This is a great article, that I'll need to reread to really absorb. I hope you'll take "Zimmer-esque" (after Carl) as a compliment. The main lines I take away from a quick read are that
(1) Nature does its own gain-of-function research, it's called evolution. It has been doing so for a billion years, on a scale far beyond what we could imagine
(2) Even at the scale of bacteria and even viruses, there's a lot more genetic mixing than we thought even a few decades ago. Viruses have a lot of sex (metaphorically)!
(3) Human directed gain-of-function research isn't something unique or sinister, we're just trying to anticipate what nature might do next, at much smaller scale. We're not so smart that we can match the scale of the natural experiments.
They don’t understand it, thus it must be devious intent . If we take that they are Christian nationalists in US - then we can understand , then, the reason they do not accept this is that they really do not accept evolution . In order to accept it, you’d need to study basics and accept things that have been studied but that any individual may not be able to see or fully comprehend . They don’t accept the age of the earth, cosmos either. And that is integral as well . I don’t understand everything - but I grant that I must accept that others do - and not chalk it up to nefarious activity .
In the US, it did not help that we had in DJT a leader that does not understand the simplest concepts , doesn’t accept that he need not fully understand concepts but that others do , and that always has to blame others for everything . This has not stopped - he incorrectly places blame for the recent crash in DC.
1) Nature indeed does this, and given that there are no endemic sarbecoviruses with a furin cleavage site, after thousands of years of contact between humans and animals, and none has been present in any of the hundreds of such viruses known to science, it is clear that such a feature is exceedingly rare in natural viruses. On the other hand, is is extremely likely to exist in an engineered virus in Wuhan, given that leaked documents indicated that scientists were engineering such a feature there.
2) There is a lot of genetic mixing, but humans are only exposed to such mixing in places with lots of human-animal interactions, i.e., not Wuhan, with its tiny wildlife trade on the order of 1/1000 the size of that in Guangzhou prior to SARS.
3) Yes, but the difference is, the human experiments took place in Wuhan, whereas the natural experiments took place in remote mountain caves in SE Asia.
4) I am much more comfortable with natural experiments in the mountains, with hardly anyone around to result in onward transmission chains, than human experiments in a huge city with plenty of onward chains possible.
Great, invaluable in fact and much appreciated, I don't use the usual social media. I found you via a excellent commentator "BillyJoe on the excellent Neurologica blog Steven Novella runs.
There is a typo in the citations. "Bat calls are destinct" should be, of course, 'distinct'. That is in the "Social Lives of Bats" section. Like 911Truther grand conspiracies I expect this one to run for ever; I lost friends over that one and will on this one too. I am not going to enter into phony 'debates' mostly though.
Baric also testified he does not believe research showing a market origin for #SARSCoV2 holds up, due to genomic evidence pointing to earlier start date (Oct. 2019) for pandemic. The research has a "major problem" with its timeline, he told Congressional investigators. /5https://twitter.com/KatherineEban/status/1785639498883166611
Are you just clarifying something Baric said or supporting it, it isn't clear to me? My impression is that you are trying to introduce some 'factoid' you think counters what Phillip is saying? Could you clarify if I am wrong? And apologies in advance for the tone of this comment. Which is rather dismissive, I am sick and tired of this topic. "SARS-CoV-2 was an animal-to-human spillover event that occurred in the western section of the Huanan Wholesale Seafood Market in late 2019. This is no longer a scientific controversy. Unfortunately, it’s still a cultural controversy." That was in a recent email from Paul Offit. It is correct.
There is however a major problem with the deflection and general s**t show that the congressional investigators, including the democrats, are running regarding the theatrical and irrelevant inquiry. Which is not inquiring into anything that really matters.
There is no reason and no real evidence to give any earlier date. Other than, of course, than it encourages a 'lab leak' grand conspiracy theory. I also point out, that on this one, just like 911Trutherism, nothing will ever be good enough. For example. If we did or had found an animal sample, dated correctly and so on, in the Huanan market, Cargo Cult scientists would be saying something like "Well the virus does jump from humans to animals too..."; which is true in fact, White tailed deer in Pa are full of Alpha strains still as of 2024-05-28 . That is, what many, including the excellent Steven Novella and others call, confusingly and wrongly, a 'smoking gun', that is a direct animal sample of some unspecified kind: there is no such thing really, since any physical or empirical evidence can now be pretzeled into some grand conspiracy theory.
Excuse the long reply and also the rather pointed refusal to pretend we are having a 'sciency discussion' we aren't.
if Baric, the expert for Bat Corona viruses, does not believe that Covid started at the sea food market, how can you claim that there is no scíentific controversy about the origin?
Also Andersen doesn't claim that the case is settled.
Worobey and Markolin's claims that there is no scientific controversy are quite lonesome claims in the scientific community.
No they are not, here, though I mentioned Offit you ignored that. That is clear statement from a very centrist and cautious individual with the necessary knowledge.
There is a certain cohort, Steven Novella and others who, as good empiricists, keep options open, standard caveats. We could say it about anything and everything actually. Should new evidence show up we would condider it kind of thing. Same goes for Loch Ness monster and the Cookie monster as the wicked engineer of SARS-CoV-2 .
It is really confusing for the public though.
I am here to support Phillip in his endeavor not to bandy a pointless back and forth with the ignorant: which frankly you clearly are. Don't try to speak for community either.
Anderson doesn't think there is any option for the PROXIMATE origin other than Huahan, period. The question was more open at one time, unecessarily in my view, but is not closed.
But that is it for me, I don't have time to waste on comments sections and social media. I have no doubt that in five years 2/3 of the public will still think the virus was a lab event. I couldn't care less actually, what do they know? However I am duty bound to defend the community involved here and really, the truth in a sense. So good day to you.
the comparison to the 911 truthers is not fair. The 911 truthers believe that the US gouverment conspired to kill thousands of innocent Americans purposely. No one is saying that Covid was started purposely. There were risky experiments going on - and the US gouverment was involved in the fundling - and tried to hide the involvement - and tried to silence the lab thesis as "crackpot conspiracy theory".
