More and more people are starting to take an interest in issues that have already been raised by 'wappies'. The 'With today's knowledge' argument is also increasingly being used, 'they couldn't have known that then'. There is also the Lab Leak theory, for which FOI (or FOIA) documents have now provided additional evidence. In the heated discussion of the last few weeks, I sometimes feel like in a time vortex: there is excitement about things that we really (could) have known for a long time. I therefore reread this translation of the book published in May 2021 article by Nicholas Wade, whether I remembered that correctly. It's a lot of text, but if you've read this, you'll be wondering, just like me: why all the additional evidence, that consternation, that consternation...? Is the time finally ripe for it? I myself have fragments that I find significant Bolded.

The Origins of COVID: Have Humans or Nature Opened Pandora's Box in Wuhan?

ThroughNicholas Wade| 5 May 2021

Introduction

The COVID-19 pandemic has disrupted lives around the world for more than a year. The death toll will soon reach three million people.[Note: this article is dated May 5, 2021!] Yet the origins of the pandemic remain uncertain: the political agendas of governments and scientists have erected smokescreens that the mainstream press helplessly wants to stay far away from.

In what follows, I will examine the available scientific facts, which contain many clues as to what happened, and provide readers with the evidence to make their own judgments. I will then try to assess the complex issue of guilt, which begins with, but extends far beyond the government of China.

By the end of this article, you may have learned a lot about the molecular biology of viruses. I will try to keep this process as painless as possible. But science cannot be avoided, because for the time being, and probably for a long time, it provides the only sure thread through the maze.

The virus that caused the pandemic is officially known as SARS-CoV-2, but it can be referred to as SARS2 for short. As many people know, there are two main theories about its origins. One is that it naturally jumped from wildlife to humans. The other is that the virus was studied in a laboratory, from which it escaped. That makes a lot of difference when it comes to preventing a second such incident.

I will describe the two theories, explain why each is plausible, and then ask which one gives the better explanation of the available facts. It is important to note that so far there have beenthere is no direct evidencefor both theories. Each depends on a range of reasonable suspicions, but so far there is a lack of evidence. So I only have clues, not conclusions, to offer. But those clues point in a certain direction. And after distracting that direction, I'm going to delineate some of the wires in this tangled strand of disaster.

A story of two theories.After the pandemic first broke out in December 2019, the Chinese authorities reported that many cases had occurred on the 'Wet Market' – a place where wild animals are sold for meat – in Wuhan. This reminded experts of the SARS1 epidemic of 2002, in which a bat virus had first spread to civets, an animal sold in those markets, and from civets to humans. A similar bat virus caused a second epidemic in 2012, known as MERS. This time, camels were the intermediate host.

The decoding of the genome of the SARS-2 virus showed that it belonged to a viral family known as beta-coronaviruses, which also includes the SARS1 and MERS viruses. That relationship supported the idea that it was also a natural virus that had managed to jump from bats, via another animal host, to humans. The connection to the Wet Market, the main point of similarity with the SARS1 and MERS epidemics, was quickly broken: Chinese researchers found previous cases in Wuhan where the link with the Wet Market Lacked.But that didn't seem to matter; More evidence in support of natural emergence was expected in the near term.

However, Wuhan is home to the Wuhan Institute of Virology, a leading world center for coronavirus research. Thus, the possibility that the SARS2 virus had escaped from the laboratory could not be ruled out. There were therefore two plausible scenarios of origin on the table.

From the beginning, the perceptions of the public and the media were shaped in favor of the natural emergence scenario by strong statements made by two scientific groups. Initially, these statements were not viewed as critically as they should have been.

"We are speaking out collectively to strongly condemn conspiracy theories suggesting that COVID-19 has no natural origin," a group of virologists and others wrote in theLanceton February 19, 2020, when it was really way too early for anyone to be sure what happened. Scientists "overwhelmingly conclude that this coronavirus originates in wildlife," they said, with a rousing call for readers to join Chinese colleagues on the front lines of fighting the disease.

Contrary to what the letter writers claimed, the idea that the virus may have escaped from a lab was an accident, not a conspiracy. It certainly had to be examined, not dismissed out of hand. A characteristic trait of good scientists is that they go to great lengths to distinguish between what they know and what they don't know. According to this criterion, the signatories of the Lancet letter behaved like bad scientists: they assured the public of facts they were not sure were true.

For virologists like Daszak, the stakes were high in assigning blame for the pandemic. For twenty years, they played a dangerous game, usually out of public view.In their laboratories, they routinely created viruses that were more dangerous than those found in nature.They argued that they could do this safely and that by getting ahead of nature, they could predict natural spillovers and thus prevent the transmission of viruses from an animal host to humans. If SARS2 had indeed escaped such a laboratory experiment, a huge backlash could be expected, and the storm of public outrage would hit virologists worldwide, not just in China. "It would shatter the scientific edifice from top to bottom,"SaidAntonio Regalado, editor ofMIT Technology Review, in March 2020.

A second statement that had a huge impact on public opinion was aletter(so an opinion piece, not a scientific article) published in the journal on 17 March 2020Nature Medicine was published. The authors were a group of virologists led by Kristian G. Andersen of the Scripps Research Institute."Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully engineered virus," the five virologists stated in the second paragraph of their letter.

Unfortunately, this was another case of bad science, in the sense defined above. It's true that some older methods of cutting and pasting viral genomes retain clear signs of manipulation. But newer methods, called "no-see-um" or "seamless" approaches, don't leave any distinctive traces. Nor other methods of manipulating viruses, such as serial passage, the repeated transmission of viruses from one cell culture to another. If a virus has been manipulated, either by a seamless method or by serial passage, there is no way of knowing that this is the case. Andersen and his colleagues assured their readers of something they couldn't know.

The discussion portion of their letter begins: "Sars-CoV-2 is unlikely to have been created by laboratory manipulation of a related SARS-CoV-like coronavirus." But wait, the leadership didn't say the virusclearwas not manipulated? The authors' degree of certainty seemed to slip a few notches when it came to expounding their reasoning.

The reason for the slip is clear once the technical language has penetrated. The two reasons the authors give for assuming that manipulation is unlikely are by no means convincing.

[Note vv: Later, their mutual Slack communication revealed that they thought very differently about it than what they wrote publicly.]

First, they say that sars2's spike protein binds very well to its target, the human ACE2 receptor, but does so in a different way than would fit best according to physical calculations. Therefore, the virus must have been created by natural selection, not by manipulation.

If this argument seems difficult to understand, it's because it's so far-fetched. The authors' basic assumption, which has not been further explained, is that anyone trying to get a bat virus to bind to human cells can only do so in one way. First, they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus attaches to it. They would then design the spike protein accordingly (by selecting the appropriate set of amino acid units that make it up). Since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, it could therefore not have been manipulated.

