with SARS-1).

dean said...

"Wouldn't call it an "evidence" but "considerations"

So you're admitting no evidence or support for your ramblings but you're still tossing it out. Conspiracy theory is the correct term.

Ted said...

Larry Moran What happened to your blog? On Chrome and Edge it is all dark and I can't click on anything. Firefox works for now, but...

Ted said...

@Larry Moran. I think DK's scenario is a cover-up theory rather than a conspiracy theory. Cover-ups are much more plausible and common than conspiracies.

Larry Moran said...

DK’s speculations suggest that the scientists at WIV were secretly working in 2019 with a virus that could start a pandemic. They deliberately hid this project from all their collaborators in other countries and from American funding agencies. They were possibly working with the Chinese military. They were working under lax safety standards but lying to the regulatory agencies about their safety protocols.

None of that is part of a coverup. The coverup only begins when they were presumably caught.

ERV said...

Me: "Do you have *any* idea how much work, and failure, and chance, and possible preternatural knowledge it would take to do what you just proposed as casual 'why not...'?"

DK: *babbles*

Me: You could have just said 'no'.


Yes said...

Larry, did you read the DEFUSE DARPA grant proposal by EcoHealth?

Specifically the part about taking collecting Sars-like Bat CoVs throughout Southeast Asia, and inserting a furin cleavage site at the S1/S2 junction? And determining the effect of this modification on infectivity of such chimeric engineered Sars-like Bat CoVs in human HAE and humanized ACE2 mice?

Yes said...

Worobey is added because he actually understands viral evolution quite well and is adept at explaining away inconvenient sequence data (e.g. FCS) as fully consistent with natural origins.

If you want to judge the competing hypotheses by the credentials of the scientists who are pushing it, by objective criteria (Impact factor, Prestige of home institution, membership in National Academy, NIH funding), the lab leak crowd win by a long shot.

Here are scientists who have expressed the view that there is circumstantial evidence for lab leak (no serious researcher would claim proof)

David Baltimore (Caltech)
Richard Ebright (Rutgers)
David Rellman (Stanford)
Jesse Bloom (Fred Hutch)
Trevor Bedford (Fred Hutch)
Micheal Lin (Stanford)

To this list, you could add many more who have stated that lab leak needs to be fully investigated.

Akiko Iwasaki (Yale)
Ralph Baric - yes, the Ralph Baric.

Alina's role has had the courage to speak up when a lot of academics stayed quiet, lest they be associated with helping Trump. She also debated Peter D, Kristian A, and Angela R on twitter, and unlike these three, she backed up her arguments with citations and data whilst her opponents used arguements by authority.

Yes said...

They didn't hide it from their collaborators, they actually wrote a grant together, and submitted it to DARPA. In the DEFUSE proposal, the exact step by step experiments to create SarsCoV2 are nicely laid out. Not to make a weapon, to determine what molecular steps it would take to turn a BatCoV Sars-like virus into something that can infect and proliferate in human cells. The only thing unknown to their international collaborators were the exact sequences of the the Sars-like CoV backbone they used in that experiment.

Aram said...

Slightly off-topic but is there a list of which bats SARS-Cov-2 can infect? Can it infect horseshoe bats? What about pangolins? Is this something that experts all know about so don't bother to write down?
Thanks in advance!

Dr Citrus said...

I see no attempt to deal with the issue of conditional probability/Bayesian inference. Of all the places in the world this could have started, it starts right next to a lab studying precisely the subset of viruses from which SARS-COV-2 comes (and, as we now know, looking to pursue GoF research on them), despite this area not featuring significant human contact with such viruses in the natural environment.

Of note: under such circumstances, the more chances there are for such a pandemic to have started naturally in places other than Wuhan, the MORE we should be struck by the fact that it actually started IN Wuhan. This is not always an intuitive step for people who don't understand probability terribly well (they tend to think it counts in favour of the zoonosis hypothesis, when it does not).

The zoonosis argument, while of course plausible, has to address this striking coincidence. The lab leak hypothesis does not.

This is not some minor issue that can be hand-waved away with an appeal to precedent. It's a serious problem for the zoonosis argument.

Anonymous said...

Larry: your text sounds well-intentioned, but shows a clear bias towards a natural zoonosis, and much misconception over research-related scenarios. In order to assess competing hypotheses you need to check them all, not merely the hypothesis decreed more likely by some 'experts', based on cherry-picked data in order to dispel a nightmare scenario for their own field.

Borrowing on your Feynman quote, "details that could throw doubt on your interpretation must be given, if you know them." I take it that you don't.

StevenQuay said... Please review these 14 documents on the origin of SARS-CoV-2 and review them in your blog. Thanks, Steve

dean said...

