[HN Gopher] Endonuclease fingerprint indicates a synthetic origi... ___________________________________________________________________ Endonuclease fingerprint indicates a synthetic origin of SARS- CoV-2? Author : johnwdefeo Score : 100 points Date : 2022-10-20 19:11 UTC (3 hours ago) (HTM) web link (www.biorxiv.org) (TXT) w3m dump (www.biorxiv.org) | excalibur wrote: | Of course the lab leak origin is probably accurate, it appeared | right in the vicinity of the lab and is the exact thing they were | studying. This shouldn't be controversial, it shouldn't have been | politicized to the point where the truth matters far less than | whose narrative it supports. We should have taken it as an | accident, learned lessons, improved processes, and moved on. | Instead we tore ourselves apart, and now we're back to playing | nuclear Russian roulette, with maybe half the chambers loaded | this time. Good job humans. | graeme wrote: | Popular science summary of paper from one of the authors: | https://alexwasburne.substack.com/p/a-synthetic-origin-of-sa... | puffoflogic wrote: | fdgsdfogijq wrote: | True story, in early January of 2020, on an academic virology | forum, which I wont link, it was known the virus was synthetic. | Before the story hit the mainstream media, professors were | sharing data about the virus fingerprint. There were concerns | about the integrity of the data shared by the Chinese. One | specific comment I will never forget by a Harvard professor when | discussing the implications: | | "Should we turn on the bat signal" | | Which I always interpreted it to mean should we alert the | authorities. A week later all posts were deleted and nothing | could be found. | Dig1t wrote: | Is there a wayback machine archive of that conversation? | shikshake wrote: | > which I wont link | | Why not? HN promotes logical evidence-backed discussion. The | least you can do is link the forum. | sneak wrote: | "it was known" are weasel words on wikipedia. | | Known by whom? Why? Based on what evidence? Can we know it, | too? | m0llusk wrote: | There are at least a couple of suspicious points in this study: | | First and foremost the central claim is that 5 potential | restriction binding sites versus 2 means that SARS-CoV2 is non | natural. That does not necessarily follow. Just as SARS-CoV2 is | unusually infectious and damaging to humans it could just happen | to have an additional 3 restriction binding sites. So there is | nothing inconsistent with natural selection of viral | characteristics, only a comparison between wild and lab viruses. | | Second, the evidence for the wet market origin is trivialized. | That argument points out that genetic drift is well characterized | and the presence of two closely related SARS-CoV2 variants | cultured from the wet market is extremely strong evidence that is | where the virus initially appeared. Both arguments make use of | detailed genetic evidence, but the wet market argument based on | genetic drift is quite robust while this alternative theory | merely presents similarities while not ruling out natural | selection. | | Thirdly, this paper emphasizes the strong impact of the COVID | pandemic and asserts that understanding the origins of the virus | would necessarily aid in preventing future pandemics. This does | not clearly follow. Especially if the virus had natural selection | origins there is no clear and obvious way of systematically | reducing risk. Simply living or traveling where host populations | like bats live could be enough to generate exposures and it is | not simple to clear people off of rural habitations. | | These second and third criticisms are not direct against the | evidence and logic presented, but show a dangerous level of | sloppiness in the research that makes this paper appear more like | slanted analysis from someone with an agenda than a critical | thinking scientist genuinely interested in the truth and | therefore needing to consider alternatives and potential | falsification of the hypothesis. | s1artibartfast wrote: | >Thirdly, this paper emphasizes the strong impact of the COVID | pandemic and asserts that understanding the origins of the | virus would necessarily aid in preventing future pandemics. | | I strongly disagree. If of natural origin, there are a plethora | of simple controls that could be implemented. Control doesn't | necessarily need to be perfect. Some simple controls could be | restrictions or bans on Commercial trade or transport of high- | risk animals. If not of natural origin, it obviously indicates | that BSL4 controls are inadequate or inconsistently applied. A | simple but perhaps costly solution might be to not certify bsl4 | Laboratories in dense Urban settings. | tripletao wrote: | I generally agree, but would note that the WIV worked with | novel natural or synthetic bat-origin viruses at BSL-2 or -3, | mostly not BSL-4. From an interview