Live data from Hacker News

Lab Leak 2.0?

bprice.substack.com

281–290 of 319 posts

Re: Lab Leak 2.0?

#281
post #9

All of the GoF research procedures I've read stress natural evolution, but still rely on random mutations at the end of the day, which would still leave you with a natural looking count of silent mutations in the general case. As a GoF researcher you don't want to cull 'silent' mutations because those are a major source of building blocks for useful mutations.

Damn this is the first comment contrarian to the article that acually addresses the main argument : Silent vs non-silent mutations ratio. The article pretty much convinced me and I am not sure I am really unconvinced yet but I have to thank you.

It's also much more complicated to define "silent" in the context of a virus. In a larger-genomed organism there is a relatively clear (though still not completely clear) function of a coding region, where the change of a nucleic acid will have no effect on the protein made - but still might (subtly) effect regulation in some way.

In a virus, most nucleic acids have multiple, layered, and unknown functions - it's much much harder to assign any given nucleic acid as "silent", and be confident that that is the case from an evolutionary perspective.

As another posted, it's a good hypothesis that's straightforward to test statistically against all of the other variants. But on its own, it's not necessarily convincing here that the S/NS ratio is particularly concerning (and as above, doesn't speak to how directed evolution works either).

Re: Lab Leak 2.0?

#282
post #188

Earlier quoted context omitted.

"For example, we know that the delta variant of SARS-CoV-2 leaked out of a lab in Taiwan in late 2021." - is exactly (mechanically) true in that Delta did leak out of a lab in Taiwan in late 2021. This statement does not declare that Delta’s origins were a lab leak, since late 2021 is a year after Delta was first detected in late 2020. Can’t have your origins in the future until time travel is invented. Seems therefo…

Can you explain the Delta variant lab leak theory for those of us who aren't caught up on conspiracy theories?

I don’t know the details of the Delta conspiracy theory, but the evolution of Delta looks abundantly natural, so whatever that theory is, seems unlikely.

Re: Lab Leak 2.0?

#283
It repeatedly asserts that immunocompromised patients cannot have antibodies ("weirdness" 3 & 4), but, immunocompromization is a spectrum. Many people can produce antibodies but not as many as normal.

If the piece hinges on getting this pretty basic element wrong, how wrong is it about some of the more sophisticated analyses?

Re: Lab Leak 2.0?

#284

Earlier quoted context omitted.

I had the same reaction. Those articles don’t back up that claim one bit. And I cant make sense of the timings of the events described in those articles either and how that would line up with a supposed lab leak of delta. Some of the other points made in this article were mildly compelling to me (though I don’t know enough on this topic to be able to poke holes) but that delta claim and lack of convincing data to bac…

You misread because of a poorly worded sentence. She does not claim Delta's origin was a lab leak at all but that there has been a lab leak. Instead she implicitly compares Omicron and Delta showing that Delta did evolved naturally whereas it is unlikely of Omicron.

Which is funny because Delta's NS:S ratio is also very high. So by her own logic, the NS:S ratio -- what you called her "main" argument in the other thread -- has no predictive value whatsoever for the natural vs lab leak question.

Re: Lab Leak 2.0?

#285
post #218

Earlier quoted context omitted.

What do you think of this suggestion that labs in southern Africa are not the only relevant ones? > Omicron COVID was in Italy as early as 2021-10-13 – 7 weeks before alarm from South Africa. > per upthread, Italy also where SARS-CoV2 immune-escape gain-of-function variants bred, since 2020, in less-than-max-biosecurity labs. https://twitter.com/gojomo/status/1473471612112441344 (IANA biologist)

First detection is an indicator of that, when it was first detected, not a guarantee that it was first there. Only a very small fraction of RT-PCR positive samples are sent for sequencing under normal conditions. > Omicron COVID was in Italy as early as 2021-10-13 – 7 weeks before alarm from South Africa. 7 weeks before the alarm, but only 10 days before in retrospective sampling, and even less in other places in Afr…

But Italy, hit extremely hard by early waves, and now with a much-higher vax rate than South Africa, could more easily miss a rising wave of mild cases in already-immune that don't seek treatment. There are plenty of factors in all directions, and only very spotty variant surveillance most places.

Re: Lab Leak 2.0?

#286

Earlier quoted context omitted.

All I'm saying is that my bias is towards this virus being a natural phenomenon and I think waiting for the full context will settle the case. Jumping to conclusions on the basis of flimsy evidence mainly serves political agendas. We simply will not know for a long time, months or years, where Omicron came from and that's uncomfortable, but we have to sit with that. If you DO want to get conspiratorial, you can watch…

I don’t understand how natural origin is your “bias” while everyone else is “jumping to conclusions”. There’s a lack of conclusive evidence for either scenario. And politics aside, SARS has leaked before resulting in deaths… no conspiracy required!

That's true Delta leaked in Taiwan, but that was a preexisting natural strain. Smallpox's last fatality also was a lab leak. However, most gain of function experiments use test harasses that can't infect humans or can't replicate. It's not impossible, but it's hard to have any conclusion at all at this early date with very little evidence.

The virus is infecting so many people and changes so rapidly that a natural explanation will not be surprising in the least. New variants have been expected. I think people are surprised at how bad the new variants have been, but anyone following the scientific literature wouldn't be taken completely off guard.

Re: Lab Leak 2.0?

