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Comment by bayesian_horse | Hacker News Reader

You don't understand biology. It is possible to date the divergence of genomes using a genetic clock. So they know if those spike proteins had been recombinated.

Serial passage in mice can't be ruled out but is quite out there. Lots of theories can't be completely ruled out, but wild speculation like that is not very productive.

For the lab-leak theory to be true, a "pandemicable" zoonotic virus (a VERY rare thing) has to somehow make it into a lab undetected. Additionally and alternatively scientists have to undergo something like this "serial mice passage". Which is not proven that it could work. And then they would need to somehow let the virus escape through an accident even though they knew it could be dangerous. And it would have to accidentally be able to infect Humans extremely well (which is a tall ask still). It's just... highly improbable.

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> For the lab-leak theory to be true, a "pandemicable" zoonotic virus (a VERY rare thing) has to somehow make it into a lab undetected.

That's not a necessary condition and it's ridiculous to think that's the only hinge by which the hypothesis stands. Another far more plausible idea is that a mistake occurred somewhere and it was covered up. This has occurred before in authoritarian regimes before.

An input to a molecular clock is a mutation rate, which I imagine would be hard to quantify given the unknown source and the possibility of gain of function research.

Of course it is a necessary condition. In order to leak from the lab, the virus has to be collected and be propagated in the lab. And all the rest isn't plausible if they knew the bat virus they had in their vials had the potential to cause a pandemic. But it must have had some rare "talent" that was as yet undiscovered. Otherwise nothing of the "lab leak" hypothesis makes sense. You can't "gain-of-function" just any virus and end up with a killer pandemic.

You can interpret a molecular clock or a phylogenetic tree qualitatively, and you would expect to see multiple samples with the protein in question, but which have individually acquired so many mutations that they must have diverged before the dynamic. That would mean the protein sequence in question predates the pandemic by a long shot, unless you think the Wuhan lab tested the Virus in Laos...

I guess the disagreement is around the word "undetected". It's possible some failure was covered up and I trust the Chinese government to be capable enough to do that.

> virus has to be collected and be propagated in the lab

That's a weaker statement than the one I replied to. I'm referring to the how it's necessary that it needs to a "pandemicable" virus that enters a lab "undetected" and I guess leaves the lab "undetected". There's several possible ways the virus could have made it into Wuhan:

- Improper handling occurs somewhere in transporting the samples from bat caves (w/e) to the lab.

- Improper handling of samples in the lab.

- Improper disposal of samples in the lab.

- Entering a more speculative area; bat samples are used in experiments and improper handling or disposal occurs.

- Deeper into speculation: Improper handling/disposal of viruses used in gain of function research.

And when any of the above occurs, use the state's staggering power to cover it up.

> You can interpret a molecular clock or a phylogenetic tree qualitatively

I'm sure that could work but I imagine the error bars are quite wide as otherwise that's definitive proof and we wouldn't be discussing this online.

> unless you think the Wuhan lab tested the Virus in Laos

Nice attempt at absurd rhetoric. Strengthens the argument doesn't it?

The whole point is that the virus that was collected would already need to have some properties that predispose it to become a dangerous pandemic. Which is unlikely because those Viruses are pretty rare.

And the rest of your comment just tells me you know nothing about biology.

So the crux of your argument is that it's more likely that a virus with that type of predisposition occured in nature in a specific area around the Wuhan market as opposed to being sampled from one of many areas, potentially modified, and then leaked into said area? Seems unlikely considering the rarity as you pointed out.

>And the rest of your comment just tells me you know nothing about biology.

No need to resort to ad-hominems ; all it achieves is tainting your future responses on the topic with a lingering question of whether they are being made in good faith.

It's not ad-hominem if it's true. I really don't have the energy to debunk every "argument" that is borne out of misunderstandings about basic biology.

The alternative hypothesis is not that a very dangerous zoonotic virus emerges in a specific area around Wuhan (which also isn't really the agreed upon origin anyway), but rather that it emerges anywhere and causes a pandemic. Your argument here is a basic misunderstanding about how random processes work. Our observation that Wuhan was the first epicenter of this pandemic already preconditions us to assume a pandemic-capable Virus emerged there in some form or another.

Such viruses are indeed rarities. But they exist and every once in a while they come into contact with Humans and cause a pandemic. However this is not the same likelihood as with the lab leak hypothesis, because collecting viruses for labs is an event that happens multiple orders of magnitude less often than contacts between animals and Humans. So while it is a rare coincidence that a lab would collect a killer virus when randomly collecting bat viruses, it is not so strange that every once in a while a novel pandemic virus makes the jump from animals to Humans somewhere in the world.

Non sequitor. That's not the statement I'm referring to. It's certainly the case a virus emerged from nature with all or most of the properties we saw in the original. Unless it was engineered in Loas lol

Good job defending your point. If the error bars weren't so wide on the biological clock idea why we would we be having this discussion? Does the west supress that, and you're one of the few smart ones who have the truth?

Wait, wait...does this whole debate hinge around the idea that you think the WIV staff are reliable, honest agents? The very idea is hilarious. They operate within an authoritarian regime that restricts their freedom of speech and makes threats against them and their families for non-compliance. It is irrational to trust anything they report as being true.