with Dr. Shi: | | > A: The coronavirus research in our laboratory is conducted | in BSL-2 or BSL-3 laboratories. [...] | | https://web.archive.org/web/20210727042832/https://www.scien. | .. | iso1337 wrote: | Their claims around Type IIS assembly are also suspect. eg in | Golden Gate assembly, you choose Type IIS that reach over and | cut, so the restriction site is absent from the final assembled | product. | | "Additionally, because the final product does not have a Type | IIS restriction enzyme recognition site, the correctly-ligated | product cannot be cut again by the restriction enzyme, meaning | the reaction is essentially irreversible" | | https://en.wikipedia.org/wiki/Golden_Gate_Cloning ---- | | The choice of focusing on a particular RE pair also smells of | p-hacking. Their claim that BsaI/BsmBI makes for easy | mixing/matching genomes doesn't make sense in this day and age, | when you can use other techniques to make hybrids more | effectively (eg, you are not restricted to the natural location | of those restriction enzyme sites) | tripletao wrote: | > That argument points out that genetic drift is well | characterized and the presence of two closely related SARS-CoV2 | variants cultured from the wet market is extremely strong | evidence that is where the virus initially appeared. | | I assume you're referring to Pekar et al. here? The two | lineages are literally just two SNPs apart, so it's near- | impossible to distinguish whether they arose from two separate | introductions, or just from two super-spreading events after | cryptic evolution in humans from a single earlier introduction. | Pekar builds an epidemiological model that purports to find | that evolution in humans is p ~ 0.5% unlikely; but that result | is highly sensitive to the assumptions in that model, most | notably their choice of a scale-free infection network (and | thus power-law distribution of number of other people each | patient infects). Robustness to that infection network isn't | studied. | | The author of this endonuclease fingerprint preprint also has a | preprint on Pekar's model, | | https://www.biorxiv.org/content/10.1101/2022.10.10.511625v1 | | Note that I'm criticizing Pekar here, not endorsing the | endonuclease preprint. I don't have a great sense of the | correct Bonferroni correction (to borrow Prof. Balloux's | framing) to apply to the latter's probabilities. | Dig1t wrote: | I really don't see how saying that the pandemic was a bad thing | and that there is value in understanding its origin is "a | dangerous level of sloppiness". | nl wrote: | Well considering that's not what the OP said at all I guess | it's ok you don't see that. | swamp40 wrote: | > third criticisms...show a dangerous level of sloppiness | Dig1t wrote: | >These second and third criticisms are not direct against | the evidence and logic presented, but show a dangerous | level of sloppiness in the research | | OP _literally_ said that. | _jal wrote: | The accusation of sloppiness is based on two claims, and | you're only responding to a bastardization of one of them. | lizardactivist wrote: | throwawaymaths wrote: | This is brilliant: it looks at the negative space in restriction | enzymes cut patterns to determine the likelihood that these sites | have been engineered out. I don't see details on why they picked | BSM-B1 to analyze, but the only thing is if they looked at | several re sites and only reported the interesting one, that | alters the meaning of the statistics to the negative of the | hypothesis. (I happen to believe the lab leak hypothesis -- there | are receipts if you search hard, but I think we should be careful | about our evidence) | Traubenfuchs wrote: | So biotech companies secretly manufacturing illnesses that are | just deadly enough to the old and sick to cause international | panic and then offering the cure or vaccination for it is now a | totally possible scenario, or even something to expect? | | Maybe the the latest international slightly more infectious and | STD-like monkeypox wave was another example of this? It certainly | lead to a lot of vaccinations... | KoftaBob wrote: | More likely it's academic laboratories doing reckless gain of | function research because it keeps the grant money rolling in, | and in Wuhan Lab's case, they also half ass the safety | precautions. | ishche wrote: | Isn't it enough infections already to sell tons of drugs, why | to design the new for this case? | Ancapistani wrote: | Well, if you own the patent on the only approved drug for the | condition, it would make financial sense. | | _NOTE_ : I am emphatically not asserting that this is the | case with SARS-CoV-2. I am only responding to the parent | comment's criticism of a possible financial motive for | hypothetical biotech companies to purposefully engineer | pathogens for profit. | funnymony wrote: | mrkramer wrote: | >So biotech companies secretly manufacturing