Virus

https://nymag.com/intelligencer/article/coronavirus-lab-escape-theory.html
The Lab-Leak

Hypothesis
For decades, scientists have been hot-wiring viruses in hopes of preventing a pandemic, not causing one. But what if …?

What happened was fairly simple, I’ve come to believe. It was an accident. A virus spent some time in a laboratory, and eventually it got out. SARS-CoV-2, the virus that causes COVID-19, began its existence inside a bat, then it learned how to infect people in a claustrophobic mine shaft, and then it was made more infectious in one or more laboratories, perhaps as part of a scientist’s well-intentioned but risky effort to create a broad-spectrum vaccine. SARS-2 was not designed as a biological weapon. But it was, I think, designed. Many thoughtful people dismiss this notion, and they may be right. They sincerely believe that the coronavirus arose naturally, “zoonotically,” from animals, without having been previously studied, or hybridized, or sluiced through cell cultures, or otherwise worked on by trained professionals. They hold that a bat, carrying a coronavirus, infected some other creature, perhaps a pangolin, and that the pangolin may have already been sick with a different coronavirus disease, and out of the conjunction and commingling of those two diseases within the pangolin, a new disease, highly infectious to humans, evolved. Or they hypothesize that two coronaviruses recombined in a bat, and this new virus spread to other bats, and then the bats infected a person directly — in a rural setting, perhaps — and that this person caused a simmering undetected outbreak of respiratory disease, which over a period of months or years evolved to become virulent and highly transmissible but was not noticed until it appeared in Wuhan.

There is no direct evidence for these zoonotic possibilities, just as there is no direct evidence for an experimental mishap — no written confession, no incriminating notebook, no official accident report. Certainty craves detail, and detail requires an investigation. It has been a full year, 80 million people have been infected, and, surprisingly, no public investigation has taken place. We still know very little about the origins of this disease.

...

That same month, a group of French scientists from Aix-Marseille University posted a paper describing their investigation of a small insertion in the genome of the new SARS-2 virus. The virus’s spike protein contained a sequence of amino acids that formed what Etienne Decroly and colleagues called a “peculiar furin-like cleavage site” — a chemically sensitive region on the lobster claw of the spike protein that would react in the presence of an enzyme called furin, which is a type of protein found everywhere within the human body, but especially in the lungs. When the spike senses human furin, it shudders, chemically speaking, and the enzyme opens the protein, commencing the tiny morbid ballet whereby the virus burns a hole in a host cell’s outer membrane and finds its way inside.

The code for this particular molecular feature — not found in SARS or any SARS-like bat viruses, but present in a slightly different form in the more lethal MERS virus — is easy to remember because it’s a roar: “R-R-A-R.” The letter code stands for amino acids: arginine, arginine, alanine, and arginine. Its presence, so Decroly and his colleagues observed, may heighten the “pathogenicity” — that is, the god-awfulness — of a disease.

Botao Xiao, a professor at the South China University of Technology, posted a short paper on a preprint server titled “The Possible Origins of 2019-nCoV Coronavirus.” Two laboratories, the Wuhan Center for Disease Control and Prevention (WHCDC) and the Wuhan Institute of Virology, were not far from the seafood market, which was where the disease was said to have originated, Xiao wrote — in fact, the WHCDC was only a few hundred yards away from the market — whereas the horseshoe bats that hosted the disease were hundreds of miles to the south. (No bats were sold in the market, he pointed out.) It was unlikely, he wrote, that a bat would have flown to a densely populated metropolitan area of 15 million people. “The killer coronavirus probably originated from a laboratory in Wuhan,” Xiao believed. He urged the relocation of “biohazardous laboratories” away from densely populated places. His article disappeared from the server.

And late in the month, a professor at National Taiwan University, Fang Chi-tai, gave a lecture on the coronavirus in which he described the anomalous R-R-A-R furin cleavage site. The virus was “unlikely to have four amino acids added all at once,” Fang said — natural mutations were smaller and more haphazard, he argued. “From an academic point of view, it is indeed possible that the amino acids were added to COVID-19 in the lab by humans.” When the Taiwan News published an article about Fang’s talk, Fang disavowed his own comments, and the video copy of the talk disappeared from the website of the Taiwan Public Health Association. “It has been taken down for a certain reason,” the association explained. “Thank you for your understanding.”

...

SARS-2 seems almost perfectly calibrated to grab and ransack our breathing cells and choke the life out of them. “By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission,” Alina Chan and her co-authors have written, whereas SARS, when it first appeared in 2003, underwent “numerous adaptive mutations” before settling down. Perhaps viral nature hit a bull’s-eye of airborne infectivity, with almost no mutational drift, no period of accommodation and adjustment, or perhaps some lab worker somewhere, inspired by Baric’s work with human airway tissue, took a spike protein that was specially groomed to colonize and thrive deep in the ciliated, mucosal tunnels of our inner core and cloned it onto some existing viral bat backbone. It could have happened in Wuhan, but — because anyone can now “print out” a fully infectious clone of any sequenced disease — it could also have happened at Fort Detrick, or in Texas, or in Italy, or in Rotterdam, or in Wisconsin, or in some other citadel of coronaviral inquiry. No conspiracy — just scientific ambition, and the urge to take exciting risks and make new things, and the fear of terrorism, and the fear of getting sick. Plus a whole lot of government money.

