Lab Leak 2.0? • Hacker News Board

Re: Lab Leak 2.0?

#261

Post by rleigh » Tue, Jan 04, 2022, 1:45 PM UTC

toper-centage wrote: post #254

rleigh wrote: post #249

Earlier quoted context omitted.

Evolution occurs gradually, one base-pair at a time through replication error (or various other effects). Occasionally you get big changes through duplication, transposition or deletion of whole parts of a sequence. But the latter hasn't occurred here--we're looking only at the former. When we study evolution over time, we can look at the accumulation of silent and non-silent point mutations. And we can also pick up…

But we never have the full picture. 2020 was a year where several countries closed their borders and restricted domestic travel. Many countries were not sequencing the virus. It's not that far fetched that we'd see a descendent of an ancient variant if it had been in hiding in some remote isolated village in a poor country.

While what you say is certainly possible, it's not (IMHO) very likely. It doesn't matter that countries closed borders and restricted travel, or that not all countries were sequencing with the same rigour. That doesn't affect the eventual outcome as we randomly sample patients in the rest of the world.

If a country were hypothetically completely isolated and not sequencing, then we could have a new unknown variant develop. But from a given previously known origin genome, it would be mutating within that population over time at a fairly predictable rate, which would lead to a family of variants rooted at that known origin. We would see a spectrum of variants in a cluster branching from the origin. However, it clusters far from its origin, and this does raise a red flag.

It's possible that as we collect more data, we will "fill in the gaps" and get a better picture of how it evolved to the point it is at today. If there is a hypothetical country where this evolved naturally, those variants will still exist within the local population, and we will gradually sample a range of them in other countries over time as they too travel abroad where they can be detected.

If however it is not natural, then those intermediates will not exist, or will only exist as frozen down passages in a lab freezer. Maybe we'll identify the lab in time, if that's the case. They should be able to match it if they sequenced it.

Whichever hypothesis is correct, the data can't lie. We will know one way or the other fairly definitively in time.

Re: Lab Leak 2.0?

#262

Post by dls2016 » Tue, Jan 04, 2022, 1:49 PM UTC

tehjoker wrote: post #177

TeeMassive wrote: post #151

Earlier quoted context omitted.

> The entire world has been blanketed in Coronavirus and as far as I know Africa has seen a mix of action that has been different from how Western countries have experienced it. The rates of infection are different, the rates of vaccination are different. Two VOCs have come out of South Africa, but who's to say that an earlier version from 2020 wasn't bumping around the continent and returned to South Africa? You're…

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!

Re: Lab Leak 2.0?

#263

Post by tshaddox » Tue, Jan 04, 2022, 2:00 PM UTC

zzt123 wrote: post #188

d23 wrote: post #167

Earlier quoted context omitted.

Where to even begin with this. I'm unfairly biased because I misread what he said? After re-reading, I can see that he may not have been making the point I thought he was making. I'd argue he should make a point like that more clear, but fine, it's on me that I misinterpreted. > the hysteria on HN is ridiculous. "Hysteria"? How do you get hysteria from my response? Because I asked for citations for what I thought was…

"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…

It’s also abundantly clear if you’re reading the whole article from the start, because the whole article is claiming Omicron is the second virus to originate from a lab, after the original strain.

Re: Lab Leak 2.0?

#264

Post by rleigh » Tue, Jan 04, 2022, 2:07 PM UTC

croes wrote: post #256

rleigh wrote: post #249

Earlier quoted context omitted.

Evolution occurs gradually, one base-pair at a time through replication error (or various other effects). Occasionally you get big changes through duplication, transposition or deletion of whole parts of a sequence. But the latter hasn't occurred here--we're looking only at the former. When we study evolution over time, we can look at the accumulation of silent and non-silent point mutations. And we can also pick up…

You are confusing our lack of knowldege of the intermediate steps with the lack of interim steps. They might simply have been lost in the crowd or not even noticed, depending on where they were posted. How carefully have we studied the variants in animals?

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 sample availability biasing the sampling). Assuming that mutations occur randomly and with equal probability, then you would naively expect if the distance is between the cluster and the root is n base pair changes, then there would be n raised to the fourth power variants (assuming equal selective pressure). The reality is a bit more subtle than that, but I hope it illustrates the general scope and scale of what has taken place here. Given that scope and scale, the complete lack of any sequence data to date is astonishing. Particularly when we do see all those intermediate states for the other variants. Does that make sense?

As for variants in animals, that's a possibility. But it's more likely to be a red herring. Domestic animals will be infected with the same strain as their owners, and any reinfection would be very likely to be similar to the original. Transfer to a wild animal reservoir and back into the human population is so rare and unlikely that it is barely credible. Infection of humans from wild animal reservoirs is a rare event. To have it happen both ways within 12 months is not credible.

I could be wrong. This will only be answered by collecting more data to improve our understanding.

Re: Lab Leak 2.0?

#265

Post by acconrad » Tue, Jan 04, 2022, 2:08 PM UTC

I’m flagging this as misinformation and surprised this is scoring so high on HN.