The comparison was not meant to be exact obviously.
There were no risky experiments being conducted really. Depends what you mean by 'risky'. There was no attempt to hide anything either., don't be ridiculous Though the recent Kangaroo courts in Congress were designed to make the gullible think there was. That comment alone shows you know nothing about the actual science, process or really what was being done. None of it, we know for sure, had, anyway any connection to the SARS-CoV-2 virion.
Stopping research and work into virus origins and 'hot spots' is way more 'risky' in my view. Which is what was already going on during the Trump years, foolishly closing research for no reason.
In fact the congressional circus you have so much time for is a very thinkly veiled attempt to vindicate Trump's actions during the early pandemic. In fact to scapegoat the few people who knew about the impending risks, were studying them and in fact had warned about them many times.
People like you in fact, disgust me with your lazy, idle thinking and scapegoating and your pretentions to 'science'. Cargo Cult science I call it. I shouldn't maybe say that, but since that is the phony outrage tone being introduced against good scientists, I will make an exception. As I said, that is the last response you get from me. I will comment in support of Phillip's excellent and clear and thorough work though. He will go far as they say: one smart cookie.
Since you know so much about it what do you think of the far more pressing 'experiment' we are conducting with high intensity chicken farming and, in China, wild animal trafficking of animals known to be reservoirs of virions?
To date, no artificially bred virion or one with enhanced properties as it were or pathogen of any kind has ever escaped a lab. ZERO. In fact it is almost impossible, and hasn't been done yet, to even get a GMO plant to survive, either by accident or design in the wild. There are some cases which have 'returned to type'. Some polio virions have done that. If you want to discuss this aspect of the biology, I am happy too. I am not discussion it as 'evidence' for or against the 'lab leak' though.
A strain of flu, which had, evolved in the 'wild' previously and burnt out, did escape from a Russian lab a couple of decades ago. And shouldn't have of course.
Since statistical evidence alone give empirical certainty that SARS-CoV-2 's proximate origin was in the Huanan market. With about a 10 MILLION to one odds on. In fact in my view, stonger than that. Again ask me if you wish to amplify.
There is nothing of scientific interest in your comments though you think there is. My interest is in the conspiracy theory, so your remarks are of interest: not in the way you think though. They are of interest in the sense that you and your false and motivated beliefs are the subject of a rational inquiry on my part: this is a 'conversation' that is inherently one sided as a result and it is both patronizing and unfair to you for me to continue.
It is not a dispute about the science of the proximate origin of SARS-CoV-2. Which, if you understood half of what Phillip is saying, you would know was the Huanan Market. Period.
The reality is, and even Phillip doesn't actually go this far, is that the lab leak theory is not only nonsense but nonsense on stilts.
To see clever clogs scientists like Matt Ridley talking it up, and being 'Popperian' about it all, shows how weak some of our institutions are now. That is another matter. I write mainly in case a third party is interested. I don't want to clog up Phillip's pages though. So unless you have a specific question you would like me to address regarding the real science I outlined, that is good day from me.
When you say that there were no risky experiments going on in Wuhan, were you aware that the Sarbecovirus experiments were carried out in the Wuchang BSL2 facility near the city centre? Would you characterise working on SARS2 under BSL2 as non-risky, and why?
You don't seem to understand some things about this. The risks are those associated with the wild virus. The reason, obviously for precautions with say the Small pox virus are due to the risks of handling small pox, obviously, which is a known and very contagious danger everywhere. I travelled a year ago to new England via New York on the highway: that was horribly risky, they drive like loons. Do you think Philadelphia is more risky to drive round?
Modified viruses are more or less risk free. Very few scientists would see it as I do though, so you better ask Philipp directly about it or some other professional since I still need to write up my full and rather outlier views on the topic and full set of evolutionary reasonings regarding these quasi-species.
To date no novel or modified virus has ever, let me repeat, ever, caused an accident or illness. An outbreak of flu in the USSR in the 70s was from an old but wild variant that had been, I think, frozen and escaped from a lab via ventilation shafts if I remember.
Some vaccine polio virus does, as is said, 'revert' to a wild type rapidly and does survive for some time as modified. It only takes a point mutation which it seems to need for a very tight niche in the stomach. I don't use the term 'revert' I think it misleading, in my view it re-evolves into what must be a very tight niche. However the benign vaccine version could, at a push or for an interesting discussion be seen as a 'lab leak'. They discussed it once on This Week in Virology which I suggest you listen to: you might learn something. One of the hosts made, in fact, the point I have. Cost benefit calculations, in my view somewhat justify the continued use of the vaccine but it would be best corrected in my view.
Maybe USAID can get some new funding one day, or Moderna might have a crack at a better solution? mRNA even!!! who knows and how exciting scientifically. Agreed?
I know what you mean but really it is not "SARS 2"; the name of the quasi species is "SARS-CoV-2", it is irritating and marks you as a crank straight away I am sorry to say. Does it really matter? probably not but I mention it for your edification. You can waste time with the fools on anti vaxx and MAGA sites of course who won't correct you probably.
I was, unlike some, Kristian Andersen at Scripps for example, very skeptical about the lab leak stories, though I took the possibility seriously: I no longer do. From the start my views on how hard it is for any modified organism to survive in the wild did influence my opinions: too much I now think, we all live and learn and Kristian is, in fact, a better and more thorough investigator than me and did, in fact, test the theses to destruction. There are several lab leak theories and that is part of the problem.
You think making a virion that can survive in the wild with novel features you would have just guessed at is easy even if you try hard let alone by accident? Try it, you will, I guarantee, fail as has every attempt to modify bio weapons.
