Again with the appeal to authority. Argue the merits of the argument. Not who is making it (which is almost all you've done). Except in this case, the merits of the argument were pretty weak and superficial, and only applied to people who weren't expert enough to realize that no one is suggesting CRISPR-Cas9 was used to make 1200 edits to a virus lmao. There's no talking your way out of that one. Anyone who knows anything about molecular biology or virology knows clearly that that was a total strawman rebuttal. I won't suggest motive, just that it was not ever a good faith argument.
>Okay, let me know when you wanna talk about it like adults!
If you point out where I'm not in that reply, I'll happily edit it to be less offensive.
*Still waiting for you to refute my hypothesis with an actual argument, by the way.*
Until you agree to that, I'm good.
Thanks for the interesting thoughts, but I think for my own mental health, I'm good.
https://news.ycombinator.com/item?id=26757986
You don't have any molecular biology refutation that I can find.
Let me go back to my original hypothesis, and then try to restate your arguments, and you can tell me where I'm restating them incorrectly.
My original hypothesis: 1) Major point of differentiation for this virus is that compared to it's closest known relatives, it has acquired a furin site (eukaryotic protein cleavage site) that enhances its virulence.
You said: >And in there, I describe exactly how wrong your point 1 is.
I honestly can't find anything that refutes what I said. Please, just paste the line that points out how this is, to quote you, wrong. As in, disproves that compared to its closest known relatives (RATG-13) it has acquired a furin site, which increases its virulence"
I can find absolutely nothing* in either your Reddit posts, or your posts here on HN, that refute this. I can find plenty of things explaining how natural evolution could cause it, but nothing saying that it hasn't acquired a furin site that enhances its virulence that its closest known relative doesn't have.
2) That furin site RNA contains a non-canonical amino acid codon
To be fair, you didn't dispute this.
3) That non-canonical codon contains a restriction site that could easily be used to track, whether, say, your added furin site is surviving multiple cell passages, by performing a restriction digest and running the fragments on a cell.
You said:
>how misguided your point 3 is.
OK, let's examine my point #3. It is non-canonical, as in only 5% of the arginines in SARS-CoV 2 contain it. I guess we can get into what exactly non-canonical means, and you do make some points there, but at the end of the day, 5% is 5%, and 5%*5% is 0.25%, so it seems to me that the usage of the term "non-canonical" to describe a site that has a 0.25% chance of occurring is fitting.
OK, so let's talk about the restriction site. You don't dispute the presence of it anywhere, at least not that I can find. Please, if you have something to dispute the presence of it, just paste it in reply to this because I legitimately can't find it. You also don't dispute the usefulness of using a restriction site to track genetic engineering, presumably because it's done all the time.
So with all this in mind, it seems to me like your disagreement with me is not with any of the 3 major points I made, or even the two of those three points you called out in your initial reply. So I'm thoroughly confused by what you're trying to debate. Are you debating the interpretation of those facts? Because that interpretation appears to be almost entirely of your own imagination. Nowhere did I offer (at least not that I can see) an interpretation of those facts beyond speculating that they are a possibility. In fact, my entire first post was just to reframe the argument as I understood it, and comment that it's very difficult to rule out because of the nature of the evidence. For the record, I find the likelihood that it was a lab leak extremely slim, but I'm not going to discount it, especially not concretely.
On the other hand, the post you linked to was very much dancing around any of the concrete arguments about the topic, making absurd insinuations like that people are claiming the 1200 mutations came from engineered Cas9 usage, which I've personally never seen claimed (by the way I'm still waiting for you to address this). All while ignoring crucial facts like that the furin site was an insertion, not a polymorphism.
I'm thoroughly confused by whatever point you're trying to make here. To me, it seems like you've been arguing against words you imagined me saying.
Do you think these two possibilities are equally likely?
Do you think one is more likely than the other?
Which?
You say that you find the lab possibility not very likely, so do you find the zoonotic scenario any more likely? If so, then you and I are in agreement, of a kind. You never said that above, and you definitely argued in a way that implied something else. Especially given the CGG codons.