"This is not always an intuitive step for people who don't understand probability terribly well "

Given your freshmen level hand waving (no intent to insult my freshmen students, should any be reading) it seems you're in the group you describe.

Yes said...

Why are the Chinese authorities obstructing the investigation?

All of this debate could be put to rest by the Chinese authorities, by in depth patient tracing, as was done for Sars1 with much more rudimentary tech. The WHO team, made up of scientists hand-picked (read: China-friendly) by the Chinese authorities, was shocked by the superficial job the authorities did on patient tracing. This was commented on by @PeterFoodSafety at the time (, and re-iterated, more diplomatically, in a Nature paper earlier this year (

Obvious tracing-steps, like testing blood banks or medical samples from the Oct -Nov 2019 period has not been performed. When asked about this, the WHO team was told "Chinese privacy laws" precluded testing of such samples.

The "privacy" argument is difficult to accept given the urgency of the question and that privacy laws seem to be selectively enforced (

Even the must dis-interested observer could not help conclude that there is a distinct lack of will, if not outright obstruction by the Chinese authorities.

The lab leak hypothesis (or simply, the Chinese authorities fear that it MIGHT be true) most parsimoniously explains this obstruction. The consequences if proven true, would possibly entail financial compensation on a scale unprecedented in human history.

Larry Moran said...

I’d be happy to discuss any scientific evidence that supports the lab leak conspiracy theory. Please post it here.

I’d already posted several articles on the various unfounded speculations that gave rise to the conspiracy. Please let me know if you think any of them need more attention.

Also, please explain all of my “misconceptions over research-related scenarios.”

Yes said...

"If a claim is only referred to indirectly without fleshing out the actual scenario then you should be cautious. For example, if a scientist claims that SARS-CoV-2 was created in a lab but doesn't spell out how this might have been done other than hand-waving statments about furin cleavage sites then you have to ask yourself why they don't produce a specific scenario that can be examined. It usually means that the writer has not thought through their claim and has not considerd the implications. Those are bad signs."

It is explained in pretty detailed steps in this proposal by EcoHealth, WiV (contrary to what is asserted in this grant, the chimera work is done at WiV not UNC, a fact confirmed by Peter D in emails to NIH obtained by FOI.).

On page 13 of the document (page number 11 of the actual proposal)

Step 1. Collect Sars-like bat CoVs
Step 2. Look for incomplete human protelytic (furin) cleavage sites at the S1/S2 junction
Step 3. Engineer a functional human furin cleavage site
Step 4. Determine the effect on infectivity of this modification of chimeric virus on human airway respiratory cells (HAE) and humanized ACE2 mice

The only thing missing from this detailed description is which bat sars-like CoV would be used as a backbone. But worry not - the proposal explains where those will be collected, "our cave" in Yunnan.

We don't know how many and what the sequences are of Bat sars-like CoVs collected from the trips. That's why the take down on Sep 2019 of the pathogen sequencing database at the WiV is problematic - exactly the place where one would find a backbone.

Larry Moran said...

The international team of investigators tested various bat coronavirus spike protein sequences to see if any of them were evolving the ability to bind ACE2. This would be an early warning sign of a potential pandemic. Some of the experiments we done in America labs.

The backbone they used was a well-known mouse coronavirus used for many years in labs all over the world.

Larry Moran said...

I did not read any grant proposal that included creating a furin cleavage site. Please post the link here.

As far as I know, the furin cleavage site is not used to infect the mouse cell lines with the human ACE2. In fact, if it is present it is usually lost on serial passage in such cells.

Larry Moran said...

I see that part of the proposal and I agree that your interpretation is plausible. However, I’m not sure that it’s the only interpretation because the wording is ambiguous.

What are you suggesting? Are you suggesting that the WIV scientists secretly discovered and reconstructed a bat virus that was identical to SARS-CoV-2 except for the furin cleavage site then they deliberately introduced that furin cleavage site creating SARS-CoC-2? Then they allowed this virus to escape and start the pandemic?

A few months before this, they accidentally posted the virus sequence on their website then took down the website. Somehow they managed to purge the secret virus sequence from the sites were the data had been cached. There must have been several dozen people who knew about this secret activity and none of them have talked.

Do you really think this is what happened?

SJNJ said...

Your blogpost talks a lot about history but you neglect to cover the history of bio-security lab leaks of which there have been 32 since 1903
( that there are two extensive governmental coverups by USSR (1977 and 1979) and two during SARS1 by China. The issue is not the leak as much as the subsequent coverup.

SJNJ said...