All of this is irrelevant in a way. Since the virus has to be placed at the lab for a leak to be plausible and it never has been, end of story, spurious assessments of 'risks' are irrelevant. The virus has, and evidence is increasing, been placed at the market, end of story.
Remember now you sneaky Racoon Dog you, it is SARS-CoV-2, I have it on an automatic snippet so I never get it wrong. that is an useful hack for a lot of technical terms.
You are claiming that SARS2 is a wild virus. I think we can all agree that experimenting on it at BSL2 in a big city would risk causing an outbreak. They already knew the wild relatives from Mojiang were capable of infecting humans, and as they were carrying out experiments to adapt animal viruses that were “poised to emerge” to infect humans, it’s pretty obvious they should have been using BSL3 at the very least, but they wanted to save time and money so they could publish their big Nature paper sooner and get more funding and glory.
It's pretty obvious that if the virus first characterised was a natural virus, it was some time since it had first infected humans, as it did not display the rapid evolution and genetic diversity characteristic of a virus that has recently jumped species. That is why Baric said in his testimony to Congress that the virus almost surely had been circulating in humans long before there were any cases at the market.
Ralph Baric, just to be crystal clear, said nothing of the kind about how long it had been circulating in humans that I can find. Give the exact quote can you?
It is possible in my view that some jumps had taken place in farms and transport facilities and burned out as most do, maybe he went to deep into the weeds for the propagandists in Congress to try to understand properly?
I do see a lot of mis understandings as to what is said and written and some of it understandable as some of the detail is, in fairness to you, hard to parse. Ralph has actually said specifically and I quote directly "that yet little information is available concerning the molecular, genetic and evolutionary mechanisms that regulate the establishment and dissemination of such a virus within a newly adopted host". We don't understand it well. The threat of emerging viruses remains and Ralph was one of those who warned us well in advance: we, or the Trump admin, totally ignored the threat in my view.
"A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence." the authors as listed..
V Menachery, B Yount, K Debbink, S Agnihothram, L Gralinski, J Plante, R Graham, T Scobey, X Ge, E Donaldson, S Randell, A Lanzavecchia, W Marasco, Z Shi, R Baric (2015). Nature medicine, 21(12), 1508-13.
No that isn't what is on page 101, you have misread it, really mis interpreted it badly.
I could and maybe should, out of respect for this excellent site, stop there. Unless Philipp actually endorses it or intervenes himself, and I think he should stop your sea-lioning, I won't respond again to a comment by you.
Baric is saying on page 101 there that the suspicious 'illnesses' claimed for people who worked at the Lab COULD NOT have been the first ones even if they had been Covid, due to the date at which they are documented.
Baric said the reported illnesses of WIV staff about a month before any reported cases at the market could not possibly have been the first cases. Does this, or does this not, logically imply that the December market cases, about a month after the November WIV cases, COULD NOT possibly have been the first cases?
"If you look at the molecular clock of the virus, it emerged in the middle of October, late October, not the middle or end of November. So people who say those were the first cases, no chance. There were five or six transmission cycles at least before they would have been infected.
Non-sense. Where did you get that baloney. Coronaviridae burn out in various mammals all the time, probably jump species thousands of times a year in relevant regions into humans. Very few 'catch' and most burn out, often unnoticed and, other than sheer numbers to push a point, 'jumping species' has no effect on mutation rates.
Certain mutations will survive better in new niches they can get a grip in obviously. It is a very complicated and poorly understood topic. I think you mis understood some point Baric might have made. mutations don't speed up with new niches or in new species. As always in biology, somewhere and somehow there will be an exception of course: not among these quasi species though.
The market was an ideal place for a jump into humans to take place. The lab was not, in fact it was a very poor site for such an accident to happen and then to persist.
Even with huge numbers it is easy to over estimate the direction and degree of mutation: there are some factors in hosts that can affect rates but they are, actually marginal in my view. One can quibble no doubt.
The fact is that, and the reasons must be relevant but are totally ignored, very few virions get to be dangerous. Most that do are stuck in a niche, obviously, that is very tight and incredibly stable and lasts for centuries.
Look up the rate of mutations when viruses made species jumps from civets to humans (SARS), camels to humans (MERS), humans to deer or mink (SARS2). heightened evolutionary pressure occurs when a species jump happens. This did not happen in the case of SARS2 in the December 2019 epoch, implying the virus, if natural, had already adapted to humans, which would likely have taken a couple of months at least, hence Baric said it was on at least the sixth generation. The more likely explaination is that the virus had already adapted in the lab.
You are confusing mutations that fix to put it crudely with mutation rates per se. Among other things as far as I can guess. I don't, by the way, need to 'look things up' at this level, you do.
Basically more nonsense from you. SARS-CoV-2 evolved heavily in that period. There is no absolute measure of that at a very fine scale. And species that haven't jumped are under, in fact, more pressure arguably from selection than those that manage to jump.
It is why some virions persist for hundreds of years, despite their rates of mutation, huge numbers and short reproduction times, it is quite incredible and rarely remarked. Polio is the best example, which will rapidly re-evolve (not revert as the literature puts it) back into its niche even if passaged and modified as in some vaccines. It takes one point mutation from the attenuated virus and that is, to be fair, not such a hard lift. It always goes that way though if it survives. Always.
Google AI by the way gets this the wrong way round too, so you are in good company.
What on earth "December 2019 epoch" means I don't know. The virus evolved quite rapidly in that period and after. From a viral point of view it was an 'epoch' I suppose, nice one. 😉
Basically though to 'clock' something you go for mutations which have no effect. To rule out the hypothesis that the virus was engineered in a laboratory, scientists measured the ratio of non-synonymous mutations (which alter the resulting protein sequence) to synonymous mutations (which keep the protein sequence the same). That is ones that have no effect on the Phenotype roughly and hence are not under any direct selection. It isn't quite as simple as that but that is the rough idea of the techniques used.