illnesses.... | | They are not but they profit from lab leaks liked Covid. | jalino23 wrote: | do I understand this correctly? that the paper is saying that | covid 19 is highly likely a synthetic virus? | shadowgovt wrote: | It's claiming that there are sequences on the viral code that | are unlikely to have occurred naturally, but are really | convenient for slicing the genetic sequence in a lab context. | | Sort of like if you shaved the fur on a hyena and discovered a | "THIS END UP" tattoo on its skin. | jalino23 wrote: | oh damn! thats very interesting | adamredwoods wrote: | Coincidentally, Alex Washburne is also trying to get his startup | going: https://selvasci.substack.com/p/coming-soon | someuser54541 wrote: | Genuinely surprises me that there are people out there who think | or have been persuaded the virus is of natural origin. The lab | right next to the market was literally studying and experimenting | with the exact same type of virus. How can a someone think that | that's just a coincidence? | | Add that to the fact that the funding for that research lab was | _approved by the same guy who become the de facto thought leader | on the virus in the U.S._ , AND funded by the foundation of one | of the most recognizable American billionaires. To put the cherry | on top, even suggesting a synthetic origin resulted in bans on | most social platforms! | | This stuff is common sense...Occam's razor comes to mind. No | wonder there were so many "conspiracy theories". | whydid wrote: | https://en.m.wikipedia.org/wiki/Sagan_standard | | Extraordinary claims require extraordinary evidence. This is | why people are skeptical. | MockObject wrote: | Great attempts are made to prevent lab leaks, so a failure of | procedure can't be considered extraordinary. | arisAlexis wrote: | It depends on bayesian priors.how mahy coronaviruses were | studied, how frequently a new virus is found next to a biolab | of said virus by chance etc. The extraordinary claim could be | that it is of natural origin actually. | bequanna wrote: | How is it an extraordinary claim? | | It is by far the simplest and most obvious explanation. | beiller wrote: | I have the opposite Occam's razor thoughts. My opinion is we | are not capable of developing in a lab a virus that is so | transmissible and survivable in human species only. I think the | complexity of the virus machinery and its interactions inside | of our bodies and immune system is beyond astronomical in | complexity. It's laughable to suggest that we are so | intelligent as to invent a better version of the machinery that | is hypothesized as the very machinery responsible for creation | of multi cellular life itself. | someuser54541 wrote: | > My opinion is we are not capable of developing in a lab a | virus that is so transmissible and survivable in human | species only. I think the complexity of the virus machinery | and its interactions inside of our bodies and immune system | is beyond astronomical in complexity. It's laughable to | suggest that we are so intelligent as to invent a better | version of the machinery that is hypothesized as the very | machinery responsible for creation of multi cellular life | itself. | | The very first synthetic virus created in 2002 and was | modeled after polio, which is fairly transmissible and | affects humans. That virus was made 20 years ago; synthetic | biology has come a very long way since then. | | Does that fact alter your opinion? | iso1337 wrote: | There is a huge variety of viruses, just because someone | wrote the equivalent of "Hello World" doesn't mean you can | write a complicated CMS anytime soon. | | Synthetic biology (the actual synthesis of DNA) has come a | long way, we don't understand all the components yet | though. | beiller wrote: | Sorry it does not. Was that virus more deadly, effective, | or in any other measure better than the original polio? Or | was it "polio" with a spike protein glued to it's head? | johnwdefeo wrote: | Speaking as an artist, many (most?) of my enduring works were | the result of an accident of some kind. I call them "happy | accidents" because I recognized that the mistake was better | than whatever the vision was that I had at the time. | | As a corollary, there are unhappy accidents, and with respect | to life forms in a chaotic system, such accidents can | perpetuate and endure without human recognition. | bee_rider wrote: | > Genuinely surprises me that there are people out there who | think or have been persuaded the virus is of natural origin. | The lab right next to the market was literally studying and | experimenting with the exact same type of virus. How can a | someone think that that's just a coincidence? | | It seems plausible, at least, that it leaked from the lab, in | the sense that labs aren't magically impenetrable and leaks | could happen. | | > Add that to the fact that the funding for that