But this ignores the way virologists actually get spike proteins to bind to chosen targets, which is not by computation, but by spike protein genes from other viruses or by splicing serial passage. With serial passage, every time the offspring of the virus is transferred to new cell cultures or animals, the more successful ones are selected until one emerges that makes a really close bond with human cells. Natural selection has done all the heavy lifting. The Andersen paper's speculation about designing a viral spike protein through computation has no bearing on whether or not the virus is manipulated by either of the other two methods.

The authors' second argument against manipulation is even more artful. While most living things use DNA as their hereditary material, a number of viruses use RNA, the close chemical cousin of DNA. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are based on RNA, will first convert the RNA genome into DNA. They manipulate the DNA version, either by adding or changing genes, and then cause the engineered DNA genome to be converted back into infectious RNA.

Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus would "probably" have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, it is therefore not manipulated. But the argument is strikingly inconsistent. DNA backbones are fairly easy to create, so it's just possible that SARS2 was engineered with an unpublished DNA backbone.

And that's it. These are the two arguments made by the Andersen group in support of their statement that the SARS2 virus has clearly not been manipulated. And this conclusion, based on nothing but two inconclusive speculations, convinced the world press that SARS2 could not have escaped from a laboratory. A technical critique of Andersen's letter catches upharsher words.

Science is supposedly a self-correcting community of experts who constantly check each other's work. So why didn't other virologists point out that the Andersen group's argument was full of absurdly large holes?Perhaps because in today's universities, speech can be very costly. Careers can be destroyed if they step out of line. Any virologist who questions the community's position runs the risk of having their next grant application rejected by the panel of fellow virologists advising the government grant distribution agency.

[Note vv: it is questionable whether virologists do not accept GoF research and undersecurity as well-kept guild secrecy to secure research. In addition, there are also bio-military interests at play that are not discussed in this entire piece.]

Daszak and Andersen's letters were in fact political, not scientific, statements, but still amazingly effective. Articles in the mainstream press repeatedly stated that a consensus of experts had ruled that escape from the laboratory was out of the question or extremely unlikely. Their authors largely relied on the letters of Daszak and Andersen and did not understand the gaping gaps in their arguments. The mainstream newspapers all employ science journalists, as do the major networks, and these specialized reporters should be able to question scientists and check their claims. But Daszak and Andersen's claims went largely unchallenged.

Doubts about natural origin

Natural origin, zoonosis, was the media's preferred theory until around February 2021 and the visit of a World Health Organization (WHO) committee to China. The composition and access of the committee were strictly controlled by the Chinese authorities. Its members, including the ubiquitous Daszak, continued to argue that escape from the lab was extremely unlikely; before, during and after their visit. But this was not quite the propaganda victory that the Chinese authorities had hoped for. What became clear was that the Chinese had no evidence that the committee would provide support for the zoonosis theory.

The lack of evidence was surprising because both the SARS1 and MERS viruses had left abundant traces in the environment. The intermediate host species SARS1 waswithin four monthsafter the outbreak of the epidemic and the host of MERS within nine months. But some 15 months after the SARS2 pandemic began, and after a presumably intensive search, Chinese researchers had not found the original bat population, or the intermediate species to which SARS2 would have jumped, or any serological evidence that any Chinese population, including that of Wuhan, had ever been exposed to the virus before December 2019. The natural genesis remained a conjecture that, however plausible, had not amassed a shred of supporting evidence in more than a year.

And as long as that remains the case, it makes sense to pay serious attention to the alternative suspicion, that SARS2 escaped from a laboratory.

Why would anyone want to create a new virus that can cause a pandemic? Ever since virologists have been given the tools to manipulate a virus's genes, they have claimed that they can get ahead of a potential pandemic by examining how close a particular animal virus might be to making the jump to humans. And that justified laboratory experiments to increase the ability of dangerous animal viruses to infect humans, virologists claimed.

With this rationale, they recreated the 1918 influenza virus, showed how to synthesize the nearly extinct polio virus from the published DNA sequence, and introduced a smallpox gene into a related virus.

These enhancements of viral capabilities are known as "gain-of-function" experiments. In the case of coronaviruses, there was particular interest in the spike proteins, which protrude around the spherical surface of the virus and virtually determine which species it will target. In 2000, Dutch researchers earned the gratitude of rodents for using the spike protein of a mouse coronavirusmanipulated in such a waythat it would only attack cats.

Virologists began seriously studying bat coronaviruses after they were found to be the source of both the SARS1 and MERS epidemics. In particular, researchers wanted to understand what changes needed to take place in a bat virus's spike proteins before it could infect humans.

Researchers from the Wuhan Institute of Virology, led by China's leading expert on bat viruses, Shi Zheng-li or "Bat Lady," undertook frequent expeditions to the bat-populated caves of Yunnan in southern China and collected about a hundred different bat coronaviruses.

Shi then collaborated with Ralph S. Baric, a leading coronavirus researcher at the University of North Carolina.Their workfocused on increasing the ability of bat viruses to attack humans to "investigate the emergence potential (i.e., the potential to infect humans) of circulating bat CoVs [coronaviruses]". To achieve this goal, they created a new virus in November 2015 by taking the backbone of the SARS1 virus and replacing the spike protein with one from a bat virus (known as SHC014-CoV). This manufactured virus was able to infect the cells of the human respiratory tract, at least when tested against a laboratory culture of such cells.

"If the virus escaped, no one would be able to predict its trajectory,"

SaysSimon Wain-Hobson, a virologist at the Pasteur Institute in Paris.

The SHC014-CoV/SARS1 virus is known as a chimera because its genome contains genetic material from two virus strains. If the SARS2 virus had been created in Shi's lab, then the direct prototype would have been the SHC014-CoV/SARS1 chimaera, the potential danger of which worried many observers and sparked heated debate.

Baric and Shi refer to the clear risks in their article, but argue that these must be weighed against The Advantage of Predicting Future (Zoonosis) Infections. Scientific review committees, they wrote, "may find similar studies of building chimeric viruses from circulating strains too risky to continue." Given the various limitations imposed on GOF (gain-of-function) research, they believe that "concerns about GOF research have reached a crossroads; The potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens. When developing policies for the future, it is important to weigh the value of the data generated by these studies and consider whether these types of studies on chimeric viruses warrant further research versus their inherent risks."

That ruling was made in 2015. In hindsight, in 2021, one can say that the value of gain-of-function studies in preventing the SARS2 epidemic was zero.In fact, the risk was catastrophic, if the SARS2 virus was indeed generated in a gain-of-function experiment.

