The Ongoing Mystery

Magazine Account | of Covid’s Origin Give this article 614

The Ongoing
Mystery of Covid’s
We still don’t
Origin
know how the pandemic started. Here's what we
do know — and why matters. it

Illustration by Jules Julien

Give this article 614

By David Quammen
David Quammen is the author of “Breathless: The Scientific Race to Defeat a Deadly
Virus,” about Covid-19, and “Spillover: Animal Infections and the Next Human Pandemic,”
among other books.
July 25, 2023 Updated 10:28 a.m. ET

Where did it come from? More than three years into the pandemic
and untold millions of people dead, that question about the Covid-
9 coronavirus remains controversial and fraught, with facts
sparkling amid a tangle of analyses and hypotheticals like
Christmas lights strung on a dark, thorny tree. One school of
thought holds that the virus, known to science as SARS-CoV-2,
spilled into humans from a nonhuman animal, probably in the
Huanan Seafood Wholesale Market, a messy emporium in Wuhan,
China, brimming with fish, meats and wildlife on sale as food.
Another school argues that the virus was laboratory-engineered to
infect humans and cause them harm — a bioweapon — and was
possibly devised in a “shadow project” sponsored by the People’s
Liberation Army of China. A third school, more moderate than the
second but also implicating laboratory work, suggests that the
virus got into its first human victim by way of an accident at the
Wuhan Institute of Virology (W.I.V.), a research complex on the
eastern side of the city, maybe after well-meaning but reckless
genetic manipulation that made it more dangerous to people.

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Ifyou feel confused by these possibilities, undecided, suspicious of

overconfident assertions — or just tired of the whole subject of the
pandemic and whatever little bug has caused it — be assured that
you aren’t the only one.
Some contrarians say that it doesn’t matter, the source of the virus.
What matters, they say, is how we cope with the catastrophe it has
brought, the illness and death it continues to cause. Those
contrarians are wrong. It does matter. Research priorities,
pandemic preparedness around the world, health policies and
public opinion toward science itself will be lastingly affected by the
answer to the origin question — if we ever get a definitive answer.

The Great Covid-19 Debate The question of the pandemic’s origins has been
divisive, and often politicized, from the beginning. In this article, the science writer
David Quammen retraces both the evidence and the debate’s contours. Along the
way, he describes how, in the absence of definitive proof, participants in the
debate — including experts, and journalists like himself — are sometimes
influenced by their prior beliefs to favor one explanation over another.

But much of the evidence that might provide that answer has
either been lost or is still unavailable — lost because of failures to
gather relevant material promptly; unavailable because of
intransigence and concealment, particularly on the part of Chinese
officialdom at several levels.
Take the natural-spillover hypothesis, for instance, and assume
that the virus passed to humans from a wild animal — maybe a
raccoon dog (a foxlike canine) or a Malayan porcupine —
somewhere in the Huanan market. To test that hypothesis, you
would want samples of blood, feces or mucus taken from the
raccoon dogs, porcupines and other wildlife that languished, caged
and doomed, in the market. You would screen those samples for
signs of the virus. If you found the virus itself, or at least sizable
bits of its genome, you would then make a comparative analysis of
genomes, including some from the earliest human cases, to deduce
whether people got the virus from the wildlife or vice versa.

Illustration by Jules Julien

But you can’t do that, because whatever raccoon dogs or

porcupines or other wild animals were on sale in the market during
December 2019 had vanished by Jan. 1, 2020. On that date, the
market was closed by order of Chinese authorities, with no
(reported) effort to sample the most suspect forms of wildlife.
Or take the lab-engineered-bioweapon hypothesis, as recently
offered in an article in The Sunday Times of London. The two
Times reporters cited unidentified “U.S. investigators” who
“scrutinized top-secret intercepted communications” and
concluded that the Chinese military was supporting a covert
project to develop a weaponized coronavirus. The article also
posited a related vaccine effort, to protect China’s populace once
the killer virus was unleashed on the world. It’s a riveting
narrative. The virus engineering occurred, according to this
account, at the Wuhan Institute of Virology. The reporters didn’t
name their intelligence sources or supply evidence to make their
allegations concrete, but if they did, it would be explosive news.
Or take the lab-leak scenario, some versions of which point
accusingly at a nonprofit organization in New York, EcoHealth
Alliance, and its collaborative relationship with Dr. Zhengli Shi, a
senior researcher at the W.I.V. Shi and her team study
coronaviruses, especially those carried by bats, extracting
fragments of viral RNA (the molecule in which coronavirus
genomes are written) and occasionally live virus, from samples of
guano and other bodily material, and assembling whole genome
sequences, like jigsaw puzzles, from the fragments. They perform
experiments, sometimes combining an element of one virus with
the backbone of another, to learn how that element might function
in the wild; and they publish scientific papers, warning which bat
viruses could pose a threat to humans. What if a researcher or
technician under Shi’s leadership, handling a virus very much like
SARS-CoV-2, became infected by accident and then spread the
infection to others? That question became, from the early months
of the pandemic, a suspicion and then a hypothesis and then an
accusation.
Even now, the trade in claims and counterclaims remains brisk.
Last month, in a Substack newsletter called Public, three authors
asserted — citing unnamed “U.S. government officials” — that one
of the first people infected with SARS-CoV-2 was a scientist named
Ben Hu, from Shi’s lab. That assertion was significant, and
important if true, but no proof or identified sourcing so far supports
it.Ten days later, the Office of the Director of National Intelligence
released (as required by a law passed three months earlier) a
declassified report outlining whatever was known to the U.S.
Intelligence Community about potential links between the Wuhan
Institute of Virology and the origins of the pandemic. The report
concluded, among other things, that W.I.V. personnel had
collaborated at times on coronavirus work with scientists
associated with the People’s Liberation Army, but that (so far as
available evidence showed) such work involved “no known viruses
that could plausibly be a progenitor of SARS-CoV-2.”
And then, on July 11, the House Select Subcommittee on the
Coronavirus Pandemic, led by Representative Brad Wenstrup, an
Ohio Republican, convened a hearing at which he and colleagues
interrogated two scientists, Kristian Andersen and Robert Garry,
about their authorship of an influential 2020 paper that appeared in
the journal Nature Medicine. That paper was titled “The Proximal
Origin of SARS-CoV-2.” The tenor of the hearing was foretold by its
own announced title: “Investigating the Proximal Origin of a
Cover-Up,” and the proceedings that day consisted of accusation
and defense, without shedding any new light, let alone yielding
certitude about the origin of the virus.
Certitude is an elusive goal and a high presumption, even for
science, even for a director of national intelligence, even for the
chairman of a select congressional subcommittee. Philosophers
have recognized that, and so have novelists and poets. “I was of
three minds,” wrote Wallace Stevens, “Like a tree/In which there
are three blackbirds.” In the poem, Stevens found 13 different ways
of looking at a blackbird. There are at least that many ways of
viewing the origin of SARS-CoV-2, and to do justice to the question,
you’ll need, like him, to hold several possibilities in your mind at a
time.
How you regard a blackbird or an origin hypothesis may be
influenced by where you’re coming from. That’s an old truth, but I
was reminded of it during a conversation with Jesse Bloom, an
evolutionary biologist at the Fred Hutchinson Cancer Center in
Seattle, and one of the best-qualified among those who argue that
the lab-leak hypothesis deserves robust investigation. Bloom
studies the evolution of viruses, for two reasons: It happens fast,
and therefore illuminates evolution in general, and it has large
implications for public health.
When I spoke with him back in February 2021, a year into the
pandemic, and asked about the origin question, Bloom said, “I
think what you have is a lot of people strongly defaulting to their
prior beliefs.” Scientists who study zoonotic diseases (those that
spill over from nonhuman animals into people) might be inclined to
assume a natural origin. Scientists who have long argued against
the risks of “gain of function” research (experimental work
exploring the evolutionary capacities of potentially dangerous
pathogens) might readily assume a lab leak. National security
experts with strong views of the oppressive, secretive Chinese
government might lean toward scenarios involving Chinese
malfeasance and cover-up.
More recently, Bloom told me that his own “prior” inclination
would be toward a natural spillover. “But you certainly wouldn’t
think it’s, like, 99.99 percent the most likely explanation,” he said,
adding, “There could be other possibilities.”
That gave me pause to consider my own priors. For the past 40
years, I’ve written nonfiction about the natural world and the
sciences that study especially ecology and evolutionary biology.
it,

