1. Gain of function research primarily uses samples collected from nature, and seeks to stimulate their evolution in as natural a way as possible to learn how viruses evolve in nature. If such viruses were to escape the lab, they would appear "natural"
2. It's not xenophobic for people from the US to suggest the possibility of a lab leak, because the US was itself funding gain of function research on novel coronaviruses in the Wuhan BSL4 lab
3. Lab leaks happen more often than most people realize[1]
[1]https://www.vox.com/future-perfect/2019/3/20/18260669/deadly...
There is, from my understanding, reasonable evidence to conclude the virus was not engineered from the perspective of "we took genes from one virus and moved them to this virus," but there's no evidence disproving the idea that it was the result of gain of function research.
My personal feeling is that these statements are true:
* The virus is unlikely to have been engineered (in the way I described above) and leaked.
* There is circumstantial evidence the virus was the result of gain of function research and it leaked.
* There is circumstantial evidence the virus was a natural research sample and it leaked.
* There is circumstantial evidence the virus was introduced by an animal/person who traveled to the wet market.
Some of these are more likely than others, and an individual's own calibration for what is likely or unlikely will probably come into play more than evidence in the short term and possibly long term as well. I can say the vast majority of us are not qualified to answer the question either way though.
1) Chimeric viruses (copy and paste) are what scientists make in the lab. They take a piece of one virus and paste it into the genome of another, en masse. This is very different from what SARS-2 is, which is more accurately described as a "mosaic" (lots of little changes all over the genome). This is much much more difficult (if not very close to impossible in the case of SARS-2) to make in the lab, at least not and have it be done and "cooked" by the time the pandemic started. See the part of my post here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
2) He makes it sound like the techniques Shi Zhengli uses in the lab could create SARS-CoV-2. This is not true. For the reasons I describe above in point 1, and others, this is not really a likely possibility. Modern virology just does not have the tools to do this. Only mother nature with its many millions of hosts and diversity of hosts (in different mammals) could do this in the span of time molecular clock analysis says it took to take similar viruses like RaTG-13 and mutate them into SARS-CoV-2. I go into extreme detail about this in this part of my original post: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
3) He also says things like "Considering the heights of user friendliness and automation that genetic engineering tools have attained, creating a synthetic CoV2 via the above methodology would be in reach of even a grad student." Yeah, in 2020. Not in 2000 when they would have needed to start doing this. We did not have these tools back then. We did not understand enough about viruses, and this is /before/ we even discovered SARS-CoV-1!
The molecular clock + the synonymous/nonsynonymous criteria + the mosaic nature of the virus together put constraints on how this virus could have evolved. The first says it takes about 50-70 years to evolve a virus like this, evolving as fast as it does in nature. The second says it evolved in a fashion that wasn't putting more selective pressure on it than nature usually does. The third says it happened in a semi-random way, the way natural mutations occur. All of these together (plus other stuff) mean that it's unlikely that anyone /grew/ the virus in a lab intentionally.
I go into extreme detail about the synonymous nonsynonymous stuff in 3.1.1 of my post.
4) Also, it doesn't actually look like a virus that was grown in a petri dish or one that was grown in a single species of animals. It has O-linked glycans on it that cell culture wouldn't add. See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
Also, if it were grown in a single species of animal, then the SARS-2 spike protein would bind most tightly to that receptor. That's not actually what it is. As best we can tell, the S from SARS-2 binds just ~okay~ to a lot of different ACE2 receptors, and it just happens to work to bind human ACE2 kinda well. It's not at all how anyone would have actually designed it if they wanted to make a virus that kills humans. If they were designing it that way, they were some really shitty super villains, let me tell you that. I go into some extreme detail about this in this part of my post: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
5) Yuri gets really hot and bothered about the furin cleavage site. But what he seems to misunderstand is that these cleavage sites have evolved in nature too. It's likely either A) a recombinatorial event between SARS-2 and similar viruses in nature or B) it mutated over a short period of time in a way similar to other "mutagenicity islands." We have actually seen this before in nature. See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
He even says it has been shown to be disabled in a relatively short period of time in lab animals, so why wouldn't it be able to show up in nature in 50-70 years in millions of wild animals? It's really not that unlikely when you consider that certain areas of viral genomes mutate a lot faster than others in the wild.
6) He even points out that the only viruses in nature that share the cleavage site share only 40% of the rest of their genomes with SARS-2. But that just shows it's likely that SARS-2 and one of these other viruses happened to infect the same animal at the same time, and their genomes had a cross-over event. This happens ALL. THE. TIME. in viruses in nature. It's basically how flu pandemics occur. See:
-https://www.nature.com/articles/nrg2053 -https://www.euro.who.int/en/health-topics/communicable-disea... -https://academic.oup.com/mbe/article-pdf/26/1/177/13640305/m...
Why is it not likely this sort of thing was involved in this coronavirus pandemic?
Honestly I can't keep going because I need to be studying for the most important exam of my career (USMLE Step 1) but I can tell you just from the first couple pages of this extremely long thing that Yuri is not a virologist and has never taken a formal viral genetics class. He is making fundamental mistakes in how viruses evolve and change over time. He clearly knows a lot about biochemistry and regular genetics, but viruses are a whole different ballgame.
RaTG13 was such a virus (collected 2013, published post-pandemic), but it's very unlikely to be the ancestor for the reasons that you note. No one outside the WIV (and thus, no one beyond the physical control of the Chinese government) knows what other viruses they had in their freezer or database. Deigin has recently published an article claiming to have discovered a novel coronavirus in contamination of agricultural samples sequenced at the same facility:
https://arxiv.org/abs/2104.01533
To be clear, the new virus that he "discovered" absolutely is not an ancestor of SARS-CoV-2, and he absolutely isn't claiming that is; but it's (more) evidence that the WIV had unpublished coronaviruses.
