How credible is the theory that COVID19 escaped from a Wuhan Lab?

post by Alexander Gietelink Oldenziel (alexander-gietelink-oldenziel) · 2020-04-03T06:47:08.646Z · LW · GW · 1 comment

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    16 CellBioGuy
    9 Alexander Gietelink Oldenziel
    6 landfish
    2 waveman
    -13 jbash
None
1 comment

It sounds like a conspiracy theory. Apparently, it's big on the Chinese Internet.

https://www.econjobrumors.com/topic/chinese-internet-thinks-patient-zero-was-a-grad-student-at-the-wuhan-lab

which links

https://www.youtube.com/watch?v=bpQFCcSI0pU

The details in the video are rather vague since I don't speak Chinese I have trouble evaluating its credibility. What do you think?

Answers

answer by [deleted] · 2020-04-03T20:54:19.268Z · LW(p) · GW(p)

Closely related viruses have leaped into humans twice in the last 17 years via completely standard zoonosis, neither time of which was directly from bats but instead through an intermediary amplifying animal. While a laboratory keeping a culture of or animals infected with a wild virus is a possibility, as is laboratory accidents... these things DO happen naturally.


I must also reiterate that the sequence analyses reveal that all the interesting attributes of this virus were already present in a closely related virus that has been circulating in bats for at least fifty years, and there is evidence that related viruses have passed through pangolins.


What is the proposed timeline of this theory? There are known patients in China that have been confirmed as infected in the community as far back as November 17 now...

comment by Jiri Severa (jiri-severa) · 2020-04-17T16:49:10.420Z · LW(p) · GW(p)

Transmission via intermediary species is obviously possible. That the virus has 96% genetic structure to a known RatGN-13 virus in horseshoe bat i s not disputed. Neither is the real possiblity of SARS-Cov-2 originating in a natural gene swapping. What is not credible are the naive assertions of experts discounting a possible lab origin, by repeating essentially the "straw man" argument by K.G.Andersen, asserting that "synthetic lab origin" is impossible because of its proximity to known bat viruses. But no-one is arguing that. There is a very real possibility that a bat virus was modified in WCDC lab by inserting new genetic sequences and the resulting product escaping. This scenario appears even more real when one learns that the head of the bat viruses research in Wuhan, She Zhengli, conducted virus recombination in the lab for a number of years, and published papers on it.

Replies from: None
comment by [deleted] · 2020-04-12T18:19:38.029Z · LW(p) · GW(p)

But there is little evidence of recent major recombination in the history of this particular virus, since its common ancestor with the 2013 virus. It looks like it has a pretty much vertical inheritance from its common ancestor with the 2013 bat sequence.

Check out the paper "Evolutionary origins of the SARS‐CoV‐2 sarbecovirus lineage responsible for the COVID-19 pandemic" (https://www.biorxiv.org/content/10.1101/2020.03.30.015008v1). They run a sliding window along the SARS-CoV-2 sequence and compare it to the sequence of many other viruses. The conservation is not constant across the genome, but different regions are under different evolutionary constraint, and the *relative* conservation across the genome looks more or less consistent rather than there being big sharp jumps in homology as you would expect from distant recombination and see in other more distantly related viruses.

Some have argued that recombination could account for the origin of the specific receptor binding domain since it seems very similar to that found in a pangolin virus. But overall there is very little recombination evidence.

The only idea that is really open at all is 'Poor procedure resulting in viral transfer from a wild lab animal', not 'recombination experiments in the lab creating something unusual'.

answer by Alexander Gietelink Oldenziel · 2021-05-15T15:56:33.303Z · LW(p) · GW(p)

An update. 

This recent article by Nicolas Wade: https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ is particularly damning, going into details into many lines of evidence all pointing towards COVID-19 accidently being released from the Wuhan Lab.  

I recommend anybody interested in reading the article. It has made me update substantially towards an accidental-lab-release origin for COVID-19.

My current estimate for such a lab-release origin is ~85%. 

