Jeffrey Sachs Presents Evidence of Possible Lab Origin of Covid-19
An
article in the Proceedings of the National Academy of Sciences calls
for an independent investigation of information held by U.S.-based
institutions that could shed light on the origins of Covid.
In an article
published Thursday, economist Jeffrey Sachs called for an independent
investigation of information held by U.S.-based institutions that could
shed light on the origins of the Covid-19 pandemic. Writing in the Proceedings of the National Academy of Sciences,
Sachs and his co-author, Neil Harrison, a Columbia University professor
of molecular pharmacology and therapeutics, said that federal agencies
and universities possess evidence that has not been adequately reviewed,
including virus databases, biological samples, viral sequences, email
communications, and laboratory notebooks. Sachs and Harrison also
highlighted a tantalizing scientific detail that may be an indication
that SARS-CoV-2, the coronavirus that causes Covid-19, originated in a
laboratory: a sequence of eight amino acids on a critical part of the
virus’s spike protein that is identical to an amino acid sequence found
in cells that line human airways.
Sachs and Harrison are hardly the first to suggest that SARS-CoV-2
might have been created in a lab. Since its genetic sequence was first published
in February 2020, scientists have puzzled over the furin cleavage site,
an area on the virus’s spike that allows it to be cleaved by a protein
on the membrane of human cells and makes the coronavirus particularly
dangerous to people. Once split, the virus releases its genetic material
into the cell and reproduces. While attaching to cells and spike
cleavage is part of how all coronaviruses work, SARS-CoV-2 is the only
one of its class, sarbecoviruses, that can use furin for the cleavage.
As with past discussion of a possible lab origin of SARS-CoV-2, this
latest theory has already been met with considerable pushback. Even some
scientists who are open to the idea that a lab accident could have
sparked the pandemic remain unconvinced by the particular trail of
evidence laid out by Sachs and Harrison.
The
journal article offers a scientific road map for how this unusual
sequence of amino acids could have made its way into the furin cleavage
site, or FCS, of the virus. Sachs and Harrison acknowledge that the
sequence could have arisen naturally. But they also lay out another
possibility: that scientists might have purposefully inserted this
particular string of amino acids into a bat coronavirus in the course of
their work. They focus particularly on scientists who submitted an unfunded grant proposal
to a division of the Defense Department called the Defense Advanced
Research Projects Agency, or DARPA, laying out plans to insert a furin
cleavage site into a bat coronavirus.
“We do not know whether the insertion of the FCS was the result of
natural evolution — perhaps via a recombination event in an intermediate
mammal or a human — or was the result of a deliberate introduction of
the FCS into a SARS-like virus as part of a laboratory experiment,”
Sachs and Harrison write. “We do know that the insertion of such FCS
sequences into SARS-like viruses was a specific goal of work proposed by
the EHA-WIV-UNC partnership within a 2018 grant proposal (“DEFUSE”)
that was submitted to the US Defense Advanced Research Projects
(DARPA).”
EHA
is a reference to EcoHealth Alliance, a nonprofit research group based
in New York City that has received more than $118 million in grants and
contracts from federal agencies. WIV, or the Wuhan Institute of
Virology, is a Chinese research organization that collaborated with
EcoHealth Alliance in the past and was listed as a subcontractor on the
DARPA grant. UNC is mentioned because Ralph Baric, a molecular biologist
at the University of North Carolina, Chapel Hill, was to have conducted
part of the work pitched to DARPA. The grant proposal touted Baric’s
“two-decade track record of reverse engineering [coronavirus] and other
virus spike proteins.”
The intent of the DARPA proposal was to prevent emerging pathogenic
threats, but the work, if conducted, could have created a novel virus
capable of infecting humans. “We will introduce appropriate
human-specific cleavage sites and evaluate growth potential in [a type
of mammalian cell commonly used in microbiology] and [human airway
epithelial cell] cultures,” the proposal stated.
Several scientists interviewed about the DARPA proposal in September
told The Intercept that scientists often begin research before seeking
funding and thus that some of the experiments described in the proposal
could have already been completed. But when asked about that possibility
in an interview,
Peter Daszak, the president of EcoHealth Alliance, rejected it: “The
DARPA proposal was not funded. Therefore, the work was not done.
Simple.”
