The Chairman of The Lancet’s COVID-19 Commission has called for an independent inquiry into the origins of the SARS-CoV-2 virus. Jeffrey Sachs, a world-renowned economics professor, stated on May 19 that U.S. laboratory experiments may have contributed to the emergence of COVID-19. In an argument published in PNAS, a peer-reviewed journal of the National Academy of Sciences (NAS), Sachs has called on universities to open up their databases for close examination amid fears that laboratories were genetically modifying viruses.

Sachs maintains that “there is much important information that can be gleaned from U.S.-based research institutions, information not yet made available for independent, transparent, and scientific scrutiny.” He insists that critical data available in the U.S. from these institutions “would explicitly include, but are not limited to, viral sequences gathered as part of the PREDICT project and other funded programs, as well as sequencing data and laboratory notebooks from U.S. laboratories.” He wrote:

“We call on U.S. government scientific agencies, most notably the NIH, to support a full, independent, and transparent investigation of the origins of SARS-CoV-2. This should take place, for example, within a tightly focused science-based bipartisan Congressional inquiry with full investigative powers, which would be able to ask important questions—but avoid misguided witch-hunts governed more by politics than by science.”

Sachs, who wrote the article with Neil L. Harrison, said it was apparent scientists from the University of North Carolina (UNC) and New York-based EcoHealth Alliance (EHA) had been working with the Wuhan Institute of Virology (WIV) to manipulate viruses. The authors note that the bulk of the work done at WIV “was part of an active and highly collaborative U.S.-China scientific research program funded by the U.S. Government (NIH, Defense Threat Reduction Agency [DTRA], and U.S. Agency for International Development [USAID]).”

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Furthermore, they point out that although the work was coordinated by researchers at EcoHealth Alliance (EHA), it also involved researchers at several other U.S. institutions. The article states, “For this reason, it is important that U.S. institutions be transparent about any knowledge of the detailed activities that were underway in Wuhan and the United States,” adding, “The evidence may also suggest that research institutions in other countries were involved, and those too should be asked to submit relevant information (e.g., with respect to unpublished sequences).”

Indeed, in addition to EHA, participating U.S. institutions include the University of North Carolina (UNC), the University of California at Davis (UCD), the NIH, and the USAID. Under a series of NIH grants and USAID contracts, the authors note that EHA coordinated the collection of SARS-like bat CoVs from the field in Southwest China and Southeast Asia. Researchers then “coordinated the sequencing of these viruses, the archiving of these sequences (involving UCD), and the analysis and manipulation of these viruses (notably at UNC).” Undoubtedly, a large part of the research was done in the United States. The authors point out:

“The exact details of the fieldwork and laboratory work of the EHA-WIV-UNC partnership, and the engagement of other institutions in the United States and China, has not been disclosed for independent analysis. 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.

Instead of disclosing their research activities to the U.S. scientific community and the general public, the EHA, UNC, NIH, USAID, and other research partners have insisted they were not involved in any experiments that could have resulted in the emergence of SARS-CoV-2. Specifically, the NIH has stated there is “a significant evolutionary distance between the published viral sequences and that of SARS-CoV-2 and that the pandemic virus could not have resulted from the work sponsored by NIH.”

The authors argue this assertion by the NIH is only as good as the limited data on which it is based, adding the validation of this assertion relies upon gaining access to any other unpublished viral sequences that are deposited in relevant U.S. and Chinese databases. They remarked:

“On May 11, 2022, Acting NIH Director Lawrence Tabak testified before Congress that several such sequences in a U.S. database were removed from public view, and that this was done at the request of both Chinese and U.S. investigators.”

Sachs and Harrison insist that even though the NIH and USAID have “strenuously resisted” full disclosure of the details of the EHA-WIV-UNC work program, several documents leaked to the public or released through the Freedom of Information Act (FOIA) have raised concerns. The experts refer to particular circumstances surrounding the presence of an “unusual furin cleavage site (FCS)” in SARS-CoV-2 that augments the pathogenicity and transmissibility of the virus related to viruses like SARS-CoV-1.” Describing their concern in more depth, they explain:

“SARS-CoV-2 is, to date, the only identified member of the subgenus sarbecovirus that contains an FCS, although these are present in other coronaviruses. A portion of the sequence of the spike protein of some of these viruses is illustrated in the alignment shown in Fig. 1, illustrating the unusual nature of the FCS and its apparent insertion in SARS-CoV-2. From the first weeks after the genome sequence of SARS-CoV-2 became available, researchers have commented on the unexpected presence of the FCS within SARS-CoV-2—the implication being that SARS-CoV-2 might be a product of laboratory manipulation. In a review piece arguing against this possibility, it was asserted that the amino acid sequence of the FCS in SARS-CoV-2 is an unusual, nonstandard sequence for an FCS and that nobody in a laboratory would design such a novel FCS.”

origins
This alignment of the amino acid sequences of coronavirus spike proteins in the region of the S1/S2 junction illustrates the sequence of SARS-CoV-2 (Wuhan-Hu-1) and some of its closest relatives. The furin cleavage site (FCS) is indicated (PRRAR’SVAS), and furin cuts the spike protein between R and S, as indicated by the red arrowhead. Adapted from Chan & Zhan (15).

Emphatically, the duo insists the argument that the FCS in SARS-COV-2 is “an unusual, nonstandard amino acid sequence” is false. Offering an in-depth explanation in their paper, Sachs and Harrison say they “do not know whether the insertion of the FCS was the result of evolution—perhaps via a recombination event in an intermediate mammal or human—or was the result of deliberate introduction of the FCS into a SARS-like virus as part of a laboratory experiment.” Noting that the researchers were already familiar “with several experiments involving the successful insertion of an FCS into SARS-CoV-1 and other coronaviruses,” they added:

“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 U.S. Defense Advanced Research Projects Agency (DARPA). The 2018 proposal to DARPA was not funded, but we do not know whether some of the proposed work was subsequently carried out in 2018 or 2019, perhaps using another source of funding.”

origins
Amino acid alignment of the furin cleavage sites of SARS-CoV-2 spike protein with (Top) the spike proteins of other viruses that lack the furin cleavage site and (Bottom) the furin cleavage sites present in the α subunits of human and mouse ENaC. Adapted from Anand et al. (16).

Harrison and Sachs write that the EHA-WIV-UNC research team would also be familiar with the FCS sequence and the FCS-dependent activation mechanism of human ENaC, which was extensively characterized at UNC. They insist while the “molecular mimicry of ENaC within the SARS-CoV-2 spike protein might be a mere coincidence,” it is unlikely that is the case. Indeed, they explain the exact FCS sequence present in SARS-CoV-2 was recently introduced into the spike protein of SARS-CoV-1 in the laboratory in a series of “elegant” experiments with predictable consequences in terms of improved viral transmissibility and pathogenicity.

Reflecting on the fact several researchers raised genuine concerns in Feb. 2020 over the possibility that SARS-CoV-2 emerged from a research-associated event, Sachs and Harrison maintain transparency from the federal government is essential. They explain, based on the previous work executed by these government-funded researchers, the probability of a lab producing and releasing a novel pathogen like COVID-19 is high, adding:

“These simple experiments show that the introduction of the 12 nucleotides that constitute the FCS insertion in SARS-CoV-2 would not be difficult to achieve in a lab. It would therefore seem reasonable to ask that electronic communications and other relevant data from U.S. groups should be made available for scrutiny.”

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