• Origin of Covid - Following the Clues - Did people or nature open Pando

    From Ubiquitous@21:1/5 to All on Mon May 24 04:37:27 2021
    XPost: alt.tv.pol-incorrect, alt.fan.rush-limbaugh, alt.politics.usa
    XPost: sci.med.diseases

    The Covid-19 pandemic has disrupted lives the world over for more than
    a year. Its death toll will soon reach three million people. Yet the
    origin of pandemic remains uncertain: the political agendas of
    governments and scientists have generated thick clouds of obfuscation,
    which the mainstream press seems helpless to dispel.

    In what follows I will sort through the available scientific facts,
    which hold 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 blame, which starts 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 the science cannot be avoided because for
    now, and probably for a long time hence, it offers the only sure thread
    through the maze.

    The virus that caused the pandemic is known officially as SARS-CoV-2,
    but can be called SARS2 for short. As many people know, there are two
    main theories about its origin. One is that it jumped naturally from
    wildlife to people. The other is that the virus was under study in a
    lab, from which it escaped. It matters a great deal which is the case
    if we hope to prevent a second such occurrence.

    I’ll describe the two theories, explain why each is plausible, and then
    ask which provides the better explanation of the available facts. It’s important to note that so far there is no direct evidence for either
    theory. Each depends on a set of reasonable conjectures but so far
    lacks proof. So I have only clues, not conclusions, to offer. But those
    clues point in a specific direction. And having inferred that
    direction, I’m going to delineate some of the strands in this tangled
    skein of disaster.

    A Tale of Two Theories

    After the pandemic first broke out in December 2019, Chinese
    authorities reported that many cases had occurred in the wet market — a
    place selling wild animals for meat — in Wuhan. This reminded experts
    of the SARS1 epidemic of 2002 in which a bat virus had spread first to
    civets, an animal sold in wet markets, and from civets to people. A
    similar bat virus caused a second epidemic, known as MERS, in 2012.
    This time the intermediary host animal was camels.

    The decoding of the virus’s genome showed it belonged a viral family
    known as beta-coronaviruses, to which the SARS1 and MERS viruses also
    belong. The relationship supported the idea that, like them, it was a
    natural virus that had managed to jump from bats, via another animal
    host, to people. The wet market connection, the only other point of
    similarity with the SARS1 and MERS epidemics, was soon broken: Chinese researchers found earlier cases in Wuhan with no link to the wet
    market. But that seemed not to matter when so much further evidence in
    support of natural emergence was expected shortly.

    Wuhan, however, is home of the Wuhan Institute of Virology, a leading
    world center for research on coronaviruses. So the possibility that the
    SARS2 virus had escaped from the lab could not be ruled out. Two
    reasonable scenarios of origin were on the table.

    From early on, public and media perceptions were shaped in favor of the
    natural emergence scenario by strong statements from two scientific
    groups. These statements were not at first examined as critically as
    they should have been.

    “We stand together to strongly condemn conspiracy theories suggesting
    that COVID-19 does not have a natural origin,” a group of virologists
    and others wrote in the Lancet on February 19, 2020, when it was really
    far too soon for anyone to be sure what had happened. Scientists “overwhelmingly conclude that this coronavirus originated in wildlife,”
    they said, with a stirring rallying call for readers to stand with
    Chinese colleagues on the frontline of fighting the disease.

    Contrary to the letter writers’ assertion, the idea that the virus
    might have escaped from a lab invoked accident, not conspiracy. It
    surely needed to be explored, not rejected out of hand. A defining mark
    of good scientists is that they go to great pains to distinguish
    between what they know and what they don’t know. By this criterion, the signatories of the Lancet letter were behaving as poor scientists: they
    were assuring the public of facts they could not know for sure were

    It later turned out that the Lancet letter had been organized and
    drafted by Peter Daszak, president of the EcoHealth Alliance of New
    York. Dr. Daszak’s organization funded coronavirus research at the
    Wuhan Institute of Virology. If the SARS2 virus had indeed escaped from research he funded, Dr. Daszak would be potentially culpable. This
    acute conflict of interest was not declared to the Lancet’s readers. To
    the contrary, the letter concluded, “We declare no competing

    Peter Daszak, president of the EcoHealth Alliance

    Virologists like Dr. Daszak had much at stake in the assigning of blame
    for the pandemic. For 20 years, mostly beneath the public’s attention,
    they had been playing a dangerous game. In their laboratories they
    routinely created viruses more dangerous than those that exist in
    nature. They argued they could do so safely, and that by getting ahead
    of nature they could predict and prevent natural “spillovers,” the
    cross-over of viruses from an animal host to people. If SARS2 had
    indeed escaped from such a laboratory experiment, a savage blowback
    could be expected, and the storm of public indignation would affect
    virologists everywhere, not just in China. “It would shatter the
    scientific edifice top to bottom,” an MIT Technology Review editor,
    Antonio Regalado, said in March 2020.

