Molecular biology clues portray SARS-CoV-2 as a lab manipulation of RaTG13 | Hacker News Reader

Molecular biology clues portray SARS-CoV-2 as a lab manipulation of RaTG13

pubs.acs.org

190 pointsMistletoe118 comments

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FYI, a couple of things to keep in mind:

1. This is a letter to the editor, and is not peer-reviewed[1]

2. This author does not have what some would consider a sterling history of submitted papers[2]

[1] - Difference between Letters and Letters to the Editor: https://pubs.acs.org/page/amclct/about.html

[2] - https://en.wikipedia.org/w/index.php?title=Ariel_Fernandez&o...

I appreciate your skepticism. Unfortunately “skepticism” is basically the only credence given to the lab leak theory for the last year. Was the public intentionally mislead via the MSM? Personally I’m ready to entertain the theory because I no longer trust the institutional word.

I am not a biologist and am not qualified to comment on the content whatsoever. I was just doing background research on the article I was reading and the author of the paper, and wanted to bring to light what I found.

That's a shame. Dams are extremely useful even if ecologicaly damaging. They provide clean and carbon free power generation and freshwater for farms and irrigation that would otherwise run out to the sea.

Hopefully we can invest in more research to reduce and remove the ecological burden of dams.

Nonetheless:

1. Fauci runs funding for gain of function research 2. Attributing COVID-19 to gain of function research hurts future gain of function research 3. Cui bono

Some context: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484390/

> Fauci runs funding for gain of function research

Fauci has denied multiple times that they funded gain of function research. Please cite your sources.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524054/

ACKNOWLEDGMENTS

This work was supported by NIH grants R01AI089728; (to F.L.) and R01AI110700 (to R.S.B. and F.L.).

"To evaluate the potential genetic changes required for HKU4 to infect human cells, we reengineered HKU4 spike, aiming to build its capacity to mediate viral entry into human cells."

Fauci has been director of NIAID since 1984, which is excessive.

Fauci has categorically denied on record that they don't fund gain of function research. I am not qualified enough to comment if the re-engineering mentioned here is the same.

I trust Fauci to not lie in a public hearing and to know what he is saying.

Like when he said we shouldn’t use masks?

https://www.google.com/amp/s/mobile.reuters.com/article/amp/...

Being wrong is not at issue, especially when the source reverses their position as better info arises. What's at issue is malevolent intent — knowingly spreading falsehoods. I'm aware of no credible basis for believing the latter about Fauci.

There's this other article https://thebulletin.org/2021/05/the-origin-of-covid-did-peop... which among other things explains that gain of function is technically defined as modifying existing human viruses to make them more dangerous.

The SARS2 quite likely isn't based on an existing human virus but on a bat coronavirus.

The NIH has been apparently funding modifying bat coronaviruses in Wuhan with minimal guardrails as to be able to infect humanized lab mice but that's not gain of function as per that definition.

Well, despite your technical definition, it would seem it gained function.

It gained function without involving any of what are formally considered gain-of-function operations. So, Fauci could fund it, and also truthfully testify under oath that he didn't fund anything that, by the definition, would count as GoF work. That a virus did gain function, by operations not covered by the definition, is a separate problem: The definition should be widened enough to cover what really happened.

https://factcheck.thedispatch.com/p/fauci-paul-niaid-researc...

The link you provide as context contradicts 1, if I'm reading it right? It says that Fauci does not want to fund this research.

(Maybe I'm misunderstanding the posited conspiracy and the idea is that if the NIH doesn't fund something, Fauci pockets the unspent money?)

The link (2012) does not contradict 1 and does not say that Fauci does not want to fund "this" [SARS] research.

> This is a letter to the editor, and is not peer-reviewed

True enough.

On the other hand, they did publish it, which I'm positive they don't do with letters they believe are pure crackpottery, or otherwise without merit (of which I'm sure they get their share).

According to Google Scholar, he has dozens of papers, 10000 citations, and an h-index of 37. What do you have?

And if you follow through, at least a couple of the four retractions mentioned on Wikipedia appear to be nothing but some acknowledgment/funding related trivia.

It doesn't matter what a commenter on HN has. A rare ironic case where the original comment isn't ad-hominem, but the dinging rebuttal is.

> This author does not have what some would consider a sterling history of submitted papers

This is ad hominem. The link provided only supports the accusation with previous accusations.

No, it’s not. In a discussion about the credibility of an academic researcher, their track record is entirely relevant. The same isn’t true of an HN comment.

Slight of hand. We were not discussing the credibility of an academic researcher, we were to discuss the contents and logical merit of their submission.

Both were ad-hominem. The first one also suffers from a pompous bias: What does it even matter if the submission is not peer-reviewed? It could have been posted on a blog! It is dropping little seeds of doubt, to weaken and attack something you don't want to attack directly:

"A warning to everyone that the linked website does not adhere to Wikipedia guidelines for being a credible source."

