12 ms·

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

190 points by JohnJamesRambo 5y ago

ttflee 5y ago
IMHO, this [https://news.ycombinator.com/item?id=24476300 https://news.ycombinator.com/item?id=24476300] should be de-flagged.
- woodruffw 5y ago
  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 […]
  - ttflee 5y ago
    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.
    - bonzini 5y ago
      This one possibly should be flagged instead. See here about the codons of the cleavage site: https://threadreaderapp.com/thread/1391507230848032772.html https://threadreaderapp.com/thread/1391507230848032772.html
    - woodruffw 5y ago
      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 https://orcid.org/0000-0002-5102-4294
- late2part 5y ago
  More than de-flagged, this should prompt a review of the culture and attitude that caused it to be flagged, and for that flag to stand. Also, Epstein did not kill himself; for an example of other unpopular assertions that are often censored.
pmcollins 5y ago
> 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?
- scarmig 5y ago
  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.
- tptacek 5y ago
  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.
  - deleted 5y ago
    [deleted]
  - ithkuil 5y ago
    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.
    - tptacek 5y ago
      Thanks! My only point here is to push back on any idea that GoF research on viruses is unprecedented or necessarily malign.
  - deugo 5y ago
    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.
apalmer 5y ago
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.
tomp 5y ago
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).
- ttflee 5y ago
  It referred to the viral cDNA as the sequencing was performed on, hence the 'T'.
- rich_sasha 5y ago
  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?
  - sudosysgen 5y ago
    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.
    - COGlory 5y ago
      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.
MPSimmons 5y ago
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 https://pubs.acs.org/page/amclct/about.html [2] - https://en.wikipedia.org/w/index.php?title=Ariel_Fernandez&oldid=1024897239#Career https://en.wikipedia.org/w/index.php?title=Ariel_Fernandez&o...
- ed25519FUUU 5y ago
  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.
  - MPSimmons 5y ago
    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.
    - ed25519FUUU 5y ago
      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.
- late2part 5y ago
  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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484390/
deleted 5y ago
[deleted]
AprilArcus 5y ago
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.202000240 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.202000325 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.
cal5k 5y ago
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-people-or-nature-open-pandoras-box-at-wuhan/ 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.
- scarmig 5y ago
  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.
  - scotty79 5y ago
    Or his investment into lab leak hypothesis is just another symptom of him going into the fringe.
hirenj 5y ago
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!).
- lamontcg 5y ago
  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.
ajarmst 5y ago
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-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.
- deleted 5y ago
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- deleted 5y ago
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pizza234 5y ago
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?
- lamontcg 5y ago
  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.
IIAOPSW 5y ago
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 https://europepmc.org/article/PPR/PPR241540 Some context: https://www.firstpost.com/health/in-preprint-of-new-research-paper-chinese-scientists-claim-coronavirus-may-have-originated-in-india-or-bangladesh-9063581.html https://www.firstpost.com/health/in-preprint-of-new-research...
- cal5k 5y ago
  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.
  - scotty79 5y ago
    And in a year there's basically zero progress in hard facts supporting this hypothesis.
vfclists 5y ago
Is it safe? Is it safe? Is it safe ... to discuss... this delicate matter ... now? Is it safe? Terrible toothache coming on.
- vfclists 5y ago
  The speed at which this post has been downvoted is frightening, just 4 minutes in? Makes you think it is monitored for comments that disagree with the MSM agenda/consensus. PS. Just because you are paranoid doesn't mean they are not out to get you!!
  - dqv 5y ago
    If you read any comment thread on HN, the ones that don't contribute anything meaningful to the discussion get downvoted rather fast. That's the only consensus you're seeing.
    - deugo 5y ago
      I do feel their frustration. For many this has been on their mind for over a year now, and science and media painted them as racist conspiracy theorists. I am not sure about HN. But on everywhere else on the internet right now, this issue is still incredibly astro-turfed. And it has not ended yet! We will see the frozen-food theory or "It came from Italy" disinformation espoused soon, by prominent scientists, repeated in the media. The tooth ache is just beginning. https://www.propublica.org/article/leaked-documents-show-how-chinas-army-of-paid-internet-trolls-helped-censor-the-coronavirus https://www.propublica.org/article/leaked-documents-show-how... https://www.straitstimes.com/asia/east-asia/taiwan-accuses-chinese-trolls-of-sowing-coronavirus-panic https://www.straitstimes.com/asia/east-asia/taiwan-accuses-c... https://www.foxnews.com/world/china-used-internet-troll-army-to-shape-coronavirus-narrative-report https://www.foxnews.com/world/china-used-internet-troll-army... But maybe HN is unique? One thing to control a narrative you can't control, is to have a post flagged. I am getting sleepy. Is it safe yet?
bungle 5y ago
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?
lamontcg 5y ago
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-scientists-to-research-bat-coronavirus/ 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_coronavirus 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.
jonnycomputer 5y ago
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.
InTheArena 5y ago
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.
deugo 5y ago
Just me and my homies in a flagged thread downvoting the last comment. Taiwan is a country. Edit: 2 minutes! Rather fast, indeed.
JohnJamesRambo 5y ago
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.
tway223 5y ago
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.
ArkanExplorer 5y ago
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-deaths-1851.jpg 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.
- anoyesnonymous 5y ago
  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.
haihaibye 5y ago
> 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.
techbooger 5y ago
"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"
- dang 5y ago
  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 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=comment&storyText=false&prefix&page=0&query=community%20identity%20by:dang https://hn.algolia.com/?sort=byDate&dateRange=all&type=comme...
agvaughan 5y ago
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-investigating-paper-ariel-fernandez/ https://retractionwatch.com/2015/01/09/plos-genetics-investi...

