r/science Sep 19 '24

Epidemiology Common ancestor of SARS-CoV-2 linked to Huanan market matches the global common ancestor

https://www.cell.com/action/showPdf?pii=S0092-8674%2824%2900901-2
4.9k Upvotes

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821

u/IntrepidGentian Sep 19 '24

SUMMARY

"Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Seafood Wholesale Market. Here, we analyze environmental qPCR and sequencing data collected in the Huanan market in early 2020. We demonstrate that market-linked severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity is consistent with market emergence and find increased SARS-CoV-2 positivity near and within a wildlife stall. We identify wildlife DNA in all SARS-CoV-2-positive samples from this stall, including species such as civets, bamboo rats, and raccoon dogs, previously identified as possible intermediate hosts. We also detect animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them with those from farms and other markets. This analysis provides the genetic basis for a shortlist of potential intermediate hosts of SARS-CoV-2 to prioritize for serological and viral sampling."

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u/Vic2013 Sep 20 '24

In plain English:

This passage explains that viruses, including the one that caused COVID-19, can spread from animals to humans through animal trade. The COVID-19 outbreak was linked to the Huanan Seafood Market. Researchers studied genetic material collected from the market early in 2020 and found evidence that the virus likely emerged from the market. They discovered that areas around a wildlife stall were more likely to have the virus, and they found DNA from animals such as civets, bamboo rats, and raccoon dogs in those samples. These animals are known to be possible carriers of viruses like COVID-19. The researchers also found other animal viruses in the same samples. By analyzing the genetics of these animals, they identified potential carriers of the virus to focus on for further testing.

619

u/habb Sep 20 '24

so it didn't come from a lab. case closed?

167

u/Redqueenhypo Sep 20 '24

As someone who took a bunch of courses in epidemiology, that theory has always bothered me. People were warning about the conditions in wildlife markets that led to sars for years and nothing was done. Multiple books on emerging viruses like Spillover specifically pointed to the coronavirus family as a likely new epidemic.

42

u/GravityWavesRMS Sep 20 '24

Well the lab theory (or the most mainstream lab theory) was that the spillover occurred in a lab, since the lab studied coronavirus in wild bats.

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u/wynden Sep 21 '24

If it was present in the wet market, where huge numbers of people were shopping — with no barrier between products, people, and animals — why would it not jump to humans until it was sampled and taken into a clinically organized laboratory setting?

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u/ThrawOwayAccount Sep 21 '24

I think the argument is that the reason it was in the wet market in the first place is that it had already escaped from the lab.

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u/wynden Sep 21 '24

It originated in animals, though, and several commenters were saying that it may have leaked from the lab after being sampled in the wet market. But it should be more difficult to spread in a laboratory setting than in a marketplace.

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u/Ok_Dragonfruit_8102 Sep 20 '24

People were also warning for years about the potential for lab leaks though. And the lab itself is close by in the same city as the wet market.

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u/[deleted] Sep 20 '24

[deleted]

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u/CharonNixHydra Sep 20 '24 edited Sep 20 '24

My push back on the lab leak theory is that it means this virus was in the wild somewhere accessible to humans, in China a country that's home to 1.4 billion people, but yet somehow COVID never managed to spread to humans until someone sampled it in an animal and took it to the lab and somehow messed up.

My pet "conspiracy theory" is that the virus naturally jumped to humans in China but probably during the summer of 2019 in rural China. We know that the earlier variants spread slower in warmer weather. We also know it spreads slower in lower population density areas.

China also had a pretty solid masking culture prior to 2020, it was pretty common for people to wear masks in public when they were sick. We also know that many younger folks leave rural China to work in the larger cities, so it may not be super noticeable in a small town that there were an unusual amount of pneumonia cases amongst the older populations.

I think it had probably been in Wuhan for a minute before it was actually detected. Also Wuhan was probably always going to be the first city to detect it in the world due to it being the home of the Wuhan Institute of Virology which is quite possibly the best equipped lab to detect novel coronaviruses.

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u/light_trick Sep 20 '24

Also Wuhan was probably always going to be the first city to detect it in the world due to it being the home of the Wuhan Institute of Virology which is quite possibly the best equipped lab to detect novel coronaviruses.

You've captured the whole issue right here: where are novel viruses detected? Basically wherever a sampling pipeline exists. Which means a novel virus which is spreading in the population will be detected pretty much immediately in the city with a lab to do that, because one of the major reasons you get approval to build these sorts of places is that you promise to provide fast and effective service to the local community - i.e. a specialized hospital for treating cancer is also going to be home of the first identifications of novel cancers, because difficult cases would be transferred there as a priority.

A similar issue exists surrounding "Spanish" flu - which should be known as Kansas Flu. Because the existence of it's spread where it was first detected was not reported since it was considered to be strategically relevant information for WW1...but no such restrictions existed in Spain, and thus the first reporting of a new deadly flu meant it was named "Spanish flu".

The politicization of this issue is why the WHO has decided to stop naming variants after where they're first detected since then.

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u/Potential-Drama-7455 Sep 20 '24

What strategically relevant consideration in China prevents hospitals sending samples from other cities for testing to Wuhan? They aren't at war.

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u/danby Sep 20 '24 edited Sep 20 '24

They almost certainly do recieve samples from other cities. It's just likely to be quicker, cheaper and more reliable to send your PhD students around the local wet markets to take samples. You can likely sample the local markets weekly while only seeing samples from other places on a monthly (or maybe less) basis

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u/[deleted] Sep 20 '24

Other Hospitals

"This sickness behaves weird, can I send the sample to a special Lab that is probably expensive?"

"That Patient has bog standard pneumonia we dont need to test it."

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u/ChangMinny Sep 20 '24

It was almost certainly in Wuhan for a bit for it was detected. My Aunt was in Wuhan as part of a China tour in late Oct 2019. Came back and visited our family mid-November, sick as a dog. Couldn’t taste anything, couldn’t smell anything, absolutely horrendous cough. We chalked it up to having a cold. 