 

Update: Some further googling brought up some skepticism towards some of Nicolas Wade's claims, here and here

my best estimate is now 65% for a lab-release. This is still a substantial update from my initial ~20% for a lab release origin for COVID-19 (estimated in hindsight).

comment by Alexander Gietelink Oldenziel (alexander-gietelink-oldenziel) · 2021-07-06T12:30:47.830Z · LW(p) · GW(p)

Update: I have again updated away from the lab leak theory. Most of the evidence for a lab leak seems overstated after a closer look. See for instance this skeptical take by potholer54.

Replies from: habryka4
comment by habryka (habryka4) · 2021-07-06T18:31:56.266Z · LW(p) · GW(p)

Do you have a new probability?

Replies from: alexander-gietelink-oldenziel
comment by Alexander Gietelink Oldenziel (alexander-gietelink-oldenziel) · 2021-07-09T12:12:01.618Z · LW(p) · GW(p)

I hesitate to give a probability.

Hindsight is 20/20 but the 85% probability was too high in a certain sense. 

I am talking about the following phenomenon: if you had forced me to bet a given fixed amount of money either way right at that moment I would take the 85% implied betting odds. However, if you had (i) offered me such a bet freely, (ii) allowed me to set the amount of money in the bet, (iii) and/or given me more time to research the issue I would ahve refused (i), only bet a small amount on (ii) and certainly spend more time researching the core claims (iii).

The above considerations show the problems with simply giving fixed probability distributions for belief. Certainly, the following phenomena should be considered:

  • There is a measure on how strongly a belief is held. The strength is often measured in the bet size.
  • A difference between belief and belief-in-belief
  • Somebody offering you a bet is implictly giving information about adversarial optimization (I once spoke with a guy in Finance that the bid-ask spread in markets is a measure of this)
  • There some sort of parameter in a reasoners brain that determines how long that reasoner will spent researching a given issue. Presumably this is set abnormally - perhaps dangerously so! - in the median rationalist.

I am sure there is a literature on this topic which I am now excited to check out! I am sure LessWrongers have thought about this... I would be grateful for any references!

Two important reasons I now favor natural causes: (i) most of the technical evidence seemed to have fallen through - it is always hard to ascertain the validity of technical evidence as a layman, but that was my impression. My initial update rested a lot on (a) not having much evidencemass either way so being easily convinced (b) the lableak piece by Nicholas Wade - even if some of the evidence holds up I feel it overstated its case/omitted contrary evidence. 

 (ii) the a priori probability of a lab leak origin of COVID-19 should be quite small; of all viri we are confident of a source it is natural, and though lab leaks have happened in the past, there are many more naturally- caused pandemics than human-caused pandemics

**************************************************************************

"Okay, that was all very very interesting... but please .... I insist"

You put a gun to my head

 "What are your bettings odds?" 

"Okay, okay 80% chance natural cause, 20% something else".

answer by Jeffrey Ladish (landfish) · 2020-04-03T22:39:37.213Z · LW(p) · GW(p)

I would like to see someone collect information about this hypothesis is a more organized fashion (not a youtube video), specifically to outline which labs are a possibility, who the people were at the labs, what their prior publications were, etc.

Also, for the other zoonosis, how did they arise? (I.e., in a city? In the country? etc.) Same question for other lab escapes.

This Nature article argues that two new features of SARS-CoV-2 look like they've undergone selection for humans or human-like hosts: the "receptor-binding motif (RBM) that directly contacts ACE2" and the "polybasic (furin) cleavage site". They argue that the virus had to acquire these features somewhere other than bats, and investigate several hypotheses:

https://www.nature.com/articles/s41591-020-0820-9

1. Natural selection in an animal host before zoonotic transfer
2. Natural selection in humans following zoonotic transfer
3. Selection during passage

They think the third option is unlikely, though I don't entirely follow their argument:

"In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation19.

The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system"

I think their argument boils down to "it's more parsimonious that SARS-CoV-2 ended up with RBD sites with ACE2 affinity via recombination with a pangolin virus than that it acquired it via selection in animal or cell culture, given the virus had not previously been described". I think this argument could be made cleaner, and that better steelman arguments for both "lab escape" and "zoonosis" origin could be produced.

comment by [deleted] · 2020-04-04T00:15:28.506Z · LW(p) · GW(p)

In particular, the combination of the glycans right next to the polybasic cleavage site suggests that the selection for the cleavage site probably occurred in the presence of an immune system rather than in culture.

comment by jmh · 2020-04-11T19:27:51.473Z · LW(p) · GW(p)
Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.

