The Ongoing Mystery of Covid’s Origin

On January 11, 2020, In Shanghai, just 11 days after the first reports of the outbreak in Wuhan circulated globally, a team of scientists led by Yong-Jen Zhang of Fudan University released a draft genome sequence of the novel virus through a website called The genome was provided by Edward C. Holmes, a British Australian evolutionary biologist based in Sydney and a collaborator of Zhang’s on the genome-assembly project. Holmes is famous among virologists for his work on the development of RNA viruses (including the coronavirus), his bald head, and his outspokenness. Everyone in the field knows him as Eddie. The posting was made at 1:05 a.m. Scottish time, by which time the site’s curator in Edinburgh, a professor of molecular evolution named Andrew Rambaut, was alert and ready to speed things up. he and holmes composed A Brief Introductory Note on Genome: “Please feel free to download, share, use and analyze this data,” it said. They knew “data” was plural, but they were in a hurry.

Immediately, Holmes and a small group of colleagues set out to analyze the genome for clues about the virus’ evolutionary history. He based this on the background of known coronaviruses and his understanding of how such viruses form in the wild (as described in Holmes’s 2009 book, “The Evolution and Emergence of RNA Viruses”). They knew that coronaviruses can evolve rapidly, driven by frequent mutations (single-letter changes in the roughly 30,000-letter genome), recombination (one virus swapping genome sections with another virus when both replicate together in the same cell) and Darwinian natural selection acting on those random changes. Holmes exchanged ideas in Edinburgh with Rambaut, a friend of three decades, and two other colleagues: Christian Anderson at Scripps Research in La Jolla, California; and Robert Gary at Tulane University School of Medicine in New Orleans. Ian Lipkin of Columbia University’s Mailman School of Public Health later joined the group. The five will form a sort of long-range study group with the aim of publishing a paper on the genome of SARS-CoV-2 and its possible origins.

Holmes, Anderson and their colleagues recognized this virus’s similarity to bat viruses, but with more study, they noticed a pair of “remarkable features” that gave them pause. Those features, two tiny blips of the genome, make up a very small percentage of the whole, but are of potentially high importance to the virus’ ability to capture and infect human cells. They were technical-sounding elements familiar to virologists that are now part of the Covid-origin vernacular: a furin cleavage site (FCS), as well as an unexpected receptor-binding domain (RBD). All viruses have RBDs, which help them attach to cells; FCS is a feature that helps some viruses get in. The original SARS virus, which horrified scientists around the world but caused only 800 deaths, did not resemble the new coronavirus in any way. How did SARS-CoV-2 take this form?

Anderson and Holmes were actually concerned at first, that it might have been engineered. Were those two features intentionally added, inserted into some coronavirus backbones by genetic manipulation, intentionally making the virus more infectious and pathogenic among humans? Had to think about it. Holmes called on Jeremy Farrar, a pathologist who was then director of the Wellcome Trust, a foundation in London that supports health research. Farrar understood and immediately arranged a conference call between an international group of scientists to discuss intriguing aspects of the genome and possible scenarios for its origin. The group included Robert Gary at Tulane and a dozen others, most of them distinguished European or British scientists with relevant expertise, such as Rambaut in Edinburgh, Marian Koopman in the Netherlands, and Christian Drosten in Germany. Also on the call was Anthony Fauci, then head of the National Institute of Allergy and Infectious Diseases, and Francis Collins, then director of the National Institutes of Health and therefore Fauci’s boss. This is the famous February. 1 call — if you believe some critical voices — Fauci and Collins persuaded others to quell any notion that the virus may have been engineered.

“The story that’s going around is that Fauci told us, change your mind, yada, yada, yada, yada. We’ve been paid,” Holmes told me. “It’s done [expletive],

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