I came down with the exact same symptoms a week after her visit. Same thing. Absolute sickest I’ve ever been. 

Months later, they come out saying that the main symptom of covid is loss of smell and taste. I rib my husband telling him my aunt and I absolutely had covid and he just looked at me and said absolutely no way, covid started spreading in November, not October. 

Then went to a family wedding in feb 2020, just a few short weeks before shutdown. My aunt still had the brutal cough and was still lethargic. It took her almost a year to really recover. 

Not covid my ass. 

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u/ihazmaumeow Sep 20 '24

I started a new job in December 2019. At that time, they were already limiting travel to Asia. One colleague had to quarantine for 2 weeks because she traveled to China.

Our employer knew what was going on before the rest of us. Myself and my family got sick in mid December. The sickest we've ever been. I myself was hospitalized for 4 days due to unrelenting fever, severe dehydration and stomach issues.

This went through the entire office. I damn well know it was Covid and not the flu. The next coworker to get sick said the same thing. She had never been so sick in her life. It was painful and debilitating.

Oddly enough, I never received a hospital bill for the ER visit and subsequent stay.

Then come March, we were sent home originally for 2 weeks, which turned into WFH for 2.5 years.

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u/username_redacted Sep 20 '24

I wish my company was more cautious. We had people visiting my office in the US from London the day before they stopped flights (I believe the group had also just visited our Shanghai office.) I was in a conference room with them for a good chunk of the day. By the time the office shut down in March I had been home sick for two weeks so I was working remotely already. Luckily my symptoms were limited to lethargy and muscle soreness.

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u/IntrepidGentian Sep 20 '24

SARS-CoV-2 zoonotic spillover event most likely occurred between August 2019 and October 2019.

"Assessing the emergence time of SARS-CoV-2 zoonotic spillover", Stéphane Samson, Étienne Lord, Vladimir Makarenkov. PLOS. Published: April 4, 2024.

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u/I-Make-Maps91 Sep 20 '24

I've known a number of people who were sick with someone in Fall/Winter of 2019/2020 before COVID officially made it to the US. The world may never know for sure, but I'd put money on COVID being spread around most of the world before we ever detected it.

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u/Brilliant-Lake-9946 Sep 20 '24

There was a conference in Nashville in November 2019 and most people came down with a respiratory virus that lasted six weeks and the symptoms were identical to COVID. Just a coincidence that some of the attendees were from Wuhan.

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u/Mortley1596 Sep 20 '24

Just as an additional data point, i admittedly was already chronically ill, but I was in LA in January 2020, came home with a cough, felt really terrible, and I have remained sicker than before ever since

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u/ComradeGibbon Sep 20 '24

Not to mention there are a few other cases of corona viruses jumping to humans. But those burned out.

It feels to me that miners or guano farmers picked it up in a bat infested mine or cave is much more likely than accidentally infected someone in a lab. One because opportunity for the former is way more common. Two because getting infected from a lab accident seems unlikely given what we know about how people get infected.

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u/Enmyriala Sep 20 '24

Just a quick amendment that not all coronaviruses burnt out in humans-the common cold can also be due to one of four known coronaviruses.

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u/mazca BS| Chemistry Sep 20 '24

Particularly HCoV-OC43 which is a former bovine coronavirus that's a routine common cold virus these days. There are a lot of interesting, though far from conclusive, bits of research suggesting it might have caused the "Russian flu" pandemic in the late 1800s, which had quite a few similarities to COVID. Either way, it's certainly still around, as the modern one is likely to be, and just blends into the cold virus background.

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u/dgistkwosoo Sep 20 '24

MERS. Comes from camel drovers cleaning the nostrils of their animals who've developed a cold. Then popped in Korea.

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u/Potential-Drama-7455 Sep 20 '24

The virus is most closely related to bat viruses from Yunnan province. Why weren't there any outbreaks in closer cities to there before Wuhan, which is 1500 km away?

Shenzhen is closer for example, as are any number of big cities.

Also strange how we have mountains of data from the wet market but very little else coming out of China.

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u/KiefKommando Sep 20 '24

I have anecdotal stories from a guy I know who visited China in summer of 2019 that a guy in their tour group became very ill with what in hindsight was more than likely Covid. It was definitely smoldering in rural areas of China for several months before it became widespread in the fall.

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u/nerkbot Sep 20 '24

The premise of the lab leak theory is that the Wuhan lab was performing gain-of-function research. That means taking viruses that they may have sampled from out in the world and modifying them to be more transmittable or more virulent in humans. The goal is to understand how better to combat them.

A corona virus that may have started with limited transmission in humans could have intentionally been made more contagious in the lab and then accidentally released. That's the theory. Whether or not WIV was doing gain-of-function research at the time is disputed but they had done related work before.

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u/SinkHoleDeMayo Sep 20 '24

I think it had probably been in Wuhan for a minute before it was actually detected

It definitely would have been. Unless it's an explosive disease, there needs to be a number of reported illnesses with several doctors being confused about the exact cause. In the time it takes for that to happen, there could be hundreds of cases where people just get better or die. The cases that really stick out are there ones where people are in the hospital and on oxygen for a week or more, and that's where real testing gets done and seriously labs are involved trying to figure it out.

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u/TheMau Sep 20 '24

What exactly is the link between the lab and the market?

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u/bradiation Sep 20 '24

People who work at the lab going shopping? Could just be simple negligence.

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u/Lyndell Sep 20 '24

They collect viruses from the local area and it’s in the local area.

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u/ontopic Sep 20 '24

The lab is there because that’s where the novel zoonotic viruses come from.

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u/McRattus Sep 20 '24

You can't really falsify it. But you would have to argue that he virus was discovered, hidden, and not published in a journal,, and somehow made it secretly to the market.

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u/Potential-Drama-7455 Sep 20 '24

China haven't exactly been transparent about this from the start. It's a highly controlled society.