A Rational Choice
As Sachs and Harrison note, the part of a protein on the cell
membrane that shares its amino acid sequence with the bat coronavirus is
critical for lung function. Known as an epithelial sodium
channel-alpha, or ENaC-alpha, it is found in human airway cells, as well
as in human kidneys and colons. Intriguingly, like SARS-CoV-2,
ENaC-alpha, which facilitates the absorption of fluid in cells, is also
activated by the unusual furin cleavage site. Harrison, a physiologist
affiliated with Columbia’s Department of Molecular Pharmacology and
Therapeutics, studies ion channels, the larger category to which
ENaC-alpha belongs.
Other scientists have already pointed out the match between the amino
acid series in the furin cleavage site of SARS-CoV-2 and the ENaC-alpha
found in human airways. In 2020, a team from the biomedical company Nference suggested
that the overlap between the virus and the sequence found in human
lungs is part of the reason that Covid-19 is so damaging to the
respiratory system. Those scientists described the sequence as having
evolved naturally.
Sachs
and Harrison, in contrast, suggest that researchers may have inserted
the string of amino acids into a bat coronavirus precisely because of
its known importance to lung function. “For a research team assessing
the pandemic potential of SARS-related coronaviruses, the FCS of human
ENaC — an FCS known to be efficiently cleaved by host furin present in
the target location (epithelial cells) of an important target organ
(lung), of the target organism (human) — might be a rational, if not
obvious, choice of FCS to introduce into a virus in order to alter its
infectivity, in line with other work performed previously,” they write.
Such a choice, they point out, would have been in keeping with
another viral research project on which EcoHealth Alliance, the Wuhan
Institute of Virology, and UNC’s Baric collaborated: a 2014 grant from the National Institute of Allergy and Infectious Diseases that involved increasing the transmissibility and pathogenicity of bat coronaviruses.
Growing List of Coincidences
The intriguing theory of viral engineering hinges on two
observations: that the amino acid sequences match and that experts in
both the ENaC-alpha furin cleavage site
and the insertion of genetic sequences into bat coronaviruses happen to
work at the same academic institution: the University of North
Carolina, Chapel Hill.
Baric, whose work aims to prevent and create treatments for viral outbreaks, has previously inserted segments of DNA and RNA into viruses and created an infectious clone of SARS using his own patented “No See’m” method of inserting genetic materials without a trace. He has also collaborated
on coronavirus research with scientists from a center for lung studies
at UNC-Chapel Hill who are knowledgeable about ENaC-alpha. In one 2016 study, the scientists created a new virus using the spike of a bat coronavirus that had been isolated and characterized
by the Wuhan Institute of Virology. The experiment found that the new
virus “replicated efficiently” in human airway cells that were cultured
in a lab.
In another
paper, published a year earlier, Baric, along with the Wuhan Institute
of Virology’s Shi Zhengli and a lung expert UNC-Chapel Hill’s lung
institute, described creating a hybrid virus using a SARS-like virus
from a bat and a “mouse-adapted” coronavirus. The new virus caused mice
to get sicker than those exposed to the original virus. The goal of
these experiments was to prepare for the possibility that a virus might
jump naturally from animals to humans, as SARS had in 2003. But even
before the pandemic, the experiment drew criticism from other scientists, who were concerned because the researchers had created a virus that was able to spread in humans.
Sachs and Harrison note that the scientists who co-authored the DARPA
grant proposal would have been aware of research on coronavirus furin
cleavage sites, including one 2006 experiment
in which a furin cleavage site was inserted into a coronavirus. “The
research team would also have some familiarity with the FCS sequence and
the FCS-dependent activation mechanism of human ENaC, which was
extensively characterized at UNC,” they write.
“The list of coincidences is getting verrrrrrrrrrry long.”
Still,
both the overlap in the amino acid sequence and the fact that experts
in the furin cleavage site of the ENaC-alpha and insertion of genetic
material into bat coronaviruses work at the same university could be
coincidental, as Harrison and Sachs acknowledge. Some virologists,
though, say that the coincidence strains credulity.
“Could be,” Richard Ebright, a molecular biologist at Rutgers
University, wrote in an email to The Intercept when asked about the
possibility that these things are both chance occurrences. “But the list
of coincidences is getting verrrrrrrrrrry long.”
Ebright, a proponent of investigating the origin of SARS-CoV-2 and of
investigating both natural-spillover and research-related-spillover,
whom Harrison and Sachs thank “for helpful commentary on the
manuscript,” spelled out some of the other Covid coincidences that he
considers questionable, including its initial outbreak in a city that, well before 2019,
had already been pegged as a biosafety risk. Ebright also noted Wuhan’s
1,000-mile distance from the nearest wild bats that carry the type of
SARS-related coronaviruses that caused the pandemic. And he pointed to
the particular coding of the amino acids in the furin cleavage site of
SARS-CoV2.
