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[parent] [thread] 34 comments
1. guesst+(OP)[view] [source] 2021-05-07 05:08:00
The China aspect is probably a red herring. Gain-of-function research was internationally funded, including by the US. The perils had been pointed out for years by virologists [1], some of whom managed to get an editorial in the New York Times against it [2].

If Covid turns out to be a lab escape (which is a big if), the nation or lab it happened in is just the proximate cause. Deeper responsibility would lie with the institutions and individuals that pushed it despite the risks. No one knows the answer to this (edit: I mean to whether covid escaped from a lab), but it's an open question that deserves credible investigation. Having the investigator be one of the principal funders of the research being investigated is such...bad optics, to put it nicely, that one wonders how anyone thought that would be ok.

[1] https://mbio.asm.org/content/3/5/e00360-12

[2] https://www.nytimes.com/2012/01/08/opinion/sunday/an-enginee...

replies(7): >>rramad+Z1 >>willma+o4 >>roca+e5 >>thu211+J5 >>kbenso+N6 >>inciam+S7 >>BlueTe+Cb
2. rramad+Z1[view] [source] 2021-05-07 05:28:48
>>guesst+(OP)
You make a very good point (and thanks for the links).

However i would not let China off the hook until we have figured out exactly what happened. If nobody is held "accountable" (for a certain definition of this word) it is bound to happen again and the next time it most certainly will be "biological warfare".

This needs to be treated as seriously and as comprehensively the way we treat Nuclear Weapons.

replies(1): >>guesst+n2
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3. guesst+n2[view] [source] [discussion] 2021-05-07 05:31:53
>>rramad+Z1
I really think it's just the other way around. The more people make this about China, the less likely we are to find out the truth. If it's used as a geopolitical chess piece, it will get bogged down forever in political mud, which is kind of where the question is right now anyways. People will decide what they think about it based on how they feel about China. That's crazy.
replies(3): >>rramad+gd >>misja1+Re >>mattm+D01
4. willma+o4[view] [source] 2021-05-07 05:50:46
>>guesst+(OP)
SARS-2-CoV was almost assuredly not natural, and RaTG13 was a keyboard virus. The only question is if it was accidentally leaked or if it was intentional. We'll never know, the CCP destroyed the evidence.

There are many videos and articles on this site about how SARS-2-CoV was not zoonotic. I don't necessarily blame China, but the funders of the research.

https://www.peakprosperity.com/more-evidence-covid-19-may-no...

replies(1): >>guesst+O5
5. roca+e5[view] [source] 2021-05-07 05:57:28
>>guesst+(OP)
One of the things Wade brings up is that gain-of-function research was justified by its proponents on the grounds that it would help prevent and/or deal with future pandemics. So a good question that needs to be addressed now is: did gain-of-function research on bat coronaviruses help us deal with COVID19, and if so, how?
6. thu211+J5[view] [source] 2021-05-07 06:03:44
>>guesst+(OP)
The article in question (assuming it's the same one I read on his blog) actually does tell us these things. The research was largely funded by the United States and the funding would appear most likely to have been signed off by ... Anthony Fauci. So if that's true then the guy ultimately responsible in money terms is the guy who the government put in charge of fighting it, almost certainly without realising. This set of events ensures that whatever the truth, we can never expect an honest investigation of any kind from the governments (plural) that would appear responsible.
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7. guesst+O5[view] [source] [discussion] 2021-05-07 06:04:30
>>willma+o4
You're treating that question as settled. To me that is the mirror image of the media outlets trying to shut down an open question by claiming it's a "conspiracy" that has been "debunked". I would say what's needed is a credible, independent investigation, one that reasonable people can trust. We haven't had that yet.
replies(2): >>thu211+A6 >>willma+zW
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8. thu211+A6[view] [source] [discussion] 2021-05-07 06:11:52
>>guesst+O5
How is the article not that? Wade is a life long journalist, now independent, who has done extraordinary research, and who had relied heavily on research done by other independents as well, which is itself based strongly on credible micro-biology. Wade is nonetheless careful not to exaggerate his case but point out the mere balance of probabilities.

I'm not sure you can get more credible or independent than his work.

9. kbenso+N6[view] [source] 2021-05-07 06:14:09
>>guesst+(OP)
> If Covid turns out to be a lab escape (which is a big if), the nation or lab it happened in is just the proximate cause. Deeper responsibility would lie with the institutions and individuals that pushed it despite the risks.

That's the rational response. The fact that it can be played for political gain means it will be played for political gain, regardless of how rational it is.