During my attention went mainly to large,

the first half of that,
visible creatures like bears, crocodiles and bumblebees and to wild
places like the Amazon jungle and the Sonoran Desert. I came to
the subject of emerging viruses in 1999, during a National
Geographic assignment, when I walked for 10 days through Ebola-
irus habitat in a Central African forest. Later I spent five years
writing a book about zoonotic diseases and the agents that cause
them, including the SARS virus, the earlier killer coronavirus now
often called SARS-CoV-1, which emerged in 2002 and spread in
human travelers from Hong Kong to Singapore, Toronto and
elsewhere, alarming experts deeply. Scientists traced SARS-CoV-1
to palm civets, a type of catlike wild carnivore sold as food in some
South China markets and restaurants. But the civets proved to be
intermediate hosts, and its natural host was later identified as
horseshoe bats.
The story of SARS is only one chapter in the saga of dangerous
new viruses emerging from animals. The grim tale of how H.I.V.
got into humans and caused the AIDS pandemic is another — a tale
known partly by inference and partly by molecular evidence, and
traceable back to a single blood-mingling event between a person
and a chimpanzee, probably hunter and hunted, in the
southeastern corner of Cameroon around the start of the 20th
century. Human contact with nonhuman animals accounts for our
influenzas as well, which usually emerge from wild aquatic birds.
Hendra virus, in Australia, comes to humans from bats, generally
through an intermediate host: horses. Machupo virus, in Bolivia,
abides in rodents when not infecting people. Hantaan virus,
discovered in Korea, and its relative Sin Nombre virus, in the
American Southwest, also spill over from rodents. Nipah virus, in
Bangladesh and some surrounding countries, comes from bats. It’s
excreted in bat feces, saliva and urine, and when certain fruit bats
visit date palm trees that are being tapped for their sugary sap — a
custom in Bangladesh — the virus contaminates the sap, which is
sold fresh on the street to local customers, some of whom die.
These cases and many others like them are among my own priors,
and no doubt they do incline me toward the idea of natural
spillover. It happens often, sometimes with dire consequences.

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Research accidents have occurred, too, in the history of dangerous

new viruses, and longtime concerns over such accidents constitute
the priors of some who favor the lab-leak hypothesis for Covid.
Such accidents might number in the hundreds or the thousands,
depending on where you put the threshold of significance and how
you define “accident.” There was an event that (probably)
reintroduced a 1950s strain of influenza in 1977, causing that year’s
flu pandemic, which killed many thousands of people, and a 2004
needle-stick injury of a careful scientist, Kelly Warfield, while she
was doing Ebola research (but she proved uninfected by Ebola).
Also in 2004, just a year after the global SARS scare, two workers
at a virology lab in Beijing were independently infected with that
virus, which spread to nine people in total, one of whom died. This
followed two other single-case lab-accident infections with SARS
virus the previous year, one in Singapore, one in Taiwan.

Illustration by Jules Julien

When known cases of an “atypical pneumonia” began

the first
turning up Wuhan hospitals in late 2019, and then exploded into
at
a coronavirus outbreak in early 2020, the location itself seemed to
fit,in different ways, the priors that might incline one toward either
a natural-origin explanation or a lab-leak explanation. The
potential lab-leak connection was easiest to note: The city
contained a research facility, the Wuhan Institute of Virology, with
a well-known laboratory devoted to coronavirus research. On the
other hand, Wuhan was also a major nexus for the significant
national trade in wild animals for food, fur and traditional
medicines (estimated at more than $70 billion annually), where
such creatures, and the viruses they carry, were sold at many
crowded markets — one of which, Huanan, lay at or near the
center of the spatial pattern of earliest known cases.
So, starting from simply those circumstances, was a lab accident
more a natural spillover? And under either of those
“likely” than
scenarios, how much did Chinese-government pressure and
obscurantism constrain the availability of evidence for assessing
one or the other? Because there exists no definitive account — yet
— of the particular events that delivered SARS-CoV-2 into the
human population, even experts are forced to frame their views as
probabilities, based on data and circumstance, influenced variously
by prior beliefs as to how the world works.
In assessing the probabilities for yourself, you might want to step
back from the noise, anger, vitriol and politicization that have
clouded the controversy and focus on the evidence we do have. To
that end, it may help to note some events in the order they
occurred.
On Jan. 11, 2020, in Shanghai, just 11 days after first reports of the
outbreak in Wuhan circulated globally, a team of scientists led by
Yong-Zhen Zhang of Fudan University released a draft genome
sequence of the novel virus through a website called
Virological.org. The genome was provided by Edward C. Holmes, a
British Australian evolutionary biologist based in Sydney and a
colleague of Zhang’s on the genome-assembly project. Holmes is
famous among virologists for his work on the evolution of RNA
viruses (including coronaviruses), his pristinely bald head and his
mordant candor. Everyone in the field knows him as Eddie. The
posting went up at 1:05 a.m. Scotland time, at which point the
curator of the site there in Edinburgh, a professor of molecular
evolution named Andrew Rambaut, was alert and ready to speed
things along. He and Holmes composed a brief introductory note to
the genome : “Please feel free to download, share, use and analyze
this data,” it said. They knew that “data” is plural, but they were in
a hurry.