Expect better. If you demand peer-review, then review the contents as a peer! You have the opportunity to get what you want, instead of needlessly attacking a fellow scientist' credibility.

> Both were ad-hominem

Surely a distinction can be made between attacking someone's character and attacking their claim to authority. Within every scientific paper there's an implicit claim to authority and here the track record has weight alongside whatever qualifications they may have.

It's "sleight", from the middle English for "skill", not "slight".

"Valid ad hominem arguments occur in informal logic, where the person making the argument relies on arguments from authority such as testimony, expertise..."

https://en.m.wikipedia.org/wiki/Ad_hominem

It appears that the original comment was valid ad hominem, but still ad hominem.

Any ad hominem cannot inform you about the quality of an argument. It _can_ inform you that you should look at an argument critically but, even in the "valid" form, it doesn't address the argument.

...what? Attacking the past of the person making an argument, rather than his argument itself, is the textbook example of ad hominem.

Wait, does this mean that I am not allowed to criticize someone just because I ... don't have their skills? That doesn't make any sense.

This paper is not peer-reviewed. It should end there.

No. I'm just not convinced at all by his comment about the author's publication history.

>This paper is not peer-reviewed. It should end there.

So you think scientists aren't allowed to communicate with one another and the public except through peer reviewed articles? 'Tis absurd. Anyway, peer review means very little nowadays. I publish 3-5 papers per year in top journals in my field, and many of the referee reports I see are hilariously insignificant, effortless, and/or just totally off the point.

> This paper is not peer-reviewed. It should begin there.

FTFY

It seems that the most common response to arguments in favour of a lab leak is always to attack the messenger. First "It's Trump so don't listen to him", then "Nicholas Wade is a racist so don't read him" and now "Ariel Fernandez is only writing a letter and someone anonymously complained about one of his papers once but they were never told what the complaint was actually about and the generic expressions of concerns never went anywhere". That's weak sauce.

I think most of us don't care who he is, only whether what they say is true. The claims in this article aren't actually new anyway, it was all covered in Wade's article already. So if it's wrong, let's hear why. That would certainly be interesting.

DDGing his name and institute gets me here: http://www.arielfernandez.net/daruma-institute2.html

Yeah, I can't tell if the biology paper is credible or not, but I smell crap when reading that institute's program. I think whether Covid is lab-engineered or natural doesn't affect me that drastically, the reality has been what this last year and more has been. My interest in the virus' origin is mainly in the popcorn-worthy political drama.

But after reading that institute blurb I'll just set aside the popcorn because this work doesn't seem to be the smoking gun that will set off popcorn-worthy political consequences. Unless someone else who I judge more credible endorses that letter to the editor...

> First "It's Trump so don't listen to him".

People also didn't listen to him about wind turbines causing cancer. Or about vaccines causing autism. Or about global warming being a hoax by the Chinese to harm US manufacturing. Or about injecting disinfectants to fight COVID.

There was not (and still isn't) any indication that he had any more evidence to back up his COVID origin claims than he had for any of those other claims. All you can safely conclude is that Trump saw a YouTube video or a website or TV commentator that claimed that, and uncritically accepted it.

Could you post the source for the injection claim? It seems to me you uncritically accepted some YT video, website or TV commentator.

https://www.youtube.com/watch?v=33QdTOyXz3w, you are welcome.

> People also didn't listen to him about wind turbines causing cancer.

Asked why he was not in favor of wind mills, Trump answered once, that "they say" it can cause cancer. "They say" is https://en.wikipedia.org/wiki/Wind_turbine_syndrome

> Or about vaccines causing autism

Trump sues outlets for speculating one of his sons has autism. "Many such cases" may hit close to home here. And a cute test: how much are you willing to bet (hard $) to back this a-causality? Didn't the general courts had to make a special vaccine court to deal with many such (autism) claims? https://en.wikipedia.org/wiki/National_Vaccine_Injury_Compen...

> Or about global warming being a hoax by the Chinese to harm US manufacturing.

Global warming is used by the Chinese, in the sense that they completely ignore it, while fostering climate change activism in Western countries, so to reduce their energy footprint from within, and gain unfair advantage.

> All you can safely conclude is that Trump saw a YouTube video or a website or TV commentator that claimed that, and uncritically accepted it.

Trump was clearly not the best to give that conference. He was leaning towards his science advisors, to fill in the gaps. They told Trump about potential methods using UV-rays or disinfectants.