    A second statement which had enormous influence in shaping public
    attitudes was a letter (in other words an opinion piece, not a
    scientific article) published on 17 March 2020 in the journal Nature
    Medicine. Its 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
    manipulated virus,” the five virologists declared in the second
    paragraph of their letter.

    Kristian G. Andersen, Scripps Research

    Unfortunately this was another case of poor science, in the sense
    defined above. True, some older methods of cutting and pasting viral
    genomes retain tell-tale signs of manipulation. But newer methods,
    called “no-see-um” or “seamless” approaches, leave no defining marks.
    Nor do other methods for manipulating viruses such as serial passage,
    the repeated transfer of viruses from one culture of cells to another.
    If a virus has been manipulated, whether with a seamless method or by
    serial passage, there is no way of knowing that this is the case. Dr.
    Andersen and his colleagues were assuring their readers of something
    they could not know.

    The discussion part their letter begins, “It is improbable that SARS-
    CoV-2 emerged through laboratory manipulation of a related SARS-CoV-
    like coronavirus”. But wait, didn’t the lead say the virus had clearly
    not been manipulated? The authors’ degree of certainty seemed to slip
    several notches when it came to laying out their reasoning.

    The reason for the slippage is clear once the technical language has
    been penetrated. The two reasons the authors give for supposing
    manipulation to be improbable are decidedly inconclusive.

    First, they say that the spike protein of SARS2 binds very well to its
    target, the human ACE2 receptor, but does so in a different way from
    that which physical calculations suggest would be the best fit.

    Therefore the virus must have arisen by natural selection, not

    If this argument seems hard to grasp, it’s because it’s so strained.
    The authors’ basic assumption, not spelt out, is that anyone trying to
    make a bat virus bind to human cells could do so in only one way. First
    they would calculate the strongest possible fit between the human ACE2
    receptor and the spike protein with which the virus latches onto it.
    They would then design the spike protein accordingly (by selecting the
    right string of amino acid units that compose it). But since the SARS2
    spike protein is not of this calculated best design, the Andersen paper
    says, therefore it can’t have been manipulated.

    But this ignores the way that virologists do in fact get spike proteins
    to bind to chosen targets, which is not by calculation but by splicing
    in spike protein genes from other viruses or by serial passage. With
    serial passage, each time the virus’s progeny are transferred to new
    cell cultures or animals, the more successful are selected until one
    emerges that makes a really tight bind to human cells. Natural
    selection has done all the heavy lifting. The Andersen paper’s
    speculation about designing a viral spike protein through calculation
    has no bearing on whether or not the virus was manipulated by one of
    the other two methods.

    The authors’ second argument against manipulation is even more
    contrived. Although most living things use DNA as their hereditary
    material, a number of viruses use RNA, DNA’s close chemical cousin. But
    RNA is difficult to manipulate, so researchers working on
    coronaviruses, which are RNA-based, will first convert the RNA genome
    to DNA. They manipulate the DNA version, whether by adding or altering
    genes, and then arrange for the manipulated 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, therefore it
    was not manipulated. But the argument is conspicuously inconclusive.
    DNA backbones are quite easy to make, so it’s obviously possible that
    SARS2 was manipulated using an unpublished DNA backbone.

    And that’s it. These are the two arguments made by the Andersen group
    in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two
    inconclusive speculations, convinced the world’s press that SARS2 could
    not have escaped from a lab. A technical critique of the Andersen
    letter takes it down in harsher 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 for stepping out of line. Any
    virologist who challenges the community’s declared view risks having
    his next grant application turned down by the panel of fellow
    virologists that advises the government grant distribution agency.
    The Daszak and Andersen letters were really political, not scientific statements, yet were amazingly effective. Articles in the mainstream
    press repeatedly stated that a consensus of experts had ruled lab
    escape out of the question or extremely unlikely. Their authors relied
    for the most part on the Daszak and Andersen letters, failing to
    understand the yawning gaps in their arguments. Mainstream newspapers
    all have science journalists on their staff, as do the major networks,
    and these specialist reporters are supposed to be able to question
    scientists and check their assertions. But the Daszak and Andersen
    assertions went largely unchallenged.

