Proximal Origin

The Proximal Origin is a reference to a scientific correspondence titled "The proximal origin of SARS-CoV-2" and the events of scientific and political controversies arising from it. The letter, published in the journal Nature Medicine on 17 March 2020, was written by a group of virologists including Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes and Robert F. Garry. The authors examined possibilities of an accidental leak of a natural or manipulated virus from a laboratory, and concluded that genomic analyses indicated that "SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus."

The letter was highly influential in establishing the natural origin of COVID-19 in the early stages of the pandemic and generated controversy over the arguments it made against any lab-based origin scenario, and the link later drawn between its authors and public health officials alleged to have funded gain-of-function research at the Wuhan Institute of Virology prior to the pandemic. Three years after the publication, in 2023, the US Republicans raised an allegation that the scientific paper was a coverup to suppress the COVID-19 lab leak theory.

The private deliberations of the authors (during the writing of the paper) accidentally became public and became a topic of discussion and debate.

Background
From the early outbreak of the COVID-19 pandemic, rumors and speculation arose about the possible lab origins of SARS-CoV-2, the causative agent of the COVID-19 disease. Different versions of the lab origin hypothesis present different scenarios in which a bat-borne progenitor of SARS-CoV-2 may have spilled over to humans, including a laboratory-acquired infection of a natural or engineered virus. Some early rumors focused on the deliberate leak of a virus as a bioweapon or accidental leak of an engineered virus. In an earlier email obtained by public records request, Proximal Origins lead author Kristian Andersen said they were focused on dispelling these rumors, saying "the main crackpot theories going around at the moment relate to this virus being somehow engineered with intent."

Conference call with Anthony Fauci
According to emails obtained by BuzzFeed News and the Washington Post through FOIA, in the weeks before the publication of the paper, the authors held a teleconference with Anthony Fauci and Francis Collins organized by Jeremy Farrar, with 11 other scientists, including coronavirologists Marion Koopmans and Ron Fouchier.

The original publication
On 17 March 2020, Nature Medicine published a correspondence article titled "The proximal origin of SARS-CoV-2" that discussed the origin of the coronavirus that caused COVID-19 pandemic from genetic perspective. The article focused on analysing SARS-CoV-2's genome, and the sites that enable it to bind to human cells. It was reported by Kristian G. Andersen (The Scripps Research Institute, La Jolla, USA), Andrew Rambaut (University of Edinburgh, UK), W. Ian Lipkin (Mailman School of Public Health of Columbia University, New York, USA), Edward C. Holmes (The University of Sydney, Australia) and Robert F. Garry (Tulane University, New Orleans, USA). The scientists stated: "We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus." It was the first scientific report to "firmly determine" that SARS-CoV-2 was not a human-made infection that came from a laboratory.

The report concluded with a statement:"The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible."The theories postulated in the report were that the coronavirus could only had come by biological evolution in either of two ways:


 * 1) Natural selection occurred in an animal host before infection to humans (zoonotic transmission), as indicated by the coronavirus in the Malayan pangolins (Manis javanica) that has similar spike proteins of SARS-CoV-2 essential for infecting human cells. Since bat coronavirus like RaTG13 from a Rhinolophus affinis are genetically related with SARS-CoV-2 (having ~96% genome similarity), genome mixing (recombination) in animals could have produced the human-infective viruses.
 * 2) Natural selection produced the human coronavirus by mutation in humans. The spike protein of SARS-CoV-2 interacts with furin, an enzyme found in human cells. Furin-like sites are present in other viruses such as HIV and Ebola virus, but not in bat or pangolin coronaviruses, suggesting that the specific furin interaction developed only in humans.