Look at the whole mask debacle of the last year. If we assume people can and do act rationally, then both sides wouldn't have played it up as much and made it a defining issue or lied about portions of it, but instead we had both people and organizations/parties using it to rally their base (on both sides) and an authority that decided to use half-truths to trick people into doing what they thought they should do given the resources available at the time (to put it kindly).

That's the reality of the world we lived in for the last 12 months, and I see no reason to assume it's all of a sudden different. I'm not sure that means we shouldn't know, but let's be real clear on what the the likely outcome is if it's found to have escaped from some lab in China, regardless of who funded what or who was working on it, and that's that it would be a complete and utter shit show for the West and China, and possibly the entire world.

10. inciam+S7[view] [source] 2021-05-07 06:24:10
>>guesst+(OP)
> If Covid turns out to be a lab escape (which is a big if),

It seems like we don't have evidence, but the natural evolutionary experiment that's occurred provides a staggering amount. We can see from the virus phylogeny that:

1. The virus entered the human population in October 2019. All known SARS2 sequences are related in a single clade that, under very soft assumptions about mutation rate, would coalesce in late fall 2019. The first sequences we got, in early 2020, had only a handful of mutations between them. Nothing has ever arisen outside of this clade.

2. The virus entered humans with it's spike protein already fully adapted to the human ACE receptor protein. We can see this because there was not an accelerated evolution in this protein. We did not see changes in the viral genome resulting in a significant phenotypic change until the b.1.1.7 and other "third wave" variants arose. This stands in intense contrast to every other zoonotic transfer we know of. Adaptation always occurs because biology is different enough that different viral configurations provide immediate gain, and through continuous mutation the virus is exploring a huge space of these all the time. The fact that it doesn't mutate rapidly indicates it is near a strong local optimum.

One way of understanding the significance of this is by thinking of the virus as a learned model which is learning a solution to the problem of its own survival. What this evidence shows is that is appeared already optimized. We see this because over an incredible number of update steps (many quadrillions perhaps, with each human infection being like a minibatch, and each viral replication like a step) there was no significant reduction in test loss (viral survival). We randomly picked a perfect initial model. Either that first virus was lucky in a way that is similar to guessing a perfect solution, which has a probability so low as to be fanciful, or it had already in incorporated all the readily-usa le information about the human ACE receptor.

Do we have evidence? What is the probability of this pattern occuring in the case of a natural spillover? It's 1:atoms-in-the universe level. Finding a virus already so optimized to humans by randomly sampling from existing ones is like the kind of collision probability level that we comfortably use to build cryptocurrency castles that assume key non-collision. In the case of a virus optimized by serial passage in the lab? Frankly it's indistinguishable from that.

replies(7): >>alexne+c8 >>guesst+19 >>nl+j9 >>flukus+8a >>XorNot+1t >>yread+3t >>tomp+wt
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11. alexne+c8[view] [source] [discussion] 2021-05-07 06:28:08
>>inciam+S7
Except if china covered up that it was a lab leak for political reasons, one can argue the entire pandemic was their fault. Alas, the crime is covering it up, even if all the institutions set the safety standards. No different than any other crime. It’s like hiding a chemical fire when it’s burning down your neighbors house and then they throw water on it and make it worse.
replies(1): >>curati+oN
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12. guesst+19[view] [source] [discussion] 2021-05-07 06:35:56
>>inciam+S7
If the evidence is that overwhelming, then why are so few researchers saying so? I can understand things being extremely skewed at the political and policy level - that's expected - and I can understand the media being skewed because I'm familiar with that on other issues. But if your argument is right then this is also basically a total collapse of the scientific community. That's harder to swallow. From your comment I assume that you're either a biologist or trained as such, so I'd like to hear how you explain that.
replies(2): >>misja1+hd >>swader+je
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13. nl+j9[view] [source] [discussion] 2021-05-07 06:38:31
>>inciam+S7
> What is the probability of this pattern occuring in the case of a natural spillover? It's 1:atoms-in-the universe level.

This is untrue. I'd point to this quote:

“It’s pretty apparent that there’s this evolutionary arms race between the receptor binding domain and ACE2 that’s happening within the bats themselves,” says Tyler Starr, a postdoc in the lab of genome scientist Jesse Bloom at Fred Hutchinson Cancer Research Center. “Whatever it’s doing is ratcheting up this evolution and sometimes spitting out things that can bind potentially to many different ACE2s, including ours.”[1]

The unique thing about COVID is the transmission and the long incubation time.

There are plenty of naturally occurring mutations that have occurred that are more contagious than COVID (AIDS R0=~4.5, Ebola=~2.5 are two major ones that spring to mind). And SARS1 had a very similar binding behaviour, and the jumping behavior via civets is very similar to COVID.