SARS-CoV-2 has an unusually low mutation rate for an mRNA virus because it has a proof reading mechanism. I think it is a feature of a lot of Coronaviridae though so should cancel out as it were in comparisons.
Another source for confusion. Unless I get direct encouragement from Philpp I won't respond to you again. So keep up the sea lioning since you are here to convince yourself nobody else.
“SARS-CoV-2 evolved heavily in that period. There is no absolute measure of that at a very fine scale.”
All of the early sequences are practically the same, they did not mutate rapidly, as observed in all previously studied zoonotic jumps, e.g. SARS2 from humans to mink, the mutation rate increased by 4-13 times.
I’ll have to re-read with more focus and maybe do some deep dives to get a better grasp on some of these concepts. But it seems like your case has more to do with the engineering and manufacturing of a virus from scratch. Just because the genetic material is messy and structured haphazardly would that necessarily mean it wasn’t in the lab to begin with?
Also, wouldn’t these same evolutions happen with gain of function research? Especially in a lab with a larger variety of related but disparate viruses that could utilize recombination?
Good article, thanks for the roundup of current arguments for a natural origin.
I though the section about relative transmissibility between SARS and SARS2 in ferrets was interesting. Note that “The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets” Peacock et al. (2021), since with the FCS removed, transmission did not occur. This fact means the FCS likely evolved before it ever infected intermediate hosts, since ferrets are one of the intermediate hosts susceptible to the virus, so if an FCS-free SARS-CoV-2 doesn’t transmit in ferrets, it’s even less likely to transmit in other animals that are much less susceptible to, like racoon dogs.
The section about governments being sensitive about scientists publishing viruses similar to SARS-CoV-2 was also particularly thought provoking.
“Especially sarbecoviruses are a sensitive subject almost everywhere. Governments are currently not interested in discovering where these dangerous chimeras are circulating in the wild or what drives their emergence.”
This was likely also true after the 2002 SARS outbreak, which the Chinese government successfully covered up for 3 months before the respiratory viruses season and the Chinese New Year holiday caused the outbreak to get out of control and it alerted the WHO about in 2003. Political sensitivity might explain why the WIV only published a small fraction of the viruses in its collection - no doubt, researchers would have had to get sign off from political authorities before publishing anything related to politically sensitive topics such as SARS.
Given that only a small fraction of the viruses in the WIV’s collection were ever published, very likely for the above political reason, we should be mindful of placing too much weight on arguments that the absence of a published backbone in the record is strong evidence of absence of such a backbone in the WIV’s sarbecovirus collection, which is the largest in the world.
I like to take a zoomed-out view of the origins debate. Briefly, there are only two places in Asia known to have contained viruses similar to SARS2 in 2019: remote mountain caves in SE Asia, and the Wuhan Institute of Virology. The virus on the loose in Wuhan almost surely arrived from one of these two sources, via an unknown chain of events. We need to figure out which chain of events is more likely. Salient facts include:
1) WIV has the world's largest collection of SARS-like viruses, including many unpublished ones.
2) It is not traditional to eat wildlife in Wuhan, so the level of trade, ~1 racoon dog per day sold in the city, was only about 1/1000 as great as the level of trade in Guangzhou, where eating wildlife is traditional, prior to the SARS outbreak.
3) The remote mountain caves in SE Asia harbouring similar viruses are at least a 1800km+ drive away, and no outbreaks reportedly happened along the supply chain.
4) There were many wildlife farms in Hubei province raising animals including potential intermediate hosts like racoon dogs, which were highly unlikely to have been exposed to SE Asian viruses. Hubei province exported wild animals to Guangdong, which is by far the biggest market for such produce in China. Due to transportation costs, farmed wild animals from nearby Hubei would be much cheaper then ones transported a vast distance from SE Asia, so for economic reasons, it is highly unlikely that a significant number of potential intermediate host species made the long journey from SE Asia to Wuhan.
5) There is no record of the most relevant animal species, bats and pangolins, ever being traded in Wuhan, but the WIV had a colony of live Rhinolophus bats, the host species for viruses like SARS2, that it experimented on.
6) WIV publications indicate WIV scientists experimented on related viruses at BSL2, which is wholly inadequate to contain a virus like SARS2.
7) The Chinese government did not allow WHO or any independent scientists to gather or verify data independently, and with certain exceptions, did not publish any raw data, hence the early case data, including a ver low-resolution case map, that are a key part of the argument for natural emergence at the Huanan Seafood Market were completely unverified, and unverifiable.
8) The market environmental sample data that some say indicates an association of positive samples with a wildlife stall was taken from a paper published by the China CDC that used those data to explain that they showed a market origin was unlikely.
9) In contrast to other recent zoonotic outbreaks, the Chinese government was extremely secretive, and placed a series of gag orders on Chinese scientists, preventing them from publishing anything about the outbreak without government approval.
I have omitted other information, such as the reported zero cases of lineage A at the market, zero cases amongst animal sellers, and the extreme asymmetry between positive samples of lineage B and A at the market, that appear to make a market origin unlikely, as they are based on unverified data published by the Chinese government, which had a strong interest in minimising the publication of embarrassing things about the outbreak. I also omitted the China/WHO report's statement that there were zero infections amongst WIV staff, which, if true, would mean a laboratory outbreak was not possible, since given the large outbreak in the city (4% seroprevalence according to a CDC study), the chance of zero out of 600+ staff being infected was essentially zero, indicating the Chinese government was lying about this dataset.
Please feel free to roast the points above, and add any key facts of your own, by which I mean known and verifiable facts, not information published by the Chinese government with no verification or raw data.