Note that Lab leaks have been happening since 1903 ( USSR tried to covered up two (1977 and 1979) and CCP in 2003 SARS1. Read "China Syndrome" by Karl Taro Greenfeld to see psychology of coverup in China pre XJP. The book reads like Anthony Bourdain telling a story about a pandemic

Larry Moran said...

The history of lab leaks is irrelevant in the absence of evidence that the WIV was working with SARS-CoV-2 before the pandemic. You first have to prove that they had the virus before you start accusing them of leaking it.

Larry Moran said...

No thank-you. Those posts of full of lies, misconceptions, and misinformation.

Anonymous said...

Misconception 1: genetic analysis can tell us whether a virus is 100% natural or not. Misconception 2: a natural virus wouldn't be involved in a lab leak (all lab escapes recorded in history involved naturally existing pathogens, including several SARS-CoV-1 lab acquired infections). Misconception 3: if WIV scientists had been working on SARS-2-like viruses in 2019, we would know about it (for a variety of reasons, research is often published months or years later, or even not published at all). Misconception 4: if it was lab leak, a big conspiracy would be needed to cover it up (see e.g. Sverdlovsk anthrax leak). Misconception 5: only the lab leak explanation requires people to believe there was a cover-up (the timeline and extent of the Wuhan outbreak were thoroughly covered up, by a drip-feed of muddled data, sample destruction, suppression of records, censored research and scrubbed databases).

There's a lot more to be said, but I'm out of time now

Larry Moran said...

#1. An analysis of the sequences of various coronaviruses can tell us a lot about whether SARS-CoV-2 could have evolved naturally. It certainly looks like it did, but you can't rule out a few genetic manipulations in a lab. You don't accuse scientists of lying based on that kind of speculation.

#2. Of course a naturally occurring virus could have been studied in a lab and then leaked from a lab. You don't accuse the WIV scientists of lying and starting a pandemic just because you can imagine such a possibility. You have to have evidence that SARS-CoV-2 was being secretly studied in the lab before the pandemic started. Do you have such evidence?

#3. We can judge the honestly of the WIV scientists by their past behavior. That's not foolproof but you would need evidence to accuse them of completely reversing their past behavior and lying about SARS-CoV-2. Just wanting it to be true doesn't count.

#4. When you accuse scientists of lying and covering up their mistakes with no evidence to support your accusation, that's a conspiracy theory. If it involves dozens of scientists and government officials then it's a big conspiracy.

#5. You really like conspiracy theories and cover-ups, don't you?

Dan said...
This comment has been removed by the author.
Dan said...

Your reply here is nonsense, and you should know better. If you are going to go off preaching about critical thinking, you should ask yourself if you are genuinely engaging your own critical thinking facilities.

Let me illustrate: the history of zoonotic spillovers is irrelevant in the absence of evidence that SARS-CoV-2 had ever been in any intermediate host. You first have to prove that an intermediate host had the virus before you start asserting that it has been spilled-over.

And before you tell me there is evidence of an intermediate host, you might want to consider Bill Gallaher's opinion:

"There are zero data that any animal but a bat served as a host to SARS-CoV-2 prior to its introduction into humans."

This entire post is largely the exact kind of speculation that Gallaher chides Garry for.

Yes said...

I believe that the WIV collected hundreds of Bat Covs, and that some of these BaTCoVs have sequence similarities to (but not identical) SarsCov2 greater than RaTG13 and BANAL

One such CoV was engineered with a human FCS at the S1/S2 junction using a 12 NT insert, passaged in human airway epithelial cells and than in human ice hACE2 mice. At this point this virus was nearly SarsCov2 - it then infected a lab tech, perhaps during a dissection of an infected hACE2 mouse. That virus replicated in this worker (perhaps even asymptomatically) and this worker infected others.

Larry Moran said...

Why do you believe that? You must have a reason.

DK said...

"The backbone they used was a well-known mouse coronavirus used for many years in labs all over the world."

Ummm, Larry - there is a huge difference between "mouse coronavirus" (something they haven't used) and "mouse-adapted bat coronavirus"(something they have). Come on, you ought to know the difference!

DK said...

It can "infect" all bats, all canids, all felines and A LOT of other mammals. The replication rates after productive infection is a different matter. Symptomatic infection is another matter yet. There got to be a lot of host-specific restriction happening.

Anonymous said...

Oh look, documents demonstrating scientists were indeed doing gain of function research on coronavirus. Since it was asked in the discussion ...

Anonymous said...

Since ERV insists saying it's impossible, here are NIH documents describing how some scientists were perfectly successful in doing more infectious coronavirus
At the Wuhan virology institute they were making more infectious coronavirus

I don't know where you get the idea it's so hard to make.