research lab | was approved by the same guy who become the de facto thought | leader on the virus in the U.S., AND funded by the foundation | of one of the most recognizable American billionaires. To put | the cherry on top, even suggesting a synthetic origin resulted | in bans on most social platforms! | | I don't understand what this is supposed to mean. How does the | fact that this guy (Fauci?) approved some funding make COVID | seem more likely to have been leaked from a lab? It seems | natural that somebody who's been working in government on | medical topics at a high level for a long time would have | approved funding on lots of things, and also likely that they'd | become a figurehead in a pandemic, but I don't see any deeper | links. | arisAlexis wrote: | Add to that that China forbade investigations and furthermore | these regimes have a long history of obscurity | AnonymousPlanet wrote: | Studied and then escaped from a lab does _not_ equal synthetic. | | Exactly nothing in your post supports a synthetic origin over a | sample from nature that got studied in a lab. | | Jumping to these kinds of one sided conclusions should be a red | flag. | jhgkjhlkhjkljk wrote: | kelseyfrog wrote: | My Occam's razor says that every other virus has a natural | origin, why wouldnt this one too? Maybe your razor needs | sharpening? | MockObject wrote: | How can you prove that _natural origin_ is the hypothesis | selected by the razor in this particular case? | shadowgovt wrote: | The point of Occam's Razor is you _can 't_ prove the things | the Razor leans you to. Not in a way sufficient to remove | the need to invoke the Razor. But you can say that one | explanation is simpler than another (such as a pandemic | virus being more closely patterned to every other pandemic | in human history than to a novel mechanism that has never | become a pandemic before). | | I see a bright glow on the eastern horizon about 7AM and | it's probably the sun coming up. It _could_ be the first | strike in a world-ending nuclear exchange. I can 't prove | it isn't. | | ... but it's probably not. | MockObject wrote: | I wasn't asking for a proof of the phenomenon, but a | proof that the razor points to that phenomenon. | shadowgovt wrote: | That's going to come down to an individual observer's | priors on probabilities of "pandemic virus being more | closely patterned to every other pandemic in human | history" vs. "pandemic introduced via a novel mechanism | that has never become a pandemic before." | MockObject wrote: | Wasn't the lab working with coronaviruses? So maybe some | of it escaped. I really don't see how that's an | unnecessary multiplication of entities. Is the objection | simply that, pandemics have emerged from markets, but not | labs? But we know that an escape of a coronavirus could | lead to a pandemic. | | I see nothing needlessly complex here, and certainly not | extraordinary. | someuser54541 wrote: | > My Occam's razor says that every other virus has a natural | origin, why wouldnt this one too? | | That's simply not true. There's an entire branch of virology | dedicated to synthetic viruses; the first was made over 20 | years ago. | kelseyfrog wrote: | Thanks for the info. I'm updating my Occam's razor so that | all new viruses are of synthetic origin. | jhgkjhlkhjkljk wrote: | adamredwoods wrote: | Seeing how the previous SARS-CoV was from natural origins, | most likely the following ones will be, too. | | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113851/ | | >> In most bat families, both alpha- and betacoronaviruses | are known, and these detections have originated from both | frugivorous and insectivorous bat hosts. Lack of detection in | the remaining bat families is likely due to non-exhaustive | sampling of the almost 1200 extant bat species (Schipper et | al., 2008, Simmons, 2005, Teeling et al., 2005). This void | may be filled in future studies. | jgeada wrote: | So a likely extremely controversial paper being shared publicly | to a non-expert audience prior to any peer-review. | | Is this going to be yet one more of those "will be withdrawn | after peer scrutiny but by then it is too late because the false | meme has been injected into the public consciousness" things? | johnwdefeo wrote: | I sincerely hope not. From one of the authors: | | "Scientists publish papers not because the paper is the end of | science, but because it is a unit of research that is valuable | to share with others so that others can use this brick of | knowledge and either build with it... or find its weakness and | break it down...We wrote our entire analysis in R and shared | our code with the world. I tried SO hard to check every single | line of code and make our pipeline clear & easy to reproduce. | However, despite nearly giving myself stomach ulcers checking | every line and stressing about these findings, it's possible | someone finds a mistake