[1] https://cen.acs.org/biological-chemistry/infectious-disease/...

replies(1): >>roca+W9
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14. roca+W9[view] [source] [discussion] 2021-05-07 06:45:18
>>nl+j9
If that's true, then there's a straightforward experiment that would boost confidence in the natural-origin theory: culture the earliest available SARS-CoV-2 virus, and see what it's good at infecting other than humans. Surely someone has done this?
replies(1): >>nl+jb
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15. flukus+8a[view] [source] [discussion] 2021-05-07 06:47:05
>>inciam+S7
> What this evidence shows is that is appeared already optimized.

There are plenty of viruses from animals known to infect humans, viruses that have never been in humans and are not evolved to infect them, this happens alarmingly regularly. Here's a couple you've probably never heard of: https://en.wikipedia.org/wiki/Australian_bat_lyssavirus , https://en.wikipedia.org/wiki/Hendra_virus

There is absolutely nothing amazing about covid being able to infect humans, it's exceptional because it can pass from human to human and because it's airborne(ish).

replies(1): >>eggie+ko
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16. nl+jb[view] [source] [discussion] 2021-05-07 06:57:22
>>roca+W9
Yeah, it's pretty good with Pangolin.

This is a good summary of the current consensus:

It is clear from our analysis that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. The unsampled diversity descended from the SARS-CoV-2/RaTG13 common ancestor forms a clade of bat sarbecoviruses with generalist properties—with respect to their ability to infect a range of mammalian cells—that facilitated its jump to humans and may do so again. Although the human ACE2-compatible RBD was very likely to have been present in a bat sarbecovirus lineage that ultimately led to SARS-CoV-2, this RBD sequence has hitherto been found in only a few pangolin viruses. Furthermore, the other key feature thought to be instrumental in the ability of SARS-CoV-2 to infect humans—a polybasic cleavage site insertion in the S protein—has not yet been seen in another close bat relative of the SARS-CoV-2 virus.

https://www.nature.com/articles/s41564-020-0771-4

replies(1): >>roca+Fe
17. BlueTe+Cb[view] [source] 2021-05-07 06:59:39
>>guesst+(OP)
I remember an article from about a decade ago where a virologist was saying that China shouldn't be trusted with the highest danger (lvl 4?) labs (IIRC at the time when Westerners were about to or starting to help them build them) because Western labs themselves could barely (or not) be trusted with something as dangerous, and (s)he expected the Chinese to not be able and/or not be willing to fully respect the procedures involved.

This article suggests that lvl2 protocols were indeed used for lvl4 biohazards.

replies(1): >>guesst+Ue
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18. rramad+gd[view] [source] [discussion] 2021-05-07 07:16:58
>>guesst+n2
Whether we like it or not, the narrative has already become about China. That is the reality. Geopolitics, Military brinkmanship, Economic realities all are at play here. In spite of all this muddying, our Scientists/Investigators need to work together to get at the truth. Else the Racists/Jingoists/Warmongers will paint a facade to further their nefarious agendas. Condoning it now will truly open the Pandora's box of "Biological Weapons".
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19. misja1+hd[view] [source] [discussion] 2021-05-07 07:17:05
>>guesst+19
You're a bit too trustful towards the flawless functioning of the scientific community. Scientists are humans and are prone the same group think errors like everyone else. Historical examples are plenty, e.g. Darwin was ridiculed by his peers about his theory of evolution, or the more recent erratic theory that coronary diseases are purely caused by eating too much fat and not by sugar.

In this case, as the article mentions, there was a conflict of interest as well that might well have motivated some leading scientists in the field to campaign against the theory that the Wuhan lab was the source of the outbreak.

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20. swader+je[view] [source] [discussion] 2021-05-07 07:25:41
>>guesst+19
Anyone versed well enough to call this man made likely has a lot of skin in the game and doesn't want to risk being ostracized and cast out. It would probably be a career limiting move.
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21. roca+Fe[view] [source] [discussion] 2021-05-07 07:30:02
>>nl+jb
This paper doesn't seem to have anything to do with the experiment I suggested.
replies(1): >>nl+Qi
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22. misja1+Re[view] [source] [discussion] 2021-05-07 07:32:34
>>guesst+n2
It's too late to keep politics out of this, politics were at the heart of this from the very start. Without politics the consequences of the outbreak would probably have been much less severe.