    Doubts about natural emergence

    Natural emergence was the media’s preferred theory until around
    February 2021 and the visit by a World Health Organization commission
    to China. The commission’s composition and access were heavily
    controlled by the Chinese authorities. Its members, who included the
    ubiquitous Dr. Daszak, kept asserting before, during and after their
    visit that lab escape was extremely unlikely. But this was not quite
    the propaganda victory the Chinese authorities may have been hoping
    for. What became clear was that the Chinese had no evidence to offer
    the commission in support of the natural emergence theory.

    This was surprising because both the SARS1 and MERS viruses had left
    copious traces in the environment. The intermediary host species of
    SARS1 was identified within four months of the epidemic’s outbreak, and
    the host of MERS within nine months. Yet some 15 months after the SARS2 pandemic began, and a presumably intensive search, Chinese researchers
    had failed to find either the original bat population, or the
    intermediate species to which SARS2 might have jumped, or any
    serological evidence that any Chinese population, including that of
    Wuhan, had ever been exposed to the virus prior to December 2019.
    Natural emergence remained a conjecture which, however plausible to
    begin with, had gained not a shred of supporting evidence in over a

    And as long as that remains the case, it’s logical to pay serious
    attention to the alternative conjecture, that SARS2 escaped from a lab.
    Why would anyone want to create a novel virus capable of causing a
    pandemic? Ever since virologists gained the tools for manipulating a
    virus’s genes, they have argued they could get ahead of a potential
    pandemic by exploring how close a given animal virus might be to making
    the jump to humans. And that justified lab experiments in enhancing the
    ability of dangerous animal viruses to infect people, virologists

    With this rationale, they have recreated the 1918 flu virus, shown how
    the almost extinct polio virus can be synthesized from its published
    DNA sequence, and introduced a smallpox gene into a related virus.

    These enhancements of viral capabilities are known blandly as gain-of-
    function experiments. With coronaviruses, there was particular interest
    in the spike proteins, which jut out all around the spherical surface
    of the virus and pretty much determine which species of animal it will
    target. In 2000 Dutch researchers, for instance, earned the gratitude
    of rodents everywhere by genetically engineering the spike protein of a
    mouse coronavirus so that it would attack only cats.

    The spike proteins on the coronavirus’s surface determine which animal
    it can infect. CDC.gov
    Virologists started studying bat coronaviruses in earnest after these
    turned out to be the source of both the SARS1 and MERS epidemics. In particular, researchers wanted to understand what changes needed to
    occur in a bat virus’s spike proteins before it could infect people. Researchers at the Wuhan Institute of Virology, led by China’s leading
    expert on bat viruses, Dr. Shi Zheng-li or “Bat Lady”, mounted frequent expeditions to the bat-infested caves of Yunnan in southern China and
    collected around a hundred different bat coronaviruses.

    Dr. Shi then teamed up with Ralph S. Baric, an eminent coronavirus
    researcher at the University of North Carolina. Their work focused on
    enhancing the ability of bat viruses to attack humans so as to “examine
    the emergence potential (that is, the potential to infect humans) of circulating bat CoVs [coronaviruses].” In pursuit of this aim, in
    November 2015 they created a novel virus by taking the backbone of the
    SARS1 virus and replacing its spike protein with one from a bat virus
    (known as SHC014-CoV). This manufactured virus was able to infect the
    cells of the human airway, at least when tested against a lab culture
    of such cells.

    The SHC014-CoV/SARS1 virus is known as a chimera because its genome
    contains genetic material from two strains of virus. If the SARS2 virus
    were to have been cooked up in Dr. Shi’s lab, then its direct prototype
    would have been the SHC014-CoV/SARS1 chimera, the potential danger of
    which concerned many observers and prompted intense discussion.

    “If the virus escaped, nobody could predict the trajectory,” said Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris.