This is a great article, that I'll need to reread to really absorb. I hope you'll take "Zimmer-esque" (after Carl) as a compliment. The main lines I take away from a quick read are that
(1) Nature does its own gain-of-function research, it's called evolution. It has been doing so for a billion years, on a scale far beyond what we could imagine
(2) Even at the scale of bacteria and even viruses, there's a lot more genetic mixing than we thought even a few decades ago. Viruses have a lot of sex (metaphorically)!
(3) Human directed gain-of-function research isn't something unique or sinister, we're just trying to anticipate what nature might do next, at much smaller scale. We're not so smart that we can match the scale of the natural experiments.
(4) 1-3 make some people uncomfortable.
They don’t understand it, thus it must be devious intent . If we take that they are Christian nationalists in US - then we can understand , then, the reason they do not accept this is that they really do not accept evolution . In order to accept it, you’d need to study basics and accept things that have been studied but that any individual may not be able to see or fully comprehend . They don’t accept the age of the earth, cosmos either. And that is integral as well . I don’t understand everything - but I grant that I must accept that others do - and not chalk it up to nefarious activity .
In the US, it did not help that we had in DJT a leader that does not understand the simplest concepts , doesn’t accept that he need not fully understand concepts but that others do , and that always has to blame others for everything . This has not stopped - he incorrectly places blame for the recent crash in DC.
1) Nature indeed does this, and given that there are no endemic sarbecoviruses with a furin cleavage site, after thousands of years of contact between humans and animals, and none has been present in any of the hundreds of such viruses known to science, it is clear that such a feature is exceedingly rare in natural viruses. On the other hand, is is extremely likely to exist in an engineered virus in Wuhan, given that leaked documents indicated that scientists were engineering such a feature there.
2) There is a lot of genetic mixing, but humans are only exposed to such mixing in places with lots of human-animal interactions, i.e., not Wuhan, with its tiny wildlife trade on the order of 1/1000 the size of that in Guangzhou prior to SARS.
3) Yes, but the difference is, the human experiments took place in Wuhan, whereas the natural experiments took place in remote mountain caves in SE Asia.
4) I am much more comfortable with natural experiments in the mountains, with hardly anyone around to result in onward transmission chains, than human experiments in a huge city with plenty of onward chains possible.
Great, invaluable in fact and much appreciated, I don't use the usual social media. I found you via a excellent commentator "BillyJoe on the excellent Neurologica blog Steven Novella runs.
There is a typo in the citations. "Bat calls are destinct" should be, of course, 'distinct'. That is in the "Social Lives of Bats" section. Like 911Truther grand conspiracies I expect this one to run for ever; I lost friends over that one and will on this one too. I am not going to enter into phony 'debates' mostly though.
Baric also testified he does not believe research showing a market origin for #SARSCoV2 holds up, due to genomic evidence pointing to earlier start date (Oct. 2019) for pandemic. The research has a "major problem" with its timeline, he told Congressional investigators. /5https://twitter.com/KatherineEban/status/1785639498883166611
Not really, Philip's dates look fine to me.
Are you just clarifying something Baric said or supporting it, it isn't clear to me? My impression is that you are trying to introduce some 'factoid' you think counters what Phillip is saying? Could you clarify if I am wrong? And apologies in advance for the tone of this comment. Which is rather dismissive, I am sick and tired of this topic. "SARS-CoV-2 was an animal-to-human spillover event that occurred in the western section of the Huanan Wholesale Seafood Market in late 2019. This is no longer a scientific controversy. Unfortunately, it’s still a cultural controversy." That was in a recent email from Paul Offit. It is correct.
There is however a major problem with the deflection and general s**t show that the congressional investigators, including the democrats, are running regarding the theatrical and irrelevant inquiry. Which is not inquiring into anything that really matters.
There is no reason and no real evidence to give any earlier date. Other than, of course, than it encourages a 'lab leak' grand conspiracy theory. I also point out, that on this one, just like 911Trutherism, nothing will ever be good enough. For example. If we did or had found an animal sample, dated correctly and so on, in the Huanan market, Cargo Cult scientists would be saying something like "Well the virus does jump from humans to animals too..."; which is true in fact, White tailed deer in Pa are full of Alpha strains still as of 2024-05-28 . That is, what many, including the excellent Steven Novella and others call, confusingly and wrongly, a 'smoking gun', that is a direct animal sample of some unspecified kind: there is no such thing really, since any physical or empirical evidence can now be pretzeled into some grand conspiracy theory.
Excuse the long reply and also the rather pointed refusal to pretend we are having a 'sciency discussion' we aren't.
if Baric, the expert for Bat Corona viruses, does not believe that Covid started at the sea food market, how can you claim that there is no scíentific controversy about the origin?
Also Andersen doesn't claim that the case is settled.
Worobey and Markolin's claims that there is no scientific controversy are quite lonesome claims in the scientific community.
No they are not, here, though I mentioned Offit you ignored that. That is clear statement from a very centrist and cautious individual with the necessary knowledge.
There is a certain cohort, Steven Novella and others who, as good empiricists, keep options open, standard caveats. We could say it about anything and everything actually. Should new evidence show up we would condider it kind of thing. Same goes for Loch Ness monster and the Cookie monster as the wicked engineer of SARS-CoV-2 .
It is really confusing for the public though.
I am here to support Phillip in his endeavor not to bandy a pointless back and forth with the ignorant: which frankly you clearly are. Don't try to speak for community either.
Anderson doesn't think there is any option for the PROXIMATE origin other than Huahan, period. The question was more open at one time, unecessarily in my view, but is not closed.
But that is it for me, I don't have time to waste on comments sections and social media. I have no doubt that in five years 2/3 of the public will still think the virus was a lab event. I couldn't care less actually, what do they know? However I am duty bound to defend the community involved here and really, the truth in a sense. So good day to you.
the comparison to the 911 truthers is not fair. The 911 truthers believe that the US gouverment conspired to kill thousands of innocent Americans purposely. No one is saying that Covid was started purposely. There were risky experiments going on - and the US gouverment was involved in the fundling - and tried to hide the involvement - and tried to silence the lab thesis as "crackpot conspiracy theory".