I too would tell the president if I knew about advances in research such as https://pubmed.ncbi.nlm.nih.gov/8346001/ (Inactivation of respiratory syncytial virus by detergents and disinfectants, 1993), but still hope that he does not run with it and shoots it from the hip. Maybe that was too much to hope for. But don't let people 20 years later remember the lie that "Trump said to inject people with bleach to cure COVID". There is plenty of other embarassing true stuff.

Correct me if I'm wrong. RaTG13's genome was published in 2020 after the pandemic started by Shi and the Wuhan Institute of technology.

Doesn't seem likely they'll voluntarily publish a paper on a virus they used as the backbone to manufacture SARS-CoV-2...

Even if it was a lab leak, it's unlikely RaTG13 was the progenitor.

We don't know if there ever was a wild RaTG13. If WIV is under suspicion, anything WIV said about RaTG13 is equally suspect. If it is faked, one might be surprised they did not fake it in a way less likely to encourage suspicion.

Nobody seriously suspects WIV engineered the SARS-CoV2 to deliberately cause a pandemic, but negligently letting it escape is itself obviously worth covering up. Whether that happened or not, it is their misfortune that it doesn't look more like a natural chimera.

I have assumed early insistence that it was natural was considered necessary to get any possibility of cooperation from the Chinese gov't. Now that they have become uncooperative, there is no more reason to maintain the fiction.

> Shi and the Wuhan Institute of technology. Doesn't seem likely they'll voluntarily

Shi and WIT are not related to WIV, are they? This could be independent and without explicit consent of WIV?

Shi directs the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology. https://en.wikipedia.org/wiki/Shi_Zhengli

The original article, the https://en.wikipedia.org/wiki/COVID-19_misinformation comments, and "urban" food security arguments, which rate near the necessity of cannibalism, distract from continuing to ban the most likely sources of zoonotic diseases and wildlife smuggling that are the wet markets.

This isn't really anything new, but nicely summarizes the best case (as far as I've read about it) explanation of the lab-leak theory of COVID origin.

Basically, it hinges on:

1. SARS-CoV-19 doesn't have a direct predecessor virus

2. it has a "weird" furin cleavage site on its spike protein, where "weird" means:

2a. it encodes the amino acid arginine by an CGG RNA codon, which is "rare" for SARS-CoV-19's closest relative

2b. the inserted furin cleavage site coding sequence is misaligned, breaking the codon TCA into two parts, which is (citation:) "very odd, clearly pointing to an artificial origin"

Also interesting that the article refers to "T", which is a DNA nucleotide, as opposed to "U", which is the corresponding RNA nucleotide (SARS-CoV-2 is a RNA virus).

It referred to the viral cDNA as the sequencing was performed on, hence the 'T'.

If this is the "peak lab leak" argument, which seems still more rejected than accepted by scientist, what is the general rebuttal? "Yes it's unlikely but less unlikely than a leak"? Or something more technical?

The rebuttal is that the above argument is a mischaracterization of the evidence. The fact we haven't seen an ancestor virus is absolutely expected and normal, and has happened for every other virus. Furin cleavage sites are present in a dozen other coronaviruses. The closest relative known is fairly likely not to be an ancestor, so there is no real expectation you wouldn't see an arginine. It's totally normal for there to be a misalignment, that's exactly what you would expect for random evolution, to find anything that works.

So basically, there is almost no argument above, and zoonoses have happened hundreds of times and are thus expected.

My understanding is that the interesting bit is not about the misalignment, but rather the fact that the furin site is an insertion, not a mutation. Additionally, a non-canonical codon that encodes a restriction site.

The idea as I understand is something like this:

1) I want to study what makes coronaviruses go from infecting bats to infecting humans

2) I add a furin site because my hypothesis is that a furin in the spike protein is important (because other coronaviruses like MERS have it)

3) I then try to passage the virus through many generations to see if it preserves the furin site I added (i.e. selects for it) because if it mutates at less than baseline, I know it's important (this also explains the "mosaic" aspect of the other mutations in the virus)

4) To be able to track that, when I add the furin site, I make sure to insert a restriction site that isn't found elsewhere in the genome, so I can do a quick RNA extraction, and restriction digest to see if it's preserved.

Please note. That is my understanding of this one aspect of the lab leak hypothesis. It's not necessarily what I believe to be true. Additionally, it is not the only piece of evidence cited as part of the lab leak hypothesis, either.

Thanks, this is really interesting.

What about the SARS-CoV-2 virus being a chimera of 2 other viruses? Is that wrong, or not unusual, or irrelevant? Sorry if I’m barking up a wrong tree...

> 1. SARS-CoV-19 doesn't have a direct predecessor virus

That we know of. We do way way too little research on viruses in animals. We may never know predecessor in nature, and that doesn't mean it's created in a lab. Same as the fact that we don't know how universe behaved in first moments after big bang doesn't mean that god exists.