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

woodruffw 5y ago
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 […]
- ttflee 5y ago
  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.
  - bonzini 5y ago
    This one possibly should be flagged instead. See here about the codons of the cleavage site: https://threadreaderapp.com/thread/1391507230848032772.html https://threadreaderapp.com/thread/1391507230848032772.html
  - woodruffw 5y ago
    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 https://orcid.org/0000-0002-5102-4294
late2part 5y ago
More than de-flagged, this should prompt a review of the culture and attitude that caused it to be flagged, and for that flag to stand. Also, Epstein did not kill himself; for an example of other unpopular assertions that are often censored.

pmcollins 5y ago

> 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?

scarmig 5y ago
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.
tptacek 5y ago
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.
- deleted 5y ago
  [deleted]
- ithkuil 5y ago
  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.
  - tptacek 5y ago
    Thanks! My only point here is to push back on any idea that GoF research on viruses is unprecedented or necessarily malign.
- deugo 5y ago
  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.

apalmer 5y ago

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.

tomp 5y ago

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).

ttflee 5y ago
It referred to the viral cDNA as the sequencing was performed on, hence the 'T'.
rich_sasha 5y ago
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?
- sudosysgen 5y ago
  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.
  - COGlory 5y ago
    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.

MPSimmons 5y ago

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 https://pubs.acs.org/page/amclct/about.html [2] - https://en.wikipedia.org/w/index.php?title=Ariel_Fernandez&oldid=1024897239#Career https://en.wikipedia.org/w/index.php?title=Ariel_Fernandez&o...

ed25519FUUU 5y ago
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.
- MPSimmons 5y ago
  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.
  - ed25519FUUU 5y ago
    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.
late2part 5y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484390/

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AprilArcus 5y ago

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.202000240 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.202000325 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.

cal5k 5y ago

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-people-or-nature-open-pandoras-box-at-wuhan/ 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.

scarmig 5y ago
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.
- scotty79 5y ago
  Or his investment into lab leak hypothesis is just another symptom of him going into the fringe.

hirenj 5y ago

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!).

lamontcg 5y ago
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.

ajarmst 5y ago

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-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.

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pizza234 5y ago

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?

lamontcg 5y ago
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.

IIAOPSW 5y ago

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 https://europepmc.org/article/PPR/PPR241540 Some context: https://www.firstpost.com/health/in-preprint-of-new-research-paper-chinese-scientists-claim-coronavirus-may-have-originated-in-india-or-bangladesh-9063581.html https://www.firstpost.com/health/in-preprint-of-new-research...

cal5k 5y ago
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.
- scotty79 5y ago
  And in a year there's basically zero progress in hard facts supporting this hypothesis.

vfclists 5y ago

Is it safe? Is it safe? Is it safe ... to discuss... this delicate matter ... now? Is it safe? Terrible toothache coming on.

vfclists 5y ago
The speed at which this post has been downvoted is frightening, just 4 minutes in? Makes you think it is monitored for comments that disagree with the MSM agenda/consensus. PS. Just because you are paranoid doesn't mean they are not out to get you!!
- dqv 5y ago
  If you read any comment thread on HN, the ones that don't contribute anything meaningful to the discussion get downvoted rather fast. That's the only consensus you're seeing.
  - deugo 5y ago
    I do feel their frustration. For many this has been on their mind for over a year now, and science and media painted them as racist conspiracy theorists. I am not sure about HN. But on everywhere else on the internet right now, this issue is still incredibly astro-turfed. And it has not ended yet! We will see the frozen-food theory or "It came from Italy" disinformation espoused soon, by prominent scientists, repeated in the media. The tooth ache is just beginning. https://www.propublica.org/article/leaked-documents-show-how-chinas-army-of-paid-internet-trolls-helped-censor-the-coronavirus https://www.propublica.org/article/leaked-documents-show-how... https://www.straitstimes.com/asia/east-asia/taiwan-accuses-chinese-trolls-of-sowing-coronavirus-panic https://www.straitstimes.com/asia/east-asia/taiwan-accuses-c... https://www.foxnews.com/world/china-used-internet-troll-army-to-shape-coronavirus-narrative-report https://www.foxnews.com/world/china-used-internet-troll-army... But maybe HN is unique? One thing to control a narrative you can't control, is to have a post flagged. I am getting sleepy. Is it safe yet?

bungle 5y ago

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?

lamontcg 5y ago

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-scientists-to-research-bat-coronavirus/ 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_coronavirus 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.

jonnycomputer 5y ago

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.

InTheArena 5y ago

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.

deugo 5y ago

Just me and my homies in a flagged thread downvoting the last comment. Taiwan is a country. Edit: 2 minutes! Rather fast, indeed.

JohnJamesRambo 5y ago

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.

tway223 5y ago

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.

ArkanExplorer 5y ago

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-deaths-1851.jpg 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.

anoyesnonymous 5y ago
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.

haihaibye 5y ago

> 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.

techbooger 5y ago

"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"

dang 5y ago
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 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=comment&storyText=false&prefix&page=0&query=community%20identity%20by:dang https://hn.algolia.com/?sort=byDate&dateRange=all&type=comme...

agvaughan 5y ago

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-investigating-paper-ariel-fernandez/ https://retractionwatch.com/2015/01/09/plos-genetics-investi...