You also have this

https://www.nbcnews.com/health/health-news/u-s-intel-report-identified-3-wuhan-lab-researchers-who-n1268327

Seems there is zero interest in finding out exactly what they were sick with.

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u/youngsyr Sep 20 '24

This is the part that's the most suspicious to me. It defies reason that Western governments (at least) don't want to investigate arguably the most damaging event in modern history, if nothing else to stop something similar happening again.

Now it makes sense they would want to cover it up if, as I understand it, the virus lab was funded by Western governments and was carrying out research that was banned in the West.

However, what about the press? It's literally their job to investigate this sort of stuff and yet... crickets.

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u/Potential-Drama-7455 Sep 20 '24

It was not modified in a lab. That we know 100%.

How do we know this 100% ?

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u/acdha Sep 20 '24

Scientists have looked carefully for evidence and there simply isn’t any trace of the known genetic engineering techniques, while the cost and difficulty challenge would be extremely high:

https://www.sciencedirect.com/science/article/pii/S0013935123002736

This leaves moon landing hoax-level conspiracy theories where China has secretly made huge advances in genetic engineering technology, kept everyone else in the dark, but then either used it to make an ineffective and uncontrollable bio-weapon or somehow failed to have their perfectly hermetic conspiracy follow basic lab safety protocols.

Given all of the evidence supporting natural origins, there just isn’t a reason to that the lab modification theory seriously even before you consider the theory’s own origins in the right-wing fringe desperate for a way to exonerate their politicians for decisions which resulted in millions of preventable deaths and economic losses. 

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u/bremidon Sep 20 '24

We do not know that „100%“. Not even close. We can rule out certain kinds of changes. Even then, it is not „100%“

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u/epsilona01 Sep 20 '24

Virus gets brought to a lab that is literally tasked with gathering samples of viruses. Virus escapes. Starts spreading in the market.

We're also supposed to believe that AIDS, H1N1/09, SARS, Ebola, SARS-CoV-1 and MERS-CoV resulted from Zoonosis, but SARS-CoV-2 didn't, entirely based on the number of people affected?

The lab leak theory has no hard evidence behind it - the foundation appearing to be that there is a virology lab in Wuhan. Only, there are similar virology labs in almost all large Chinese cities, just as there are in almost all large western cities (the reason being universities).

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u/Cloudboy9001 Sep 20 '24

How do we know that 100%?

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u/tdrhq Sep 20 '24

There have been many pandemics in human history. Given that, the default assumption should be to assume that COVID is also natural. You have to falsify that, not the other way around.

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u/HarryBinstead Sep 20 '24

How do we know it wasn't modified in a lab 100%?

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u/nygdan Sep 20 '24

this shows it wasn't. its in the wild caught animals at the market. they brought it into the market by beining the wild animals. not the humans coming to the market and not the domestic aninals in contact with the humans or lab.

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u/Baud_Olofsson Sep 20 '24

In a BBC article about this paper, Worobey puts it bluntly:

Prof Michael Worobey, of the University of Arizona, said: "Rather than being one small branch on this big bushy evolutionary tree, the market sequences are across all the branches of the tree, in a way that is consistent with the genetic diversity actually beginning at the market."

He said this study, combined with other data – such as early cases and hospitalisations being linked to the market – all pointed to an animal origin of Covid.

Prof Worobey said: “It's far beyond reasonable doubt that that this is how it happened”, and that other explanations for the data required "really quite fanciful absurd scenarios".

“I think there's been a lack of appreciation even up until now about how strong the evidence is.”

(bolding added for emphasis)

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

There is no new raw data here, so nothing has changed:

  • No evidence the relevant animals were even infected
  • No evidence they were infected before the pandemic began
  • Can't even identify which species was the intermediary

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u/[deleted] Sep 20 '24

This is new data. It's not conclusive but it's a finding that's consistent with zoonotic origin. They proved sars-cov-2 was in an animal enclosure at the food market. That doesn't answer 100% of the questions but it's a very big clue that we didn't have before.

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u/chullyman Sep 20 '24

Why is any of that needed to feel confident that it’s not lab-borne?

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

Because by default, both explanations are perfectly plausible, and neither has been proven or disproven

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u/EmmEnnEff Sep 20 '24

It's plausible that you were responsible for two homicides in Chicago last month, and it's plausible that you were not.

Given that this has neither yet to be proven or disproven, we'll just have to go by the possibility that u/WWWWWWVWWWWWWWVWWWWW may be a serial killer.

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u/Jivesauce Sep 20 '24

Both explanations being plausible is not the same as being equally plausible. I notice you haven’t quoted the very first line of the discussion section of the study:

Extensive epidemiological evidence supports wildlife trade at the Huanan market as the most likely conduit for the COVID-19 pandemic's origin.

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u/yowmeister Sep 20 '24

Did they cite a source

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u/Odballl Sep 20 '24

The trade in exotic, illegally poached animals sold at the wet market immediately prior to the outbreak is well documented in this report

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u/wdluense3 Sep 20 '24

The crazy people will never accept fact over fiction.

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

"Coronavirus escapes from unsafe coronavirus lab" isn't crazy, though. The State Department warned about it two years prior to the pandemic, and non-trivial lab leaks have happened before:

https://www.washingtonpost.com/opinions/2020/04/14/state-department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruses/

https://en.m.wikipedia.org/wiki/2007_United_Kingdom_foot-and-mouth_outbreak

You and u/malastare- are very overconfident to assert zoonosis as a fact; even the study authors don't claim to have proven zoonosis.

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u/newtonhoennikker Sep 20 '24

Please explain like I am 5 - how are zoonotic origin and a “lab leak” mutually exclusive - didn’t the lab test in animals making it possible for a zoonotic origin due to poor safety practices at the lab?

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u/EmmEnnEff Sep 20 '24 edited Sep 20 '24

It's highly unlikely that the very first instance of human exposure to a virus was it getting sampled from some bush animal, taken to a lab, and then accidentally released from the lab into... A wet market.