The counterargument mounted by Wade and others is that the world has been searching for such a transmission path for the last year with far greater resources than normally allocated, as obviously, China would very much like to find such a path. However no such animal has been found. The lack of any discovery despite great effort is not itself proof, as you can't prove a negative, but it does seem suggestive.

> but it does seem suggestive.

As pointed out by others, we don't even know who COVID's patient zero is, nor whether or not an intermediate host was even required after bats.

The original SARS-CoV virus has never been isolated in animals. HIV's origins in chimps is still murky.

The Spanish flu wasn't Spanish, but otherwise ... And, Ebola. ?

We humans aren't owed an answer, and juxtaposed against our investigative history, I don't understand how the current state of our understanding here is suggestive of anything.

> . it has a "weird" furin cleavage site on its spike protein, where "weird" means:

From what I know that is unusual but not rally that unusual or weird.

> SARS-CoV-19 doesn't have a direct predecessor virus

Us not knowing a "close by/directish" predecessor is also not uncommon for a virus which jumped from wield animals to humans. It's a different thing if it's a virus which was a well known one already spread in humans or human cattle/pets and then mutated. But if you look at the wield there are viruses which survived for decades e.g. in bat colonies with some small mutations here and there, for that example case it would be very strange if we would know a predecessor with might already have gone extinct... And similar thinks might very well apply to SARS-Cov-2.

> 2b. the inserted furin cleavage site coding sequence is misaligned, breaking the codon TCA into two parts, which is (citation:) "very odd, clearly pointing to an artificial origin"

But what is odd about this? I don't know of any mechanism for mutagenesis, natural or otherwise, which respects codon boundaries. Codon boundaries don't exist in the DNA, then only arise through its interpretation by the ribosome.

On the contrary, if i was engineering a polypeptide to add a furin cleavage site, i probably would align it to codon boundaries, so as not to disrupt the sequence.

I don't understand that either.

Other virologists seem to interpret the out-of-frame insert as being counterproductive.

Furin cleavage sites have evolved and are present in multiple coronaviruses:

- HCoV-OC43 (infects humans)

- HCoV-HKU1 (infects humans)

- MHV-A59

- ChRCoV-HKU24

- BtCoV-ENT

- BtNeCoV-PML-PHE1

- BtCoV-HKU4

- BtCoV-HKU5

- MERS-CoV

- BtHpCoV-Zhejiang2013

- SARS-CoV-2

Phylogenetic analysis suggests that it has evolved independently at least 6 times that we know of.

https://www.sciencedirect.com/science/article/pii/S187350612...

After that article was published a team in Thailand found furin cleavage sites in sarbecoviruses closely related to SARS-CoV-2 called RacCS203 (91.5% similarity to SARS-CoV-2) and RmYN02 (93.3% similarity to SARS-CoV-2)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/

Furin cleavage sites are common, nature understands how to utilize that trick very well, and continuously has re-discovered it.

The author has a pretty good CV, but as his Wikipedia entry notes, there is a concerning history to some of his publications. The WP entry cites several expressions of concern, which are worth a read. See, in particular, the note at the link below from Retraction Watch (one of the better sources for checking a researcher's bona fides):

Researcher who threatened Retraction Watch with lawsuit corrects funding source for several papers (https://retractionwatch.com/2013/10/17/researcher-who-threat...)

The argument made in the article seems well-supported, but I'm not competent to evaluate it. Given that this is an un-reviewed letter to the editor from a single (albeit apparently quite well-qualified) researcher, I'm going to wait for more (peer-reviewed) evidence before trying to form an opinion.

Uh this article is terrible.

There's a claim in there that the US funded GoF research at WIV, blaming it on Obama in 2015, but following the references I only arrive at:

https://nationalfile.com/faucis-niaid-funded-wuhan-lab-scien...

Which is about bat coronavirus in pigs:

https://en.wikipedia.org/wiki/Swine_acute_diarrhea_syndrome_...

Nothing to do with RaTG13 (or GoF).

> SARS-CoV-2 is a chimera, with most of its sequence identical to that of the bat CoV RaTG13, except for the receptor binding domain (RBD), which is almost identical to that of a pangolin (Manis javanica) CoV and has been optimized to bind the ACE2 receptor in human cells.

That claim is also wildly overstating what the reference it is citing can claim. The original reference states "The biggest divergence between SARS-CoV-2 and RaTG13 is observed in the RBD of their spike proteins" which is nowhere near the same as "most of its sequence identical to that of the bat CoV RaTG13", which is a false statement. The 4% sequence difference between SARS-CoV-2 and RaTG13 is more than the difference between humans and apes, they aren't "almost identical" anywhere. They are decades of evolution away from each other, along its whole genome.

This article is very, very bad.