in our work. We don't share this work | happily - this is the saddest paper I've ever written. We've | shared our code precisely for that reason: we want you to see | exactly what we've done, and if we've done something wrong we | are open to hearing it." | | As to your original concern, it is a valid one. I wrote this is | response to pre-prints popularized via the press earlier this | year: | | -> Make bold, unjustifiable claims in the preprint; -> Ensure | widespread coverage in the science press; -> Walk back those | claims during peer-review; -> Get published; and then -> Watch | blue checks tout original claims as "Fact!" | iso1337 wrote: | Any publicity is good publicity. Sprinkle in some words about | "this needs further study" and hope someone comes along to | fund the next few years of your lab. | spookthesunset wrote: | > Is this going to be yet one more of those "will be withdrawn | after peer scrutiny but by then it is too late because the | false meme has been injected into the public consciousness" | things? | | They only get withdrawn if they go against the narrative. Any | kind of paper that says masks work, lockdowns work, or any | paper suggesting Covid is worse than any virus ever... it's | totally cool to share publicly. Doesn't even matter if it is | poorly constructed or turns out to be false. | graeme wrote: | They did share it with scientists. Here's Francois Balloux | saying he replicated the results, tried to find holes, couldn't | | https://mobile.twitter.com/BallouxFrancois/status/1583165259... | jshaqaw wrote: | guelo wrote: | I've seen several papers with the opposite conclusion. Why do we | only see the lab leak hypothesis front paged on HN? | callesgg wrote: | I Honestly thought it was common belief that corona come from | that lab in china. | | But now after reading this, I searched a bit and read up on it | and I guess it is still a somewhat honest debate on the topic. | | Even if it was lab made, it would be sort of stupid to dig in to | it, due to the political nature of the matter. What happened | happened, most likely the release would have been accidental, so | why play blame games. | navhc wrote: | I don't think it's all about blame, knowing it came from a lab | would also pull into question the practice of engineering | viruses and the safety and security standards required. | callesgg wrote: | True, it would be helpful in that kind of way. The risks does | seam to outweigh the benefits. | | That said, the blame game would still be there, and people | would pull that card... | sneak wrote: | If it is possible that viruses of this type could be | engineered, then lab safety needs to be upgraded anyway (or | GoF research banned, or both) regardless of the origin of | this specific virus. | | It's all about blame. Blame is a useful geopolitical tool. | danbtl wrote: | > why play blame games | | Because of the question of liability: If it was lab made and | accidentally released, was it due to recklessness or criminal | negligence? Is someone guilty of involuntary mass-manslaughter? | Or if this was state-sponsored research, could they be found | liable for the damage caused? | pencilguin wrote: | What court would usefully find this? What authority would | enforce it? | cybertronic wrote: | US court? | ISL wrote: | If it was released from a lab, no matter whether or not it was | accidental, Covid would be the mother of all torts. The entire | planet can show harm and will be _very_ interested in | recovering their losses from the entity that mis-handled a | lethal virus. | rlpb wrote: | It'd be much like trying to recover money stolen by a drug | addict though. Instant bankruptcy and proportionally nothing | recovered, to the point that it's not even really worth it. | ISL wrote: | A drug addict with a $14T GDP. | | With ~7M deaths and a ~$1-10M value of human life [1], | that's $7-70T in losses in lives alone, before lost | productivity and economic value. | | [1] https://en.wikipedia.org/wiki/Value_of_life#:~:text=In% | 20Wes.... | rlpb wrote: | Only if liability transfers to the state. Even if state- | owned, plenty of state-owned enterprises have limited | liability. | adamredwoods wrote: | Even the big paper publishers say "No conclusive evidence for | either theory." | | https://www.science.org/content/article/do-three-new-studies... | | >> Still, Worobey and his co-authors concede, even that | evidence might not be enough to end this polarizing debate. | "With the way that people have been able to just push aside any | and all evidence that points away from a lab leak, I do fear | that even if there were evidence from one of these samples that | was full of red fox DNA and SARS-CoV-2 that people might say, | 'We still think it actually came from the handler of that red | fox,'" Worobey says. ___________________________________________________________________ (page generated 2022-10-20 23:00 UTC)