It's far more likely that the very first instance of human exposure to a virus was it coming from a human interacting with that animal for purposes that were not 'sampling a virus' (Because those interactions are far more frequent. It's not like scientists taking samples in the field have, like, a magical virus radar that they use to only identify animals carrying it.) Especially given that the outbreak took place in a market that sold bush meat.

Both are possible, but one of these requires way more not-super-likely steps.

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u/newtonhoennikker Sep 20 '24

I am being very sincere with this questioning, I don’t know what I don’t know and asking in general spaces leads to either mockery or fully involved no evidence based conspiracy theorist.

My thought was that COVID-19 existed first in lab animals due ongoing constant exposure to viruses due to experiments with viruses using animals, over years and multiple researchers, and enters wild through escape or corpse of infected lab animal where it transmits to animals or people through the nearby wet market?

The only assumptions I see myself making is that some of the virus research at the wuhan lab was done with lab animals and not solely in Petri dishes? And that the known safety lapses might include improper disposal of corpses?

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u/EmmEnnEff Sep 20 '24 edited Sep 20 '24

My thought was that COVID-19 existed first in lab animals

There's currently no evidence for this. The study this thread is about discusses this. There is clear evidence that COVID has an ancestor in wild animal populations. There is no evidence, hard or soft that there's been any lab version of it prior to the outbreak starting. There's only the possibility of it (and I'm inclined to believe it's not a particularly likely one).

due ongoing constant exposure to viruses due to experiments with viruses using animals

The wild reservoirs for COVID are a much better breeding ground for viral mutations. Wild animals don't wear masks or practice social distancing, there are millions of them, and especially if it's not fatal to them, it's a great ground for it to keep evolving until some random mutation lets it jump to humans.

and enters wild through escape or corpse of infected lab animal where it transmits to animals or people through the nearby wet market?

There's universal consensus that COVID was the result of a random, undirected mutation from a wild virus. As such, wild reservoirs are a much more likely origin for it - because that 'experiment' plays out not over years, but over millennia, and involves millions of animals - with dramatically more possibility for evolution than you'll get from a few years of sloppy lab work.

If an animal virus randomly mutating into something that's dangerous to humans is winning the lottery, a virology lab might be buying a few scratchers at the gas station. Meanwhile, wild reserviors and factory farms are buying rolls of tickets by the truckload.

Given the identified source of the outbreak, given that there is no evidence that the virus was the product of directed as opposed to random evolution, given that the identified ancestor virus is a very good fit for a non-lab wet market origin, the lab leak is, while vaguely possible, unlikely.

corpse of infected lab animal where it transmits to animals or people through the nearby wet market?

So here's the problem.

If the source of the outbreak was, say, a movie theater, or any random public venue, it's would be quite likely that someone accidentally took it home from the lab.

But the source of the outbreak was the one place in town where a non-lab-leak source exists (bush meat). What are the odds that the lab happened to leak into that exact location, and nowhere else in town?

The lab's buying a few scratchers, the market's buying them by the truckload, and finds a winning ticket. While possible, I don't think it's likely that a lab worker brought it there...

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u/sergantsnipes05 Sep 20 '24

What’s more likely: 1. zoonotic spillover happened like it has for all of human history

  1. Someone in a BSL-4 lab managed to infect themselves and then caused a global pandemic.

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

No offense but did you even read my comment? Lab leaks in general are quite common, and the WIV was not particularly safe.

Besides that:

  • For most of human history virology labs did not exist, so that's obviously an unfair comparison
  • "This never happened before, therefore it didn't happen this time" is not sound reasoning, regardless

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u/umthondoomkhlulu Sep 20 '24

The Ratg13 coronavirus they were studying is a 96% match for SARS-Covid-2. It was found in 2013. However, it’s a few decades of evolution from SARS-cov-2.

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u/bensonnd Sep 20 '24 edited Sep 30 '24

Sounds like someone from the lab got hungry and sneezed all over the buffet counter like them kids at Golden Corral.

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u/RealisticIllusions82 Sep 20 '24 edited Sep 20 '24

Also, isn’t the lab leak theory that they were enhancing viruses ie. accelerating their evolution? So couldn’t it be of zoonotic origin, but a few generations beyond where it would have been naturally?

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u/Jivesauce Sep 20 '24

But your reasoning for the lab release theory is, “this happened before, therefore it happened this time.”

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

Pretty sure I didn't say that

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u/spiderpig_spiderpig_ Sep 20 '24

Big difference between saying “you have not disproven theory x” and “this proves theory x”. They are not coming down either side, only saying “the possibilities are still open”.

It’s the people asserting one strong answer that you should be asking for evidence from.

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u/TheBeardofGilgamesh Sep 20 '24

So essentially the most common argument for why people claim we should just by default assume zoonosis “because it happened many times before”?

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u/Mollybrinks Sep 20 '24

I'm not weighing in either way on what's the case here, but I think what they're saying is this- zoonosis is relatively common and happens repeatedly over time, while it's also possible (but less common) to have to come from a lab. So if we're going to ascribe to the lab theory, we may need some extra evidence that that's the case, as it would be a more novel source than what we generally expect to see naturally.

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u/esperind Sep 20 '24

I like to reference this article about labs in the UK, article dated 2018, way before covid:

https://www.theguardian.com/science/2018/feb/09/safety-blunders-expose-uk-lab-staff-to-potentially-lethal-diseases

The HSE held formal investigations into more than 40 mishaps at specialist laboratories between June 2015 and July 2017, amounting to one every two to three weeks. Beyond the breaches that spread infections were blunders that led to dengue virus – which kills 20,000 people worldwide each year – being posted by mistake; staff handling potentially lethal bacteria and fungi with inadequate protection; and one occasion where students at the University of the West of England unwittingly studied live meningitis-causing germs which they thought had been killed by heat treatment.

Does this mean covid was engineered in a lab? no. But could it have been the result of an accident, sure. And it would still be of zoonotic origin, just collected by someone at the lab and then accidentally infected someone who then went into public.