In the beginning of January 2020, president Trump was already informed by an advisor who had close contacts in Wuhan that the outbreak was much more severe than China made it look like. But he chose not to act on that, because the USA were in the middle of closing a trade deal with China. However later that month he changed his mind when the first infections in the USA happened, and later even more when a Chinese official came out with a theory that it might actually have been an USA sports team that visited Wuhan in late 2019 that was the source of the Corona outbreak (https://www.nytimes.com/2020/03/13/world/asia/coronavirus-ch...)

So this is not about 'people making this about China', it has been China from the start trying to cover this up and trying to make it about other countries. A more transparent Chinese policy would have given other countries the chance to react early and save thousands of lives.

replies(1): >>dirtyi+Bj
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23. guesst+Ue[view] [source] [discussion] 2021-05-07 07:32:45
>>BlueTe+Cb
Right, but the Western sponsors of the work would have been aware of this. This whole thing was a major dispute among virologists, major enough to end up in a NYT editorial. That makes the lab escape scenario an international failure, not a national one.
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24. nl+Qi[view] [source] [discussion] 2021-05-07 08:09:50
>>roca+Fe
a) There's no need for there to be an intermediary species. The "What is the probability of this pattern occuring in the case of a natural spillover? It's 1:atoms-in-the universe level" statement in the comment I replied to is just wrong - it's unusual, but nothing like as mind bogglingly impossibly rare are they claim.

b) Genetic analysis indicates that it most likely came from bats directly to humans, but picked up the ACE2 receptors from a Pangolin virus that was passed back to bats, evolved there and then infected humans. To quote the same nature article I lined above:

However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. 2, bottom) show that SARS-CoV-2 is unlikely to have acquired the variable loop from an ancestor of Pangolin-2019 because these two sequences are approximately 10–15% divergent throughout the entire S protein (excluding the N-terminal domain). It is RaTG13 that is more divergent in the variable-loop region (Extended Data Fig. 1) and thus likely to be the product of recombination, acquiring a divergent variable loop from a hitherto unsampled bat sarbecovirus28. This is notable because the variable-loop region contains the six key contact residues in the RBD that give SARS-CoV-2 its ACE2-binding specificity27,37. These residues are also in the Pangolin Guangdong 2019 sequence. The most parsimonious explanation for these shared ACE2-specific residues is that they were present in the common ancestors of SARS-CoV-2, RaTG13 and Pangolin Guangdong 2019, and were lost through recombination in the lineage leading to RaTG13. This provides compelling support for the SARS-CoV-2 lineage being the consequence of a direct or nearly-direct zoonotic jump from bats, because the key ACE2-binding residues were present in viruses circulating in bats.

and:

Although the human ACE2-compatible RBD was very likely to have been present in a bat sarbecovirus lineage that ultimately led to SARS-CoV-2, this RBD sequence has hitherto been found in only a few pangolin viruses.

https://www.nature.com/articles/s41564-020-0771-4

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25. dirtyi+Bj[view] [source] [discussion] 2021-05-07 08:17:53
>>misja1+Re
>So this is not about 'people making this about China', it has been China from the start

Military games / Fort Detrick vaping disease troll was in response to Tom Cotton and co. formally spewing lab leak theory. Note earlier date in Feb.

https://www.washingtonpost.com/politics/2020/02/16/tom-cotto...

US politicized first, when soft measures failed a month after warning Wuhan lockdown. There was ample warning, enough that many of PRC neighbors with high traffic contained well with at least some effort in coordination. PRC position up until then was let science figure it out, Wuhan was very covid19 was first discovered but doesn't mean originated there. The brief domestic deflection in early Feb was possible import from ASEAN. Even early PRC "dis"info campaigns emphasized harsh lockdown not lockdown skepticism. Countries that didn't take Wuhan lockdown seriously got burned. Queue west being prominent source of exporting covid world wide by taking lax measures. This is seen in import statistic of every country that rigorously tracked imported covid cases - PRC exported very little cases, and essentially none few weeks after lockdown. North America / Europe, magnitudes more.

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26. eggie+ko[view] [source] [discussion] 2021-05-07 09:06:16
>>flukus+8a
> There are plenty of viruses from animals known to infect humans

Yes, absolutely. AFAIK that's where almost all viruses that infect humans come from.

> it's exceptional because it can pass from human to human

With extremely high efficiency, from the first appearance of the virus! If it were not already optimal, then the initial transmission rate would have been lower, and the genome would have had to rapidly change in the process of surviving. This was seen with SARS1. It's seen with other epidemics. The fact that it isn't seen here is very, very weird. Why did SARS2 not have to adapt to its new host?

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27. XorNot+1t[view] [source] [discussion] 2021-05-07 09:59:48
>>inciam+S7
This is complete speculative junk.

