101–110 of 250 posts
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…
Asserting that understanding the origins of a virus helps control its adverse impacts is completely bog-standard fare in the literature. Finding it suspicious in this case smacks of an isolated demand for rigor and unfamiliarity with the field. Even a cursory look at papers making a case for a zoonotic origin is likely to reveal statements to the same effect, here's just two for example: https://www.sciencedirect.com…
I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?
I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?
1) It makes the pandemic deterministic (bad lab security means an outbreak) instead of stochastic (wildlife spillover). That is, to be frank, even as an epidemiologist who is very skeptical of the lab leak hypothesis, a comforting thought.
2) It's a popular topic in the Substack/Medium set, because it moves the pandemic back into their wheelhouse of expertise, international relations, policy, etc. It becomes a human problem with human solutions.
3) It appeals to the contrarian mindset.
4) All of the lab leak papers at least attempt to show definitive proof. In contrast, actually finding the source of spillover events is the work of decades (and isn't always or even often successful). "Science is slow and uncertain" is a less compelling narrative.
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)...
Earlier quoted context omitted.
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.
Double zoonosis? The virus jumped to us and then to dogs, cats, tigers, hippos, pigs, etc. 29 known species! An unfathomable triple zoonosis that happened many, many times (thousands?) over the years. I’d say double zoonosis isn’t too uncommon.
The initial SARS presumably passed from bat to intermediate host to humans in a wet market. This exact type of event happened in China just 20 years ago.
And there isn’t “no trace” of an intermediate host. There are suspected intermediate hosts but none confirmed. Similarly SARS had a couple potential intermediate hosts, and MERS had a potential intermediate host but unanswered questions around that, too. Scientists had more confidence in those theories, but still uncertainties.
Again, I think both theories are plausible. But being a repeat to what we’ve seen before _is_ simpler. When you hear hooves, think horses not zebras.
> "The evidence we find is independent of other genomic evidence suggestive of a lab origin of SARS-CoV-2, such as the furin cleavage site (FCS) found in SARS-CoV-2 yet missing from all other known sarbecoviruses. However, the BsaI sites in SARS-COV-2 flank the S1 gene and S1/S2 junction, and a similar design has been used before for substitutions in this region. The restriction map alone also does not indicate the lab of origin."
> 100,000 random in silico mutants were generated for both RaTG13 and BANAl-20-52...Only 1.2% of RaTG13 mutants resulted in a BsaI/BsmBI restriction map with a larger z-score than SARS-CoV-2. BANAL52 is the closer relative to SARS-CoV-2 by over 200 nucleotides, yet only 0.1% of mutants yielded z-scores as great or greater than SARS-CoV-2
1.2% of 100,000 is a weird way to express an occurrence rate. Because 1.2% is a little over 1 in 100. Which means from random perturbation they generated almost 1,200 candidates which would also match their conclusions. The 0.1% mutant number would still be about 100, by sheer random chance.
They also don't support this argument with any reference to the observed mutation rates of any of their candidates in the environment. How often, in nature, do we expect a new mutation to arise? They claim to use data for nucleotide substitution frequencies, so they're addressing the fact that mutation is a process with a temporal component, but not what the time span is.
If 1 in 100 commercial jetliners crashed every year, we'd regard that as so common as to make commercial aviation unsafe.
They then conclude:
> It’s unlikely such an idealized reverse genetic system would evolve by chance from the close relatives of SARS-CoV-2
From 1 in 100 occurrence rates? Of a virus?
Now we do in fact have data on how frequently viral mutation happens. During cell cultures it appears to be about at a rate of 9e-7 substitutions per nucleotide per replication cycle of 12 hours for RaTG13 (reproduced from culture in animal tissue too[2]). With a ~29,800 BP genome, that means 0.02 nucleotide substitutions on average per replication cycle. So about 25 days for a single virus strain, serially replicating, to substitute 1 base pair.
Of course, this is all ignoring the fact that viral mutation is highly parallel - which they also do not mention in reference to this conclusion. How many mutations are necessary to generate a z-score match which would fool their detection method? 1, 2, 10? How many potential restriction enzyme cleavage sites exist which would become cleavage sites by a single base-pair flip? What's the dynamic addition/removal rate of restriction enzyme sites expected to be? We have per nucleotide estimates for this for RaTG13, so it's also not an independent variable: to achieve the distribution of cleavage sites they propose, what is the mean-number of mutations for it to happen in the 1 in 100 candidates which achieved it? A virus doesn't explore it's mutation space serially, it explores it in a massively parallel way every single replication cycle.
This paper leads with some very specific claims, is based purely on simulation, and fails to ask obvious control questions based on it's own methods.
[1] https://doi.org/10.1371/journal.ppat.1000896 [2] https://doi.org/10.1371/journal.ppat.0030005
I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?
To my mind, there are a few reasons: 1) It makes the pandemic deterministic (bad lab security means an outbreak) instead of stochastic (wildlife spillover). That is, to be frank, even as an epidemiologist who is very skeptical of the lab leak hypothesis, a comforting thought. 2) It's a popular topic in the Substack/Medium set, because it moves the pandemic back into their wheelhouse of expertise, international relati…
"Bad lab security means an outbreak" is also stochastic though?