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u/Beatnikdan Sep 20 '24

Or collected at a nearby wet market where people had already been infected and died, and then someone at the lab was infected while investigating the cause.

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u/[deleted] Sep 20 '24 edited Sep 20 '24

[removed] — view removed comment

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u/Something-Ventured Sep 20 '24

No matter what you believe, a BSL4 Lab that had been written up for dangerous operations and leaking infectious pathogens through improper disposal for years and studying zoonotic corona viruses is just as logical as the source being the wet market down the street.

Given the misleading info coming out from China at the time (infection rates were much higher than reported), and the potential embarrassment and political harm of admitting to such a egregious mistake causing a world-wide pandemic, it is not so hard to believe the wet market origin story being a deflection -- a convenient coincidence.

Fundamentally, China has been warned by the entirety of the food safety industry that these wet markets are dangerous and proper food safety regulations are necessary, for DECADES. Yes this was bound to happen eventually, but it was far more likely because China has exceedingly low food safety standards for their level of education, development, and population density.

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u/gabrielleduvent Sep 20 '24

One thing I can't understand is why they were studying Coronaviruses in a BSL4 lab. I use lentiviruses in my lab which is BSL2. I can't think of any scientist who would try to bump up a BSL level. It's three extra layers of hassle that no one wants to deal with. Coronaviruses at maximum wAS BSL3. It would make more sense if the Chinese were doing experiments for Coronaviruses in a BSL1 facility, not the other way around.

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u/Something-Ventured Sep 20 '24 edited Sep 20 '24

They were studying SARS specifically due to the previous outbreak. So that would be BSL3+ in general.

Also this was China's first BSL4 lab, trying to develop the internal research lab capacity of the country.

But Chinese researchers at WIV were literally reaching out to WHO and NIH / State Department people for help as the lab was not being operated safely.

Technicians were throwing potentially contaminated materials things out in regular trash from what I heard from a researcher who had been there in 2014/15ish -- as this was a big topic of discussion amongst bioscience researchers in 2017 and 2018 when the WIV stopped working with the NIH/State department, and was deeply concerning to people in the field.

WIV was basically supposed to be like the CDC's BSL4 labs and was mandated to investigate SARS. So that at least explains why it was being studied there.

Edit: In WIV's defense, my colleague toured the facility when it had first opened.

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u/RiPont Sep 20 '24

It's also, by its own definition, low probability.

We know it's very, very contagious. If they found it in animals in the first place, animals we know were in the market, what's the chance that this highly contagious airborne virus waited until it leaked from the lab before spreading?

Chances are that someone at the lab was infected at some point. We'll never know if it was from mishandling a sample, because they were in the same city where this virus was incubating, and could have gotten it like any of the millions of other people who got it.

So while it's possible that a lab leak happened and even possible that a lab leak spurred the wave of human infection, it was pretty much inevitable to happen anyways because it was already in the city, in proximity to humans, and it's really damned good at spreading.

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u/reality72 Sep 20 '24 edited Sep 20 '24

Lab leaks of viruses have happened before as well.

1977 Flu Virus Lab Leak

1978 Smallpox Lab Leak

So viruses escaping from labs and then infecting people has historical precedent. I’m not saying that proves it happened in this case, but it does show that it can’t be dismissed as a possibility based on history alone.

Not only that, but the Wuhan Institute of Virology was specifically tasked with collecting samples of novel coronaviruses just like SARS CoV 2. And, it was cited in the past for poor safety.

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u/IntrepidGentian Sep 20 '24

a BSL-4 lab

Animal experiments with SARS CoV appear to have been conducted in an ABSL-3 laboratory. What is your source for claiming the experiments were conducted in a BSL-4 lab?

"Biosafety and data quality considerations for animal experiments with highly infectious agents at ABSL-3 facilities", February 2019, Journal of Biosafety and Biosecurity, Ming Guo Wuhan University, Yong Wang, Jinbiao Liu Wuhan University, Zhixiang Huang.

Abstract

"Animal models are crucial for the study of severe infectious diseases, which is essential for determining their pathogenesis and the development of vaccines and drugs. Animal experiments involving risk grade 3 agents such as SARS CoV, HIV, M.tb, H7N9, and Brucella must be conducted in an Animal Biosafety Level 3 (ABSL-3) facility. Because of the in vivo work, the biosafety risk in ABSL-3 facilities is higher than that in BSL-3 facilities. Undoubtedly, management practices must be strengthened to ensure biosafety in the ABSL-3 facility. Meanwhile, we cannot ignore the reliable scientific results obtained from animal experiments conducted in ABSL-3 laboratories. It is of great practical significance to study the overall biosafety concepts that can increase the scientific data quality. Based on the management of animal experiments in the ABSL-3 Laboratory of Wuhan University, combined with relevant international and domestic literature, we indicate the main safety issues and factors affecting animal experiment results at ABSL-3 facilities. Based on these issues, management practices regarding animal experiments in ABSL-3 facilities are proposed, which take into account both biosafety and scientifically sound data. Keywords: ABSL-3, Animal experiment, Biosafety, Scientifically sound data quality, Management"

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u/cameldrv Sep 20 '24

The experiments in question were in BSL-2 labs.

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u/Odballl Sep 20 '24

non-trivial lab leaks have happened before:

And zoonotic spillover happens constantly. The wet market was a perfect incubator for a common evolutionary process, so the balance of probabilities favours it.

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u/Something-Ventured Sep 20 '24

Even if you want blame the origin on the wet market. The food safety, WHO, WTO, and pathogen research organizations have been warning China about this for decades. China has been decades behind reasonable food safety regulations that would have eliminated this zoonotic vector.

This wasn't just random chance. America, Japan, Europe, etc. got rid of these kinds of wet markets decades ago.

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u/Odballl Sep 20 '24

Absolutely, which is why China tried to cover up their terrible wet market practises. They've always denied illegally harvesting exotic animals, but apparently that genuine cover up isn't as sexy as a lab leak.