    Dr. Baric and Dr. Shi referred to the obvious risks in their paper but
    argued they should be weighed against the benefit of foreshadowing
    future spillovers. Scientific review panels, they wrote, “may deem
    similar studies building chimeric viruses based on circulating strains
    too risky to pursue.” Given various restrictions being placed on gain-
    of function (GOF) research, matters had arrived in their view at “a
    crossroads of GOF research concerns; the potential to prepare for and
    mitigate future outbreaks must be weighed against the risk of creating
    more dangerous pathogens. In developing policies moving forward, it is important to consider the value of the data generated by these studies
    and whether these types of chimeric virus studies warrant further
    investigation versus the inherent risks involved.”

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

    Inside the Wuhan Institute of Virology

    Dr. Baric had developed, and taught Dr. Shi, a general method for
    engineering bat coronaviruses to attack other species. The specific
    targets were human cells grown in cultures and humanized mice. These
    laboratory mice, a cheap and ethical stand-in for human subjects, are genetically engineered to carry the human version of a protein called
    ACE2 that studs the surface of cells that line the airways.

    Dr. Shi returned to her lab at the Wuhan Institute of Virology and
    resumed the work she had started on genetically engineering
    coronaviruses to attack human cells.

    Dr. Zheng-li Shi in a high safety (level BSL4) lab. Her coronavirus
    research was done in the much lower safety levels of BSL2 and BSL3

    How can we be so sure?

    Because, by a strange twist in the story, her work was funded by the
    National Institute of Allergy and Infectious Diseases (NIAID), a part
    of the U.S. National Institutes of Health (NIH). And grant proposals
    that funded her work, which are a matter of public record, specify
    exactly what she planned to do with the money.

    The grants were assigned to the prime contractor, Dr. Daszak of the
    EcoHealth Alliance, who subcontracted them to Dr. Shi. Here are
    extracts from the grants for fiscal years 2018 and 2019. “CoV” stands
    for coronavirus and “S protein” refers to the virus’s spike protein.
    “Test predictions of CoV inter-species transmission. Predictive models
    of host range (i.e. emergence potential) will be tested experimentally
    using reverse genetics, pseudovirus and receptor binding assays, and
    virus infection experiments across a range of cell cultures from
    different species and humanized mice.”

    “We will use S protein sequence data, infectious clone technology, in
    vitro and in vivo infection experiments and analysis of receptor
    binding to test the hypothesis that % divergence thresholds in S
    protein sequences predict spillover potential.”

    What this means, in non-technical language, is that Dr. Shi set out to
    create novel coronaviruses with the highest possible infectivity for
    human cells. Her plan was to take genes that coded for spike proteins possessing a variety of measured affinities for human cells, ranging
    from high to low. She would insert these spike genes one by one into
    the backbone of a number of viral genomes (“reverse genetics” and
    “infectious clone 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 people.

    The methodical approach was 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 indeed may have
    created the SARS2 virus itself with the right combination of virus
    backbone and spike protein.

    It cannot yet be stated that Dr. Shi did or did not generate SARS2 in
    her lab because her records have been sealed, but it seems she was
    certainly on the right track to have done so. “It is clear that the
    Wuhan Institute of Virology was systematically constructing novel
    chimeric coronaviruses and was assessing their ability to infect human
    cells and human-ACE2-expressing mice,” says Richard H. Ebright, a
    molecular biologist at Rutgers University and leading expert on

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

    The lab escape scenario for the origin of the SARS2 virus, as should by
    now be evident, is not mere hand-waving in the direction of the Wuhan
    Institute of Virology. It is a detailed proposal, based on the specific
    project being funded there by the NIAID.

    Even if the grant required the work plan described above, how can we be
    sure that the plan was in fact carried out? For that we can rely on the
    word of Dr. Daszak, who has been much protesting for the last 15 months
    that lab escape was a ludicrous conspiracy theory invented by China-

    On 9 December 2019, before the outbreak of the pandemic became
    generally known, Dr. Daszak gave an interview in which he talked in
    glowing terms of how researchers at the Wuhan Institute of Virology had
    been reprogramming the spike protein and generating chimeric
    coronaviruses capable of infecting humanized mice.

    “And we have now found, you know, after 6 or 7 years of doing this,
    over 100 new sars-related coronaviruses, very close to SARS,” Dr.
    Daszak says around minute 28 of the interview. “Some of them get into
    human cells in the lab, some of them can cause SARS disease in
    humanized mice models and are untreatable with therapeutic monoclonals
    and you can’t vaccinate against them with a vaccine. So, these are a
    clear and present danger….