The only interesting citation in this paper is (3) Segreto & Deigin "The genetic structure of SARS-CoV-2 does not rule out alaboratory origin" (DOI: 10.1002/bies.202000240). The other citations are political and unscientfic (1,5), scientific and neutral (4,6) or scientific and opposed (2).

Full text of citation (3) is available at https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202000..., and a rebuttal is available at https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202000.... Interested readers should refer to both of these articles, rather than to this strangely written summary.

I'm deeply skeptical of any 'science' that happens to perfectly fit an ideological narrative. Imagine the exact same thing with the opposite agenda, trying to show the virus didn't even start in China. In fact we don't have to imagine, there was literally a scientific-looking paper published as a pre-print which did just that [1]. Long story short the "theory" was that corona-virus actually came into China via imported frozen food (subtext: everything bad is a foreigners fault).

I know the seafood theory is bullshit nationalistic motivated reasoning. But I don't know how to refute the actual paper per se. I'm not a biologist. If for patriotic reasons I were predisposed to believe the sea food theory, and both scientists and the media were telling me the seafood theory is true, I might never notice how blatantly bullshit it is. Using the format of an academic article makes bullshit highly non-obvious.

So the lab leak theory. We have this thing that is very convenient to people predisposed to believe certain 'patriotic' things. The media seems to be picking it up out of no where for 'reasons that are surely free of agenda'. Some very academic looking articles have been published promoting the theory. If the 'science' going on here is actually just non-obvious bullshit mixed with nationalistic motivated reasoning, will I recognize it? Will you?

1. https://europepmc.org/article/PPR/PPR241540

Some context: https://www.firstpost.com/health/in-preprint-of-new-research...

The difference is that the lab leak hypothesis is being vigorously debated out in the open for all to see, by journalists and scientists from multiple countries, with references cited and available for perusal. China (allegedly) has gone out of its way to restrict access to records that might cast serious doubt on the lab leak theory and is peddling fairly preposterous alternative theories from state-controlled media outlets.

And in a year there's basically zero progress in hard facts supporting this hypothesis.

The debate so far looks like

   10 LET A = 0
   20 PRINT "Scientists: Look there is no evidence of a lab leak"
   30 PRINT "Journalists: What about" HYPOTHETICAL$(A)
   40 PRINT "Scientists: that very unlikely"
   50 PRINT "Journalists: So there is a chance!"
   60 A = A + 1
   70 GOTO 10

    65 REM ?
    70 GOTO 20

The "vigorous open debate" only began when the initially vehement denial of the possibility of a lab leak (from many Chinese and American scientists, officials, and press alike, e.g. Daszak's early 2020 publications) failed to convince

In any case, if the hypothesis turns out correct, the important question is not "who is to blame", it's "how exactly did this happen" and "following a detailed and public risk/benefit analysis, should we allow this kind of research to continue"

Whether something fits an ideology or political agenda should be irrelevant. Either it was engineered and escaped a lab or it didn’t.

Also in this case the GoF research was partly US funded and involved US researchers, so it can’t be blamed exclusively on China. If the lab leak hypothesis is true there will be lots of egg on lots of faces.

Should be irrelevant isn't the same as is irrelevant. You can't derive ought from is.

The methods of science and peer review and open debate only work when a majority of the participants are good faith disinterested truth seekers. When bad faith motivated reasoners start to crowd out the former, you end up with something akin to a show-trial. The process is technically followed by the result is a fraud.

There is so much political interest in the lab leak question that I think good faith scientists are strongly outnumbered. There's a truth value to the lab leak question, but I can't possibly expect to know it in this environment. Anyone making a claim to the contrary is a bullshitter.

> fit an ideological narrative.

That a narrative becomes attached to by a particular ideology does not make the narrative ideological itself.

> Imagine the exact same thing with the opposite agenda

uhm, you mean something like "this virus is 120% zoonotic and any suggestion otherwise is racist"

> Shi’s goal was to turn the bat CoVs into huACE2-binding molecules, that is, to design promoters of human infection.

what is the scientific use of creating viruses that are harmful to mankind?

It's a bad idea (regardless of whether it's how COVID originated or not), but there are theoretical benefits. Make a GoF virus, observe how it interacts with humanized nice, see how different therapeutic agents work.

The issue is that it's unlikely that any knowledge gained from the GoF research meaningfully accelerates the delivery of treatments or a vaccine, which is the hypothetical benefit that makes up for the increased risk of escape.

It's a basic research tool used in viral vaccinology. The US had a ban on GoF research that was rescinded in 2018 in part so GoF work could be conducted on MERS.

Important detail: it wasn't even a ban. It was a moratorium that prevented public funding for GoF research. Privately funded research was still allowed.

Thanks! My only point here is to push back on any idea that GoF research on viruses is unprecedented or necessarily malign.