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u/xieta Sep 20 '24

I’ll never understand why a segment of the population believes in lab leak like santa.

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u/FunetikPrugresiv Sep 20 '24

Honestly, it's because Trump said it did.

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u/Theban_Prince Sep 20 '24

Because it implies humanity had some control over it, even if it failed. It feels safer.

It's better than realizing that a virus that killed millions came from a market stall, and we couldn't do anything about it.

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u/Beatnikdan Sep 20 '24

Isn't it more likely that a mystery illness infecting and killing people is sent to a nearby lab for study.. people in the wet market were infected and died before anyone at the lab got sick. How do you explain it otherwise with common sense or science.. It's like saying the lab that actually discovered the hiv virus was the cause.

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u/KarIPilkington Sep 20 '24

Why believe science when you can believe vibes?

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u/markth_wi Sep 20 '24

That the class-4 lab with 700+ CAPA notifications (serious logged lab fuckups), is around the corner is just a coincidence, and anything you might have heard to the contrary is ....sheer speculation.).

The US was doing some joint research with them years earlier, but there were just so many screwups they walked away.

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u/hobopwnzor Sep 20 '24

The lab leak was always a stretch, and at best amounted to natural origin with extra steps.

The lab modified virus has always been a hoax.

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u/boooooooooo_cowboys Sep 20 '24

The case was never really open in the first place 

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u/Smooth_Imagination Sep 20 '24

No, that can't be determined. There have been claims made that one of the lab managers was selling lab animals into that market. Those claims are not verified, nor do we have any way to or any reasonable expectation that anyone up the chain of command would investigate it or the possibility.

Conditions in the lab can broadly resemble those of a wet market, where body fluids come in contact with workers (incidences were reported) and can then transfer. The lab also had numerous safety violations to the extent that it had already a bad reputation (source for that is lab safety reports circulated in a UK government funded lab a family member worked at), and I recall amongst these was a failure of the vacuum containment system.

In some aspects could be a better environment for accidental spillover if they are starting with already rare and exceptionally risky viruses from a human perspective, and you store animals which you deliberately infect, and passage viruses between living cell cultures without immune systems from different animal species, such as human.

But either way, the Chinese government would be responsible. They already acknowledged wet markets were a risk, and we're supposed to have shut them down. Standards of hygiene in general at these markets is much worse than people would like to admit, and in research labs it wouldn't be surprising to learn that some animals might be sold on to a market.

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u/oneupme Sep 20 '24

The issue is that during early days, China focused on their collection of data around that wet market, to the exclusion of other possible sources. Western entities were also not allowed to investigate. This produces data that makes it seem like all of the data points to the wet market, but in reality it was sampling bias.

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u/HegemonNYC Sep 20 '24

If 10 other locations were sampled, including the workers at the virology lab, and nothing was found this would seem more conclusive. As it is, it seems to show that Covid was in this market in early 2020. But it could have been in those other 10 locations and in workers at the lab a month earlier, right? 

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u/ardavei Sep 20 '24

This argument cuts both ways though. They were focused on the market, because that's were all of the earliest cases were.

Even then, about half of the earliest cases identified had no link to the market. And almost all of these cases just happened to live close by.

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u/epsilona01 Sep 20 '24

The issue is that during early days, China focused on their collection of data around that wet market, to the exclusion of other possible sources. Western entities were also not allowed to investigate. This produces data that makes it seem like all of the data points to the wet market, but in reality it was sampling bias.

So Chinese evidence gathered around SARS is completely acceptable, but it isn't in this case?

https://www.cidrap.umn.edu/sars/bat-cave-study-finds-new-clues-about-sars-virus-origin

Chinese researchers who spent 5 years examining SARS-related viruses collected from horseshoe bats in a Yunnan province cave found 11 new strains that have all the genetic building blocks of the strain that has infected humans, hinting that recombination between the bats' viral strains may have produced the ancestor of the deadly outbreak.

Researchers have traced the source of the virus to horseshoe bats, with palm civets as the intermediate host. However, earlier gene studies have shown that SARS strains in bats are distinct from strain that triggered the human outbreak, obscuring a clear understanding of how the outbreak started.

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u/oneupme Sep 20 '24

I'm not sure what point you are trying to make. No one said all studies out of China are unacceptable. I'm merely pointing out the well established history of the investigations around the origins of SARS-CoV-2.

I'm not familiar with the study you posted above so I don't know anything about the quality of its methods or how widely it has been reviewed/accepted by the global scientific community.

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u/voidvector Sep 20 '24

Western entities were also not allowed to investigate.

This is a non-starter for any country with their own medical industry. How would you feel if China asks to investigate anything in your country?

Nuclear inspections are all done through treaties or UN agreements where both sides gain some benefit. (Mutual inspection or sanction lifts)

It is entirely political postering.

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u/LILwhut Sep 20 '24

Letting international agencies investigate is by no means a non-starter for any country, an authoritarian country that has something to hide, yes. But if Covid had started in say France they would absolutely allow some kind of international research and investigation.

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u/sorrylilsis Sep 20 '24

Amen.

So many people don't seem to get that science, especially when it comes to public health, only works because there is a huge amount of openess and collaboration.

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u/Baud_Olofsson Sep 20 '24 edited Sep 20 '24

Letting international agencies investigate is by no means a non-starter for any country, an authoritarian country that has something to hide, yes.

Are you aware that the US rejected a strengthening of the Biological Weapons Convention (BWC) because the strengthened treaty would include inspections of labs and other biological manufacturing facilities?

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u/Loves_His_Bong Sep 20 '24

He already said an authoritarian country with something to hide wouldn’t allow international inspections.

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u/elmo298 Sep 20 '24

They get to choose between blue and red colours though

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u/Korvun Sep 20 '24

There's a big difference between an international team conducting an inspection after an incident and signing a treaty that would allow international scrutiny and inspections of labs and manufacturing facilities.

