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Comment by karpierz | Hacker News Reader

Is there a way to disprove the lab leak hypothesis?

Yes, clear animal reservoirs, viral lineage, old samples from human or animal infections with precursor variants. No position on the question, just answering your question about proof.

That would only disprove the genetic manipulation part, but not necessarily lab leak. A WIV lab staff can easily contract virus from a bat inside the lab. This essentially what happened in Taiwan, where a lab staff got infected with COVID from a mouse [1]. To disprove lab leak you also have to show either 1. WIV or any other labs in Wuhan didn't have any virus samples that can be an ancestor of SARS-CoV2 2. we can establish a very clear and well understood route how the ancestor of SARS-CoV2 arrived at Wuhan from Yunan province, where the horseshoe bats live, including how it became so good at infecting humans in a very short period of time.

[1] https://fortune.com/2021/12/10/taiwan-investigates-covid-lab...

With SARS original they found the source as infected animals at a local food market. Something like that would pretty much disprove a lab leak as the source as it did that time.

If a virus essentially identical to the original wild type SARS-CoV-2 is found in a wild animal population that would be fairly strong evidence against the lab leak hypothesis, although not an absolute disproof. Researchers have looked and not found such, so it remains an open question.

So far the closest we've come is a bat virus in Laos but it has some significant genetic differences.

https://www.nature.com/articles/d41586-021-02596-2

Also Ecohealth Alliance and WIV collected viruses in Laos. So in terms of natural origin vs. lab leak the viruses found in Laos don't increase probability on either side.

Couldn’t someone just inject the original virus into a nearby animal population and say ‘look what we found!’ ?

I'm not a biologist but I believe it should be repeatable, i.e. the animal should be able to pass it on in lab.

Non-human animal-to-animal transmission has been observed, like on Danish mink farms. But you can sequence the virus from many human and non-human infections and build a phylogenetic tree from the sequences, knowing that each variant should have all the mutations of its ancestor plus maybe some new ones. In such a tree, the proximal zoonotic host should have infections with no human-infection ancestor. This was observed for the original SARS (palm civets) and MERS (camels), each within about a year. For SARS-CoV-2, we're still waiting.

No. The only way to disprove lab leak theory is for the CCP to disclose the WIV databases and records of what they were studying. Otherwise, just because it was found in some animal doesn’t quite disprove it. WIV was actively collecting virus samples from mammals for research funded by the US tax payer money through Eco Health Alliance.

If you are inclined to think the CCP knows / is covering up a lab leak; you are also inclined to think that they'd release fake disclosure data to cover it up.

I prefer an independent third party audit.

Faking data is much harder: it’s easy to forget to remove something, change numbers so they don’t match other numbers, or make up numbers which have the statistical signal of manufactured data. Even being a great power does not prevent these kind of mistakes, because of the skill level censors would need in multiple scientific fields to make a good forgery. People get away with it in minor papers in the social sciences all the time, but with a million eyes on the data sets in this case, someone’s gonna see it.

They wouldn't have to actually fake scientific data - they'd just release everything else they were working on, omit the problematic files, and go "see? we showed you everything - there's nothing to see here!".

Time tables, budgets, staffing docs, those are readily forgeable. Any leftover discrepancies can be chocked up to clerical error. This is doubly so if the problematic research was classified or compartmentalized - files pertaining to those programs are often designed to be easily expunged.

Ultimately, China could release as many files as people ask, and never be able to settle the debate. You can't prove/disprove the existence of files they claim do not exist.

Our best bet would be whistleblowers - ideally multiple trusted and independent ones - who can testify to a hidden program. However, we can't use the lack of whistleblowers to prove the lack of a program, which is where we're stuck today.

Well, who says they haven't tried to do that. The 2013 Mojiang mining incident was claimed to be a fungal infection, while it was later proven it was a viral infection.

The Mojiang mine viral outbreak actually occurred in 2012.

https://www.reuters.com/business/healthcare-pharmaceuticals/...