...

There are, in fact, some helpful points of agreement between zoonoticists — those who believe in a natural origin of the SARS-2 virus — and those who believe that it probably came from a laboratory. Both sides agree, when pressed, that a lab origin can’t be conclusively ruled out and a natural origin can’t be ruled out either — because nature, after all, is capable of improbable, teleological-seeming achievements. Both sides also agree, for the most part, that the spillover event that began the human outbreak probably happened only once, or a few times, quite recently, and not many times over a longer period. They agree that bat virus RaTG13 (named for the Rinolophus affinus bat, from Tongguan, in 2013) is the closest match to the human virus that has yet been found, and that although the two viruses are very similar, the spike protein of the bat virus lacks the features the human spike protein possesses that enable it to work efficiently with human tissue.

Zoonoticists hold that SARS-2’s crucial features — the furin cleavage site and the ACE2 receptor — are the result of a recombinant event involving a bat coronavirus (perhaps RaTG13 or a virus closely related to it) and another, unknown virus. Early on, researchers proposed that it could be a snake sold at the seafood market — a Chinese cobra or a banded krait —but no: Snakes don’t typically carry coronaviruses. Then there was a thought that the disease came from sick smuggled pangolins, because there existed a certain pangolin coronavirus that was, inexplicably, almost identical in its spike protein to the human coronavirus — but then, no: There turned out to be questions about the reliability of the genetic information in that diseased-pangolin data set, on top of which there were no pangolins for sale at the Wuhan market. Then a group from China’s government veterinary laboratory at Harbin tried infecting beagles, pigs, chickens, ducks, ferrets, and cats with SARS-2 to see if they could be carriers. (Cats and ferrets got sick; pigs, ducks, and most dogs did not.)

...

So how did we actually get this disease?

Here’s what I think happened. In April 2012, in a copper mine in Mojiang, China, three men were given an awful job — they were told to shovel bat guano out of a mine shaft. They went to work and shoveled guano for seven hours a day in the confined, insufficiently ventilated space of the mine shaft, and by the end of the week, they were sick with a viral pneumonia of unknown etiology. Three more, younger shovelers were hired to replace the ones who were out sick.

The viral load in their lungs was so huge, because of all the guano dust, that their lungs became a kind of accelerated laboratory passaging experiment, as Jonathan Latham and Allison Wilson have written, forcing the virus to switch its allegiance from bats to humans. SARS experts were consulted, and the disease was judged to be SARS-like but not SARS. It was something new. (Shi Zhengli told Scientific American that the guano shovelers had died of a fungal disease, but, as Monali Rahalkar pointed out, they were treated with antivirals, and their symptoms were consistent with viral pneumonia with attendant secondary fungal infections.)


Although it was a severe disease, and in the end three of the shovelers died, there was no resultant epidemic. It was actually a case of industrial overexposure to an infectious substance — what we might call a massive OSHA violation. The bat disease that the men encountered wasn’t necessarily all that dangerous except in an environment of immunosuppressive overload.

Peter Daszak and Shi Zhengli were interested, of course, because this unidentified coronavirus disease involved bats and people. Of the fragmentary bits of virus Shi retrieved from the mine shaft, one was SARS-like, and Shi sequenced it and called it BtCoV/4991 and published a paper about it. Several times — in 2016 and 2018 and 2019 — this most interesting sample, a portion of what we now know as RaTG13, was taken out of the freezers in Shi’s lab and worked on in undisclosed ways. (Peter Daszak claims that these samples have disintegrated and can’t be validated or studied.) Samples of the nameless human disease also traveled back to the Wuhan Institute of Virology — few specifics about these valuable specimens have been released by Chinese sources, however.

This is the period in the story that demands a very close investigation, when chimeric assemblages may have been created and serially passaged, using BtCoV/4991, a.k.a. RaTG13, and other bat viruses, perhaps along with forms of the human virus. It’s when Shi and Baric both published papers that were about what happened when you hot-swapped mutant spike proteins between bat viruses and human viruses.

The link, via the renamed sample BtCoV/4991, to the copper mine is of exceptional importance because of the one huge difference between the unnamed guano shovelers’ virus and the SARS-2 virus that is now ravaging, for example, California: transmissibility. Airborne human-to-human transmissibility — the kind of thing that gain-of-functioneers like Ron Fouchier and Ralph Baric were aiming at, in order to demonstrate what Baric called “lurking threats” — is COVID-19’s crucial distinguishing feature. If six men had gotten extremely sick with COVID-19 back in 2012 in southern China, doctors and nurses in the hospital where they lay dying would likely have gotten sick as well. There might have been hundreds or thousands of cases. Instead, only the shovelers themselves, who had breathed a heavy concentration of guano dust for days, got it.

