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Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

biorxiv.org

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Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#81

Post by timr »

m0llusk wrote: post #18

There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…

> First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection of viral characteristics, only a comparison between wild and lab viruses.

No, you've completely misunderstood the analysis. The number of restriction sites is not what is important. It's the location of the sites, and the spacing between them. This is suspicious, and has a high degree of variability, as is shown in Figure 3c. They also generated 100,000 random mutations to RaTG13 and BANAL52, and found that only ~1.2% and 0.1% of these, respectively, had restriction maps as deviant as the one found in SARS CoV2 (Figure 4).

The spacing here alone is suspicious, but couple with the number of synonymous (silent) mutations, and you're looking at an outcome extremely unlikely to be found in nature.

https://www.biorxiv.org/content/10.1101/2022.10.18.512756v1....

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#82

Post by xyzzy123 »

adamredwoods wrote: post #64
callesgg wrote: post #15

I Honestly thought it was common belief that corona come from that lab in china. But now after reading this, I searched a bit and read up on it and I guess it is still a somewhat honest debate on the topic. Even if it was lab made, it would be sort of stupid to dig in to it, due to the political nature of the matter. What happened happened, most likely the release would have been accidental, so why play blame games.

Even the big paper publishers say "No conclusive evidence for either theory." https://www.science.org/content/article/do-three-new-studies... >> Still, Worobey and his co-authors concede, even that evidence might not be enough to end this polarizing debate. “With the way that people have been able to just push aside any and all evidence that points away from a lab leak, I do fear that even if there were evidence from…

> Even the big paper publishers say "No conclusive evidence for either theory."

They initially claimed their evidence was "dispositive" but their peer reviewers (correctly, IMHO) made them take it out.

https://ayjchan.medium.com/evidence-for-a-natural-origin-of-...

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#83

Post by divided »

arisAlexis wrote: post #46
whydid wrote: post #28

Earlier quoted context omitted.

https://en.m.wikipedia.org/wiki/Sagan_standard Extraordinary claims require extraordinary evidence. This is why people are skeptical.

It depends on bayesian priors.how mahy coronaviruses were studied, how frequently a new virus is found next to a biolab of said virus by chance etc. The extraordinary claim could be that it is of natural origin actually.

Fun fact! There are just 9,110 named virus species as of 2021. But there are estimates that mammals and birds may have as many as 1.7 million undiscovered viruses. An older source says there were ~200 some known viruses that could infect humans as of 2013. They estimate there are 800k unknown ones which could infect us. Basically every time they look for viruses, they find new ones.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#84

Post by astrange »

guelo wrote: post #66

I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?

Cynical engineers are required to believe in it because it's 1. "the opposite of the current thing" 2. contains more rationality than the other leading hypothesis (i.e. more of what happened was planned, rather than an accident) 3. and lets them blame a person rather than a bat.

An ironically fitting end for them would be that it is true, they get all similar research banned, and then the next virus is zoonotic and nobody is prepared for it due to not doing any research.

edit: added "ironically"

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#85

Post by xyzzy123 »

divided wrote: post #79
MockObject wrote: post #48

Earlier quoted context omitted.

Wasn't the lab working with coronaviruses? So maybe some of it escaped. I really don't see how that's an unnecessary multiplication of entities. Is the objection simply that, pandemics have emerged from markets, but not labs? But we know that an escape of a coronavirus could lead to a pandemic. I see nothing needlessly complex here, and certainly not extraordinary.

I don’t believe anyone is saying it’s needlessly complex, but Occam’s Razor isn’t “the second simplest explanation is usually the correct one.” On one hand you have the market which housed animals that throughout its history some have had and spread different coronaviruses naturally. Every prior pandemic has been believed to have been from animal to human transmission, it’s seemingly the simplest explanation. The lab…

Entities should not be multiplied without necessity.

Put another way, the simplest explanation that fits the available evidence is most likely to be correct.

At this point it seems to me that a lab origin that superspreads at a market looks rather simpler than a market origin with double zoonosis and no trace of an intermediate host.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#86

Post by astrange »

someuser54541 wrote: post #22

Genuinely surprises me that there are people out there who think or have been persuaded the virus is of natural origin. The lab right next to the market was literally studying and experimenting with the exact same type of virus. How can a someone think that that's just a coincidence? Add that to the fact that the funding for that research lab was approved by the same guy who become the de facto thought leader on the…

> The lab right next to the market was literally studying and experimenting with the exact same type of virus. How can a someone think that that's just a coincidence?

If they built the lab next to the viruses that were already there, then it would be reverse causation, which isn't a coincidence, but also kind of is one.

That's the meaning of "correlation is not causation".

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#87

Post by astrange »

beiller wrote: post #29
someuser54541 wrote: post #22

Genuinely surprises me that there are people out there who think or have been persuaded the virus is of natural origin. The lab right next to the market was literally studying and experimenting with the exact same type of virus. How can a someone think that that's just a coincidence? Add that to the fact that the funding for that research lab was approved by the same guy who become the de facto thought leader on the…

I have the opposite Occam's razor thoughts. My opinion is we are not capable of developing in a lab a virus that is so transmissible and survivable in human species only. I think the complexity of the virus machinery and its interactions inside of our bodies and immune system is beyond astronomical in complexity. It's laughable to suggest that we are so intelligent as to invent a better version of the machinery that…

Well, SARS-CoV-2 isn't transmissible in humans only; it survives just fine in many other mammals, including pets.

This is basically the reason we can't get rid of it. Even if we had a perfect human vaccine that blocked transmission, it wouldn't help.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#88

Post by jfoster »

m0llusk wrote: post #18

There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…

You're suggesting that the species jump is likely to have happened in the wet market, but also claiming that there's no clear & obvious way to reduce risk in the future? That's inconsistent, isn't it?

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#89

Post by Shish2k »

guelo wrote: post #66

I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?

Now that you mention it, I wonder if there’s any correlation between the startup-mindset (believing that success comes from hard work more than good luck), and the conspiracy-mindset (believing that disaster comes from hard work more than bad luck)...

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#90

Post by slibhb »

m0llusk wrote: post #18

There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…

Your summary of the paper is unfair. From one of the author's blog:

> Recap: BsaI/BsmBI are particularly useful restriction enzymes to use if you wanted to study a bunch of chimeric coronaviruses like the close relatives of SARS-CoV-2. The SARS-CoV-2 BsaI/BsmBI cutting sites look regularly-spaced (ish). The maximum fragment length is in the bottom percentile of all CoVs digestions in the idealized fragment-number range, the bottom 0.07% for all type IIS digestions within the idealized range, and the number of fragments is also in the idealized range. The SARS-CoV-2 BsaI/BsmBI restriction map looks a lot more like known pre-COVID infectious clones than a wild coronaviruses. All sticky ends are unique & meet other nice criteria for good assembly. All mutations separating these sites from close relatives are silent, and there’s a significantly higher rate per nucleotide of silent mutations within BsaI/BsmBI recognition sites than the rest of the viral genome.

> The odds of meeting any one of these criteria vary, from 1%-0.07% of having such a small maximum fragment length to 1/250 to 1/100 million odds of having such high concentration of silent mutations within BsaI/BsmBI recognition sites. The odds of meeting every single one of these criteria are even smaller. Much smaller.

https://alexwasburne.substack.com/p/a-synthetic-origin-of-sa...

So it's not just "5 vs 2" sites, it's the spacing of the sites, the fact that the site mutations are silent, and the fact that the "sticky ends" are unique.

This paper should move your needle toward "synthetic origin". Similar to how some other papers published in the last few months (the wet market paper among them) should have moved your needle toward "natural origin".

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