I do not think it is basic and, in the field, hugely controversial. They tried really hard to keep that discussion inside the field, not allowing the general public to have a say in if they want to tax-fund the creation of pandemic-potential viruses in BSL2 labs. Stuxnet would be comparable to GoF coronavirus. Stuxnet also got out and hit Germany. Think they did that to research better virus scanners?

> The Director of the National Institute of Allergy and Infectious Diseases (NIAID) and the Director of the National Institutes of Health (NIH) have systematically thwarted efforts by the White House, the Congress, scientists, and science policy specialists to regulate GoF research of concern and even to require risk-benefit review for projects involving GoF research of concern.

> In 2014, the Obama White House implemented a “Pause” in federal funding for GoF research of concern. However, the document announcing the Pause stated in a footnote that: “An exception from pause may be obtained if head of funding agency determines research is urgently necessary to protect public health or national security”. Unfortunately, the NIAID Director and the NIH Director exploited this loophole to issue exemptions to projects subject to the Pause –preposterously asserting the exempted research was “urgently necessary to protect public health or national security”– thereby nullifying the Pause.

> In 2017, the Trump Administration announced a Potential Pandemic Pathogens Control and Oversight (P3CO) Framework that implemented a requirement for risk-benefit review of GoF research of concern. However, the P3CO Framework relies on the funding agency to flag and forward proposals for risk-benefit review. Unfortunately, the NIAID Director and the NIH Director have declined to flag and forward proposals for risk-benefit review, thereby nullifying the P3CO Framework.

I'm sitting next to someone who now works in the field and he disagrees with you. Moreover, you wrote a comment upthread suggesting that the real driver for all this work is military contracts, which is simply false. Perhaps you & I are best off not litigating this.

With what specifically? All of it, even the quote? If we are going to do an appeal to Oracle authority by proxy, I should at least get to interrogate it, and I agree, that would get tedious fast. Maybe he can comment?

I am not really suggesting the real driver of GoF of concern is military contracts, except maybe when looking at public funding sources.

> Meticulous investigation of U.S. government databases reveals that Pentagon funding for the EcoHealth Alliance from 2013 to 2020, including contracts, grants and subcontracts, was just under $39 million. Most, $34.6 million, was from the Defense Threat Reduction Agency (DTRA), which is a branch of the DOD which states it is tasked to “counter and deter weapons of mass destruction and improvised threat networks.”

> Most of the remaining money to EHA was from USAID (State Dept.), comprising at least $64,700,000 (1). These two sources thus total over $103 million.

https://www.independentsciencenews.org/news/peter-daszaks-ec...

I do think our back-and-forth can be useful, at least I learned something and removed some uncertainties.

If a basic research tool kills 3.5 million people, then maybe it should stop being a basic research tool.

Two: Study how to counteract them if they jump species.

Biological weapons -although an option is a pretty poor option because one, it’s not very lethal, but it can be economically effective.

Source for your first point?

Josh Rogin, who wrote a book that covers the arc of events around COVID and the work at the Wuhan lab, says the opposite. He says the people doing GoF research generally consider counteracting the viruses to be not their department.

However, he's more of an Asia expert, not a lab expert, so he could be wrong about this. That's why I wonder if your source is the same source I had originally when I had the same belief.. my source at the time was simply my own guess based on common sense, but according to Josh that's not how the research is set up.

This argument has been brewing for at least a decade from scientists creating new variants of avian flu.

https://www.scientificamerican.com/article/fears-grow-over-l...

Furthermore, did our own government fund such research in China via third party research labs? This seems to be going even beyond the initial “conspiracies” for the virus.

As Abraham Lincoln would have said: The best way to predict the future is to create it ¯\_(ツ)_/¯

Antiviral drug design, learning probable epidemic spillover pathways, immunogenetics... of course, it is still too dangerous, especially without some sort of artificial kill switch.

Even a kill switch isn't that useful. You just need a single virion to manage to drop the gene that encodes the kill switch to get your doomsday device.

A way to do bio weapons research and call it something else to avoid treaty violations?

The research is more to defend against bio weapons than to actually develop a bio weapon. A coronavirus wouldn't be an effective military weapon for a superpower like China or the USA. They already have weapons of mass destruction which are far more powerful and accurate with less "friendly fire" risk.

Plausible deniability is a top level requirement in any operation, and friendly fire is not always a serious concern.

Either way, these are only getting easier to make, and the response made it worth incalculably more.

Formally: Trying to predict spillover events. Ranking viruses by risk. They do this by having the virus infect human cells, so they can estimate if this would happen naturally in the future. Another is to work on vaccines.

Informally: Military biowarfare defense and offense.

Why are scientists doing this? Military and government funding galore. If you have the equipment and laboratory, you can publish papers forever. It is easier to do GoF, than to actually predict spillover events.