Immediately, Holmes and a small group of colleagues set to

analyzing the genome for clues about the virus’s evolutionary
history. They drew on a background of known coronaviruses and
their own understanding of how such viruses take shape in the wild
(as reflected in Holmes’s 2009 book, “The Evolution and
Emergence of RNA Viruses”). They knew that coronavirus
evolution can occur rapidly, driven by frequent mutation (single-
etter changes in a roughly 30,000-letter genome), by
recombination (one virus swapping genome sections with another
virus, when both simultaneously replicate in a single cell) and by
Darwinian natural selection’s acting on those random changes.
Holmes traded thoughts with Rambaut in Edinburgh, a friend of
three decades, and with two other colleagues: Kristian Andersen at
Scripps Research in La Jolla, Calif.; and Robert Garry at the Tulane
University School of Medicine in New Orleans. Ian Lipkin, of
Columbia University’s Mailman School of Public Health, joined the
huddle later. These five would form a sort of long-distance study
group, aimed toward publishing a paper on SARS-CoV-2’s genome
and its likely origin.
Holmes, Andersen and their colleagues recognized the virus’s
similarity viruses but, with more study, saw a pair of
to bat
“notable features” that gave them pause. Those features, two short
blips of genome, constituted a very small percentage of the whole,
but with potentially high significance for the virus’s ability to grab
and infect human cells. They were technical-sounding elements,
familiar to virologists, that are now part of the Covid-origin
vernacular: a furin cleavage site (FCS), as well as an unexpected
receptor-binding domain (RBD). All viruses have RBDs, which
help them attach to cells; an FCS is a feature that helps certain
viruses get inside. The original SARS virus, which terrified
scientists worldwide but caused only about 800 deaths, didn’t
resemble the new coronavirus in either respect. How had SARS-
come to take this form?
Andersen and Holmes were genuinely concerned, at first, that it
might have been engineered. Were those two features deliberate
add-ons, inserted into some coronavirus backbone by genetic
manipulation, intentionally making the virus more transmissible
and pathogenic among humans? It had to be considered. Holmes
called Jeremy Farrar, a disease expert who was then director of the
Wellcome Trust, a foundation in London that supports health
research. Farrar saw the point and quickly arranged a conference
call among an international group of scientists to discuss the
genome’s puzzling aspects and the possible scenarios of its origin.
The group included Robert Garry at Tulane and a dozen other
people, most of them distinguished European or British scientists
with relevant expertise, like Rambaut in Edinburgh, Marion
Koopmans in the Netherlands and Christian Drosten in Germany.
Also on the call were Anthony Fauci, then head of the National
Institute of Allergy and Infectious Diseases, and Francis Collins,
then director of the National Institutes of Health and therefore
Fauci’s boss. This is the famous Feb. 1 call on which — if you
believe some critical voices — Fauci and Collins persuaded the
others to suppress any notion that the virus might have been
engineered.
“The narrative going around was that Fauci told us, Change our
mind, yada, yada, yada, yada. We were paid off,” Holmes said to
me. “It’s complete [expletive].”
Andersen concurs. “There is no universe in which this would even
be possible,” he told me. Recently, based on selections of their
private email and Slack traffic made public, Andersen and his
colleagues have been accused of concealment and dissembling:
Their messages, critics contend, prove that even as they were
deeply concerned in private about the engineered-virus or lab-
elease possibilities, they were striving to keep both out of public
discussion. But as the researchers describe it, these apparent
contradictions were simply a reflection of their fast-evolving views.
After initial concern that the receptor-binding domain in SARS-
oV-2 might be a sign of engineering, for instance, they learned
soon after the Feb. 1 conference call of a very similar RBD in a
coronavirus that infected pangolins. It was detected from a public
database by a bioinformatician in Houston, Matt Wong, and posted
on the Virological website, where it eventually came to the group’s
attention. It showed that such an RBD had evolved in the wild and
might well have gotten into SARS-CoV-2 by recombination, the
natural gene-swapping process. Andersen and the others also
recognized that furin cleavage sites occur naturally in other
coronaviruses, like the MERS virus, though not (as so far detected)
in any other member of the subgenus to which SARS-CoV-2
belongs.
Such new data led to a new conclusion, in what Andersen called, on
Twitter, “a clear example of the scientific process.” Sixteen days
after the conference call, they posted a preprint (a draft, not yet
peer-reviewed) of their paper, and four weeks later it appeared in
the journal Nature Medicine — this was the one titled “The
Proximal Origin of SARS-CoV-2.” Andersen and his co-authors
stated their conclusion at the top: “Our analyses clearly show that
SARS-CoV-2 is not a laboratory construct or a purposefully
manipulated virus.” That still left the possibility of a natural virus,
evolved in an animal host and passed into humans by zoonotic
transfer — or perhaps a natural virus accidentally leaked? Near
the paper’s end they stated something more nuanced: that while
intentional engineering of the virus could be ruled out, “it is
currently impossible to prove or disprove the other theories of its
origin described here.” That said, they added, “we do not believe
that any type of laboratory-based scenario is plausible.”
One other coronavirus quickly came to light as the closest known
match to SARS-CoV-2. This wasn’t actually a virus “in the flesh” —
in physical presence. It was a genome sequence, assembled from
RNA fragments extracted from a fecal swab sample of a bat,
captured in a mine several years earlier in 2013. The mine was in
Yunnan Province, 1,200 miles southwest of Wuhan. The genome
was 96.2 percent identical to the SARS-CoV-2 genome as sampled
from people during the early days of the pandemic. That degree of
similarity — or a 3.8 percent difference — suggests a common
virus ancestor some years ago and independent evolution in the
years since. So this represented a cousin to SARS-CoV-2, not its
progenitor.
The work of sampling the bat and assembling the sequence (first
just a portion, then, with better technology, nearly the whole thing)
had been led by Zhengli Shi, at the Wuhan Institute of Virology. Shi
and her team labeled the sequence RaTG13, coding the facts that it
came from an individual of Rhinolophus affinis (Ra), the
intermediate horseshoe bat, captured in that mine in Tongguan
(TG), a town in the Mojiang district of Yunnan, in 2013. RaTG13 has
attained renown, not just because it constituted strong evidence of
SARS-CoV-2’s ancestry in bat viruses but also because the Mojiang
mine figures in some of the more lurid scenarios for a lab-leak
origin.
Part what makes the very name Mojiang seem lurid is that in
of
2012, three workers at the mine died of unidentified respiratory
infections after days of underground labor there. What got into
their lungs and killed them? Was it a fungus? Was it a virus? Some
lab-leak proponents suggest that those deaths, described in two
obscure medical theses written in Mandarin, represent the earliest
known fatalities from a virus — possibly RaTG13 — that either
already was, or in Shi’s lab became, SARS-CoV-2 or its immediate
progenitor (that is, something far more similar than a cousin). The
inference is that Shi’s team, a year after the mine workers died,
may have taken the virus back to Wuhan. But the Mojiang deaths
were also reported in 2014 in the journal Emerging Infectious
Diseases by scientists who found an entirely different virus, also
potentially dangerous because it had similarities to Nipah and
Hendra viruses, and was carried in the Mojiang mine by rats, not
bats. One takeaway: Sample the rats and bats and other fauna in a
mine, and you might well find a variety of viruses you wouldn’t
want in your lungs.
Another problem with the RaTG13 scenario: Its genome differs
from that of SARS-CoV-2 at more than 1,100 scattered positions
throughout its genome. To engineer SARS-CoV-2 into existence by
starting with RaTG13 would have been unreasonable and
impractical, according to Holmes and other experts in coronavirus
genomics. Furthermore, it’s important to remember that RaTG13
was a genome sequence, not a live virus: It was information, not a
biological entity. Coaxing a virus that lies dormant in bat guano to
grow in a cell culture is difficult, and usually the effort fails. Zhengli
Shi told Jon Cohen, a senior correspondent for the journal Science,
in her answer to a set of emailed questions, that she never grew
RaTG13 in her lab. She told me the same thing during a two-hour
conversation by Zoom: “No, no. We couldn’t culture any of the
sample from this cave at Mojiang.”
Shi was in Shanghai for a conference on the night of Dec. 30, 2019,
as she explained it to me, when word reached her about a
mysterious respiratory illness spreading dangerously among
people back in Wuhan. Preliminary lab results suggested a
coronavirus — not SARS virus, but something similar — might be
the cause. She was asked to help identify the thing. She put her lab
team to work on that immediately and took a train back to Wuhan
the next day. Within hours, her lab had received a partial sequence
from another lab. Her first instinct was to compare it with
sequences of viruses they had worked on themselves, “and we
found it’s different,” she told me. “So, the afternoon of Dec. 31, I