“The
sequence encoding the FCS of the pandemic virus contained two
consecutive CGG arginine codons,” Ebright explained in his email. (A
codon, or a combination of three nucleotides, supplies the genetic code
for a single amino acid, though most amino acids can be represented by
multiple different codons. Each nucleotide is represented by a letter —
for RNA, either A, C, U, or G.) “This codon usage is unusual for a
natural bat SARS-related coronaviruses (for which fewer than 1 in 30
arginine codons are CGG) but is optimal for humans (for which most
arginine codons are CGG codons).”
Still, Ebright said that at first he didn’t see the identical amino
acid sequences as particularly suspicious. “I had known for more than a
year that there was a perfect match to an eight-amino acid sequence
present in human ENaC. What I had not known was that the sequence was
known to be a functional furin cleavage site and that it was a sequence
extensively studied at UNC,” he said. “The crucial point that the ENaC
sequence was a known functional site, not just that there happens to be a
match to a protein that happens to be in humans. … That suddenly turned
it from what I thought to be largely irrelevant to being a logical and
obvious choice to proceed.”
Ralph Baric and the University of North Carolina did not immediately respond to requests for comment.
Name Calling
Other scientists dismiss the idea that the ENaC sequence might have
been purposefully inserted into a coronavirus. Scientists who are
already convinced that the new coronavirus emerged naturally are
unlikely to be persuaded by Sachs and Harrison’s article, which appears
in the opinion section of the esteemed journal. Over the past year, many
scientists involved in the debate over the origins of the pandemic have
settled into an increasingly acrimonious, coarse, and unyielding
opposition.
Some proponents of the natural origin theory became particularly
dismissive of those open to the possibility of a lab leak after the
February release of two pre-print studies
mapping the early spread of the virus at the Huanan market in Wuhan.
Angela Rasmussen, one of a team of virologists who worked on the
project, described
it on Twitter as “dispositive evidence of a zoonotic origin” that will
“drive those with personal interest in the lab leak hypothesis out of
their goddam minds.” In another tweet, Rasmussen referred
to proponents of the lab-leak theory as a “pack of ghouls, who through
gullibility, stupidity, & conspiracist thinking have decided this is
their thing despite zero expertise.”
Although the pre-prints had not been peer-reviewed and may have
simply illustrated the spread of the virus rather than its original
outbreak, the New York Times ran a front-page story
about them that quoted an epidemiologist as saying that the origins
debate “has been settled with a very high degree of evidence.” The
story, which was announced by a push notification from the paper, also
noted a lack of direct evidence for a lab leak.
Meanwhile, Kristian Andersen, another co-author of the pre-prints and
a virologist at the well-regarded Scripps Research Institute, used the “poop” emoji to criticize a deeply researched article
by Katherine Eban about EcoHealth Alliance. On Twitter, Andersen tarred
Eban, New York Times columnist Zeynep Tufekci, and others reporting on
biosafety issues that could have led to the release of SARS-CoV-2 as
“deep in conspiracy theories” and on the other side of “a clear split”
from journalists who dismiss the possibility of a lab origin, whom
Andersen referred to as “science-based.”
Even some scientists who have been vocal about the possibility that
the pandemic may have been sparked by research have expressed skepticism
about the theory suggested by Harrison and Sachs. “The pandemic virus
might have been genetically engineered. However, this could have been
done in various ways not limited to the specific theory by Harrison and
Sachs. I’m not convinced that their hypothesis is the most plausible
one,” said Alina Chan, a scientist who laid out a number of possible
routes for how the coronavirus might have emerged through
research-related incidents in her recent book “Viral: The Search for the Origin of Covid-19.”
“There’s no need for them to go hunting inside the human protein catalogue to look for cleavage sites to put into viruses.”
While
she is open to the possibility that the furin cleavage site might have
been purposefully inserted into the coronavirus, Chan said there was no
reason to think that researchers would mine humans for such material.
“These scientists literally had access to hundreds of SARS-like viruses
and sequences,” said Chan, referring to the vast collection of
coronaviruses from bats and other animals that researchers amassed at
the Wuhan Institute of Virology. “There’s no need for them to go hunting
inside the human protein catalogue to look for cleavage sites to put
into viruses.”
