[HN Gopher] Endonuclease fingerprint indicates a synthetic origi...
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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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