To whose satisfaction? Scientifically? It seems possible if the evidence still exists or could be found, based on a few of the other comments here. Politically? The faction that will never be satisfied, parted company with the scientific community, before the pandemic was even on the horizon.

As a scientist, I would have been OK with learning about the hypothesis from a credible source and letting it play out. I would have been OK with letting the public know about it. However, realistically, good faith investigation of the hypothesis would have been utterly drowned out by hysterically amplified versions of the same hypothesis that were already in circulation.

Let me respond to this question with another question. Can you disprove the existence of space aliens? No, you cannot, because they are statistically possible. Are they plausible? That isn't what is being asked here, the plausibility, just whether something is possible.

Yes - an animal host or reservoir is found. It's unusual after 2 years none has been found.

There are many animal hosts or reservoirs. The issue is that it's not obvious wether they got it from or gave it to humans. You really need the most direct ancestor virus.

AFAIK the known animal reservoirs got it from humans. Do you know any animal reservoir that we still don't know how the animals have got it?

We don't, and that's the issue, we can't know unless we find an ancestor virus. It's also very possible if could have wiped out the original virus in all original reservoirs. It's very difficult to do this now and for endemic viruses in general, and it took a very very long time to do for SARS where this wasn't a problem.

I thought they thought it might be pangolins? https://pubmed.ncbi.nlm.nih.gov/32380510/

Yeah, that's a theory, but I don't think it's settled yet

That is a very old article in pandemic research time. Pagolins aren't thought to be the likely intermediate animal any more.

A quick reminder of what scientists said in early 2020:

https://www.theguardian.com/world/2020/apr/28/how-did-the-co...

> “we really don’t know” how accurate the origin story is, she says: “There’s some sort of connection [to the Wuhan market] and there were people exposed to the market that were infected.”

> Baker says what is “very likely” is that the virus originated in a bat. “It’s a likely scenario but we will never know. The market was cleaned up quite quickly. We can only speculate.”

> “These wet markets have been identified as an issue because you do have species interacting,” she says. “It’s an opportunity to highlight the dangers of them and an opportunity to clamp down on them.”

> Turner adds: “We’ve found the ancestors of the virus, but having broader knowledge of the coronavirus in other species might give us a hint about the evolution of this thing and how it jumped.”

There has been other wet market origin stories as well, so I think absent other evidence it seemed like the Occam’s razor answer.

Turned out that it's basically impossible to test just us 7.something billion humans.

No one is out there testing a billion bats (or many more billions of mice and what not). Animal patient 0 is probably dead already anyway?

Good luck with that search.

We still aren't 100% sure about Ebola's reservoir, so that isn't necessarily a smoking gun.

Ebola didn't break out in a modern city of 10m + people.

The progenitor of the SARS-1 outbreak in 2003 wasn't found until a decade later in 2013.

There's a lot of research which is getting closer:

https://www.researchsquare.com/article/rs-871965/v1

https://www.nature.com/articles/s41467-021-21240-1

https://www.frontiersin.org/articles/10.3389/fmicb.2020.5847...

https://www.biorxiv.org/content/10.1101/2021.01.26.428212v1

https://www.sciencedirect.com/science/article/pii/S187350612...

https://www.researchsquare.com/article/rs-885194/v1

https://www.adn.com/nation-world/2021/10/11/in-search-for-co...

The immediate source - palm civets at a local market was found almost as soon as they looked, about four months after the outbreak. Tracing back where they got it from took longer.

After the discovery of WIV1 in bats it was found that it efficiently infected human airway epithelial cells, and since the palm civets were never linked to any outbreaks it is possible that the virus had directly hopped to humans from bats and that the palm civets were unnecessary as an intermediate species. It was also later found that it infects racoon dogs, ferret badgers and domestic cats. There was never any conclusive proof that raccoon dogs were responsible/required and that now looks unnecessary, which is a good example of how over a decade later what we think we know can change.