This author presumes every major VoC stemmed from a lab leak. From the wild strain to Delta to Omicron. This is sensationalist, unsubstantiated claims with weak supporting evidence.

Re: Lab Leak 2.0?

#266

Post by civilized » Tue, Jan 04, 2022, 2:13 PM UTC

cassepipe wrote: post #181

civilized wrote: post #129

This post takes many screens of text to get to the point: we don't know how omicron evolved from its last known ancestor in Spring 2020 to November 2021, when it burst into the world stage. Ergo, lab leak. It's a great deal of throat-clearing for a one-sentence argument from ignorance. Alina Chan has pointed to a more plausible alternative in this comment https://news.ycombinator.com/item?id=29789480

The main argument is the ratio of silent vs non-silent mutations. So you are actually making a false presentation of her argumentation and I believe this is called... slander ? Although the claim that there's little chance for Omicron to have developped resistance to antibodies in an immunodepressed patient (that is without antibodies) needs to be adressed to. I would love to see a reasonable fact-based response to t…

> The main argument is the ratio of silent vs non-silent mutations.

Incorrect. She claims four supporting lines of evidence and does not label any one of them as the "main" argument. The NS:S ratio is just the second of four presented. She is throwing everything at the wall and seeing what sticks, because she lacks the expertise to evaluate how strong any one of her arguments is.

> So you are actually making a false presentation of her argumentation and I believe this is called... slander ?

No, it's not called slander. I just didn't see it when scrolling through this poorly organized and low-information blog post to extract the 1-2% of text that contained novel or interesting claims. Honest mistake.

If we want to talk about this silent/non-silent ratio seriously, we need to look at the data a little more carefully and not just trust some random Twitter person's guesstimate. There is at least one other random Twitter person who doesn't agree with the ratio presented in the OP. This second person does a transparent calculation citing an authoritative source, so it's a lot higher quality claim than the first random Twitter person: https://twitter.com/TheBrettRGM/status/1471317205014900739

If you look at the counts of non-synonymous and synonymous mutations for each variant listed at https://covariants.org/variants, you will see that all variants have a very high NS:S ratio. So either the entire evolution of the virus is being guided by mad scientists in secret labs, or we armchair virologists are over-interpreting the NS:S ratio.

> Although the claim that there's little chance for Omicron to have developped resistance to antibodies in an immunodepressed patient (that is without antibodies) needs to be adressed to.

Immunocompromised people don't lack antibodies.

I think there is ample evidence at this point that this person is not an expert and the arguments made are probably much less strong than they may sound to a layman.

Re: Lab Leak 2.0?

#267

Post by civilized » Tue, Jan 04, 2022, 2:24 PM UTC

cassepipe wrote: post #180

monocasa wrote: 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.

The S:NS ratio cited in the blog post also appears to be simply incorrect: https://twitter.com/eigenrobot/status/1471336024827568130?s=...

Re: Lab Leak 2.0?

#268

Post by wand3r » Tue, Jan 04, 2022, 2:47 PM UTC

m0llusk wrote: post #224

We have a record of successfully tracing viral origins. This is extremely detailed and difficult science. The last two coronavirus outbreaks took around fifteen years to understand. The previous pandemic was HIV which took even longer than that. Thinking that there is a quick and easy way to understand the origins of SARS-CoV2 variants based on narrative inference is essentially asserting that it is different this ti…

I am in no way informed about this area but from just a layman/logical perspective:

> The last two coronavirus outbreaks took around fifteen years to understand.

Is it possible that because these diseases had less impact, less people worked on them? It seems like virtually every scientist in even a tangentially related field is working on Cov-2. Not to mention that we have made significant improvements in technology even over the last decade.

I am not saying that this proves or disproves your comment, but couldn’t it be said that more people, resources and technology could get us answers faster in 2019? Especially if we are building of research and knowledge we have acquired over the preceding 2 decades?

Re: Lab Leak 2.0?

#269

Post by civilized » Tue, Jan 04, 2022, 2:49 PM UTC

Re: the claim about the non-synonymous/synonymous mutation ratio (N:NS ratio): if you calculate this ratio for each variant listed on https://covariants.org/variants, you will see that all variants have a very high NS:S ratio. So either the entire evolution of the virus is being guided by mad scientists in secret labs, or we armchair virologists are over-interpreting the NS:S ratio.

I think there is ample evidence at this point that this person lacks expertise in virology, and the arguments they make are probably much less strong than they may sound to a layman.

Re: Lab Leak 2.0?

#270

Post by wand3r » Tue, Jan 04, 2022, 2:57 PM UTC

prirun wrote: post #108

beardedwizard wrote: post #11

So how are they keeping all the scientists involved in such a leak quiet? How many of these scientists are there?

People said the same thing about the government monitoring everyone's communications: "It could never be kept secret". Edward Snowden proved they were wrong, and this was kept a secret, for years.

To your point, it was even widely discussed in niche areas like tech blogs and HN. However, much the same way as this hypothesis it was dismissed as a conspiracy theory, widely debunked by “experts” and downplayed. Again, not claiming this makes lab leak a conspiracy, but the idea it needs to be 100% a secret does not need to be the case. The narrative just needs to be controlled to some extent.