It's even more irrational to just assume the opposite or whatever you want to be true.

Well, that's an interesting question. If the public health dept wants to inspect a restaurant to make sure its hygiene standards are adequate, and the restaurant goes out of its way to try to delay or block such an inspection, should we lean towards: a) The restaurant has something to hide and is therefore likely to have poor standards or b) It is irrational to hold ANY position on the hygiene standards of the restaurant, given the lack of dispositive data

I completely reject he analogy between health inspections of a restaurant and blaming a country for a pandemic using a highly speculative theory. It feels so ridiculous I don't know where to start.

> covered up. This has occurred before in authoritarian regimes before.

To be fair, cover ups aren't exclusive to authoritarian regimes.

Futhermore, in this case, The West seems to be willingly and shamelessly towing the Communist Party line. Can we add conspiracy to the smell being given off?

Science should be obcessed with truth. Geez. Looks like science isn't immune to cover ups and conspiracy either.

"What is the source?" will take a place next to "Who killed JFK?".

p.s. Slightly off topic, but off the media sources mentioned (e.g., CNN) how much of their revenue comes from Big Pharma or Big X that wouldn't fare well if lab leak could be supported?

You know we know exactly who killed JFK and it's not controversial by anyone who seriously looks into it right?

You missed the point. It not about what you think you know. It's about what everyone else believes.

Truth is a function of trust.

That's worth repeating: Truth is a function of trust.

Given the actions of all the Covid-related actors, only a fool would be rolling out the trust red carpet.

You know we know this, right?

JFK was an obvious government coverup not sure why you would choose to group the two.

Obvious?

I like that the two sibling comments above are "Obviously, everyone knows {polar opposites}."

To be totally honest I don't even believe in my comment but it felt like the right retort, I have literally know clue what OP is saying. Can you flag balderdash?

Magic Bullet Theory was an obvious consequence of a coverup at multiple levels, which most elementary school children understand.

I truly didn't think this was controversial. I would suggest talking to some pre->highschool kids shrug

> "pandemicable" zoonotic virus (a VERY rare thing) has to somehow make it into a lab undetected.

This is the opposite of what I understood the lab-leak theory to be: that an initially-zoonotic virus was identified and bred in a lab until someone working at that lab with lax security standards accidentally brought it out of the quarantine. This is plausible at face value.

I think a lot of the really extreme vitriolic reactions to lab-leak theory are conflating it with the accusations that a secret cabal purposefully engineered and released this virus to sow harm and discord. But that's not at all the connotation of "leak" IMO -- leak implies a lack of intention.

There's a spectrum... The zoonotic virus would need to have some rare "talent" to start with. Then there is the ominous "breeding" part, which many people describe as reckless or evil. In any case this isn't done in Humans but rather some kind of humanized model (and it's not clear that could work at all). Which is why it is quite a coincidence or accident that this process would end with a virus so well adapted to Humans that it is able to cause a pandemic. It's like winning a chess tournament after training for a Marathon.

It's only plausible if you know very little about biology. Very few people who know a lot about viruses believe that this is possible and even those usually say the zoonosis hypothesis is more likely.

> It's only plausible if you know very little about biology.

Not trolling, series question: what would these same ppl say about the monkey pox outbreaks? Why now? Why so random?

As far as I know the experts say they don't know all that much. Also the awareness of such issues has shifted a lot...

> Gain-of-function research is medical research that genetically alters an organism in a way that may enhance the biological functions of gene products. This may include an altered pathogenesis, transmissibility, or host range.

Isn't the goal to end up with an infectious agent? I don't understand why it seems so implausible that they would succeed? Why would someone give a lab money for a truly impossible task?

A virus that is optimized for mice or bats doesn't normally work well in Humans. If a bat virus somehow evolves in a lab into a pandemic in Humans, without essentially breeding the virus in Human subjects, that would be somewhat of an accidental development because the viral particles aren't specifically selected for that reason.

Something tells me those scientists were more interested in the effects on humans than on mice, and do their best to modify their analogues (ie "humanize" them) to achieve comparable results.

Something tells me you know virtually nothing about biology, medicine or the experiments involved.

It's really not that simple.

What does "date divergence of genomes using a genetic clock"? I am curious to learn about such a tecnology. If you mean https://en.wikipedia.org/wiki/Molecular_clock that is highly non-quantitative.

It is quite quantitative, just not very precise. Good enough to tell you if a Virus emerged more than a couple of years ago or not.

Can you give me a link to a good example of that (ideally, non-covid)? my understanding is that it's only good for relative rates over evolutionary time so I'd like to see a counterexample.

It's a completely common technique - the same way we're tracing the current Monkeypox outbreak.

https://www.ecdc.europa.eu/en/news-events/epidemiological-up...

And is useful from an anthropological perspective on older outbreaks, also for Monkeypox;

https://www.nature.com/articles/s41598-021-92315-8

The rate of mutations, especially for a virus as transmissible as Covid is a very strong signal.

Thanks- personally, based on my experience in functional genomics, they have far too many assumptions to be trusted as "clocks", even relative ones.