already know it’s nothing related to what we have done in our

laboratory.”
Some critics, she was well aware, had suggested that her urgency
in checking her own records was an implicit admission of error or
guilt. “It’s normal!” was her response.

Jon Cohen mentioned the possibility of a lab leak in a report

published in Science on Jan. 31, 2020, noting that not all the earliest
confirmed cases had some direct link to the Huanan market.
Fourteen of the first 41, according to one study, did not. Might those
people have picked up their infections somewhere else, and maybe
not from an animal at all? After describing a couple of vivid but
unsupported allegations, including the idea that SARS-CoV-2
resembled a snake virus (and snakes were sold at Wuhan wet
markets), Cohen added, “The Wuhan Institute of Virology, which is
the premier lab in China that studies bat and human coronaviruses,
has also come under fire.” Concerns had been voiced, he wrote,
about the security of the W.I.V.’s biosafety procedures and facilities.

Illustration by Jules Julien

Evidence regarding the virus, apart from what could

the origin of
be read from the genome
remained scarce during those early itself,
months. In place of evidence, there was the weight of scientific
authority on one side and the volume of outcry on the other. On
Feb. 19, 2020, an open letter appeared online in The Lancet, a
British journal, signed by 27 scientists, some of them eminent
senior figures in virology and public health, others researchers in
the full heat of distinguished careers. It was a statement of
solidarity with Chinese scientists and health professionals, who
were then on the front line in efforts to understand and control the
virus. The letter was organized by Peter Daszak, a British
American disease ecologist, president of EcoHealth Alliance and a
collaborator with Zhengli Shi. Besides voicing support for Chinese
colleagues, it said: “We stand together to strongly condemn
conspiracy theories suggesting that Covid-19 does not have a
natural origin.” That expression of confidence, so soon, would
prove to be counterproductive, and the phrase “conspiracy
theories” landed like bacon grease thrown into a campfire, causing
skeptics to flare and sizzle.