Jack Nunberg, a virologist at the University of Montana, was also not
immediately persuaded by the theory of engineering suggested by Sachs
and Harrison. “It’s possible,” Nunberg said of the idea that the ENaC
segment was inserted into a bat coronavirus as part of research designed
to gauge the pandemic potential of a virus. “But I don’t find their
evidence on ENaC compelling because furin cleavage sites have a lot of
common amino acids, and therefore it may just have happened by chance.”
Others say that the article adds noteworthy information to the public
conversation about the origins of the pandemic. “The defenders of the
natural origin indicate that the virus on which this type of experiment
could have been done — the backbone — has never been published and that
specialists in the furin cleavage sites would have chosen a more
commonly used furin cleavage site like RARR rather than PRRAR. The
Proceedings of the National Academy of Sciences article contradicts this
argument and indicates that specialists knew that the RRAR’SVAS site
was efficiently cleaved by furin,” Etienne Decroly, director of virology
research at the Aix-Marseille Université in France, wrote in an email to The Intercept.
Decroly added, “It is impossible to decide on the basis of the
information currently available and it is urgent that the WHO Special
Advisory Group for the Origins of Novel Pathogens investigate this
question.”
On the suggestion of an investigation, Nunberg is in agreement. “You
can’t argue with that,” he told The Intercept. “Who’s going to argue for
burying one’s head in the sand?”
For their part, Sachs and Harrison emphasize that they’re not saying
laboratory manipulation was involved in the emergence of the pandemic
virus, only “that it could have been.” They also give a nod to other
possibilities, including that an airborne virus might have infected a
laboratory worker. Rather than argue that any of these conceivable
scenarios happened, they present the clues of the matching amino acid
sequences to argue for an independent and transparent scientific
investigation of the U.S.-based evidence related to the origins of the
virus.
Among the institutions that Sachs and Harrison list as possibly
having “knowledge of the detailed activities that were underway in Wuhan
and in the United States” are the National Institutes of Health; the
Defense Threat Reduction Agency, which has provided grant funding to
EcoHealth Alliance; the Department of Homeland Security; DARPA; the U.S.
Agency for International Development, which funded the $200 million PREDICT program that catalogued potential pandemic viruses; and the University of California, Davis, which participated in that program.
The authors suggest that EcoHealth Alliance and UNC may have
particularly important untapped resources. “The exact details of the
fieldwork and laboratory work of the EHA-WIV-UNC partnership, and the
engagement of other institutions in the US and China, has not been
disclosed for independent analysis,” they write. “The precise nature of
the experiments that were conducted, including the full array of viruses
collected from the field and the subsequent sequencing and manipulation
of those viruses, remains unknown.”
A Reversal
The publication in the prestigious Proceedings of the National
Academy of Sciences marks a reversal of sorts for Sachs, the chair of
the Lancet Covid-19 Commission who, in November 2020, appointed Daszak,
the EcoHealth Alliance president, to lead a task force to investigate
the origins of the pandemic. Earlier that year, Daszak had signed on to a
public statement
published in The Lancet on behalf of scientists who said they “condemn
conspiracy theories suggesting that COVID-19 does not have a natural
origin.”
Yet
that early certainty about the pandemic’s origins — and the sense of
shared civic responsibility among members of the Lancet task force —
soon disintegrated. In February 2021, emails revealed that Daszak coordinated the public statement in The Lancet tamping down suspicions of a lab leak. And by June 2021, Sachs was expressing his openness to the possibility of a lab origin, writing
that NIH-funded research at the Wuhan Institute of Virology “deserves
scrutiny under the hypothesis of a laboratory-related release of the
virus.” Three months later, he disbanded
the task force that had been organized to “carefully scrutinize the
origin of the SARS-CoV-2 virus” in the hopes of preventing future
disease outbreaks, explaining that he had concerns that several members
of the commission had conflicts of interest because of their ties to
EcoHealth Alliance.
After leading the mainstream scientific inquiry into the origins of
the pandemic, Sachs is now skewering it. “A steady trickle of
disquieting information has cast a darkening cloud over the agency,” he
and Harrison write of the NIH, going on to accuse the entire federal
government of not doing enough to explore the possible role of its
grantees in the emergence of SARS-CoV-2 and investigate “overlooked
details” such as the matching amino acid sequences.
Noting that the NIH has insisted that “the pandemic virus could not
have resulted from the work sponsored by” the agency, Sachs and Harrison
write that “blanket denials from the NIH are no longer good enough.”
https://theintercept.com/2022/05/19/covid-lab-leak-evidence-jeffrey-sachs/?utm_medium=email&utm_source=The%20Intercept%20Newsletter
https://en.wikipedia.org/wiki/Jeffrey_Sachs