    “Interviewer: You say these are diverse coronaviruses and you can’t
    vaccinate against them, and no anti-virals — so what do we do?
    “Daszak: Well I think…coronaviruses — you can manipulate them in the
    lab pretty easily. Spike protein drives a lot of what happen with
    coronavirus, in zoonotic risk. So you can get the sequence, you can
    build the protein, and we work a lot with Ralph Baric at UNC to do
    this. Insert into the backbone of another virus and do some work in the
    lab. So you can get more predictive when you find a sequence. You’ve
    got this diversity. Now the logical progression for vaccines is, if you
    are going to develop a vaccine for SARS, people are going to use
    pandemic SARS, but let’s insert some of these other things and get a
    better vaccine.” The insertions he referred to perhaps included an
    element called the furin cleavage site, discussed below, which greatly increases viral infectivity for human cells.

    In disjointed style, Dr. Daszak is referring to the fact that once you
    have generated a novel coronavirus that can attack human cells, you can
    take the spike protein and make it the basis for a vaccine.

    One can only imagine Dr. Daszak’s reaction when he heard of the
    outbreak of the epidemic in Wuhan a few days later. He would have known
    better than anyone the Wuhan Institute’s goal of making bat
    coronaviruses infectious to humans, as well as the weaknesses in the institute’s defense against their own researchers becoming infected.

    But instead of providing public health authorities with the plentiful information at his disposal, he immediately launched a public relations campaign to persuade the world that the epidemic couldn’t possibly have
    been caused by one of the institute’s souped-up viruses. “The idea that
    this virus escaped from a lab is just pure baloney. It’s simply not
    true,” he declared in an April 2020 interview.

    The Safety Arrangements at the Wuhan Institute of Virology

    Dr. Daszak was possibly unaware of, or perhaps he knew all too well,
    the long history of viruses escaping from even the best run
    laboratories. The smallpox virus escaped three times from labs in
    England in the 1960’s and 1970’s, causing 80 cases and 3 deaths.

    Dangerous viruses have leaked out of labs almost every year since.
    Coming to more recent times, the SARS1 virus has proved a true escape
    artist, leaking from laboratories in Singapore, Taiwan, and no less
    than four times from the Chinese National Institute of Virology in

    One reason for SARS1 being so hard to handle is that there were no
    vaccines available to protect laboratory workers. As Dr. Daszak
    mentioned in his December 19 interview quoted above, the Wuhan
    researchers too had been unable to develop vaccines against the
    coronaviruses they had designed to infect human cells. They would have
    been as defenseless against the SARS2 virus, if it were generated in
    their lab, as their Beijing colleagues were against SARS1.

    A second reason for the severe danger of novel coronaviruses has to do
    with the required levels of lab safety. There are four degrees of
    safety, designated BSL1 to BSL4, with BSL4 being the most restrictive
    and designed for deadly pathogens like the Ebola virus.

    The Wuhan Institute of Virology had a new BSL4 lab, but its state of
    readiness considerably alarmed the State Department inspectors who
    visited it from the Beijing embassy in 2018. “The new lab has a serious shortage of appropriately trained technicians and investigators needed
    to safely operate this high-containment laboratory,” the inspectors
    wrote in a cable of 19 January 2018.

    The real problem, however, was not the unsafe state of the Wuhan BSL4
    lab but the fact that virologists worldwide don’t like working in BSL4 conditions. You have to wear a space suit, do operations in closed
    cabinets and accept that everything will take twice as long. So the
    rules assigning each kind of virus to a given safety level were laxer
    than some might think was prudent.

    Before 2020, the rules followed by virologists in China and elsewhere
    required that experiments with the SARS1 and MERS viruses be conducted
    in BSL3 conditions. But all other bat coronaviruses could be studied in
    BSL2, the next level down. BSL2 requires taking fairly minimal safety precautions, such as wearing lab coats and gloves, not sucking up
    liquids in a pipette, and putting up biohazard warning signs. Yet a gain-of-function experiment conducted in BSL2 might produce an agent
    more infectious than either SARS1 or MERS. And if it did, then lab
    workers would stand a high chance of infection, especially if

    Much of Dr. Shi’s work on gain-of-function in coronaviruses was
    performed at the BSL2 safety level, as is stated in her publications
    and other documents. She has said in an interview with Science magazine
    that “The coronavirus research in our laboratory is conducted in BSL-2
    or BSL-3 laboratories.”