Just to be sure I'm reading this correctly. Is that saying no lab or virologist has ever indicated having or working with a coronavirus everyone says is present in the bats and ultimately mutated to reach humans?

Replies from: jeff-ladish
comment by Jeffrey Ladish (jeff-ladish) · 2020-07-07T23:31:22.305Z · LW(p) · GW(p)

I think their claim is that labs only (or usually) work with viruses that have been described / that they have published the sequences for. And furthermore that they would have published such GoF work if they had done it (?). Like I said, not very compelling claims, especially because they're general and unclear.

answer by waveman · 2020-04-03T09:01:02.369Z · LW(p) · GW(p)

To me it sounds more like a screw-up than a conspiracy. [Also check out the origins of the term "conspiracy theory".] This is *not* the theory that this was a bioweapon that escaped.

There was a paper a while back not peer reviewed and 'withdrawn' and the Chinese authors have been keeping a "low profile" ever since:

"The possible origins of 2019-nCoV coronavirus" now at https://img-prod.tgcom24.mediaset.it/images/2020/02/16/114720192-5eb8307f-017c-4075-a697-348628da0204.pdf

by Botao Xiao
South China University of Technology

I have been following the youtuber's channel of the video in the OP for a while and found it good value for understanding China. Whether this theory is right I am not sure. But nothing in this surprises me. Yes he hates the CCP but what that may not be entirely irrational.
Things that make this possibly more likely:

  • Cover-up - CCP always covers things up, blame others (e.g. Chinese foreign ministry spokesman trying to blame the US for the CV)
  • Slack procedures - There have been many leakages of infectious material from Chinese labs
  • Selling infected animals at markets - not at all surprising in a country that has been through what the CCP inflicted in China. You do what you need to do to survive....

We will probably never know for sure as long as the CCP is in power.

answer by jbash · 2020-04-04T02:58:07.445Z · LW(p) · GW(p)
  1. This is not particularly credible.

  2. It's also not particularly important.

  3. Even if it were 100 percent true, it would be what I believe Less Wrong likes to call an "infohazard". Unless you want to literally get people killed, you don't want to spread this stuff.

comment by Alexander Gietelink Oldenziel (alexander-gietelink-oldenziel) · 2020-04-04T06:23:34.644Z · LW(p) · GW(p)

Why is it an infohazard?

Replies from: jbash
comment by jbash · 2020-04-04T15:12:15.165Z · LW(p) · GW(p)

Because it is likely to:

  1. Damage international relations and cooperation in the middle of a pandemic. You have US Senators out there pushing this thing. That's going to offend the Chinese government. At the absolute least, it will distract people from cooperating.
  2. Cause another wave of anti-Asian, and specifically anti-Chinese, racist attacks. Such attacks happened even when everybody thought the whole thing was an accident. If you make them believe it was deliberate (on edit: they will believe this even if the rumor is that it was an accident, and there's still a big problem if they only believe it was careless), they will definitely do it more.

In short, providing oxygen to rumors like this makes them more credible and more available to idiots. Idiots are predictable elements of the world, and you can reasonably anticipate their responses to the conditions you create.

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comment by Andrew_Clough · 2020-04-04T15:40:29.600Z · LW(p) · GW(p)

The people on This Week in Virology seemed convinced that the spike protein wasn't anything that had previously been seen and wasn't anything a human would design if they were working on creating a new virus.

SARS-Covid-2 doesn't look at all like a biological weapon. If they were dong experiments on trying to design a novel spike I don't think they'd do it in such an otherwise dangerous virus.

I can imagine that this virus infected someone in China, was brought to the lab for analysis then escape from the lab into Wuhan but that's a lot of burdensome details. And my guess is that if they'd had the virus in a lab then the overall response would have looked different but that's weak evidence.

So overall I'd say it isn't impossible but I'd give less than 1% odds.