The comparison was not meant to be exact obviously.
There were no risky experiments being conducted really. Depends what you mean by 'risky'. There was no attempt to hide anything either., don't be ridiculous Though the recent Kangaroo courts in Congress were designed to make the gullible think there was. That comment alone shows you know nothing about the actual science, process or really what was being done. None of it, we know for sure, had, anyway any connection to the SARS-CoV-2 virion.
Stopping research and work into virus origins and 'hot spots' is way more 'risky' in my view. Which is what was already going on during the Trump years, foolishly closing research for no reason.
In fact the congressional circus you have so much time for is a very thinkly veiled attempt to vindicate Trump's actions during the early pandemic. In fact to scapegoat the few people who knew about the impending risks, were studying them and in fact had warned about them many times.
People like you in fact, disgust me with your lazy, idle thinking and scapegoating and your pretentions to 'science'. Cargo Cult science I call it. I shouldn't maybe say that, but since that is the phony outrage tone being introduced against good scientists, I will make an exception. As I said, that is the last response you get from me. I will comment in support of Phillip's excellent and clear and thorough work though. He will go far as they say: one smart cookie.
Since you know so much about it what do you think of the far more pressing 'experiment' we are conducting with high intensity chicken farming and, in China, wild animal trafficking of animals known to be reservoirs of virions?
To date, no artificially bred virion or one with enhanced properties as it were or pathogen of any kind has ever escaped a lab. ZERO. In fact it is almost impossible, and hasn't been done yet, to even get a GMO plant to survive, either by accident or design in the wild. There are some cases which have 'returned to type'. Some polio virions have done that. If you want to discuss this aspect of the biology, I am happy too. I am not discussion it as 'evidence' for or against the 'lab leak' though.
A strain of flu, which had, evolved in the 'wild' previously and burnt out, did escape from a Russian lab a couple of decades ago. And shouldn't have of course.
Since statistical evidence alone give empirical certainty that SARS-CoV-2 's proximate origin was in the Huanan market. With about a 10 MILLION to one odds on. In fact in my view, stonger than that. Again ask me if you wish to amplify.
There is nothing of scientific interest in your comments though you think there is. My interest is in the conspiracy theory, so your remarks are of interest: not in the way you think though. They are of interest in the sense that you and your false and motivated beliefs are the subject of a rational inquiry on my part: this is a 'conversation' that is inherently one sided as a result and it is both patronizing and unfair to you for me to continue.
It is not a dispute about the science of the proximate origin of SARS-CoV-2. Which, if you understood half of what Phillip is saying, you would know was the Huanan Market. Period.
The reality is, and even Phillip doesn't actually go this far, is that the lab leak theory is not only nonsense but nonsense on stilts.
To see clever clogs scientists like Matt Ridley talking it up, and being 'Popperian' about it all, shows how weak some of our institutions are now. That is another matter. I write mainly in case a third party is interested. I don't want to clog up Phillip's pages though. So unless you have a specific question you would like me to address regarding the real science I outlined, that is good day from me.
When you say that there were no risky experiments going on in Wuhan, were you aware that the Sarbecovirus experiments were carried out in the Wuchang BSL2 facility near the city centre? Would you characterise working on SARS2 under BSL2 as non-risky, and why?
You don't seem to understand some things about this. The risks are those associated with the wild virus. The reason, obviously for precautions with say the Small pox virus are due to the risks of handling small pox, obviously, which is a known and very contagious danger everywhere. I travelled a year ago to new England via New York on the highway: that was horribly risky, they drive like loons. Do you think Philadelphia is more risky to drive round?
Modified viruses are more or less risk free. Very few scientists would see it as I do though, so you better ask Philipp directly about it or some other professional since I still need to write up my full and rather outlier views on the topic and full set of evolutionary reasonings regarding these quasi-species.
To date no novel or modified virus has ever, let me repeat, ever, caused an accident or illness. An outbreak of flu in the USSR in the 70s was from an old but wild variant that had been, I think, frozen and escaped from a lab via ventilation shafts if I remember.
Some vaccine polio virus does, as is said, 'revert' to a wild type rapidly and does survive for some time as modified. It only takes a point mutation which it seems to need for a very tight niche in the stomach. I don't use the term 'revert' I think it misleading, in my view it re-evolves into what must be a very tight niche. However the benign vaccine version could, at a push or for an interesting discussion be seen as a 'lab leak'. They discussed it once on This Week in Virology which I suggest you listen to: you might learn something. One of the hosts made, in fact, the point I have. Cost benefit calculations, in my view somewhat justify the continued use of the vaccine but it would be best corrected in my view.
Maybe USAID can get some new funding one day, or Moderna might have a crack at a better solution? mRNA even!!! who knows and how exciting scientifically. Agreed?
I know what you mean but really it is not "SARS 2"; the name of the quasi species is "SARS-CoV-2", it is irritating and marks you as a crank straight away I am sorry to say. Does it really matter? probably not but I mention it for your edification. You can waste time with the fools on anti vaxx and MAGA sites of course who won't correct you probably.
I was, unlike some, Kristian Andersen at Scripps for example, very skeptical about the lab leak stories, though I took the possibility seriously: I no longer do. From the start my views on how hard it is for any modified organism to survive in the wild did influence my opinions: too much I now think, we all live and learn and Kristian is, in fact, a better and more thorough investigator than me and did, in fact, test the theses to destruction. There are several lab leak theories and that is part of the problem.
You think making a virion that can survive in the wild with novel features you would have just guessed at is easy even if you try hard let alone by accident? Try it, you will, I guarantee, fail as has every attempt to modify bio weapons.