I believe that:

1. The closest known animal viruses to human SARS-1 were found in civet cats in 2003, within about a year of the first discovery of the virus in humans.

2. No animal viruses closer to SARS-1 have since been discovered. Dr. Shi discovered various viruses in bats that we believe are ancestral to SARS-1, including WIV-1 in 2013. This is significant because we believe SARS-1 evolved primarily in bats, but those viruses have lower genetic identity with SARS-1 than does the virus found in the civets.

If you disagree, please link a paper.

Based on the above, I don't understand why you'd think 2013 is the important date. Within about a year of the emergence of both of the previous two novel coronaviruses in humans (SARS-1 and MERS), a near-identical virus was discovered in animals (civets and camels). This is suggestive but not conclusive evidence that those animals first infected humans, and strong evidence that those viruses existed in nature--somewhere, even if not exclusively in those animals--before they emerged in humans.

For SARS-CoV-2, no such evidence has yet been found. This doesn't prove that SARS-CoV-2 is of unnatural origin, and I assume you'll mention the uncertainty in Ebola's zoonotic hosts shortly; but I don't see how anyone could treat that as irrelevant, except out of willful blindness.

Discovery of WIV1:

[Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389864/)

WIV1 grows in primary human airway epithelial cell cultures:

[SARS-like WIV1-CoV poised for human emergence](https://www.pnas.org/content/113/11/3048)

> Together, the data demonstrate that the WIV1-CoV spike can mediate infection of human airway cultures with no significant adaptation required.

And thanks for putting words in my mouth but no, I'm not confusing those with MERS.

I didn't mean to suggest that you were confusing anything with MERS. I just brought MERS up to show that not only had we found an animal infected with SARS-1 within about a year of its emergence in humans, but we'd also found such an animal for MERS, on a similar timescale. This means that SARS-CoV-2 is the 1/3 for which we haven't, not impossible just by chance but slightly more surprising than just 1/2.

And yeah, you'd mentioned WIV-1 above, and I'd assumed that's what you meant from the 2013 date. I noted this in point (2) of my grandparent comment. I just don't understand why you think that's more significant than finding the near-identical virus in civets. The SARS-1 civets might not have first transmitted SARS-1 to humans, but the WIV-1 bats definitely didn't--they're very different viruses, and while WIV-1 might indeed be able to infect humans it's definitely not what caused the actual outbreak. So why pick 2013 and not 2003?

We have no proof that civets gave us SARS-1 and not the other way around.

Since it was also found in raccoon dogs, ferret badgers and domestic cats which one of those was the actual intermediate animal? Civets were just the first identified. Either one of them gave it to us and we gave it to the other three, or possibly we got it from bats and gave it to all four. AFAIK there's no conclusive phylogenetic analysis establishing which species got it from whom.

MERS is much more obvious what happened.

I think you're strictly right there. If they'd obtained sequences then they could have built that tree; but as far as I know they didn't, perhaps because the cost of sequencing was higher back then. That's still more evidence than we have for SARS-CoV-2, though.

With SARS-1 we had the additional evidence that some wildlife traders had antibodies, presumably from mild infections by related viruses in the animals they handled. There's again no genomic evidence to exclude "reverse zoonosis" there, but the timing seems to make that pretty unlikely.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140695/

An animal sample from the wet market that was shut down. (I spooned they were all bagged).

If they were all destroyed, then go get a sample from their natural reservoir (wherever those animals came from)

Disprove it? No. We do innocent until proven guilty in our jurisprudence.

This isn't a US legal case; it's a scientific inquiry. Either lab leak or zoonosis is plausible, so you can't say one isn't the default until the other is proven. You don't flip a coin and say "heads until proven tails".

This seems like the misuse of impressive sounding words. The hypothesis has nothing to do with US law. It’s a question of whether there is sufficient empirical evidence in support of the prevailing hypothesis, that the virus originated from a market in Wuhan.

No, there isn't especially after 2 years. This does not however mean that in the absence of wet market evidence that the only possible answer is lab leak.

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