Inside the Wuhan Institute of Virology

Baric had developed a general method—and explained it to Shi—to develop bat coronaviruses in such a way that they could attack other species. The specific targets were human culture cells and humanized mice. These lab mice, a low-cost and ethically sourced replacement for human subjects, have been genetically engineered to carry the human version of the protein ACE2, which lines the surface of cells lining the airways.

Because, due to a strange twist in the story, her work was funded by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the U.S. National Institutes of Health (NIH). And grant proposals Specify exactly What she was up to to do with the money.

The grants were awarded to the main contractor, Badger bag from the EcoHealth Alliance, which outsourced them to Shi. Below are excerpts from the grants for the financial years 2018 and 2019. ("CoV" stands for coronavirus, and "S protein" refers to the spike protein of the virus.)

"Predictions of CoV transmission between species. Predictive models of host range (i.e., emergence potential) will be experimentally tested using reverse genetics, pseudovirus and receptor binding tests, and virus infection experiments in a range of cell cultures from different species and humanized mice."

"We will use S-protein sequence data,Infectious Cloning Technology, use in vitro and in vivo infection experiments and receptor binding analysis to test the hypothesis that % divergence thresholds in S-protein sequences predict spillover potential."

What this means, in non-technical language, is that Shi was out to create new coronaviruses with the highest possible infectivity to human cells. Her plan was to take genes that coded for spike proteins with a variety of measured affinities for human cells, ranging from high to low. She would insert these spike genes one at a time into the backbone of a number of viral genomes ("reverse genetics" and "infectious cloning technology"), creating a series of chimeric viruses. These chimeric viruses would then be tested for their ability to attack human cell cultures ("in vitro") and humanized mice ("in vivo"). And this information would help predict the likelihood of "spillover," the jump of a coronavirus from bats to humans.

The Methodical Approach is designed to find the best combination of coronavirus backbone and spike protein for infecting human cells. The approach could have generated SARS2-like viruses, and could indeed have created the SARS2 virus itself with the right combination of virus backbone and spike protein.

It can't yet be said whether or not Shi generated SARS2 in her lab because her data is sealed, but it seems that she was at least on the right track. "It is clear that the Wuhan Institute of Virology systematically engineered novel chimeric coronaviruses and assessed their ability to infect human cells and mice with human ACE2 expression," said Richard H. Ebright, a molecular biologist at Rutgers University and leading expert on biosafety.

"It is also clear," Ebright said, "that, depending on the constant genomic contexts chosen for analysis, this work could have produced SARS-CoV-2 or a proximal precursor to SARS-CoV-2." "Genomic context" refers to the specific viral backbone used as a testbed for the spike protein.

The lab-escape scenario for the origin of the SARS2 virus, as should be clear by now, is not just guesswork in the direction of the Wuhan Institute of Virology. It is an elaborate hypothesis, based on the specific project funded by NIAID there.

Even if the grant required the work plan described above, how can we be sure that the plan has actually been implemented? For that, we can rely on the word of Daszak, who from the beginning of 2020 already vehemently protested against the ridiculousconspiracy theoryof an escape from the lab, invented by China-bashers.

On 9 December 2019, before the outbreak of the pandemic became public knowledge, Tie bag ainterviewin which he recounted in radiant terms how researchers at the Wuhan Institute of Virology had reprogrammed the spike protein and generated chimeric coronaviruses capable of infecting humanized mice.

"And we now have, you know, after 6 or 7 years of doing this, over 100 new SARS-related coronaviruses, very close to SARS," Daszak says around minute 28 of the interview. "Some end up in human cells in the lab, others can cause SARS disease in humanized mouse models and are untreatable with therapeutic monoclonal agents and You can't vaccinate against it with a vaccine. So this is a clear and present danger....

"Interviewer: You're saying that these are different coronaviruses and you can't vaccinate against them, and not antivirals – so what do we do?

"Badgerbag: Well, I think... Coronaviruses – you can manipulate them quite easily in the lab. The spike protein determines much of what happens with coronaviruses, in zoonotic risk. So you can get the sequence, you can build the protein, and we're working a lot with Ralph Baric from UNC to do this. We insert it into the backbone of another virus and do some work in the lab. So you can predict more when you find a sequence. You have this diversity. The logical development for vaccines now is that if you're going to develop a vaccine for SARS, people are going to use pandemic SARS [?], but let's add some of these other things to get a better vaccine." The insertions he was referring to may contain an element called the furin cleavage site, discussed below, which significantly increases viral infectivity to human cells.

In incoherent style, Daszak refers to the fact that once you've generated a new coronavirus that can attack human cells, you can take the spike protein as the basis for a vaccine.

You can imagine Daszak's reaction when he heard about the outbreak of the epidemic in Wuhan a few days later. He would know better than anyone the Wuhan Institute's goal of making bat coronaviruses contagious to humans, as well as the weaknesses in the institute's defenses against the contamination of their own researchers.

But instead of providing public health authorities with the abundant information he had, he immediately launched a public relations campaign to convince the world that the epidemic could not possibly have been caused by one of the institute's souped-up viruses. "The idea that this virus escaped from a lab is pure nonsense. It's just not true," he stated in ainterviewin April 2020.

The safety features at the Wuhan Institute of Virology

Daszak may have been unaware of, or perhaps he knew all too well, the Long history of viruses that escaped from even the best-run laboratories. The smallpox virus escaped from laboratories in England three times in the 1960s and 1970s, resulting in 80 cases and 3 deaths. Since then, dangerous viruses have escaped from laboratories almost every year. In more recent times, the SARS1 virus has proven to be a true escape artist. SARS1 has escaped from laboratories in Singapore, Taiwan and no less than four times from the Chinese National Institute of Virology in Beijing.

One of the reasons SARS1 was so difficult to handle was that there were no vaccines available to protect lab workers. As Daszak noted in the Dec. 19 interview quoted above, the Wuhan researchers too had not been able to develop vaccines against the coronaviruses they had designed to infect human cells.Without a vaccine, the researchers would have been as defenseless against a self-generated SARS2 virus as their colleagues in Beijing were against SARS1.

A second reason for the serious danger of novel coronaviruses has to do with the required levels of laboratory safety. There are four safety grades, referred to as BSL1 to BSL4, with BSL4 being the most restrictive and designed for deadly pathogens such as the Ebola virus.

The Wuhan Institute of Virology had a new BSL4 laboratory, but its state of readiness was of great concern to the State Department inspectors who visited it from the Beijing embassy in 2018. "The new lab has a severe shortage of well-trained technicians and researchers needed to keep this high-containment lab operating safely," the inspectors wrote in atelegramof 19 January 2018.