All of this is irrelevant in a way. Since the virus has to be placed at the lab for a leak to be plausible and it never has been, end of story, spurious assessments of 'risks' are irrelevant. The virus has, and evidence is increasing, been placed at the market, end of story.
Remember now you sneaky Racoon Dog you, it is SARS-CoV-2, I have it on an automatic snippet so I never get it wrong. that is an useful hack for a lot of technical terms.
You are claiming that SARS2 is a wild virus. I think we can all agree that experimenting on it at BSL2 in a big city would risk causing an outbreak. They already knew the wild relatives from Mojiang were capable of infecting humans, and as they were carrying out experiments to adapt animal viruses that were “poised to emerge” to infect humans, it’s pretty obvious they should have been using BSL3 at the very least, but they wanted to save time and money so they could publish their big Nature paper sooner and get more funding and glory.
It's pretty obvious that if the virus first characterised was a natural virus, it was some time since it had first infected humans, as it did not display the rapid evolution and genetic diversity characteristic of a virus that has recently jumped species. That is why Baric said in his testimony to Congress that the virus almost surely had been circulating in humans long before there were any cases at the market.
Ralph Baric, just to be crystal clear, said nothing of the kind about how long it had been circulating in humans that I can find. Give the exact quote can you?
It is possible in my view that some jumps had taken place in farms and transport facilities and burned out as most do, maybe he went to deep into the weeds for the propagandists in Congress to try to understand properly?
I do see a lot of mis understandings as to what is said and written and some of it understandable as some of the detail is, in fairness to you, hard to parse. Ralph has actually said specifically and I quote directly "that yet little information is available concerning the molecular, genetic and evolutionary mechanisms that regulate the establishment and dissemination of such a virus within a newly adopted host". We don't understand it well. The threat of emerging viruses remains and Ralph was one of those who warned us well in advance: we, or the Trump admin, totally ignored the threat in my view.
"A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence." the authors as listed..
V Menachery, B Yount, K Debbink, S Agnihothram, L Gralinski, J Plante, R Graham, T Scobey, X Ge, E Donaldson, S Randell, A Lanzavecchia, W Marasco, Z Shi, R Baric (2015). Nature medicine, 21(12), 1508-13.
Your overconfidence is your weakness:
Page 101. He said there is no chance the market cases were the first ones.
https://oversight.house.gov/wp-content/uploads/2024/04/Baric-TI-Transcript.pdf
No that isn't what is on page 101, you have misread it, really mis interpreted it badly.
I could and maybe should, out of respect for this excellent site, stop there. Unless Philipp actually endorses it or intervenes himself, and I think he should stop your sea-lioning, I won't respond again to a comment by you.
Baric is saying on page 101 there that the suspicious 'illnesses' claimed for people who worked at the Lab COULD NOT have been the first ones even if they had been Covid, due to the date at which they are documented.
Baric said the reported illnesses of WIV staff about a month before any reported cases at the market could not possibly have been the first cases. Does this, or does this not, logically imply that the December market cases, about a month after the November WIV cases, COULD NOT possibly have been the first cases?
"If you look at the molecular clock of the virus, it emerged in the middle of October, late October, not the middle or end of November. So people who say those were the first cases, no chance. There were five or six transmission cycles at least before they would have been infected.
Non-sense. Where did you get that baloney. Coronaviridae burn out in various mammals all the time, probably jump species thousands of times a year in relevant regions into humans. Very few 'catch' and most burn out, often unnoticed and, other than sheer numbers to push a point, 'jumping species' has no effect on mutation rates.
Certain mutations will survive better in new niches they can get a grip in obviously. It is a very complicated and poorly understood topic. I think you mis understood some point Baric might have made. mutations don't speed up with new niches or in new species. As always in biology, somewhere and somehow there will be an exception of course: not among these quasi species though.
The market was an ideal place for a jump into humans to take place. The lab was not, in fact it was a very poor site for such an accident to happen and then to persist.
Even with huge numbers it is easy to over estimate the direction and degree of mutation: there are some factors in hosts that can affect rates but they are, actually marginal in my view. One can quibble no doubt.
The fact is that, and the reasons must be relevant but are totally ignored, very few virions get to be dangerous. Most that do are stuck in a niche, obviously, that is very tight and incredibly stable and lasts for centuries.
Look up the rate of mutations when viruses made species jumps from civets to humans (SARS), camels to humans (MERS), humans to deer or mink (SARS2). heightened evolutionary pressure occurs when a species jump happens. This did not happen in the case of SARS2 in the December 2019 epoch, implying the virus, if natural, had already adapted to humans, which would likely have taken a couple of months at least, hence Baric said it was on at least the sixth generation. The more likely explaination is that the virus had already adapted in the lab.
You are confusing mutations that fix to put it crudely with mutation rates per se. Among other things as far as I can guess. I don't, by the way, need to 'look things up' at this level, you do.
Basically more nonsense from you. SARS-CoV-2 evolved heavily in that period. There is no absolute measure of that at a very fine scale. And species that haven't jumped are under, in fact, more pressure arguably from selection than those that manage to jump.
It is why some virions persist for hundreds of years, despite their rates of mutation, huge numbers and short reproduction times, it is quite incredible and rarely remarked. Polio is the best example, which will rapidly re-evolve (not revert as the literature puts it) back into its niche even if passaged and modified as in some vaccines. It takes one point mutation from the attenuated virus and that is, to be fair, not such a hard lift. It always goes that way though if it survives. Always.
Google AI by the way gets this the wrong way round too, so you are in good company.
What on earth "December 2019 epoch" means I don't know. The virus evolved quite rapidly in that period and after. From a viral point of view it was an 'epoch' I suppose, nice one. 😉
Basically though to 'clock' something you go for mutations which have no effect. To rule out the hypothesis that the virus was engineered in a laboratory, scientists measured the ratio of non-synonymous mutations (which alter the resulting protein sequence) to synonymous mutations (which keep the protein sequence the same). That is ones that have no effect on the Phenotype roughly and hence are not under any direct selection. It isn't quite as simple as that but that is the rough idea of the techniques used.
