74 Scientific American, March 2022Mark Peterson/Redux PicturesFEAR AND
BLAME:
A table of
T-shirts with
antimask slo-
gans accompa-
nied a protest
outside the Jet
Blue headquar-
ters in Queens,
N.Y., on October
27, 2021. Pro-
testers were
pushing back
against the air-
line’s COVID
vaccine man-
date and mask
policies. The
instability cre-
ated by the pan-
demic is fertile
ground for con-
spiracy theories.
pathways and is therefore difficult
to rule out or confirm. At the other
extreme are the assertions that
SARS-CoV-2 was designed and en-
gineered by the WIV, perhaps as a
bioweapon, and was released either
accidentally or as a biological at-
tack. This possibility necessarily en-
tails a conspiracy among WIV sci-
entists—and potentially many oth-
ers—to first engineer a virus and
then cover up its release. Scientific
investigation of the genomic and
phylogenetic evidence can help us
determine whether SARS-CoV-2
was genetically engineered.
SARS-CoV-2 is a member of a
subgenus of the betacoronaviruses
called the sarbecoviruses, named
after their prototype member,
SARS-CoV-1, which caused the
SARS epidemic in 2002 and 2003.
The zoonotic origin of SARS-CoV-1
has been firmly established by re-
search that also showed that the
bat sarbecoviruses pose a clear and
present danger of pandemic over-
spill from bats to humans.
One key feature of sarbecovirus-
es is that they undergo extensive
amounts of recombination. Parts
of their genomes are being regular-ly swapped at a rate that implies
a vast ecosystem of these viruses is
circulating, most of which have not
been discovered. The area of the ge-
nome that is most likely to recom-
bine is also the area that encodes
the “spike” proteins—the very pro-
teins that play a crucial role in initi-
ating an infection. Many sarbecovi-
ruses encode spike proteins that
can bind to a wide range of mam-
malian cells, suggesting that these
viruses can easily move back and
forth between different species
of mammals, including humans.
SARS-CoV-2 is not as virulent
as SARS-CoV-1, but it is transmitted
far more easily between people.
Two of the most prominent features
of the SARS-CoV-2 spike are its
receptor-binding domain (RBD),
which binds very tightly to human
ACE2, the protein that allows it to
enter lung cells, and the so-called
furin cleavage site (FCS). This site
divides the spike protein into sub-
units. The FCS is present in many
other corona viruses, but so far
SARS-CoV-2 is the only sarbecovi-
rus known to include it. It allows
the viral spike protein to be cut in
half during its release from an in-fected cell, priming the virus to
spread to new cells more efficiently.
The RBD and FCS are central to
initial virological arguments by ex-
pert proponents of the lab-leak hy-
pothesis. Such arguments are based
on the supposition that neither the
RBD nor the FCS “appears natural”
and therefore that they can only
be the product of lab-based engi-
neering or selection. Nobel laureate
David Baltimore, an early propo-
nent of the lab-leak hypothesis,
referred to the FCS as a “smoking
gun” that points to a lab origin.
Although an unusual feature
of a virus can legitimately stimu-
late further inquiry, this argument
is reminiscent of the creationist
claim that humans must have been
“intelligently designed” because we
are seemingly too complex to have
evolved by natural selection alone.
This logic is fundamentally flawed
because complexity does not li-
cense dismissal of the overwhelm-
ing evidence for natural selection
and, by itself, does not mandate
any design, intelligent or otherwise.
Likewise, labeling the RBD or the
FCS “unnatural” does not mandate
lab-based engineering, and, critical-