Probabilistic thinking is the nature of the discussion in the absence of conclusive evidence. Probabilistic thinking. Heuristics. That's what I've been discussing this entire time, that's what I was talking about in my original post, and it's what your reply comments were, therefore, replying to.
I never make any claims saying either is the only possible scenario or an impossible one.
I also was not "dancing around the concrete arguments on the topic." I was directly answering arguments that had been put forth to me by random people on the internet. That's it. That's the point of the post. To answer those arguments.
I get that you've never seen it claimed that engineering made all 1200 mutations, but plenty of people claim it. You can look on my original reddit post and see people in the comments claiming it's possible because "China is so far ahead of us, they could have generated the primers 20 years ago to do something like that."
That's why it's not a strawman, I was directly answering arguments that had been made to me by people on the internet. Just because you think they are ludicrous arguments does not mean that someone has not made them. The internet is larger and more diverse in its idiocy than you have conceived of in your dreams, Horatio. etc. etc.
>2) That furin site RNA contains a non-canonical amino acid codon. To be fair, you didn't dispute this.
Hi, I have disputed the claim you've made since that the virus contains two such codons in a row. That is patently not the case in the earliest examples of the virus known. And wow, I just checked, and those three sequences from the earliest part of the pandemic I linked, they don't contain the cgg in the furin site. Literally look yourself. The earliest sequences out of China, Korea, and Iran do not have the cgg where you're talking about. It isn't there. Not that I saw, lol. Show me where it is if you find it. I just used BLOSUM similarity alignment and looked where the cleavage is supposed to be. And I don't see CGG there.
I actually address the restriction site directly in the original discussion. I don't recall you mentioning it before now. if you did, my apologies I missed it. See my comments on that copy/pasted here:
"For sticky end ligation, for example, you can examine the relative length of homologous regions around restriction enzyme cutting motifs. And sort of detect it like a photoshopped gel almost. But in sequence form. Real mutations shouldn't occur predominately around restriction enzyme motifs. But engineered mutations would. You'd have to use evolutionary comparison of similar viral species to see if there are any mutations that appear too improbable to have happened by polymerase error alone.
Is it still possible to slip one by such a method? yes, of course. Especially small insertions or deletions would be easy to hide...
[But] it literally wouldn't make sense to do it. We have established backbones that would make more sense and be easier to use. The only reason would be to "hide your work." And that's like years and years worth of genetic manipulation, several post-docs worth of work, easy. All to "hide your work." When you could just use SARS-CoV-1 and be A) more deadly, B) more "natural", and C) easier to use."
It's just really funny if we do agree about both of these being possible, but one being more likely than the other. If we both agree that the zoonotic is probably more likely, what are we arguing about? I don't disagree that it is /technically/ possible, but I also find it more likely to have occurred in nature. Restriction sites can also occur in nature, btw. This is a case of the "lottery" fallacy. There are so many goddamn restriction sites throughout any viral genome, why is this surprising?
That's called "sealioning," a term you may have heard. https://www.merriam-webster.com/words-at-play/sealioning-int...
If you did not believe in good faith the statements you made, or have substance behind the questions you asked as though you believed them to be true (CGG for example), that is very much insincere.
I am not going to be dragged into an endless debate with someone who wants to play devil's advocate. There are people with actual misunderstandings and misconceptions about science that are out there that need our help to understand the world around them.
Why waste time like this if we agree on the basic points? This is not a socratic discussion, you are not Socrates, and I am not Plato. This is not a PhD defense. It is not an academic conference.
I'm here to talk about this with people who have legitimate concerns that they actually believe about the subject matter at hand.
And please, I'm sorry if I mischaracterized your position or your actions thus far, but that's what it looks like. If you had said at some point "just playing devil's advocate here!" or "I don't 100% believe this but what about this thing I saw?" then if I had seen that, I would have engaged in a completely different way, and likely disengaged much earlier.
Thanks for the interesting ideas, but I have to go study for exams, and procrastinate in ways that are better for both of our mental health.
Have a great day, and I hope this hasn't taken up as much of your mental energy as it has mine. Because it took up a lot of mine.