The lab-leak idea, meanwhile, took hold in some political circles,

partly because it dovetailed with attitudes toward the Chinese
government, its repressive policies and its penchant for secrecy. In
late January 2020, even before Cohen’s Jan. 31 article, The
Washington Times ran an article suggesting links between the
W.I.V. and a covert bioweapons program of the Chinese military.
The article (later walked back with an editor’s note) was based
largely on assertions by a former Israeli military-intelligence
officer. Several weeks afterward, Senator Tom Cotton of Arkansas
voiced a similar suspicion about the Wuhan lab on Fox News. “We
don’t have evidence that this disease originated there,” Cotton said,
“but because of China’s duplicity and dishonesty from the
beginning, we need to at least ask the question.” Soon enough,
Donald Trump’s mind began to change. The president spoke
supportively about China throughout the early weeks of the
pandemic and on Feb. 7 said of President Xi Jinping, “I think he’s
handled it really well.” Then the winds shifted, and four months
later Trump was inciting his rally crowds by calling Covid-19 “the
kung flu.”
The attractions of the lab-leak idea weren’t entirely partisan. Jamie
Metzl is an author and political commentator who worked in the
Clinton administration and, at one point, as a Senate committee
staff member working closely with Senator Joe Biden. Metzl has a
blindingly luminescent and liberal-tinged résumé that includes a
Ph.D. from Oxford, a J.D. from Harvard Law School, a senior
fellowship at the Atlantic Council and 13 ironman triathlons. A
former member of the W.H.O. expert advisory committee on
human genome editing, Metzl called early on for an investigation
into the origins of the pandemic, including, in his words, “the
distinct possibility this crisis may stem from a research-related
incident in Wuhan.”
Having spoken up about this in the early months of 2020, Metzl
encountered resistance that seems to have startled and aggrieved
him. “When I was seeing this different story,” he told me, “and I
started speaking publicly about it, friends of mine would say two
things.” The first was, “You’re a progressive, liberal Democrat” —
but — “you’re delivering a message that’s helpful to Trump.”
Implication: Metzl should get back on the right side of scrimmage.
The second sort of comment, he says, was: “Who the F are you?
You have all these senior scientists and Nobel laureates and others
who are saying it comes from nature? Who the F are you to say
that, based on your analysis and your deductive reasoning, you
have additional questions?”
The proselytizing by Metzl and others who saw a “different story”
from natural spillover — plus the swing of Trump’s message, plus
the prevailing cultural disposition to distrust experts, plus no doubt
other factors — had an effect on public opinion and media
attention, if not on scientific consensus. According to the Pew
Research Center, polling Americans in March 2020, 43 percent
believed that the virus emerged naturally, against less than 30
percent who thought it came from a lab, developed either by
accident or intentionally. By September 2020, another polling
organization found the natural versus lab options embraced almost
equally. By June 2021, a Politico-Harvard poll put the lab-origin
idea ahead by a two-to-one margin: 52 percent of Americans
versus 28 percent.
Metzl himself has maintained the somewhat agnostic position that
accidental release is a possibility but not the only possibility. In his
eventual March 2023 testimony to Congress, he urged “fully
examining all relevant origins hypotheses, obviously including a
lab origin, but also a market origin, which some experts I respect
believe to be more probable.” Among those experts, he cited
Michael Worobey, an evolutionary virologist at the University of
Arizona.
Worobey is a Canadian-born, Oxford-educated scientist who
speaks mildly and sometimes entertains provocative theories. One
such theory was O.P.V., the “oral polio vaccine” hypothesis for the
origin of the H.I.V./AIDS pandemic. I first interviewed Worobey a
dozen years ago to hear about that. The O.P.V. hypothesis asserted
that the virus (H.I.V.-1, Group M) was put into humans,
inadvertently, during reckless trials of an oral polio vaccine on
unsuspecting African “volunteers,” including hundreds of
thousands of children. The vaccine had been developed in
chimpanzee cell cultures — so the hypothesis claimed — and
contaminated with a chimpanzee virus that became H.I.V.-1-M. In
early 2000, Worobey left his doctoral studies in Oxford, flew to a
war zone Democratic Republic of the Congo and spent weeks
in the
collecting chimpanzee dung in the forest to test that hypothesis.
His senior partner on this wildcat expedition was William
Hamilton, a famous Oxford biologist who considered the O.P.V.
hypothesis plausible. Worobey and Hamilton collected their
chimpanzee samples, with help from local forest guides, and then
scrambled out of Kisangani, Worobey with his arm in a sling from a
badly infected forest wound, Hamilton desperately ill with malaria.
They reached England, and Hamilton died soon afterward from
complications. The samples got lost in baggage handling, then
found, then tested negative for the chimpanzee virus, except for
one sample that proved inconclusive.
Such are the labors and frustrations of science. Worobey, along
with other scientists, drawing on other evidence, eventually
showed that the oral-vaccine hypothesis was false. Open-
indedness toward a provocative hypothesis, and a commitment
to confirm it or refute it as the evidence may dictate, are among his
priors.
With SARS-CoV-2, 20 years later, Worobey likewise felt inclined to
give the provocative, heterodox hypothesis all due consideration.
Concerned by what he saw as premature dismissal of the lab-leak
possibility, he signed a public letter in spring 2021, with 17 other
scientists, arguing that “greater clarity about the origins of this
pandemic is necessary and feasible to achieve. We must take
hypotheses about both natural and laboratory spillovers seriously
until we have sufficient data.” One of the letter’s other co-signers, in
fact the first as listed, was Jesse Bloom. Worobey had helped
initiate the letter, with emails to Bloom on March 21 of that year,
including the suggestion, “I have been thinking about something
like a Perspective in Science or an Op-Ed in the NY Times.”