The real problem, however, was not the unsafe state of the Wuhan BSL4 lab, but the fact that virologists worldwide do not like to work in BSL4 conditions. You have to wear a spacesuit, perform surgeries in locked closets, and accept that everything will take twice as long. So the rules that assigned each kind of virus to a certain level of safety were more lax than some might have thought sensible.

Prior to 2020, it was mandatory under the rules of virologists in China and elsewhere to conduct experiments with the SARS1 and MERS virus under BSL3circumstances. But all other bat coronaviruses could be studied in BSL2, the next level down. BSL2 requires taking free Minimum security measures, such as wearing lab coats and gloves, not vacuuming liquids into a pipette, and putting up biohazard warning signs. Still, a gain-of-function experiment conducted in BSL2 could produce an agent more infectious than SARS1 or MERS. And if so, lab workers have a high chance of infection, especially if they are unvaccinated.

A lot of Shi's work on gain-of-function in coronaviruses was carried out at the BSL2 safety level, as stated in its publications and other documents. She has in ainterviewwith the magazineSciencesaid that "the coronavirus research in our laboratory is carried out in BSL-2 or BSL-3 laboratories.“

"It is clear that some or all of this work was carried out using a biosafety standard – biosafety level BSL-2, the biosafety level of a standard U.S. dental office – which would pose an unacceptably high risk of infection to laboratory personnel upon contact with a virus with the transmission properties of SARS-CoV-2," says Ebright.

"It is also clear," he adds, "that this work should never have been funded and should never have been carried out." This is his opinion, regardless of whether the SARS2 virus has ever seen the inside of a laboratory.

Concerns about safety conditions at the Wuhan lab were not misplaced. According to aFactsheetissued by the State Department on January 15, 2021: "The U.S. government has reason to believe that several researchers within the WIV became ill with symptoms consistent with both COVID-19 and common seasonal illnesses in the fall of 2019, before the first identified case of the outbreak."

David Asher, a fellow of the Hudson Institute and former State Department adviser, gave more details about the incident during aseminar. Knowledge of the incident came from a mix of public information and "some high-quality information gathered by our intelligence community," he said. Three people working in a BSL3 lab at the institute became ill within a week of each other with severe symptoms requiring hospitalization. This was "the first known cluster that we are aware of, of victims of what we believe is COVID-19." Influenza could not be completely ruled out, but seemed unlikely in the circumstances, he said.

Comparison of the rival scenarios of SARS2 origin

The evidence above is a serious indication that the SARS2 virus could have been created in a laboratory, from which it then escaped. But the evidence, however substantial, is not enough. Evidence would consist of evidence from the Wuhan Institute of Virology, or related labs in Wuhan, that SARS2 or a precursor to the virus was in development there. In the absence of access to such data, a different approach is needed. To do so, we take some salient facts about the SARS2 virus and see how well they can be explained by the two rival scenarios of origin, that of natural origin and escape from the lab. Here are four tests of those two hypotheses. A few have some technicalities, but these are among the most persuasive for those who want to follow the argumentation.

1) The place of origin.Start with geography. The two closest relatives of the SARS2 virus were collected from bats living in caves in Yunnan, a province in southern China.If the SARS2 virus had first infected people living around the Yunnan Caves, that would strongly support the idea that the virus had naturally passed to humans. But this is not what happened. The pandemic broke out 1500 kilometers away, in Wuhan.

Beta coronaviruses, the family of bat viruses to which SARS2 belongs, infect the horseshoe-nosed batRhinolophus affinis, which is found in southern China. The range of the bats is 50 kilometers, so it is unlikely that they reached Wuhan. In any case, the first cases of the COVID-19 pandemic probably occurred in September, when thetemperatures in Hubei Provincewere already cold enough to send bats into hibernation.

What if the bat viruses first infected an intermediate host?You would need a long-term population of bats that is regularly in the vicinity of an intermediate host, which in turn often has to cross paths with humans. All these virus exchanges must take place somewhere outside Wuhan, a busy metropolis that is not known to be a natural habitat of colonies ofRhinolophus-Bats.The infected person (or animal) carrying this highly transmissible virus must have traveled to Wuhan without infecting anyone else. No one in his or her family got sick. If the person went to Wuhan by train, not one fellow passenger got sick.

In other words, it is a daunting task to allow the pandemic to break out naturally outside of Wuhan and then, without leaving any trace, make its first appearance there.

For a lab escape scenario, Wuhan is the first, obvious candidate. Wuhan is home to China's leading center for coronavirus research, where, as mentioned above, researchers genetically engineered bat coronaviruses to attack human cells. They did this under the minimum safety conditions of a BSL2 lab. If a virus with the unexpected infectiousness of SARS2 had emerged there, it would not be a surprise that it would escape.

2)Natural History and Evolution.The original location of the pandemic is a small part of a larger problem, that of natural history. Viruses don't just jump from one species to another. The coronavirus spike protein, modified to attack bat cells, needs repeated jumps to another species, most of which fail, before it gets a happy mutation. Mutation – a change in one of its RNA units – causes another amino acid unit to be incorporated into its spike protein and makes the spike protein better able to attack the cells of another species.

Through even more such mutation-driven adaptations, the virus adapts to its new host, for example an animal with which bats often come into contact. The whole process is then resumed as the virus moves from this intermediate host to humans.

In the case of SARS1, researchers have documented the sequential changes in the spike protein as the virus evolved step by step into a dangerous pathogen. After it changed from bats to civets, there were six more changes to the spike protein before it became a mild pathogen in humans. After a further 14 changes, the virus was much better adapted to humans, and with a further four, the virusEpidemic a flight.

But if you start looking for the fingerprints of a similar transition in SARS2, you're in for a strange surprise.The virus has hardly changed until recently.From the very beginning, it was well adapted to human cells. Researchers led by Alina Chan of the Broad Institute compared SARS2 to late-stage SARS1, which by then was well adapted to human cells, and found that the two viruses were equally well adapted."By the time SARS-CoV-2 was first detected in late 2019, it had already been pre-adapted to human transmission to a degree similar to the late epidemic SARS-CoV",Wrotethey.

Even those who think its origin in the lab is unlikely agree that SARS2 genomes are remarkably uniform. Baric writes that "early strains identified in Wuhan, China showed limited genetic diversity, suggesting that the virus may have been introduced from a single source."

A single source would, of course, be compatible with laboratory escape, but less so with the massive variation and selection that characterizes the way evolution operates.

The uniform structure of SARS2 genomes does not provide any indication of a passage through an intermediate animal host, and no such host has been identified in nature.

Proponents of natural emergence suggest that SARS2 was incubated in a yet-to-be-found human population before it acquired its special traits. Or that it has jumped to a host animal outside of China.