    “It is clear that some or all of this work was being performed using a biosafety standard — biosafety level 2, the biosafety level of a
    standard US dentist’s office — that would pose an unacceptably high
    risk of infection of laboratory staff upon contact with a virus having
    the transmission properties of SARS-CoV-2,” says Dr. Ebright.

    “It also is clear,” he adds, “that this work never should have been
    funded and never should have been performed.”

    This is a view he holds regardless of whether or not the SARS2 virus
    ever saw the inside of a lab.

    Concern about safety conditions at the Wuhan lab was not, it seems,
    misplaced. According to a fact sheet issued by the State Department on
    January 15,2021, “ The U.S. government has reason to believe that
    several researchers inside the WIV became sick in autumn 2019, before
    the first identified case of the outbreak, with symptoms consistent
    with both COVID-19 and common seasonal illnesses.”

    David Asher, a fellow of the Hudson Institute and former consultant to
    the State Department, provided more detail about the incident at a
    seminar. Knowledge of the incident came from a mix of public
    information and “some high end information collected by our
    intelligence community,” he said. Three people working at a BSL3 lab at
    the institute fell sick within a week of each other with severe
    symptoms that required hospitalization. This was “the first known
    cluster that we’re aware of, of victims of what we believe to be
    COVID-19.” Influenza could not completely be ruled out but seemed
    unlikely in the circumstances, he said.

    Comparing the Rival Scenarios of SARS2 Origin

    The evidence above adds up to a serious case that the SARS2 virus could
    have been created in a lab, from which it then escaped. But the case,
    however substantial, falls short of proof. Proof would consist of
    evidence from the Wuhan Institute of Virology, or related labs in
    Wuhan, that SARS2 or a predecessor virus was under development there.
    For lack of access to such records, another approach is to take certain
    salient facts about the SARS2 virus and ask how well each is explained
    by the two rival scenarios of origin, those of natural emergence and
    lab escape. Here are four tests of the two hypotheses. A couple have
    some technical detail, but these are among the most persuasive for
    those who may care to follow the argument.

    1) The place of origin.
    Start with geography. The two closest known relatives of the SARS2
    virus were collected from bats living in caves in Yunnan, a province of 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 spilled over to people naturally. But this isn’t what
    happened. The pandemic broke out 1,500 kilometers away, in Wuhan. Beta-coronaviruses, the family of bat viruses to which SARS2 belongs,
    infect the horseshoe bat Rhinolophus affinis, which ranges across
    southern China. The bats’ range is 50 kilometers, so it’s unlikely that
    any made it to Wuhan. In any case, the first cases of the Covid-19
    pandemic probably occurred in September, when temperatures in Hubei
    province are already cold enough to send bats into hibernation.
    What if the bat viruses infected some intermediate host first? You
    would need a longstanding population of bats in frequent proximity with
    an intermediate host, which in turn must often cross paths with people.
    All these exchanges of virus must take place somewhere outside Wuhan, a
    busy metropolis which so far as is known is not a natural habitat of Rhinolophus bat colonies. 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 jumped on a train to Wuhan, no fellow passengers fell ill.
    It’s a stretch, in other words, to get the pandemic to break out
    naturally outside Wuhan and then, without leaving any trace, to make
    its first appearance there.
    For the lab escape scenario, a Wuhan origin for the virus is a no-
    brainer. Wuhan is home to China’s leading center of coronavirus
    research where, as noted above, researchers were genetically
    engineering bat coronaviruses to attack human cells. They were doing so
    under the minimal safety conditions of a BSL2 lab. If a virus with the unexpected infectiousness of SARS2 had been generated there, its escape
    would be no surprise.

    2) Natural history and evolution
    The initial location of the pandemic is a small part of a larger
    problem, that of its natural history. Viruses don’t just make one time
    jumps from one species to another. The coronavirus spike protein,
    adapted to attack bat cells, needs repeated jumps to another species,
    most of which fail, before it gains a lucky mutation. Mutation — a
    change in one of its RNA units — causes a different amino acid unit to
    be incorporated into its spike protein and makes the spike protein
    better able to attack the cells of some other species.
    Through several more such mutation-driven adjustments, the virus adapts

    [continued in next message]

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