The letter was initially drafted by Bloom and two others: Alina
Chan, a molecular biologist who was an author of a preprint in 2020
arguing that SARS-CoV-2 was already well adapted to infecting
humans at the start, raising questions about its provenance; and
David Relman of Stanford, a distinguished microbiologist with a
long-term concern about biosecurity issues and some gain-of-
unction research. Others of the group contributed input, and the
letter ran in Science on May 14, 2021, under the imperative title
“Investigate the Origins of Covid-19.” But from that point, with
passing months and more research, Worobey would diverge from
the most vocal of his co-signers regarding what constitutes
“sufficient data.”
Strong tides of opinion were moving by spring 2021. An
international team of scientists, recruited by the World Health
Organization to its joint W.H.O.-China study of the origins of SARS-
oV-2, had returned from a month in Wuhan and issued its Phase 1
report, finding a laboratory leak “extremely unlikely.” That finding
took criticism from Worobey, Bloom and their co-authors of the
letter to Science, published weeks afterward. Even the director-
eneral of the W.H.O. himself, Dr. Tedros Adhanom Ghebreyesus,
hoped for further investigation. At a news conference marking the
report’s publication, Tedros said, “As far as W.H.O. is concerned, all
hypotheses remain on the table,” noting the need for continued
research. Notwithstanding Tedros’s hopes, and mainly because of
Chinese resistance, there has been no official Phase 2 follow-up
study per se. Instead, the W.H.O. created a Scientific Advisory
Group for the Origins of Novel Pathogens (SAGO), a body of
disease scientists who will continue to study the origin of SARS-CoV-2
as well as other dangerous new bugs.
Maria Van Kerkhove, the technical lead for Covid at the W.H.O., has
been vocal about the barriers to progress. “There’s very little
information that can be accessed with regard to lab leak, with
regard to breach of biosafety or biosecurity, and that’s the
problem,” she told me recently, saying that she had discussed the
issue directly with Chinese officials. “That’s what’s frustrating,” she
added. “With that lack of information, you’re left with these gaping
holes.”
Popular articles espousing the lab-leak idea also began to blossom
forth around this time, in magazines and newspapers and on web
platforms. In January 2021, New York magazine carried a Covid-
article by Nicholson Baker, who had lately published a book
on American bioweapons research in the early 1950s and his
frustrations with the Freedom of Information Act. Baker now
raised the “What if?” question about coronavirus research. In May
2021, Nicholas Wade (who once worked for The New York Times)
published a long article in The Bulletin of the Atomic Scientists
describing the collaborations between Zhengli Shi’s lab and
EcoHealth Alliance, for research on bat coronaviruses as potential
threats to human health — research that, Wade suggested, could
have led to the escape of a virus intentionally made more
dangerous to humans. Soon afterward, another science writer with
former connections to The Times, Donald G. McNeil Jr., found
himself moved by Wade’s article to do further probing and
questioning and posted a more judicious essay, concluding, “All we
have so far is speculation, and all the explanations are
unsatisfactory.” In early June, Vanity Fair followed with a feature
by the journalist Katherine Eban, suggesting that research at the
W.I.V. — or, alternatively, field collection of bat samples, and the
accidental infection of a fieldworker — might have put the virus,
engineered or not, into people.
Then came Jon Stewart. On June 14, 2021, the comedian appeared
on Stephen Colbert’s show and announced, with sublime
confidence and transcendent shallowness, his grounds for
certainty that the virus first detected in Wuhan had come from a
Wuhan lab. “If you look at the name!” he shouted. “Look at the
name!” Stewart got the name of the institution wrong, in fact — he
called W.I.V. the “Wuhan Novel Respiratory Coronavirus Lab” —
though he got the name of the city right. How much that mattered
to Colbert’s millions of viewers is unknown.

Throughout 2020 and 2021, scientists with deep expertise in

relevant fields, especially molecular evolutionary virology,
veterinary virology and molecular phylogenetics (the drawing of
family trees by comparison of genomes), were busy too. Their
efforts added data and analyses to the natural-origin side of the
balance.
One study, by two Chinese researchers and three Westerners,
showed that the wet markets in Wuhan — not just the notorious
Huanan but also three others — contained numerous shops selling
wild animals for food from May 2017 to November 2019. The
offerings included raccoon dogs, masked palm civets and Malayan
porcupines. Many of the animals showed what seemed to be
wounds from gunshots or traps, suggesting harvest from the wild
(as distinct from farm-raised wildlife), but lacked the requisite
documentation to make their sale legal under China’s Wildlife
Protection Law.
That’s important because it gave local authorities incentive, as the
pandemic spread, to close the market (as they did on Jan. 1, 2020)
and conceal whatever illegalities had been ignored by enforcement
officers there. For all the assumptions made about China’s
motivation to cover up a lab leak, it’s worth remembering that they
would have had similar motivations — including that $70 billion
national industry — to cover up a devastatingly consequential
market leak.
Another study, published by Science in July 2022, with Michael
Worobey as first author, joined by Eddie Holmes and Marion
Koopmans and many others, considered the spatial pattern of more
than 150 of the earliest Covid-19 cases from December 2019.
Worobey and colleagues found that not only were Huanan market
customers and workers (and people in contact with those
customers or workers) among those cases living close to the
market, but so were patients with no known epidemiological link to
the market. Therefore, that market was “the early epicenter” of the
pandemic, as the paper’s title declared.
A distinct but related study that appeared around the same time,
with Worobey and other co-authors but in this case with Jonathan
Pekar as first author, looked at the shape of the SARS-CoV-2 family
tree. It was unexpected. As drawn from comparison of genomes
sequenced from human samples, taken at the beginning of the
pandemic, it consisted of two thick limbs branching from a trunk,
then each limb exploding into many tiny stems, without
intermediate branches.
The two major limbs were lineages, labeled Lineage A and Lineage
B, from which all the virus’s later diversity arose. Lineage B was
the more prolific and successful, accounting for most of the world’s
Covid-19 cases, including all early cases directly linked to the
market. Lineage A had been found in the market, too, by the
Chinese team that swabbed after the place was summarily closed.
That smudge of A turned up on a pair of discarded gloves. Lineage
A was also detected in two Covid patients living near the market.
Pekar and his colleagues did a high-tech analysis of the tree
pattern — those two big limbs, then that explosion of twiggy stems
from each — and concluded that the virus probably entered
humans multiple times. The outbreak of human infections, they
judged, most likely had (at least) two separate beginnings.
Why matter? Two spillovers into people, from a
did this finding
market holding infected raccoon dogs, was more parsimonious
stall
than two separately infected laboratory workers, carrying their
infections independently to the same market. Partly that’s because
of geography: The Wuhan Institute of Virology, as Jon Stewart
tried to say, is indeed in the city of Wuhan, but it sits on the other
side of the Yangtze River, more than seven miles (as the crow flies)
from the Huanan market.
Beginning early this year, the popularity of the lab-accident idea,
which grew steadily from 2020 through 2022, received several
additional boosts. On Feb. 26, The Wall Street Journal reported that
the U.S. Department of Energy, one of the organizations assigned
earlier by President Biden to study the origin question, offered a
new judgment. Previously undecided, the D.O.E.’s intelligence
people now concluded, though with “low confidence,” that the
pandemic most likely began from a lab leak. The Journal’s
reporters had this from “a classified intelligence report,”
unavailable for scrutiny by the public but delivered to the White
House and “key members of Congress,” who were unidentified.
The next day, CNN’s website posted a follow-up story stating that
three sources, also unidentified, had told CNN that the D.O.E.
based its shift partly on information about research done at the
Wuhan Center for Disease Control and Prevention, another
disease-related facility in the city, more than seven miles from the
Wuhan Institute of Virology. This caught my attention, because I
knew that the Wuhan C.D.C., having recently relocated, was now
just a few hundred yards from the Huanan market. It occurred to
me, disquietingly, that a virus leak from the center might fit the
spatial clustering of early cases around the market, as analyzed by
Worobey and his colleagues, in a way that a putative leak from the
W.I.V. did not.
But nothing more on that provocative assertion has come from
CNN, or from any other news outlet, in the months since. I was
reminded that the Wuhan C.D.C. moved to its new location, near
the market, only on Dec. 2, 2019; that date, plus the time
presumably needed to bring laboratory work back online, might
not jibe with a viral outbreak that most likely began in late
November. In any case, two different sources with good access to
the Chinese research community told me that the Wuhan C.D.C. (as
distinct from the national C.D.C. in Beijing) had no coronavirus
research program before the pandemic. One of those sources, Jane
Qiu, a China-born independent journalist, added that the Wuhan
group’s mandate was mainly technical tasks such as disease
surveillance, rather than research. (Qiu couldn’t name her own
sources due to their potential jeopardy in China.)
Still recently, in mid-June, came the Substack article I alluded
more
to earlier,claiming that Ben Hu and two others from Zhengli Shi’s
lab were “the first people infected by the virus” and therefore the
starting point of the pandemic. Posted by Michael Shellenberger
and two co-authors, this article cited unidentified sources “within
the U.S. government.” Hu was a first author on a 2017 paper
describing the Shi group’s discovery of multiple coronaviruses
related to SARS-CoV-2, in bats from a cave (not the Mojiang mine)
in southern China, and experimental work on three of those viruses
that some critics considered risky. Hu and the other two scientists,
according to Shellenberger and his co-authors, had contracted
“Covid-19-like illnesses” in November 2019, suggesting that they
were the conduits of a lab leak. Hu himself promptly denied the
allegation in an email to Jon Cohen at Science: “I did not get sick in
autumn 2019, and did not have Covid-19-like symptoms at that
time.” Furthermore, Hu told Cohen, he and both colleagues had
tested negative for signs of recent Covid infection (antibodies) in
March 2020.
The surge of opinion toward the lab-leak idea was interrupted in
March, when Florence Débarre, a scientist working for France’s
National Center for Scientific Research, discovered another body of
interesting evidence, long missing but now found. This was
genomic data — from the swab sampling of door surfaces and
equipment and other items, including that pair of discarded gloves
— gathered at the Huanan market in early 2020 but withheld since
that time. The data were released, perhaps by mistake, and
Débarre was alert enough to spot them and recognize what they
were. A team of researchers, including Worobey, detected a pattern
in the data: strong proximity between samples containing raccoon
dog DNA and others containing SARS-CoV-2 fragments (and some
samples that contained both), from stalls in the southwest corner
of the market where wild animals had been sold as food. Malayan
porcupine DNA and Amur hedgehog DNA were also found near the
virus, but raccoon dogs were of special interest because of their
proven susceptibility to SARS-CoV-2.
These findings didn’t establish that raccoon dogs had carried the
virus into the market. But they added plausibility and detail to that
scenario.