All these conjectures are possible, but very far-fetched. Proponents of a lab leak have a simpler explanation. SARS2 was adapted to human cells from the outset because it was grown in humanized mice or in laboratory cultures of human cells, as described in Daszak's grant proposal.The genome shows little diversity because the hallmark of laboratory cultures is uniformity.

Lab escape proponents joke that the SARS2 virus, of course, infected an intermediate host species before spreading to humans, and that they identified it — a humanized mouse from the Wuhan Institute of Virology.

3)The furin cleavage site.The furin cleavage site is a minuscule part of the virus's anatomy, but one that exerts a major impact on its infectivity. It sits in the middle of the SARS2 spike protein. It's also at the heart of the puzzle of where the virus came from.

The spike protein has two subunits with different roles. The first, called S1, recognizes the target of the virus, a protein called angiotensin-converting enzyme-2 (or ACE2) that covers the surface of cells lining the human respiratory tract. The second, S2, helps the virus, once anchored to the cell, fuse with the cell membrane. After the virus's outer membrane fuses with that of the affected cell, the viral genome is injected into the cell, hijacking its protein-making machinery and forcing it to generate new viruses.

But this invasion can't begin until the S1 and S2 sub-units are taken apart. And right there, right at the S1/S2 junction, is the furin cleavage site that causes the spike protein to cleave in just the right place.

The virus, a textbook example of economic design, does not have its own cleaver. It depends on the cell to split. Human cells have a protein cutting tool on their surface known as furin. Furin will cut through any protein chain that carries its distinctive target cut site. This is the sequence of amino acid units proline-arginine-arginine-alanine, or PRRA in the code that refers to each amino acid with a letter of the alphabet. PRRA is the amino acid sequence at the nucleus of the furin cleavage site of SARS2.

Viruses have all kinds of clever tricks, so why does the furin cleavage site stand out? Because of all known SARS-related beta-coronaviruses, only SARS2 has a furin cleavage site. In all other viruses, their S2 unit is split in a different place and by a different mechanism.

So how did SARS2 get its furin cleavage site? Either the site evolved naturally, or it was inserted by researchers at the S1/S2 junction in a gain-of-function experiment.

First, consider its natural origin. Two ways in which viruses evolve are through mutation and through recombination. Mutation is the process of random change in DNA (or RNA for coronaviruses) that usually results in one amino acid in a protein chain being swapped for another. Many of these changes are detrimental to the virus, but natural selection preserves the few that do something useful. Mutation is the process by which the SARS1 spike protein gradually switched its preferred target cells from those of bats to civets and then to humans.

Mutation appears to be a less likely way to generate the furin cleavage site of SARS2, although it cannot be completely ruled out. The four amino acid units of the site are all together, and all in exactly the right place in the S1/S2 junction. Mutation is a random process triggered by copying errors (when new viral genomes are generated) or by chemical decay of genomic units. Thus, it typically affects some amino acids at different places in a protein chain. It is much more likely that a series of amino acids such as those from the furin cleavage site are all obtained together through a completely different process known as recombination.

Recombination is an unintentional swapping of genomic material that occurs when two viruses enter the same cell and their offspring are joined together with bits and pieces of RNA belonging to the other. Beta coronaviruses will only combine with other beta coronaviruses, but can acquire through recombination almost any genetic element present in the collective genomic pool. What they can't acquire is an element that the pool doesn't possess. And no known SARS-related beta-coronavirus, the class to which SARS2 belongs, possesses a furin cleavage site.

Proponents of natural emergence say SARS2 could have picked up the site from an as-yet-unknown beta-coronavirus. But vSARS-related beta-coronaviruses apparently don't need a furin cleavage site to infect bat cells, so it's not very likely that anyone has one, and so far none has even been found.

The proponents' next argument is that SARS2 obtained its furin cleavage site from humans. A precursor to SARS2 could circulate in the human population for months or years until, at some point, it gained a furin cleavage site of human cells. It would then have been ready to break out as a pandemic.

If this has happened, there should be traces in the hospital surveillance records of the people infected with the slow-developing virus. But so far, none have come to light. According to the WHOreport on the origin of the virushospitals in Hubei province, home to Wuhan, routinely monitor influenza-like illnesses and "no evidence of substantial transmission of SARSCoV-2 was found in the months leading up to the December outbreak."

Thus, it is difficult to explain how the SARS2 virus picked up its furin cleavage site naturally, either by mutation or recombination.

That leaves a gain-of-function experiment. For those who think SARS2 escaped from a lab, explaining the furin cleavage site is not a problem at all. "Since 1992, the virological community has known that the only way to make a virus more lethal is to give it a furin cleavage site at the S1/S2 junction in the laboratory," Writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2. "At least 11 gain-of-function experiments, in which a furin site is added to make a virus more infectious, have been published in the open literature, including by Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology."

4)It's a matter of codons.There is another aspect of the furin cleavage site that narrows the path for a natural origin even further.

As everyone knows (or at least remembers from high school), the genetic code uses three units of DNA to specify each amino acid unit of a protein chain. When read in groups of 3, the 4 different types of DNA units can specify 4 x 4 x 4 or 64 different triplets, or codons as they are called. Since there are only 20 types of amino acids, there are more than enough codons to go around, allowing some amino acids to be specified by more than one codon. For example, the amino acid arginine can be denoted by one of the six codons CGU, CGC, CGA, CGG, AGA, or AGG, where A, U, G, and C represent the four different types of units in RNA.

Here's where it gets interesting. Different organisms have different codon preferences. Human cells like to denote arginine with the codons CBT, CGC or CGG. But CGG is the least popular coronavirus codon for arginine. Keep that in mind when you look at how the amino acids in the furin cleavage site are encoded in the SARS2 genome.

The functional reason why SARS2 has a furin cleavage site and its cousin viruses do not can be seen by aligning (in a computer) the array of nearly 30,000 nucleotides in its genome with those of its cousin coronaviruses, the closest known to date being one called RaTG13. Compared to RaTG13, SARS2 has an insert of 12 nucleotides right at the S1/S2 junction. The insert is the sequence T-CCT-CGG-CGG-GC. The CCT encodes proline, the two CGGs encode two arginines, and the GC is the beginning of a GCA codon encoding alanine.

There are several curious features of this insert, but the strangest is that of the two adjacent CGG codons. Only 5 percent of SARS2's arginine codons are CGG, and the CGG-CGG double codon has not been found in any other beta-coronavirus. So how did SARS2 get a few arginine codons preferred by human cells, but not by coronaviruses?

Proponents of natural emergence have an uphill task to explain all the features of SARS2's furin cleavage site. They must postulate a recombination event at a site on the virus's genome where recombinations are rare, and the insertion of a 12-nucleotide sequence with a double arginine codon unknown in the beta-coronavirus repertoire, at the only site in the genome that significantly increases the infectivity of the virus.