The most prominent critic of gain-of-function research, going so far as to call it gravely irresponsible, is the molecular biologist Dr. Richard H. Ebright.

https://www.independentsciencenews.org/commentaries/an-inter...

History will remember.

It's generally the military that's interested in this kind of research, which implies something about the intended use.

The ostensible reason is research on what the range of possible threats are, where you would think that learning how to fight them would be part of that, but is instead surprisingly sometimes "not my department" according to Josh Rogin who wrote a book on this.

More unofficial and non-scientific reasons that may not necessarily be in play are weapons research, and fetishizing of harmful viruses by sociopathic scientists working alongside other scientists.

> Only about 5% of arginines in SARS-CoV-2 or RaTG13 are coded by CGG.(3) This implies that the CGGCGG in the inset would have an estimated 0.25% probability to “naturally” occur as an encoder of the RR motif

Duplications are a common source of natural mutations, so I don't think it's right to multiply 5% like that (ie it's not an independent event)

ie once a "CGG" exists, a single copying error makes "CGGCGG" rather than 2 independent events next to each other.

We know genomes have repetitive sequences, but if you want to test, you could count 2x arginines in the viral sequence and seeing what the frequency is for the codons being different vs the same.

Could someone please point me to the relevant chapter of reference 4 here, where the reference to chimeric proteins is meant to be? (i.e. the right chapter of this handbook: Maier, H. J., Bickerton, E.; Britton, P. Coronaviruses – Methods and protocols; Humana Press: London, 2015)

I've looked through the table of contents, and I don't see anything that suggests this reference is in any way relevant? People keep citing this, and the most plausible conspiracy theory I can think of is that this is a way to pump citations to this chapter (I kid!).

This paper is terribly researched, none of the citations ultimately lead to references that support the claims.

There is no evidence that the Obama administration funded GoF research at WIV. They did fund research into swine-coronavirus in 2015, which is what the references actually say.

The author is relying on everyone to read the headlines, become easily impressed with technical terms like Chimeras and not bother checking references.

IMHO, this [https://news.ycombinator.com/item?id=24476300] should be de-flagged.

I think the first response to that other posting summarizes neatly why it should remain flagged while this one shouldn’t:

> Given the extraordinary nature of the claims, the fact that this didn't see any peer review and isn't published in a real journal as well as the clear political motivations of the money behind the study […]

To me, in this letter to editor, the same story was talked again as in the flagged PDF, in a more succinct writing style. I do not see why one is published and not flagged while the other one remains flagged.

This one possibly should be flagged instead. See here about the codons of the cleavage site: https://threadreaderapp.com/thread/1391507230848032772.html

This author has a PhD in chemical physics and has previously published peer-reviewed studies on SARS-CoV-2[1]. The ACS is also a reputable journal.

The previous source was not written by a domain expert, was not published in a peer-reviewed journal, and had (as others have pointed out) obvious political conflicts of interest that made it fundamentally untrustworthy.

[1]: https://orcid.org/0000-0002-5102-4294

I'm kind of disappointed this was flagged. It's a letter in ACS Medicinal Chemistry Letters, I don't see any reason this should be flagged. I know this is a politically charged issue, but I would think we can rise above that on HN and just talk about the science of it. If what this letter says is true, maybe it can help us prevent the outbreak of another pandemic. If it isn't true, I'd like to hear those arguments as well.

When the commenter mentions a tarnished publication history, that’s an understatement: he had multiple retractions for fraud.

https://retractionwatch.com/2015/01/09/plos-genetics-investi...

The linked article by Nicholas Wade contains a more detailed rundown of what is currently known: https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...

As he mentions, neither case has been proven - but he does make a fairly compelling argument that the "accidental lab leak" hypothesis best fits the available data, although there could be alternate hypotheses not considered here.

In particular, he notes that gain-of-function research on bat coronaviruses was often permitted in BSL2 or 3 facilities, vs. the more stringent BSL4 used for Ebola and Smallpox research, and this makes sense - it would be a gigantic pain in the ass to do any research in a BSL4 facility, and I could see the strong impetus to perform seemingly low-risk research in a less restrictive environment.

One interesting dynamic: Nicholas Wade used to be a science reporter for the New York Times, but was cancelled after publishing a book on genetics and race. I wonder if being sent into the wilderness is part of what enabled him to publicize the unpopular (at least, in the mainstream media) lab leak hypothesis.

Or his investment into lab leak hypothesis is just another symptom of him going into the fringe.

Well, seems unlikely but if so will readily become consensus.

To clarify, not weighing in on the unlikeliness of lab leak, only on the unlikeliness that it is a clearly identifiable uncategorically man made Chimera with obviously manipulated genetic markers.