Illustration by Jules Julien

Notwithstanding the Débarre group’s revelations, the lab-leak

idea has remained strongly preferred by public opinion, and not
just in the United States. According to one poll, as of April 2023, 62
percent of Italian respondents, 56 percent in France and 50 percent
in the United Kingdom found the lab-leak idea most compelling,
with sizable segments of undecided (and flummoxed) people,
leaving only modest minorities embracing natural spillover. Earlier
polling showed lab-related scenarios even more strongly favored in
other countries, ranging from 73 percent
still in Kenya and 64
percent in Hungary to 58 percent in Brazil.
Various factors may account for this public drift to the lab-leak
hypothesis. In my view, a preponderance of empirical evidence is
not one of them. I agree it’s important to remain open-minded
toward a lab-leak possibility, but most of the arguments made in
support of that possibility boil down to conjecture from
circumstance and unsupported accusations.
To speak of a “lab-leak hypothesis” in the singular is, of course,
misleading. There are multiple lab-leak hypotheses, just as there
are multiple ways a natural spillover could have occurred. A more
encompassing and emollient phrase is “research-related incident,”
preferred by Jamie Metzl and some other critics. That covers
several possibilities, including the chance that misbegotten gain-of-
unction research, at the W.I.V. or the Wuhan C.D.C. or who knows
where, yielded a dangerous new hybrid virus that escaped through
a malfunctioning autoclave or an infected technician or grad
student. (In support of this scenario, proponents point to a grant
proposal known as DEFUSE — made by EcoHealth Alliance to a
U.S. defense research agency in 2018, though never funded — for
experiments that some critics construe as potentially dangerous
gain-of-function research.) Another “research-related” possibility:
the nightmare that some Chinese biowarfare program created a
murderous virus intentionally but let it escape to the world by
some catastrophic goof. Still another: the notion that a scientific
fieldworker became infected while taking samples from bats in,
say, the Mojiang mine, where Zhengli Shi’s team found RaTG13.