"Yes, but your phrasing makes this sound unlikely – viruses are specialists in unusual events," is the response of David L. Robertson, a virologist at the University of Glasgow, who considers escape from the lab to be a conspiracy theory. "Recombination is naturally very, very common in these viruses, there are recombination breakpoints in the spike protein, and these codons seem unusual, precisely because we haven't sampled enough."

Robertson is right that evolution always produces results that may seem improbable, but in fact are not. Viruses can generate an untold number of variants, but we only see the one in a billion that natural selection chooses to survive. But this argument could go too far. For example, any result of a gain-of-function experiment could be explained as a result that evolution would have achieved in time. And the numbers game can also be played the other way around. In order for the furin cleavage site to arise naturally in SARS2, a series of events must occur, each of which is quite unlikely for the reasons listed above. It is unlikely that a long chain with several improbable steps will ever be completed.

For the lab escape scenario, the double CGG codon is no surprise. The human-preferred codon is routinely used in laboratories.So anyone who wanted to insert a furin cleavage site into the genome of the virus would synthesize the PRRA-making sequence in the lab and would likely use CGG codons to do so. "When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I told my wife that this was the smoking gun was for the origin of the virus," said David Baltimore, an eminent virologist and former president of CalTech."These features pose a powerful challenge to the idea of a natural origin for SARS2," he said. [1]

[1]A third scenario of origin.There is a variation of the natural rise scenario that is worth considering. This is the idea that SARS2 jumped directly from bats to humans, without passing through an intermediate host like SARS1 and MERS did. A leading advocate is the virologist David Robertson who notes that SARS2 can attack several species other than humans. He believes that the virusdeveloped a generalist ability while it was still in bats. Because the bats it infects are widespread in southern and central China, the virus had ample opportunity to jump to humans, although it appears to have done so only on one known occasion. Robertson's dissertation explains why no one has so far found a trace of SARS2 in an intermediate host or in human populations surveilled before December 2019. It would also explain the puzzling fact that SARS2 hasn't changed since it first appeared in humans – it didn't think it was necessary because it could already attack human cells efficiently.

One problem with this idea, however, is that if SARS2 jumped from bat to humans in one jump and hasn't changed much since then, it should still be good at infecting bats. And it looks like it isn't.

"Tested bat species are poorly infected by SARS-CoV-2 and therefore are unlikely to be the direct source for human infection,"writes a scientific group thatis skeptical of natural emergence.

Still, Robertson may be on to something. The bat coronaviruses of the Yunnan Caves can infect humans directly. In April 2012, six miners cleaning up bat guano from the Mojiang mine contracted severe pneumonia with COVID-19-like symptoms, and three eventually died. A virus isolated from the Mojiang mine, called RaTG13, is still the most well-known relative of SARS2. Much mystery surrounds the origin, reporting, and strangely low affinity of RaTG13 for bat cells, as well as the nature of 8 similar viruses that Shireports thatcollected them at the same time but has not yet published them, despite their great relevance to the ancestors of SARS2. But that's all a story for another time. The point here is that bat viruses can infect humans directly, albeit only in special circumstances.

So Who else, apart from miners digging up bat guano, comes into particularly close contact with bat coronaviruses? Well, coronavirus researchers do.Shi says she and her group collected more than 1,300 bat samples during some eight visits to Mojiang Cave between 2012 and 2015, and there were undoubtedly many expeditions to other Yunnan caves.

Imagine the researchers regularly traveling from Wuhan to Yunnan and back, collecting bat guano in dark caves and mines, and you start to see a possible missing link between the two places. Researchers may have become infected during their collecting trips, or while working with the new viruses at the Wuhan Institute of Virology. The virus that escaped from the lab would have been a natural virus, not one that arose from a gain of function.

The direct-from-bat thesis is a chimera between the natural emergence and laboratory escape scenarios. It's a possibility that can't be dismissed. But on the other hand, the facts are that 1) both SARS2 and RaTG13 seem to have only a weak affinity for bat cells, so one cannot be completely sure that either of them has ever seen the inside of a bat; and 2) the theory is no better than the natural emergence scenario to explain how SARS2 got its furin cleavage site, or why the furin cleavage site is determined by arginine codons preferred in humans rather than by the codons preferred for bats.

Where we are so far

Neither the natural emergence nor the laboratory escape hypothesis can yet be ruled out. As of May 5, 2021, there is no direct evidence for both. Therefore, no definitive conclusion can be drawn at this time.

That said, the available evidence leans more strongly in one direction than the other. Readers will form their own opinions. But it seems to me that proponents of laboratory escape can explain all the available facts about SARS2 considerably more easily than those in favor of natural emergence.

It is documented that researchers at the Wuhan Institute of Virology were engaged in gain-of-function experiments designed to allow coronaviruses to infect human cells and humanized mice. This is exactly the kind of experiment that could have given rise to a SARS2-like virus. The researchers were not vaccinated against the viruses studied and worked in the minimum safety conditions of a BSL2 laboratory. So escaping a virus would not be surprising at all. Across China, the pandemic broke out on the doorstep of the Wuhan Institute. The virus was already well adapted to humans, as expected for a virus grown in humanized mice. It possessed an unusual enhancement, a furin cleavage site, which is not possessed by any other known SARS-related beta-coronavirus, and this site contained a double arginine codon that is also unknown in beta-coronaviruses.

Proponents of natural emergence have a somewhat more difficult story to tell. The plausibility of their case rests on a single assumption, the expected parallel between the emergence of SARS2 and that of SARS1 and MERS. But none of the expected evidence supporting such a parallel history has emerged so far.No one has found the bat population that was the source of SARS2, if it has indeed ever infected bats.No intermediate host has come forward, despite an intensive search by the Chinese authorities, including the testing of 80,000 animals. There is No evidence that the virus makes multiple independent jumps from its intermediate host to humans, as both the SARS1 and MERS viruses did. There is No evidence from hospital monitoring data that the epidemic gained strength among the population as the virus developed.There is no explanation why a natural epidemic should break out in Wuhan and nowhere else.There is no good explanation for this how the virus obtained its furin cleavage site, which does not possess any other SARS-related beta-coronavirus, nor why the place is composed of human-preferred codons.The theory of natural emergence disputes a series of implausibility.

The archives of the Wuhan Institute of Virology certainly contain a lot of relevant information. But it seems unlikely that the Chinese authorities will release them, given the significant likelihood of blaming the regime in the onset of the pandemic. Without the efforts of a courageous Chinese whistleblower, we may have had just about all the relevant information we're likely to get for a while.