The WIV took their database of viruses down from public access in September 2019. They say this was due to repeated hacking attempts. They haven't restored access, or provided their database in another format (e.g., a dump on a flash drive) that obviously presents no information security risk. Do you believe their claimed reason for taking it down? If not, why do you think they're lying?
I will say DDOS attacks on scientific databases are not that uncommon. This is the same reason that a lot of scientific publication data are now hosted by the publisher and not the scientist.
It's rarely actually a malicious "hacker," though. Usually it's some grad student somewhere pulling a really crappily made wget script out and accidentally using all the bandwidth.
Scientists aren't actually that great of programmers, yours truly included. Have I done this before with an independently hosted database? I can neither confirm not deny. Lol.
But seriously I have no idea. I get why you find this suspicious, but to me it is extremely circumstantial and I can think of a lot of mundane reasons for it.
For one, I don't know that the translation of DDOS and hacker or idiot script kiddie is nuanced enough between Mandarin and English.
Perhaps I could believe that a small group of virologists would have trouble keeping a website running, and that just by chance they gave up right around when a pandemic likely first entered humans, of the same type of virus that they studied in the same town--coincidences do happen. But now that this is a matter of international importance, do you really believe that no one in China has the technology to make this information available in any form? That seems impossible to me; so why don't they want to?
I appreciate the opportunity to discuss, and I do believe that you're sincerely convinced that the chance that virological research could result in such an accident is negligibly small. With respect, I'd suggest that your attitude seems typical of the profession, and that that's exactly when the worst accidents happen. Engineers are constantly taught that their work may bring catastrophe, and that it's their job to consider and manage every conceivable way that it could. I get the feeling that virologists aren't, perhaps because there are fewer past disasters to point to; though with the 1977 flu pandemic as a warning, that's not a great excuse.
An RBMK reactor cannot explode.
But this event doesn't look anything like those other lab release events.
See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395678/pdf/bul...
And nothing requires accidents to happen the same way each time. If SARS-CoV-2 was a lab accident, then it's probably an accident involving a novel bat-origin coronavirus collected from nature. The WIV probably had the biggest program sampling such viruses in the world, and that's the database they made unavailable.
Why do you think that database is unavailable now? The WIV's stated reason could possibly explain why they took it down in the first place (though it would be a spectacular coincidence), but it doesn't explain why they can't bring it back up.
Note that I asked this in my previous comment, and you chose to ignore it, instead responding to the less substantive comment from another user. You likewise ignored my original question about the database until I asked it twice. You didn't discuss the possibility of an accident involving a novel, unpublished virus (which you consider the most likely lab accident scenario, I believe correctly) until others brought it up.
I don't think that's malicious, but that's not a comforting pattern. Virologists are supposed to be the experts, so they should be the ones presenting (and refuting where applicable) the strongest and most likely scenarios for a lab accident. Instead, they (and you) seem entirely focused on defending the profession, refuting easy and wrong arguments, and waiting to see how long it takes adjacent non-specialists to learn enough to discover the harder ones. You then dismiss their arguments, because they (David Relman, Alina Chan, Richard Ebright, I assume Marc Lipsitch too; the list is getting long) are mere molecular biologists or epidemiologists or whatever, and not specialist virologists.
Regardless of what we eventually learn about the origin of this pandemic, that's not the behavior of a profession that can be trusted to regulate itself, and I believe the world is realizing that now. It would be unfortunate if important virological research gets banned because the regulations are drafted by half-informed outsiders; but if virologists themselves don't seriously engage with the possibility that their work just killed 2.9M people, that's what will happen.
Of course that's not all virologists. Étienne Decroly has been pushing quite openly for an investigation of a possible lab accident, though mostly in French-language media and perhaps you'll find something wrong with his resume too.
And just so you don't miss it: Why do you think that database is unavailable now? Please feel free to ignore everything I've written except that question.
I don't have time to address the rest of your comment I'm sorry, I have already sunk so much time into this post that I should have spent studying. This is the exam I have in 3 weeks: https://en.wikipedia.org/wiki/USMLE_Step_1 Pay particular attention to the section marked "effect on matching residency." I never should have responded or brought myself into this post in the first place.
Sorry, but I need to exit now. I hope you find the certainty you're looking for, either way. I hope you find the solace in "holding virologists to account" that you are looking for, although I'm not sure it will happen the way you are suggesting.
In any case, I certainly have work that I should be doing too, though lower-stakes than your exam. I'm not looking for solace or blame here; I just don't want another pandemic. Certainly this one might have been caused by exotic wildlife trading, or guano collection by farmers, or other nonscientific activity, and those activities should be restricted. But unless and until the WIV's collection and lab manipulation of novel potential pandemic pathogens can be confidently excluded as the cause, I don't see why anyone would permit that work either.
I'd privately guess that the Chinese government has already imposed such restrictions, and that while Shi's group may still publish occasionally for the sake of appearances their volume of risky research will fall sharply--the CCP doesn't want to lose face, but they don't want another pandemic either. Of course there's no way to confirm or refute that prediction but to wait and see.
Final note, I see that you wrote your "CoVID-19 did not come from the Wuhan Institute of Virology" post about a year ago. At the time, I would have mostly agreed with you; but since then no proximal animal host has been found, and quite a lot of Chinese-government obstruction has been. It's uncomfortable to adjust a position when you've previously made a strong statement; but that's a lot better than getting locked in to a position that you adopted based on less evidence than is available today.
Anyways, good luck on your exam. I'll continue to do everything I can to ensure that my group's designs don't explode or catch fire, and I hope you'll do the same with the risk that your (prospective) group starts a pandemic.