SARS-CoV-2 has an unusually low mutation rate for an mRNA virus because it has a proof reading mechanism. I think it is a feature of a lot of Coronaviridae though so should cancel out as it were in comparisons.
Another source for confusion. Unless I get direct encouragement from Philpp I won't respond to you again. So keep up the sea lioning since you are here to convince yourself nobody else.
“SARS-CoV-2 evolved heavily in that period. There is no absolute measure of that at a very fine scale.”
All of the early sequences are practically the same, they did not mutate rapidly, as observed in all previously studied zoonotic jumps, e.g. SARS2 from humans to mink, the mutation rate increased by 4-13 times.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9896948/
Thank you
I’ll have to re-read with more focus and maybe do some deep dives to get a better grasp on some of these concepts. But it seems like your case has more to do with the engineering and manufacturing of a virus from scratch. Just because the genetic material is messy and structured haphazardly would that necessarily mean it wasn’t in the lab to begin with?
Also, wouldn’t these same evolutions happen with gain of function research? Especially in a lab with a larger variety of related but disparate viruses that could utilize recombination?
Good article, thanks for the roundup of current arguments for a natural origin.
I though the section about relative transmissibility between SARS and SARS2 in ferrets was interesting. Note that “The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets” Peacock et al. (2021), since with the FCS removed, transmission did not occur. This fact means the FCS likely evolved before it ever infected intermediate hosts, since ferrets are one of the intermediate hosts susceptible to the virus, so if an FCS-free SARS-CoV-2 doesn’t transmit in ferrets, it’s even less likely to transmit in other animals that are much less susceptible to, like racoon dogs.
The section about governments being sensitive about scientists publishing viruses similar to SARS-CoV-2 was also particularly thought provoking.
“Especially sarbecoviruses are a sensitive subject almost everywhere. Governments are currently not interested in discovering where these dangerous chimeras are circulating in the wild or what drives their emergence.”
This was likely also true after the 2002 SARS outbreak, which the Chinese government successfully covered up for 3 months before the respiratory viruses season and the Chinese New Year holiday caused the outbreak to get out of control and it alerted the WHO about in 2003. Political sensitivity might explain why the WIV only published a small fraction of the viruses in its collection - no doubt, researchers would have had to get sign off from political authorities before publishing anything related to politically sensitive topics such as SARS.
Given that only a small fraction of the viruses in the WIV’s collection were ever published, very likely for the above political reason, we should be mindful of placing too much weight on arguments that the absence of a published backbone in the record is strong evidence of absence of such a backbone in the WIV’s sarbecovirus collection, which is the largest in the world.
I like to take a zoomed-out view of the origins debate. Briefly, there are only two places in Asia known to have contained viruses similar to SARS2 in 2019: remote mountain caves in SE Asia, and the Wuhan Institute of Virology. The virus on the loose in Wuhan almost surely arrived from one of these two sources, via an unknown chain of events. We need to figure out which chain of events is more likely. Salient facts include:
1) WIV has the world's largest collection of SARS-like viruses, including many unpublished ones.
2) It is not traditional to eat wildlife in Wuhan, so the level of trade, ~1 racoon dog per day sold in the city, was only about 1/1000 as great as the level of trade in Guangzhou, where eating wildlife is traditional, prior to the SARS outbreak.
3) The remote mountain caves in SE Asia harbouring similar viruses are at least a 1800km+ drive away, and no outbreaks reportedly happened along the supply chain.
4) There were many wildlife farms in Hubei province raising animals including potential intermediate hosts like racoon dogs, which were highly unlikely to have been exposed to SE Asian viruses. Hubei province exported wild animals to Guangdong, which is by far the biggest market for such produce in China. Due to transportation costs, farmed wild animals from nearby Hubei would be much cheaper then ones transported a vast distance from SE Asia, so for economic reasons, it is highly unlikely that a significant number of potential intermediate host species made the long journey from SE Asia to Wuhan.
5) There is no record of the most relevant animal species, bats and pangolins, ever being traded in Wuhan, but the WIV had a colony of live Rhinolophus bats, the host species for viruses like SARS2, that it experimented on.
6) WIV publications indicate WIV scientists experimented on related viruses at BSL2, which is wholly inadequate to contain a virus like SARS2.
7) The Chinese government did not allow WHO or any independent scientists to gather or verify data independently, and with certain exceptions, did not publish any raw data, hence the early case data, including a ver low-resolution case map, that are a key part of the argument for natural emergence at the Huanan Seafood Market were completely unverified, and unverifiable.
8) The market environmental sample data that some say indicates an association of positive samples with a wildlife stall was taken from a paper published by the China CDC that used those data to explain that they showed a market origin was unlikely.
9) In contrast to other recent zoonotic outbreaks, the Chinese government was extremely secretive, and placed a series of gag orders on Chinese scientists, preventing them from publishing anything about the outbreak without government approval.
I have omitted other information, such as the reported zero cases of lineage A at the market, zero cases amongst animal sellers, and the extreme asymmetry between positive samples of lineage B and A at the market, that appear to make a market origin unlikely, as they are based on unverified data published by the Chinese government, which had a strong interest in minimising the publication of embarrassing things about the outbreak. I also omitted the China/WHO report's statement that there were zero infections amongst WIV staff, which, if true, would mean a laboratory outbreak was not possible, since given the large outbreak in the city (4% seroprevalence according to a CDC study), the chance of zero out of 600+ staff being infected was essentially zero, indicating the Chinese government was lying about this dataset.
Please feel free to roast the points above, and add any key facts of your own, by which I mean known and verifiable facts, not information published by the Chinese government with no verification or raw data.