[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.
        
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