I have couple of questions, if there are two main theories: virus came from lab or through evolution:

1) can artificial viruses be injected in wild animals? (I guess so) 2) can that animal then pointed as a natural source? (I guess so)

I ask this because: 1) science has difficulty to answer what is natural and what is artificial, we have the whole genome, and yet we cannot tell if it is artificial or natural development 2) how could science say that virus in wild animal is natural or artificial?

Why don’t we inject by protocol an artificial detection sequence when we do this kind of research?

My crack-pottery detector is giving a low whine. I don't have qualified background, but even then, the arguments seem fairly weak, similar to the kinds that argue for intelligent design. The author's somewhat controversial history doesn't help either.

Could anybody explain why the virus was previously considered, at least by some, a mosaic type [in an evident way], while this paper (and the research it's based on) considers it likely to be chimeric?

Because that's a word that leads one towards assuming it was a lab leak. RaTG13 and SARS-CoV-2 are different all over their genome. They differ considerably in their spike protein because RaTG13 doesn't bind to ACE2 while SARS-CoV-2 and the pangolin coronavirus they reference do bind to ACE2 so they're more similar there. Evolutionary pressures are sufficient to explain the differences, you don't need human gene splicing. And the differences across the genome are decades different. The word "chimera" is being thrown out there to manipulate you into believing their conclusions, they don't really support it at all.

"Genomic analyses(3) show that SARS-CoV-2 is a chimera, with most of its sequence identical to that of the bat CoV RaTG13, except for the receptor binding domain (RBD), which is almost identical to that of a pangolin (Manis javanica) CoV and has been optimized to bind the ACE2 receptor in human cells.(3) Such gain-of-function chimeras can in principle arise via natural recombination, but that would be unlikely in this case. The natural recombination would require that the viruses from bat and pangolin infected the same cell in the same organism simultaneously, a rather improbable event considering the low population density of pangolins,"

The last line settles it -> "The natural recombination would require that the viruses from bat and pangolin infected the same cell in the same organism simultaneously, a rather improbable event considering the low population density of pangolins"

Could you please stop creating accounts for every few comments you post? We ban accounts that do that. This is in the site guidelines: https://news.ycombinator.com/newsguidelines.html.

You needn't use your real name, of course, but for HN to be a community, users need some identity for other users to relate to. Otherwise we may as well have no usernames and no community, and that would be a different kind of forum. https://hn.algolia.com/?sort=byDate&dateRange=all&type=comme...

It is technically not RaTG13. The labs have samples from patients who infected with RaTG13 and never publish them. I think those samples are more likely the source but it doesn't change the full picture.

For something which is supposedly lab manipulated, it seems to be doing a poor job.

For example, the YoY deathtoll changes in countries with low or minimal lockdowns (like Sweden and Ukraine) are only about 6%, and even then mainly explained by mortality shifting (weak 2019 flu season).

Deathtoll from COVID in 2020 in Sweden is about the same as the 2009 Swine Flu wave (https://swprs.org/wp-content/uploads/2020/10/sweden-monthly-... )

Deathtolls in lockdown countries are higher... due to lockdowns disrupting regular life (diets, medical care, human contact).

The bigger aspect which I think is being manipulated is the political and media response.

And the most logical explanation for that manipulation is to degrade Western economies and prepare them for massive money printing (witness the increase in wealth for the top 1%), as well as supporting a desired outcome for the 2020 US Election.

Lab manipulation doesn't necessarily mean biological warfare. It much more likely means study of a type of potential future naturally occurring virus that is dangerous to humans.

The recent article on medium by Don McNeil Jr came out, and seems to have broken the taboo around talking about this. I suspect that there is something out there not yet reported.

But at the face of it, it all breaks down to something simple - if a evolved smallpox virus emerged in Atlanta, is there anyone on the face of the planet that wouldn't believe it is a lab leak?

Lab leaks have a documented history of occurring, at least where that documentation is allowed to exist in the first place. Lab leaks have occurred where that documentation isn't allowed to exist (see USSR)

Yes, we have a coronavirus that appears to have emerged from the same city as the only BSL-4 in china, which also happens to be home of Shi Zhengli, who happens to have discovered the virus most related to SARS-COV2. Said lab was also doing "gain of function" research which was previously flagged as being dangerous on coronaviruses.

The only reason, at this point, that people are not assuming by default that this is a a lab leak, is because of the racism that some idiots engage in, Trump's actions (aforementioned idiot) and that the Chinese desperation to blame anyone but them.

The thing here is that China has spent so denying any access to WIV and than making insanely outlandish claims that they are now in a no-win situation. their stance required everyone to say "it's never creditable". Now that some say it is creditable, they either have to completely open their institutions and promote transparency (cancer for any authoritarian state) or keep access closed, and have this become if not the authoritative narrative, at least a dominate narrative.

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