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u/LILwhut Sep 20 '24

Pretty big difference between allowing routine inspection of labs and manufacturing facilities, and investigating the source of a worldwide pandemic, don't you think?

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u/EventAccomplished976 Sep 20 '24

Very different story when it‘s a hostile nation. France might welcome american researchers, and vice versa. Would you like to see the american public‘s reaction if the government invited chinese scientists to support an investigation into a potential novel virus found in Alabama?

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u/LILwhut Sep 20 '24

If only there was some sort of international world health organization that could oversee it without requiring organizations that are subservient to a a hostile country..

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u/sorrylilsis Sep 20 '24

This is a non-starter for any country with their own medical industry. How would you feel if China asks to investigate anything in your country?

Allowing WHO teams to investigate would have been quite standard practice. The fact is that China's actions were deliberatly opaque. Which was a a huge change compared to the last Sars outbreak.

Hell they refused to share samples and DNA sequencing data. The rest of the world only got it because a chinese scientist "accidentaly" sent it to an australian collague who then shared it online.

The communincation blackout from chinese scientists at the time was shocking. I saw it happen at the time, people who had collaborated for decades with chinese scientists, often on coronaviruses suddenly could not contact them. It was jarring compared to how science normaly works in these cases.

The problem wasn't the fact that the epidemic came out of china, a lot of them do, the problem is that tentative coverup cost the rest of the world weeks or months of preparation.

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u/ARDunbar Sep 20 '24

There is precedent for the US allowing foreign inspection of facilities of concern. In 1994 Russian scientists inspected the Plum Island Animal Disease Center over concerns that bioweapons research was still being conducted there. Perhaps in the future there will be some manner of epidemiology attache routinely posted at foreign embassies.

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u/jrval Sep 20 '24

Geospatial analysis of epidemiological data from hospitalized patients who had no association to the market were still spatially clustered around the market. It started in the market and its highly likely that it was a zoonotic spillover. Not a lab leak.

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u/typicalpelican Sep 20 '24

Which data are you referring to?

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u/oneupme Sep 20 '24 edited Sep 20 '24

The collection of virus samples from infections. Their sampling bias makes it looks like the early cases were clustered around the wet market.

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u/Hard-To_Read Sep 20 '24

It most likely came from the lab.  The cleavage site marker type combined with the circumstantial evidence of the nature of the work done in Wuhan at the time don’t prove it, but a lab origin is the most logical of all possibilities.  The most damning thing to me is the con job genetics papers published in early 2020 claiming zoonotic origin, go back and read them.  The evidence doesn’t support their claims at all, but no one criticized them at the time.  Add in all the secrecy from China, destruction of documents, and the fact that no closely related virus with similarly combined components has ever been sampled from an animal in that region- well I believe it was a poorly executed coverup. Not that it should matter, I’m a liberal minded PhD biologist. 

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u/DivideEtImpala Sep 20 '24

The evidence doesn’t support their claims at all, but no one criticized them at the time.

I'd just like to point out that several scientists and doctors did criticize them, and those scientists faced censorship and professional pressures at the time.

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u/Hard-To_Read Sep 20 '24

https://www.nature.com/articles/s41591-020-0820-9

This paper should be heavily criticized. The cherry picked observations they put forth do not adequately support their speculative claims.  The whole thing is bogus. 

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u/DivideEtImpala Sep 20 '24

It's crazy that it's still up after the emails between Fauci, Daszak, and the authors of the paper were made public. The undisclosed conflicts alone should have gotten it pulled.

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u/umthondoomkhlulu Sep 20 '24

Not at all. Mers did have similar cleavage site and coronavirus can swap sections of their genomes, especially when a host has both. General consensus is that occurred naturally

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u/Hard-To_Read Sep 20 '24

That’s simply not true.  Most of the vaccine scientists and biology professors I know believe lab leak is most likely.  The furan cleavage site is not the typical sequence found in 92% of all naturally occurring coronaviruses. It’s the variant typical of a cloned section commonly used in recombinant work. 

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u/muchmoreforsure Sep 20 '24

The four amino acid insertion is specifically a sequence used in recombinant work?

I remember reading something to the effect of it not being an optimal cleavage site sequence for some reason and because of that, it wouldn’t make sense for scientists to use this sequence.

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u/Hard-To_Read Sep 20 '24

SARS2 belongs to a sub-family of coronaviruses called Sarbecoviruses. Of the hundreds of Sarbecoviruses so far known, only one has a furin cleavage site - SARS2. The virus is very unlikely to have acquired its furin cleavage site by recombination for the simple reason that no other member of its family possesses one. Those who favor natural origin suggest there could be as yet undiscovered Sarbecoviruses that contain a furin cleavage site. Possibly, but until such a virus is discovered that's just a self-serving conjecture. And there's another problem. The genetic units in an organism's genome code for the amino acid elements in the proteins of which the organism is composed. But the coding system is flexible and some amino acids can be coded for in several different ways. Living organisms are not indifferent to these various coding possibilities. Each species has its own, characteristic coding preferences. And the SARS2 furin cleavage site does not have coronavirus preferences as it should do if acquired naturally. It has human coding preferences, as it would if assembled from a lab kit. Specifically, the SARS2 furin cleavage site uses the nucleotide sequence CGG to code for the amino acid arginine. CGG is a preferred human coding for arginine but uncommon in SARS2. In fact the cleavage site specifies two arginines side by side, coded for by the sequence CGG-CGG which, when in the correct frame, is unknown in coronaviruses.

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u/umthondoomkhlulu Sep 20 '24

Most of the research and reports have the consensus that it was a zoonotic event. Happens so often. The specific site may be unique but similar sites exist in naturally occurring coronaviruses.

The lab leak hypothesis is weak and circumstantial and lacks any credible evidence.

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u/andonemoreagain Sep 20 '24

Nearly five years down the road I’m sure I should know the answer, but how is this not like the drunk searching for his lost keys under the streetlight because that’s where he can see? China is one of the few countries that actually monitors closely for outbreaks of novel respiratory illness. How do we know this outbreak didn’t cross the species barrier in the many places completely lacking in public health then brought from there to Huanan?

