Science - USA (2022-03-04)

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PHOTO: AP PHOTO/DAKE KANG


SCIENCE science.org 4 MARCH 2022 • VOL 375 ISSUE 6584 947

In the new preprint, Gao and colleagues
analyzed 1380 samples from 188 animals in
the market and the environment, including
sewer wells, the ground, feather removing
machines, and “containers.” They found
SARS-CoV-2 in 73 samples. But because all
were from the environment, not the ani-
mals themselves, they assert that humans
introduced the virus to the market. The au-
thors call the market an “amplifier,” not the
source, of SARS-CoV-2.
Hewing closely to government assertions
on COVID-19’s origin, the preprint by Gao
and colleagues notes studies that have re-
ported evidence of SARS-CoV-2 in other
countries before it surfaced in Wuhan,
making no mention of critiques that attri-
bute that evidence to contamination. It also
floats a widely disputed theory that frozen
food imported to China might have been
the original source. (Authors of the paper,
including Gao, did not respond to requests
to discuss the work.)
The coronavirus lineage analysis from
Worobey and colleagues refines an ar-
gument posited by Tulane University
virologist Robert Garr y last year. In data on
the early human cases, Garry had identified
two forms of SARS-CoV-2, differing by just
two mutations, which he argued surfaced
at different Wuhan markets in December


  1. The new work, which includes Garry
    as a co-author and cites evidence from
    the Gao study, reshapes that scenario sig-
    nificantly. It concludes that both lineages,
    dubbed A and B, originated at the Huanan
    Seafood Market and soon spread in nearby
    neighborhoods. B likely jumped from ani-
    mals to humans in late November 2019,
    leading to the first detected case on 10 De-
    cember, and lineage A a few weeks later,
    the group concludes. Either way, the team
    argues the almost simultaneous emergence
    of two lineages challenges the lab-origin
    thesis, as it would require two different
    viruses leaking at roughly the same time.
    (Gao and colleagues also found both SARS-
    CoV-2 lineages in environmental samples.)
    The second preprint from the interna-
    tional team builds on a June 2021 Chinese-
    led study that spent 2 years documenting
    a tick fever disease in mammals for sale at
    specific stalls in the market. The new study
    pinpoints for the first time where species
    susceptible to SARS-CoV-2—including rac-
    coon dogs, hedgehogs, badgers, red foxes,
    and bamboo rats—were sold and maps
    those sites to the positive environmental
    samples, including one from a “container”
    the authors believe was a cage. “To anyone
    who really grasps what is in all of those
    three papers, I think it’s very hard to dis-


miss that this is a very, very, very strong
case that this pandemic started at that mar-
ket,” Worobey says.
Others say the evidence is not definitive.
“They are interesting studies, but I don’t
think they close the case on what happened
with the origins of the virus,” says Jesse
Bloom, an evolutionary biologist at the Fred
Hutchinson Cancer Research Center who
has criticized colleagues for too blithely
dismissing the lab-origin hypothesis. “I’m
especially skeptical of the conclusion that
there must have been two zoonotic jumps.”
He notes that in about 10% of human
transmissions of SARS-CoV-2, the virus ac-
quires two mutations, which means a sec-
ond lineage could have emerged after the
infection of the first human rather than
after a second zoonotic jump. Worobey,
Garry, and colleagues did a computer
simulation that challenges Bloom’s asser-
tion. They modeled many SARS-CoV-2 out-
breaks, accounting for how the virus has
been shown to mutate, and assessed each
simulation’s results against the actual vi-
ruses sequenced from Wuhan COVID-
cases through 23 January 2020. They found
there was only a 3.6% chance that a single
lineage of SARS-CoV-2 starting in one per-
son could have produced the second lin-
eage and the later known sequences.
The environmental samples from the
Wuhan market that tested positive for
SARS-CoV-2 might resolve the stalemate
over the virus’ origin if they can reveal
a specific animal source of the virus. “If
you find a positive sample with, say, lots
of raccoon dog DNA, you’ve got a hit” on
the likely source of SARS-CoV-2, says evo-
lutionary biologist David Robertson of the
University of Glasgow, who co-authored
the epicenter paper.
But the preprint by Gao and colleagues
only notes that those samples contain DNA
from many species without specifying
which ones—other than humans. “The au-
thors have already done the analysis, they
have just not put all the results needed to
interpret them in their paper,” says evolu-
tionary biologist Andrew Rambaut of the
University of Edinburgh, a co-author of
both studies. “This will undoubtedly be
fixed if the paper gets through peer review.”
Still, Worobey and his co-authors con-
cede, even that evidence might not be
enough to end this polarizing debate.
“With the way that people have been able
to just push aside any and all evidence that
points away from a lab leak, I do fear that
even if there were evidence from one of
these samples that was full of red fox DNA
and SARS-CoV-2 that people might say, ‘We
still think it actually came from the han-
dler of that red fox,’” Worobey says. j

New analyses build the case that COVID-19 originated at the Huanan Seafood Market in Wuhan, China.
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