They’re all vivid but not all logical, and it seems to me they don’t
reinforce one another. If a wild coronavirus from the Mojiang mine
was capable of infecting and transmitting among humans, for
instance, then it didn’t need a furin cleavage site to be inserted
during reckless or malevolent lab work. And if it infected a
scientific fieldworker in 2013, and that fieldworker returned to
Wuhan, where did the virus linger for six years before exploding
through the city’s population in 2019? And if the virus was
engineered in Shi’s lab, using sophisticated gene-editing methods,
or was transformed into this dangerous pathogen by passaging a
less dangerous virus through cell cultures or living mice (which
seems far-fetched), and then subsequently escaped, then the
Mojiang mine, with all its sinister narrative appeal, is irrelevant. In
other words, the various research-related-incident hypotheses may
each be plausible (some more than others), but they compete
against one another. You can’t pile them all on the scale and judge
the likelihood of an unnatural origin by their combined weight.
Lab-leak partisans have focused intently on Shi and her lab, but it’s
important to bear in mind that Shi has made her career by
publishing research and issuing warnings about potentially
dangerous coronaviruses found in the wild, not by keeping them
secret. If she had such a formidably dangerous virus in her lab in
2018 or 2019 — a virus similar to the original SARS virus but with a
receptor-binding domain and a furin cleavage site well shaped for
human infection, features that could make it even more dangerous
— she presumably would have announced that important
discovery from the pages of a leading journal, to her professional
gain as well as the benefit of the world. She didn’t.
And there’s a small body of lost evidence, recently recovered, that
seems to support this logic. In 2018, a scientist named Jie Cui led a
study of SARS-related coronaviruses in bats. His purpose was to
illuminate the evolution of the original SARS virus by placing it on
a family tree of its relatives. Cui had been a postdoctoral fellow in
Eddie Holmes’s lab, going from there to the Wuhan Institute of
Virology for a couple of years, then to a position in Shanghai. Cui
and a group of colleagues, including both Holmes and Zhengli Shi,
analyzed partial genome sequences of 60 coronaviruses detected in
bat samples collected from 2011 to 2016. They wrote a paper and
submitted it to a leading virology journal. It was rejected. They
tried another. Rejected. The journals’ reviewers wanted complete
genome sequences, but the team had only partials. So in October
2018, they gave up on that paper. They pulled it from the
submission process. They forgot about it. In the meantime, they
had submitted their partial but telling genome data to an
international database, GenBank, with a routine stipulation that it
would be embargoed, in this case for four years. The embargo
allowed them to retain exclusive access to the data for that period,
in the event they wanted to revive the project.

Four years passed, and then, in October 2022, the embargo

expired. The data, mothballed since just before the pandemic and
now publicly available, were revealing for what they did not
include: a progenitor of the pandemic virus. Here were 60
coronaviruses that Zhengli Shi and others had considered
intriguing in 2018. But nothing that matched SARS-CoV-2.
“Where’s the virus?” said Eddie Holmes, recounting this to me
recently. “The virus is absolutely not there.”
Two other arguments on the lab-leak side deserve attention. Each
can be phrased as a question. Why did SARS-CoV-2, from the start,
seem to be very well adapted to humans? And why, if its natural
host was some kind of bat, has that host not yet been found, after
three and a half years?
The those questions ignores the fact that SARS-CoV-2 has
first of
shown from the beginning, to be quite capable of infecting
itself,
other mammals (cats and dogs), and eventually a wide range of
them (tigers, gorillas, mink, white-tailed deer and others), not just
humans. The second question betrays a lack of familiarity with the
history of emerging viruses. When a novel virus appears suddenly
in humans, causing disease and alarm, the search for its natural
host is always an urgent task. But such ecological work is difficult
to do amid the public-health emergency of an outbreak, and once
the outbreak (or epidemic, or pandemic) is controlled, the sense of
urgency and the available research money tend to disappear.
Finding the host animal is sometimes easy, by luck, and sometimes
hard. Identifying horseshoe bats, with high confidence, as the likely
hosts of the original SARS virus took 15 years. Tracing the Marburg
virus to its reservoir host in Egyptian fruit bats took 41 years (or
42, if you count the time to publication). And the natural host of
Ebola virus, despite what you may think you’ve heard, is still
unidentified, 47 years after its emergence at a remote mission
hospital in what was then Zaire. The suggested linkage between
Ebola virus and some form of bat is still suppositional, not settled
scientific fact — and we have enough suppositions entangled with
this subject already.

So, what’s tilting the scales of popular opinion toward lab leak?
The answer to that is not embedded deeply in the arcane data I’ve
been skimming through here. What’s tilting the scales, it seems to
me, is cynicism and narrative appeal.
I asked about this in conversation with David Relman, the
biosecurity expert who was also an author of the “Investigate”
letter with Jesse Bloom. To some extent, Relman agreed. “When
you sow the seeds of distrust, or suggest that you haven’t been
transparent with what you knew,” he told me, “you’re setting
yourself up for a persistent, insidious, continuing distrust.” That
inclines people to assume that “there was something deliberate, or
deliberately concealed.”
The seeds of distrust have been growing in America’s civic garden,
and the world’s, for a long time. More than 60 percent of
Americans, according to polling within the past several years, still
decline to believe that Lee Harvey Oswald, acting alone, killed
John F. Kennedy. Is that because people have read the Warren
Commission report, found it unpersuasive and minutely
scrutinized the “magic bullet” theory? No, it’s because they have
learned to be distrustful, and because a conspiracy theory of any
big event is more dramatic and satisfying than a small, stupid
explanation, like the notion that a feckless loser could kill a
president by hitting two out of three shots with a $13 rifle.
Most of us don’t reach our opinions by fastidious calibration of
empirical evidence. We default to our priors, as Jesse Bloom noted,
or we embrace stories that have simple plots, good and bad
characters and melodramatic trajectories, and that seem
commensurate in scope to the event in question. The process of
scientific discovery is a complicated story involving data collection,
hypothesis testing, hypothesis falsification, hypothesis revision,
further testing and brilliant but fallible humans doing all that work.
Scientific malfeasance driven by hubris and leading to runaway
trouble, on the other hand, is a much simpler story that goes back
at least to Mary Shelley’s 1818 novel, “Frankenstein.”

Carl Bergstrom is an evolutionary biologist and an author of

commentaries on scientific misinformation. He ponders, among
other things, how students of science are taught — or at least
should be taught — about not just what science says but what
science is. I asked Bergstrom about the human affinity for dark
theories of big events.
There was something about that in Thomas Hardy, he told me. “It’s
in ‘Tess of the d’Urbervilles,’ where Tess is doomed by hapless
chance. It really sucks! To live in a world where we are at the
mercy of hapless chance.”
I had never read “Tess of the d’Urbervilles,” to my embarrassment,
so I stuck with SARS-CoV-2. “This is not a contest now, in the

public domain, between bodies of evidence,” I proposed. “This is a

contest between stories.”
“Yeah!” Bergstrom said. “That’s right.”

David Quammen is an author and a journalist based in Montana. His 18 books

include “Spillover” (2012) and “Breathless” (2022): the first, predicting a pandemic
that would be caused by a newly emerged virus; the second, tracing the scientific
effort to discover the origin and track the evolution of Covid.

A version of this article appears in print on July 30, 2023 Page 20

, of the Sunday Magazine with the headline: Points of
Origin . Order Reprints | Today’s Paper | Subscribe

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