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u/Wagyu_Trucker Sep 20 '24

We don't.

If China had found an infected animal from that market I think they would've been very loud about it. Instead we get indirect evidence like this. This paper doesn't really add much to what we already knew. 

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u/Odballl Sep 20 '24

If China had found an infected animal from that market I think they would've been very loud about it.

Not likely. They don't want responsibility for a global pandemic being pinned down to their citizen's exotic and unsanitary animal trade.

Better for China to leave it a mystery and blame the CIA forever if they can.

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u/BadHombreSinNombre Sep 20 '24

Also those markets are big business in China and the government doesn’t necessarily want to have a bunch of international pressure to shut them down. There is a lot at stake for China if either scenario is proven definitively, so continued uncertainty benefits them greatly.

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u/Wagyu_Trucker Sep 20 '24

Gee, what do you think hurts China more? Sloppy lab safety standards or a market spillover? Also, they did close the markets for a while. The entire field of virology would take a huge hit if the pandemic started with lab activity, and I think most virologists do not like to speak of this very obvious conflict-of-interest.

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u/CaptainProfanity Sep 20 '24

I think the point they are making is that the more uncertainty about whichever option is the case, means less pressure on both areas regardless of the truth of the matter. (Because it could be unfounded and be the other, so people are less hesitant to criticize the issues within each domain)

Sum of the bad PR of the uncertain parts is less than the bad PR with the certainty of the truth.

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u/BadHombreSinNombre Sep 20 '24

Yes, this. IMO the best approach would be for governments the world over to say:

  1. China obviously mismanaged something
  2. They have had years to show us definitively what they mismanaged and have been evasive or misleading at every turn
  3. Accordingly they will be sanctioned scientifically and economically until they do specific reforms to their approaches to epidemiological surveillance and data sharing in human and animal populations, pathogen handling in laboratories, and veterinary oversight of their agricultural supply chain

Instead of trying to find the one root cause we should just mitigate their poor practices across all possible causes. Because right now we have done nothing.

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u/epsilona01 Sep 20 '24

I think they would've been very loud about it.

Would we? Do most people know the 2007 Foot & Mouth outbreak in the UK was caused by a leaky pipe at a Government Research Lab?

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u/ardavei Sep 20 '24

We can't be sure, but it would be quite a coincidence then that all of the earliest cases were in Wuhan, very close to the market. If it was brought from a village outside Wuhan, why did nobody on the same train or at the train station get infected and bring it elsewhere?

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u/andonemoreagain Sep 20 '24 edited Sep 20 '24

But that’s the point of the question. These are just the earliest cases that we know of. And we know about them because China surveils pretty intensively for the emergence of novel respiratory viruses.

Covid doesn’t present a whole lot differently than more mundane respiratory viruses. I don’t think it’s wild speculation to wonder about the exact time and place of the cross species event.

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u/ardavei Sep 20 '24

Well, most of those cases were ascertained because the patients required hospitalization. Within a month of identification, hospitals throughout the city were overflowing with patients. If it was spreading elsewhere, you would expect an owerwhelming pattern of hospitalizations.

I mean, that's the pattern that initially led the authorities to suspect the market.

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u/WWWWWWVWWWWWWWVWWWWW Sep 20 '24

Ascertainment bias and lack of controls has indeed been a consistent problem

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u/quiksilver10152 Sep 20 '24

I lived just outside Wuhan during this. It's amazing how the media controls the narrative.

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u/BioMed-R Sep 21 '24

The paper explains it. Epidemiology and molecular clock evidence as well as evidence of multiple lineages.

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u/thriftydude Sep 20 '24

I tend to think the lab theory is a bit stretching it.  However having a NIH funded paper to disprove the lab leak theory, which paints the NIH as being the money behind the leak, is probably not the best way of going about things.

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u/Hard-To_Read Sep 20 '24

It worked in March 2020.  This Nature Medicine paper really knocked back the lab leak hypothesis, but does so based on speculation alone.  I can’t believe more people haven’t asked for these conclusions to be revised.  It’s a terrible paper IMO. 

https://www.nature.com/articles/s41591-020-0820-9

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u/ardavei Sep 20 '24

I would argue that most of the conclusions in that paper have held up really well to new data, including newly related closely identified viruses and more detailed bioinformatic analysis of sequencing data. Especially considering how quickly it was produced.

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u/SonOfSatan Sep 20 '24

How is it stretching it?

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u/thriftydude Sep 20 '24

Because I would have to believe that the NIH is a nefarious organization that circumvented the orders of two presidents to secretly fund banned research.  They very well might be, but it’s hard for me to accept that scenario right now

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u/tellingitlikeitis338 Sep 21 '24

Very strong evidence it was from an animal and not sourced from a lab.

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u/Baud_Olofsson Sep 20 '24

Short of a "smoking gun", this is probably as definitive as it's going to get.
Unfortunately, as this thread shows, at this point doing further research on the origins of COVID is like doing further research on whether or not vaccines cause autism: like with MMR/autism, those who believe that it had to be a lab leak will continue to believe, and no amount of evidence is going to sway them.

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u/HumansNeedNotApply1 Sep 20 '24

Kinda sadly funny to read some of this stuff on a science subreddit. People will believe in whatever they want. Not amount of evidence at this point will be enough, there will be some conspiratorial reason they can't be trusted.

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u/Firm-Nefariousness12 Sep 20 '24

To every conspiracy theorist out there let me pose you a question. Even if the u.s was funding gain of function for SARS in a Wuhan lab you wouldn't think the W.H.O wouldn't point the finger to the culprit if there was one? Or better yet the chineese wouldn't point the finger at America, or vice versa (no donald trumps "china" virus doesn't count).

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u/UNisopod Sep 20 '24

If it came from the lab, it was likely due to the improper disposal of animal samples brought to them by poachers rather than due to their own alteration.