> The virus entered humans with it's spike protein already fully adapted to the human ACE receptor protein.

1. Is a partially functional (still infectious) spike receptor protein possible? (you don't know, and present no evidence in this rant)

2. How do you know the virus shows "no accelerated evolution"...partially effective viruses would have a lower replication factor, and not become global pandemic, and would not spread far enough to preserved within the human population as anything of interest.

3. How do you know that a natural virus which was only partially effective at replication didn't in fact encounter favorable conditions when it encountered humans, having accidentally been better adapted for them?

> The fact that it doesn't mutate rapidly indicates it is near a strong local optimum.

4. How do you know that the spike protein - which is highly conserved amongst coronaviruses - can even have a range of mutations and still retain function (allowing viral entry to the cell for infectious purposes)? (you don't, research finds that the spike protein has suboptimal binding to ACE receptors - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239051/)

> This stands in intense contrast to every other zoonotic transfer we know of.

5. Does it? Because no research is proposing this. Research in fact finds that analysis of similar coronaviruses shows that the spike protein is likely the result of multiple recombinations between a few species (https://academic.oup.com/emph/article/2020/1/290/5956769).

> Do we have evidence? What is the probability of this pattern occuring in the case of a natural spillover?

6. Do you? Apparently not because there's not a single shred of peer reviewed research you care to link to support your position here, and you've done none of the legwork to support the logic part of your conclusions.

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28. yread+3t[view] [source] [discussion] 2021-05-07 10:00:35
>>inciam+S7
> The virus entered humans with it's spike protein already fully adapted to the human ACE receptor protein.

That's not really true. It was adapted to ACE but not perfectly. As the B117 shows it could do better. Coronaviruses mutate slowly and random mutation in the spike protein is a lot more likely to make non-functional than to improve it. It's good enough, not perfect. Evolution likes good enough.

EDIT: but you do raise a good point with how much better than the known coronaviruses' spikes it is. Perhaps there is another intermediate host with ACE2 closer to humans? Sars-Cov-2 infects pretty well lots of animals - almost all the cats, minks, ...

replies(1): >>triple+Gs2
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29. tomp+wt[view] [source] [discussion] 2021-05-07 10:06:46
>>inciam+S7
This sounds a plausible explanation, but I see one problem: there’s a big fear that the vaccines don’t work on the more infectious strains (South African, Brazilian, Indian, ...). Vaccines target the spike protein. So surely if the spike protein doesn’t evolve (and isn’t responsible for the increased virality of these strains), then the vaccines should still work against it?
replies(2): >>darker+eE >>fabbar+SG
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30. darker+eE[view] [source] [discussion] 2021-05-07 11:53:35
>>tomp+wt
Well, so far the vaccines do work against the variants
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31. fabbar+SG[view] [source] [discussion] 2021-05-07 12:14:17
>>tomp+wt
The vaccines do work on variants [0] with different degrees of efficacy. This actually demonstrates that the virus - after infecting millions of people over a year - hasn't significantly changed the spike protein.

Also: major changes in he spike protein could impact the ability of the virus to infect humans, so -- there is that.

[0] https://www.nejm.org/doi/10.1056/NEJMc2104974

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32. curati+oN[view] [source] [discussion] 2021-05-07 13:11:12
>>alexne+c8
What if America is covering up the leak? https://abcnews.go.com/Politics/trump-admin-pulls-nih-grant-...
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33. willma+zW[view] [source] [discussion] 2021-05-07 14:06:26
>>guesst+O5
Did you review the materials? There is hard science proving SARS-CoV-2 isn't zoonotic. It was gain of function research.
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34. mattm+D01[view] [source] [discussion] 2021-05-07 14:29:24
>>guesst+n2
Completely agree. Let's say that it was an accidental leak. If you imagine that you were the one that was involved in the leak, how likely is it that you would want be held accountable? There's such a strong motive here for a cover-up, if a leak is the real cause.

This isn't a China thing. It's a human thing. No one wants to be known as the person who destroyed the world like this.

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35. triple+Gs2[view] [source] [discussion] 2021-05-07 23:12:19
>>yread+3t
At least in silico, SARS-CoV-2 binds better to human ACE2 than for any other mammal tested. The only other animals in their "very high" category were primates with ACE2 very similar to human:

https://www.pnas.org/content/117/36/22311

Evolution doesn't require anything beyond "good enough", but it's surprising for a virus to be better-adapted to humans than to its animal hosts at the moment of its zoonotic jump--before the jump, where could that pressure come from? I don't think this is determinative, but it points weakly in favor of lab origin (e.g., from culture in human cells or in mice genetically engineered to express human ACE2).

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