So it is worth trying to assess responsibility for the pandemic, at least in a preliminary way, because the main objective remains to prevent a new pandemic. Even those who are not convinced that escape from the lab is the most likely origin of the SARS2 virus may see cause for concern about the current state of regulation of gain-of-function research. There are two obvious levels of responsibility: the first, to allow virologists to conduct gain-of-function experiments, with minimal profit and high risk; the second, if SARS2 was indeed generated in a laboratory, to allow the virus to escape and unleash a global pandemic. These are the players who would most likely be blamed.

1. Chinese virologists.First and foremost, Chinese virologists are responsible for conducting gain-of-function experiments in BSL2-level safety conditions that were far too lax to contain a virus with unexpected infectiousness like SARS2. If the virus has indeed escaped from their laboratory, they deserve the world's condemnation for a foreseeable accident that has already caused the deaths of three million people. Admittedly, Shi was trained by French virologists, worked closely with American virologists, and followed international rules for the containment of coronaviruses. But she could and should have assessed the risks she was running herself. She and her colleagues bear responsibility for their actions.

I have used the Wuhan Institute of Virology as an abbreviation for all virology activities in Wuhan. It's possible that SARS2 was generated in another lab in Wuhan, perhaps in an attempt to create a vaccine that worked against all coronaviruses. But until the role of other Chinese virologists is clarified, Shi is the public face of China's work on coronaviruses, and for now, she and her colleagues will be first in line for defamation.

2. Chinese authorities.China's central authorities did not generate SARS2, but they certainly did their best to hide the nature of the tragedy and China's responsibility for it.They suppressed all records at the Wuhan Institute of Virology and shut down the virus databases.They released a trickle of information, much of which was outright false or intended to deceive. They did their best to manipulate the WHO's investigation into the origins of the virus and led the members of the committee on a fruitless walk.So far, they are far more interested in deflecting blame than in taking the necessary steps to prevent a second pandemic.

3. The Global Community of Virologists.Virologists around the world form a loose professional community. They write articles in the same journals. They attend the same conferences. They have a common interest in seeking funds from governments and not being inundated with safety regulations.

Virologists knew better than anyone the dangers of gain-of-function research. But The power to create new viruses, and the research funding that could be obtained from it, was too tempting. They continued gain-of-function experiments.They lobbied against the moratorium imposed in 2014 on federal funding for gain-of-function research, and it was increased in 2017.

The benefits of the research in preventing future epidemics have so far been nil, the risks enormous.If research on the SARS1 and MERS viruses could only be done at the BSL3 safety level, it would certainly be illogical to allow any work with novel coronaviruses at the lower level of BSL2. Whether or not SARS2 escaped from a lab, virologists around the world are playing with fire.

Their behavior has alarmed other biologists for a long time. In 2014, scientists, who called themselves the Cambridge Working Group, urged caution when creating new viruses. In prescient words, they specified the risk of creating a SARS2-like virus. "Accident risks with newly created 'potential pandemic pathogens' raise serious new concerns,"Wrotethey. "The creation in laboratories of highly transmissible, new strains of dangerous viruses, particularly but not limited to influenza, carries significantly increased risks. An accidental infection in such an environment could cause outbreaks that are difficult or impossible to control."

When molecular biologists discovered a technique for shifting genes from one organism to another, they held a public conference in Asilomar in 1975 to discuss the potential risks. Despite much internal opposition, they drew up a list of strict safety measures that could be relaxed in the future – and were appropriate – when the potential dangers had been better assessed.

When the CRISPR gene-editing technique was invented, biologists released a joint report from the U.S., British, and Chinese National Academies of Science urging restraint in making hereditary changes to the human genome. Biologists who invented gene drives have also been open about the dangers of their work and have tried to get the public involved.

One might think that the SARS2 pandemic would spur virologists to re-evaluate the benefits of gain-of-function research, even to engage the public in their deliberations. But no. Many virologists scoff at lab escape as a conspiracy theory, and others say nothing.They have barricaded themselves behind a Chinese wall of silence that has so far worked well to dampen, or at least delay, journalists' curiosity and the public's anger. Professions that cannot regulate themselves deserve to be regulated by others, and this seems to be the future that virologists choose for themselves.

4. The U.S. role in funding the Wuhan Institute of Virology.[2] From June 2014 to May 2019, Daszak's EcoHealth Alliance received asubsidyof the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to conduct gain-of-function research with coronaviruses at Wuhan Institute of Virology. Whether or not SARS2 is the product of that research, it seems a questionable policy to outsource high-risk research to foreign laboratories with minimal safety measures.And if the SARS2 virus has indeed escaped from the Wuhan Institute, then the NIH will find itself in the terrible position of having funded a disastrous experiment that has led to the deaths of more than 3 million worldwide, including more than half a million of its own citizens.

The responsibility of the NIAID and the NIH is even more acute because for the first three years of the grant to EcoHealth Alliance, there was a moratorium on funding Gain-of-Function research. When the moratorium expired in 2017, it not only disappeared, but was replaced by a reporting system, the Potential Pandemic Pathogens Control and Oversight (P3CO) Framework, which required agencies to report any dangerous GoF work they wanted to fund for review.

The moratorium, officially called a "pause," specifically blocked funding for any gain-of-function research that increased the pathogenicity of the flu, MERS, or SARS virus. Itdefined gain of functionvery simple and broad as "research that improves a pathogen's ability to cause disease."

But then there is afootnoteon p.2 of the moratorium document that "an exception to the study pause may be obtained if the head of the USG funding agency determines that the study is urgently necessary to protect public health or national security."

This seemed to mean that either the director of the NIAID, Anthony Fauci, either the director of the NIH, Francis Collins, or perhaps both, would have invoked the exemption to allow the funds to flow into Shi's gain-of-function research and not notify the federal reporting system of her research.

"Unfortunately, the NIAID Director and the NIH Director took advantage of this loophole to grant exemptions for projects covered by the Pause—ridiculously claiming that the exempted research was 'urgently necessary to protect public health or national security'—thereby nullifying the Pause," Dr. Richard Ebright said in ainterviewwith Independent Science News.

But it's not so clear that the NIH felt it necessary to put in place any loopholes. Fauci told a May 11 Senate hearing that "the NIH and NIAID have categorically failed to fund gain-of-function research to be conducted at the Wuhan Institute of Virology."

This was a surprising statement given all the evidence about Shi's coronavirus-amplifying experiments and the language of the moratorium statute that defines gain-of-function as "any study that enhances a pathogen's ability to cause disease."

The statement may be a question of definition. Daszak's EcoHealth Alliance, for example, believes that the term gain-of-function only applies to enhancements to viruses that infect humans, not animal viruses. "So gain-of-function research specifically refers to the manipulation of human viruses to either be more transmissible, cause a worse infection, or spread more easily," an Alliance official told The Dispatch Fact Check.

