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but my friends who are tell me that's a lot of changes, and that experiments might change a few base pairs or proteins at a time. A lab leak theory doesn't explain how gain of function study resulted in so many mutations, unless they were blasting these viruses with radiation

Or explicitly creating chimeric coronaviruses, which has been the state of the are for some time. Here's https://pubmed.ncbi.nlm.nih.gov/26552008/ one of the sources of smoke on this, a 2015 paper co-authored by the Bat Woman (2nd to last author), the key sentence from the abstract:

Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone.

Have you read the fine article? It cites more than a few papers.

I've read a few articles, skimmed a few papers and sent them to friends. The counterargument is that there still aren't enough similarities.

The mutations on covid 19 are Really Different compared to the known and studied viruses. If it was a lab leak of an engineered chimera, you'd be able to see that A proteins came from virus X and B proteins came from virus Y and Z, but that hasn't been shown to be the case. From what I understand there are a bunch of smaller mutations across a lot of proteins resulting in something that doesn't really line up with known and studied genomes.

This paper actually goes through and compares the DNA of covid 19 against several other studied viruses: https://www.nature.com/articles/s41579-020-00459-7

My understanding is that this is what gain of function research is all about. Accelerated evolution within a lab towards infecting a specific species.

It doesn't have to be crispr introducing reach mutation.

RaTG13 is decades of evolution away from SARS-CoV-2, all over its genome.

You don't get there by splicing an ACE2 spike onto an RaTG13 backbone and passing it through a dozen mice. That gives you something that still looks similar to RaTG13 and infects mice.

The ACE2 spike also looks most similar to a previously unknown ACE2-binding spike protein found in malaysian pangolins.

So WIV would have had to have discovered that pangolin spike-protein, kept it secret, spliced it into an RaTG13 backbone, then not used mice but passed it through a species like that had a human-like ACE2 for a decade and millions of animals.

An alternative hypothesis is that Charles Darwin did that experiment.

Of course that says little about SARS-CoV-2 relative to all the other viruses we don't know about, either sitting in a Chinese government lab, or in a bat cave somewhere.

I guess I don't find the argument "we can't figure out how to reconstruct SARS-COV-2 from known viruses" very convincing on either side.

That's fair. I wouldn't say that it's "we can't figure it out" but rather that "doing so takes a lot of mutations and thus resources that may be difficult to do under the table"

Sitting in a cave somewhere implies not being studied, right? Which is more the "natural mutation" thing.

Sitting in some government lab is a different story and depends on belief in scientific institutions to do science and publish peer reviewed papers and all that jazz.

Another question is how you can make a virus evolve in the direction you want. 20 years of bat evolution would not necessarily bring a furin cleavage site, so how do you make sure it does?

The spike protein is the biggest difference between RaTG13 and SARS-CoV-2. To produce SARS-CoV-2 from it that would imply that WIV had unpublished sequences from the Pangolin-CoV spike protein that they used to combine with an RaTG13 backbone. You then do not get SARS-CoV-2 out of passing that through mice, you get a mouse virus. You'd need to pass it serially through something with a human-like ACE2 like minks. Then you need to do that enough to accumulate a thousand mutations which takes decades in nature and would take millions of animals.

That likely did happen, but Charles Darwin was the geneticist that executed the gain of function experiment via serial passage through that many animals.

> Have you read the fine article? It cites more than a few papers.

Yes, i read it. The ability to construct bibliographic references is also a fairly widely-held and unimpressive skill.

> To produce SARS-CoV-2 from it that would imply that WIV had unpublished sequences from the Pangolin-CoV spike protein

According to the article, the database of sequences for the WIV samples had been deleted before the pandemic became widespread, so there was no way to verify this, but also somewhat suspicious.

>you then do not get SARS-CoV-2 out of passing that through mice, you get a mouse virus. You'd need to pass it serially through something with a human-like ACE2 like minks.

From the article:

>Using the gene-editing technology known as CRISPR, the researchers had engineered mice with humanized lungs, then studied their susceptibility to SARS-CoV-2. As the NSC officials worked backward from the date of publication to establish a timeline for the study, it became clear that the mice had been engineered sometime in the summer of 2019, before the pandemic even started.

So, it's likely they had mice with humanized lung and ACE2 receptors, no?

What's the deal with you continuously referring to Zhengli-Li Shi as "Bat Woman" or "Bat Lady"? Is there some reason you can't or don't want to call her by her name?

Because everyone knows whom I'm referring to when I use that title she earned through a lot of hard work, while I've seen multiple Romanized versions of her name.

Humans are 98.8% similar to chimpanzees genetically. That 1.2% is critical. Now viruses have shorter lifecycles, blah blah blah, but 3.8% is a huge gap to overcome.

Also, "circumstantial" doesn't mean weak. It means "pertaining to circumstance". For example, the fact that the virus's origins are in the same area as the lab would be circumstantial evidence that it was created in that lab.

Many circumstances can point to a conclusion. Even the phrase "the smoking gun" which has been bandied about in the discussion of this article, is an example of circumstantial evidence. Circumstantial evidence is opposed by direct evidence, which would be eyewitnesses, video/photos of the thing taking place, etc. And eyewitness is actually one of the weakest forms of evidence because memory is faulty. So circumstantial evidence is usually the evidence that convicts a criminal.

To illustrate that, I like to point to my two favorite circumstantial convictions, Hans Reiser and Scott Peterson.

They convicted Scott Peterson based on buying porn, a dye job, and selling cars.

The convicted Hans Reiser of first degree murder of his wife, Nina, despite not even having any direct evidence that she was in fact dead. They only found the body after Reiser himself led them to Nina's body in exchange for pleading guilty to second-degree murder.

A cleaned car, a missing seat, and some books on murder investigations were the evidence they used. Entirely circumstantial. And they deduced that Nina was murdered from those same circumstances.

There's around one mutation each time it transmits between hosts (for flu it is one each time it goes cell to cell). 1,136 doesn't seem that high, say it hops 100 bats a year, that's just a divergence of 11 years of bat hopping (the more mutations that add up maybe the rate doesn't hold due to conserved regions though?). 5X less hops a year, 55 years: still a blink.

Well yeah, but that's an argument towards it being spread from the wild/against it being a lab escape, right?

It is countering him saying that mutation count must have been done in a lab, but not arguing either way.

>The closest genetic match is only 3.8% similar.

Keep in mind there is an estimated 1.5 million viruses that have not been identified yet. There might very well be a virus in nature which is the 'missing link'.

I agree! The argument is mainly one against it being a lab leak, but instead something that evolved in the wild and spread.

> The closest genetic match is only 3.8% similar.

How did you come by 3.8%?

It's not. From the article, it's 96.2% identical. 3.8% different.

"But they also reported that it was 96.2% identical to a coronavirus sequence in their possession called RaTG13, which was previously detected in “Yunnan province.” They concluded that RaTG13 was the closest known relative to SARS-CoV-2.

In the following months, as researchers around the world hunted for any known bat virus that might be a progenitor of SARS-CoV-2, Shi Zhengli offered shifting and sometimes contradictory accounts of where RaTG13 had come from and when it was fully sequenced. Searching a publicly available library of genetic sequences, several teams, including a group of DRASTIC researchers, soon realized that RaTG13 appeared identical to RaBtCoV/4991—the virus from the cave where the miners fell ill in 2012 with what looked like COVID-19.

In July, as questions mounted, Shi Zhengli told Science magazine that her lab had renamed the sample for clarity. But to skeptics, the renaming exercise looked like an effort to hide the sample’s connection to the Mojiang mine."

What the sibling comment said, I meant 3.8% different