#287

Earlier quoted context omitted.

You might find the work of David Gelernter (computer scientist) interesting. He's not a creationist, but he has abandoned the theory of evolution. > Suppose, then, that every bacterium that has ever lived contributes one mutation before its demise to the history of life. This is a generous assumption; most bacteria pass on their genetic information unchanged, unmutated. Mutations are the exception. In any case, there…

This is Intelligent Design dressed up in hand wavy math that builds on misrepresentation of cited studies and the fossil record. Read with a strong dose of skepticism.

The book is about Intelligent Design, but the reviewer (Gelernter) as far as I understand is only claiming that the theory of evolution doesn't hold. He is neither a creationist or proponent of ID

Re: Lab Leak 2.0?

#288
post #37

This is Alina Chan, one of the co-authors of Viral: The Search for the Origin of Covid-19. In defense of a natural origin of Omicron, this study describes the remarkable evolution of SARS-CoV-2 during convalescent plasma treatment of an immunosuppressed patient for 3-4 months; the mutations also reduced sensitivity to neutralizing antibodies: https://www.nature.com/articles/s41586-021-03291-y We know that there is a…

What makes you think omicron started in Africa? There is no proof of this at all.

Re: Lab Leak 2.0?

#289
post #279
post #264

Earlier quoted context omitted.

No, I'm not doing that. We might not yet have sampled the intermediate steps, if they exist, but it's inevitable that we will do so if it has a natural origin. Given the phylogenetic distance between the omicron cluster and its root in the phylogenetic tree, there should be several hundred to thousand intermediates if it's naturally occurring, of which we should be sampling many dozens (modulo selective pressure and…

Why should it be inevitable? How long do non dominant variants survive inside and outside a host? We don't even know in which country omicron originated even less who was patient zero. We could easily miss whole strains of the virus but because non of them lead to a new dominant variant we never know the even existed.

It's inevitable because even though one variant may become dominant, there will still be isolated pockets of the other variants. It's very unlikely that these variants will be entirely eliminated across the whole globe. Look at the epidemiology of HIV and the spatial distribution of variants as a point of comparison. Likewise for other viruses. Even if these other variants continue to evolve from the initial root, they will still be phylogenetically distinct from the current omicron clustering, somewhere intermediate between the root and existing omicron cluster. If it's out there in the wild, it will be picked up by PCR eventually. If it's not out in the wild, that big gap will remain, and a lab somewhere has questions to answer...

The starting point for the omicron cluster would be an interesting bit of information, but it doesn't necessarily have any bearing on where the intermediate strains are located. But none of that matters. If it's out there, it will eventually be picked up by PCR. We can use phylogenetic analysis to retrospectively reconstruct the evolutionary tree of every organism we have sequenced to date. Doing it just for the coronavirus variants is not hard (I have done it in the past including bootstrapping). Whether it's a month, a year or a decade from now, we will be able to answer the question by reconstructing the tree.

This is really basic bioinformatic analysis, in routine use for over two decades. None of this stuff is remotely new or groundbreaking.

The other questions you are asking are not really relevant to the problem. The virus does not survive long outside a host; it has no bearing upon the problem at all. The same applies to inside the host. All variants will continue to infect and propagate themselves to varying degrees within the host populations. It's endemic at this point.

One other point to bear in mind is that the mutation rate of the polymerase is effectively a constant, in terms of mutations per n kilobases. So we would expect all variants to accumulate a certain number of mutations averaged over time--the sequence will not remain static since the virus has to continually be passaged through mammalian epithelial cells to maintain and propagate itself. There will be some variation, but if it's been frozen down and manually propagated, it may have a dramatically different number of mutations compared with the other contemporary strains that have spent most of their time in living hosts.

Re: Lab Leak 2.0?

#290
post #66

Earlier quoted context omitted.

It links to a column on the Science website, and only to take a picture from it. The blog post doesn't discuss the scientific article that picture originally comes from or even he column that they link to. It uses the picture to say "omicron is weird" and jumps straight to speculation from twitter. As for the news article from the Taiwan Times, it has nothing to do with omicron which is the main topic at hand.

If we don't know the answer, are all hypotheses "speculation" What is the differentiator?

It depends on what kind of media we're talking about.

A scientific article about the origin of omicron would be expected to provide citations and evidence behind everything it says. It would also be expected to discuss all the leading theories, as well as what additional information we need to figure out which theory is the one most likely to be correct.

A news article from a journalist might interview the experts to get their opinion and summarize the scientific consensus to the general public. Ideally it should also allow an interested reader to identify what scientific publications the news is talking about, should the reader desire to find more info.

This blog post is none of that. It ignores the leading theories in order to paint a biased picture that only a lab leak is possible. Their main "evidence" is someone on twitter. A close read reveals innumerable holes and red flags. For example, it when it says that omicron couldn't have evolved in an immunocompromised patient because they "don't have the antibodies". They actually do, it's just that they don't have as many! The whole point of the immunocompromised patient theory is that a long infection with a weak immune response provides selective pressure for immune evasion, while giving enough time for mutations to develop. Things like this demonstrate that this author has little idea of what they're talking about.

Someone else made a comparison to arguments from creationists, which I think is apt. They throw a bunch of things at the wall, hoping that something sticks. But they don't paint a coherent picture and if we look close it's a mess.

Post reply on HN