Here's the second paper's methods: a molecular clock signal was estimated on the ML tree using TempEst v1.532. BEAST v1.10.433 was used for Bayesian MCMC analysis to estimate temporal nodes. As recommended in Patrono et al., we selected the simplest model: strict clock and constant population size with a HKY substitution model and four Gamma categories7. An MCMC model was run with 50,000,000 generations and a burn-in of 25,000 sampled trees. All other parameters were by default. BEAST executions were completed checking chain convergence and sufficient sampling of the posterior space (ESS > 200) with Tracer v1.7.1. The final chronogram was generated using TreeAnnotator v1.10.433.

I'd call these "time-scaled trees", not molecular clocks.

Their accuracy is completely subject to stable mutation rate and frequency of sample -- with that second paper, they were working with ~10 samples from 15 years ago vs. thousands of samples with hourly granularity and entirely traceable transmission chains in the early days of Covid. Completely different capabilities arise with Covid-level specificity.

Thanks, I'll have to give this some deep thought, it's news to me that having that much more data gives you high resolution in real time.

It's more a matter of decreasing the error bars on the rate of substitution, to have extremely specific dates for the oldest infections in each clade and the ability to run real-time backtesting to make sure your assumptions are solid. The rate of spread of Covid was a curse but was important to this type of work -- when we were looking at contact tracing and trying to assess the rate of substitution on mutations, it was useful to know that e.g. on Jan 1st there was no Covid in NYC and on Feb 1st there was.

My point is that if you find multiple samples with the same protein sequence, and those samples have independently diverged, you can easily assume those viruses did not originate by recombination from the Wuhan strain.

> has to somehow make it into a lab undetected

Undetected? The lab was specifically searching for and storing pandemic-capable viruses, and had applied for grant money to insert furin cleavage sites into them!

Nope. It was looking for bat viruses. There is no way to tell if such a virus is even able to infect Humans, without testing it out on Humans.

The grant application is not proof that they either performed such experiments at all, that they did it on that particular virus nor that it worked. And there's still a long distance between a random bat virus with a "furin cleavage site" and something that is good at infecting Humans. All this theory is so far is wild speculation.

Less probable than such a coronavirus originating in Wuhan of all places?

The WIV was in Wuhan due to the proximity of coronaviruses and other bat-borne diseases like rhabdovirusus.. this line of logic is akin to blaming shark research centers in South Africa for nearby attacks.

I don't think so? The bats are generally from Southern China, Laos, Cambodia, ..

Nowhere near Wuhan.

There are tons of horseshoe bats in Hubei, that particular misunderstanding needs to go away.

Too late to edit, but here's an article from 2018 following a group of scientists into a cave 60 miles from Wuhan to study horseshoe bats:

https://www.sixthtone.com/news/1002326/how-chinas-bat-caves-...

Unfortunately for us, tons of bats carry viruses of all types and some of them are literally found on the campus of the WIV:

18.5% of Japanese housebats sampled in one study had beta coronaviruses: https://pbs.twimg.com/media/FQ9ScdVXsAIZntp?format=png&name=...

Those bats are regularly collected for study at the same academic complex that hosts the WIV:

https://pbs.twimg.com/media/FQ9U624XoAAvQol?format=png&name=...

There are bats almost everywhere in the world, including Wuhan. The question isn't bats, but bats carrying sarbecoviruses related to SARS-CoV-2, not just betacoronaviruses. Dr. Shi herself has stated that she didn't expect such bats anywhere near Wuhan:

> We have done bat virus surveillance in Hubei Province for many years, but have not found that bats in Wuhan or even the wider Hubei Province carry any coronaviruses that are closely related to SARS-CoV-2. I don't think the spillover from bats to humans occurred in Wuhan or in Hubei Province.

https://web.archive.org/web/20201206204844/https://www.scien...

I've responded to you with this link before, and you didn't reply. It begins to feel like you are willfully disregarding all evidence contrary to your predetermined view, which is unfortunate.

The WIV was not set up in Wuhan to study bats in Hubei. That is a total misconception. It was set up in 1956 with no connection whatsoever to bat-borne sarbecoviruses. That specialization arose later, but studies were made principally in Yunnan province. There is no connection between the bat specialization of the WIV and its location in Hubei.

It was not. This is a widespread misconception. The local bat populations in Wuhan were negligible and their viruses were not being studied. Indeed, the local human population in Wuhan was used as a control in the WIV's studies because of their lack of any significant encounters with bats and their diseases.

Shi Zhengli, the "bat woman" who conducted most of her research 1000 miles south, in Yunnan province, had this immediate reaction to an epidemic of bat-borne sarbecoviruses starting in Wuhan: “I wondered if the municipal health authority got it wrong. I had never expected this kind of thing to happen in Wuhan, in central China.”

Her first panicked thought was that the outbreak might have started as a leak from her lab. Which is kind of curious, don't you think? She reported being relieved later when she found no evidence of this, but...why was that her initial thought?

There is no proof that the Virus was passed directly from bats. And as far as I recall there was evidence for at least one intermediate host. Which makes the bat-hunting rather pointless.

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