If the NIH shares the EcoHealth Alliance's view that "gain of function" applies only to human viruses, that would explain why Fauci was able to assure the Senate that it had never funded such research at the Wuhan Institute of Virology.But the legal basis of such a definition is unclear and differs from that of the moratorium language that presumably applied.

Definitions aside, the bottom line is that the National Institutes of Health supported research of a kind that could have generated the SARS2 virus, in an unguarded foreign laboratory doing work in BSL2 biosecurity conditions.

Finally

If the question of whether SARS2 originated in a lab is so substantial, why isn't it more widely known? As should be clear by now, there are many people who have reason not to talk about it. The list is, of course, led by the Chinese authorities. But virologists in the United States and Europe have no great interest in fomenting public debate about the gain-of-function experiments their community has been engaged in for years.

Nor have other scientists stepped forward to raise the issue. Government research funds are distributed on the advice of committees of scientific experts from universities. Anyone who changes course by raising difficult political issues runs the risk of not having their grant renewed and their research career being terminated. Perhaps good behavior is rewarded with the many benefits sloshing around the distribution system.And if you thought Andersen and Daszak would have tarnished their reputation for scientific objectivity after their partisan attacks on the lab's escape scenario, take a look at the second and third names on this oneList of recipientsof an $82 million grant announced by the National Institute of Allergy and Infectious Diseases in August 2020.

The U.S. government shares a strange common interest with the Chinese authorities: Neither wants to draw attention to the fact that Shi's coronavirus work was funded by the U.S. National Institutes of Health.You can imagine the behind-the-scenes conversation where the Chinese government says, "If this research was so dangerous, why did you fund it, and also on our territory?" To which the American side might reply, "It seems that it was you who let it escape. But do we really need to have this discussion in public?"

Fauci is a longtime civil servant who served with integrity under President Trump and has resumed leadership in the Biden administration in addressing the COVID-19 epidemic. It is understandable, no doubt, that Congress has little appetite for dragging him over the coals because of the apparent error of judgment in funding gain-of-function research in Wuhan.

To these contiguous walls of silence must be added that of the mainstream media. As far as I know, No major newspaper or television station has yet given readers an in-depth news story about the lab escape scenario, like the one you just read, although some have posted short editorials or op-eds.You might think that any plausible origin of a virus that killed three million people deserves serious investigation. Or whether it's worth exploring whether the wisdom of continuing gain-of-function research, regardless of the origin of the virus, is worthwhile. Or that funding of gain-of-function research by the NIH and NIAID would carry research during a moratorium on such research. What explains the media's apparent lack of curiosity?

FromOmertà of the virologistsis one of the reasons.Science reporters, unlike political reporters, have little innate skepticism about the motives of their sources; Most see their role largely as passing on the wisdom of scientists to the unwashed masses. So if their sources don't help, these journalists are at their wits' end.

Another reason may be the migration of a large part of the media to the left of the political spectrum. Because President Trump said the virus had escaped from a lab in Wuhan, editors gave little credence to the idea. They joined the virologists and considered escape from the laboratory to be a reprehensible conspiracy theory. During the Trump administration, they had no trouble rejecting the intelligence community's position that escape from the lab could not be ruled out. But when Avril Haines, President Biden's director of national intelligence, said the same thing, she too was largely ignored. This is not to say that editors should have endorsed the lab escape scenario, just that they should have fully and honestly explored the possibility.

People around the world who have been virtually confined to their homes for the past year may want a better answer than their media is giving them. Maybe one will show up in time. After all, the more months that pass without the theory of natural emergence gaining a shred of supporting evidence, the less plausible it seems. Perhaps the international community of virologists will be seen as a false and selfish guide. The common-sense perception that a pandemic breaking out in Wuhan could have something to do with a Wuhan lab cooking new viruses of maximum danger in unsafe conditions could end up crowding out the ideological insistence that whatever Trump said can't be true.

And then the reckoning can begin.

Comments:

[1] This quote was added to the article after its first publication.

[2] Section revised May 18, 2021

Credits

The first to take a serious look at the origins of the SARS2 virus was Yuri Deigin, a biotech entrepreneur in Russia and Canada. In a long and brilliantessayhe dissected the molecular biology of the SARS2 virus and, without approving it, raised the possibility that it had been manipulated. The essay, published on April 22, 2020, provided a roadmap for anyone who wanted to understand the origins of the virus. Deigin packed so much information and analysis into his essay that some doubted it could be the work of one person and suggested that some intelligence agency had written it. But the essay is written with more lightness and humor than I suspect ever found in CIA or KGB reports, and I see no reason to doubt that Deigin is the very capable sole author.

In Deigin's wake, several other skeptics of the virologists' orthodoxy have followed. Nikolai Petrovsky calculated how closely the SARS2 virus binds to the ACE2 receptors of different species and was surprised to find that itOptimizedlaymanfor the human receptor, leading him to conclude that the virus may have been generated in a lab. Alina Chan published aPaperwhich showed that SARS2 was very well adapted to human cells from its first occurrence.

One of the few established scientists who has questioned the virologists' absolute rejection of laboratory escape is Richard Ebright, who has long warned about the dangers of gain-of-function research. Another is David A. Relman of Stanford University. "While there are strong opinions, none of these scenarios can be ruled out or ruled out with certainty with the facts currently available,"streakhe. Kudos also to Robert Redfield, former director of the Centers for Disease Control and Prevention, whoCNNon 26 March 2021toldthat the "most likely" cause of the epidemic came "from a laboratory", because he doubted that a bat virus would become an extreme human pathogen overnight, without taking the time to evolve, as seemed to be the case with SARS2.

Steven Quay, a physician-researcher, hasstatistical and bioinformatic tools appliedon ingenious explorations of the origins of the virus, showing, for example, how the hospitals that receive the early patients are clustered along the WuhanNo2 Subway Linewhich connects the Institute of Virology at one end with the international airport at the other, the perfect conveyor belt to spread the virus from lab to globe.

In June 2020, Milton Leitenberg published aEarly Overviewof the evidence advancing laboratory escape from gain-of-function research at the Wuhan Institute of Virology.

Many others have contributed important pieces of the puzzle. "Truth is the daughter," said Francis Bacon, "not of authority but of time." The efforts of people like those mentioned above are what makes it so.

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Jan Bonte

The above article is from 2021 and much more information has been released since then. Everything supports the main thrust of Wade's article, from WOB documents to genetic research. The pangolin and the raccoon dog did not last long. Want to know exactly how it works? Follow Jan Bonte on X and buy the book he is working on, he just posted it again a tweet .