The existence of bat virus RaTG13 is therefore not necessarily evidence of a natural bat origin. In fact, it seems to me to imply the opposite: New functional components may have been overlaid onto or inserted into the RaTG13 genome, new Tinkertoy intermolecular manipulations, especially to its spike protein, which have the effect of making it unprecedentedly infectious in human airways.

This is where the uniquely peculiar furin insert and/or the human-tuned ACE2-receptor-binding domain may come in — although it’s also possible that either of these elements could have evolved as part of some multistep zoonotic process. But in the climate of gonzo laboratory experimentation, at a time when all sorts of tweaked variants and amped-up substitutions were being tested on cell cultures and in the lungs of humanized mice and other experimental animals, isn’t it possible that somebody in Wuhan took the virus that had been isolated from human samples, or the RaTG13 bat virus sequence, or both (or other viruses from that same mine shaft that Shi Zhengli has recently mentioned in passing), and used them to create a challenge disease for vaccine research — a chopped-and-channeled version of RaTG13 or the miners’ virus that included elements that would make it thrive and even rampage in people? And then what if, during an experiment one afternoon, this new, virulent, human-infecting, furin-ready virus got out?

For more than 15 years, coronavirologists strove to prove that the threat of SARS was ever present and must be defended against, and they proved it by showing how they could doctor the viruses they stored in order to force them to jump species and go directly from bats to humans. More and more bat viruses came in from the field teams, and they were sequenced and synthesized and “rewired,” to use a term that Baric likes. In this international potluck supper of genetic cookery, hundreds of new variant diseases were invented and stored. And then one day, perhaps, somebody messed up. It’s at least a reasonable, “parsimonious” explanation of what might have happened.

This may be the great scientific meta-experiment of the 21st century. Could a world full of scientists do all kinds of reckless recombinant things with viral diseases for many years and successfully avoid a serious outbreak? The hypothesis was that, yes, it was doable. The risk was worth taking. There would be no pandemic.

I hope the vaccine works.

MNE wrote:zar nije već ovdje utvrđeno da ne može biti laboratorijski 

bemty wrote:https://twitter.com/jburnmurdoch/status/1347200811303055364?s=21

Mór Thököly wrote:Sad kad su zabranili ovima iz SZO da vrse istrazivanja tamo gde zele, i meni se definitivno sve vise cini da je u pitanju ovo o cemu pise.

lalinea wrote:

Mór Thököly wrote:Sad kad su zabranili ovima iz SZO da vrse istrazivanja tamo gde zele, i meni se definitivno sve vise cini da je u pitanju ovo o cemu pise.

covek koji je autor ovoga je pisac, romanopisac, i opisao je jedan scenario koji je fina prica sa puno pretpostavki. Nije naveo ni jedan razlog (a tek ne dokaz) da je ovaj scenario verovatniji (i to znacajno verovatniji) od toga da je virus izmedju 2012 i 2019 - 7 godina - prosao kroz razne hostove i tu se sreo sa drugim korona virusom i rekombinovao.

MNE wrote:zar nije već ovdje utvrđeno da ne može biti laboratorijski 

lalinea wrote:

Mór Thököly wrote:Sad kad su zabranili ovima iz SZO da vrse istrazivanja tamo gde zele, i meni se definitivno sve vise cini da je u pitanju ovo o cemu pise.

covek koji je autor ovoga je pisac, romanopisac, i opisao je jedan scenario koji je fina prica sa puno pretpostavki. Nije naveo ni jedan razlog (a tek ne dokaz) da je ovaj scenario verovatniji (i to znacajno verovatniji) od toga da je virus izmedju 2012 i 2019 - 7 godina - prosao kroz razne hostove i tu se sreo sa drugim korona virusom i rekombinovao.

buffalo bill wrote:

lalinea wrote:
covek koji je autor ovoga je pisac, romanopisac, i opisao je jedan scenario koji je fina prica sa puno pretpostavki. Nije naveo ni jedan razlog (a tek ne dokaz) da je ovaj scenario verovatniji (i to znacajno verovatniji) od toga da je virus izmedju 2012 i 2019 - 7 godina - prosao kroz razne hostove i tu se sreo sa drugim korona virusom i rekombinovao.

Osnova njegove priče je u tome što je virus došao u čoveka 2019. već "spreman" za čoveka.

Mór Thököly wrote:

lalinea wrote:
covek koji je autor ovoga je pisac, romanopisac, i opisao je jedan scenario koji je fina prica sa puno pretpostavki. Nije naveo ni jedan razlog (a tek ne dokaz) da je ovaj scenario verovatniji (i to znacajno verovatniji) od toga da je virus izmedju 2012 i 2019 - 7 godina - prosao kroz razne hostove i tu se sreo sa drugim korona virusom i rekombinovao.

Nije ni rekao, koliko shvatam, da je "verovatniji". Rekao je da je - moguc. Naravno, kad bi Kina bila malo transparentnija drzava to bi se lako moglo odagnati. Ali nije. Pa onda kad, sustinski, odbija istragu ili ogranicava 1 takve organizacije kao sto je SZO, koja je sve samo ne antikineska...onda stvari postaju dosta sumnjivije.