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The Ongoing Mystery of Covid’s Origin

The Ongoing Mystery of Covid’s Origin

The Ongoing Mystery of Covid’s Origin


On Jan. 11, 2020, in Shanghai, just 11 days after first reports of the outbreak in Wuhan circulated globally, a team of scientists led by Yong-Zhen Zhang of Fudan University released a draft genome sequence of the novel virus through a website called Virological.org. The genome was provided by Edward C. Holmes, a British Australian evolutionary biologist based in Sydney and a colleague of Zhang’s on the genome-assembly project. Holmes is famous among virologists for his work on the evolution of RNA viruses (including coronaviruses), his pristinely bald head and his mordant candor. Everyone in the field knows him as Eddie. The posting went up at 1:05 a.m. Scotland time, at which point the curator of the site there in Edinburgh, a professor of molecular evolution named Andrew Rambaut, was alert and ready to speed things along. He and Holmes composed a brief introductory note to the genome: “Please feel free to download, share, use and analyze this data,” it said. They knew that “data” is plural, but they were in a hurry.

Immediately, Holmes and a small group of colleagues set to analyzing the genome for clues about the virus’s evolutionary history. They drew on a background of known coronaviruses and their own understanding of how such viruses take shape in the wild (as reflected in Holmes’s 2009 book, “The Evolution and Emergence of RNA Viruses”). They knew that coronavirus evolution can occur rapidly, driven by frequent mutation (single-letter changes in a roughly 30,000-letter genome), by recombination (one virus swapping genome sections with another virus, when both simultaneously replicate in a single cell) and by Darwinian natural selection’s acting on those random changes. Holmes traded thoughts with Rambaut in Edinburgh, a friend of three decades, and with two other colleagues: Kristian Andersen at Scripps Research in La Jolla, Calif.; and Robert Garry at the Tulane University School of Medicine in New Orleans. Ian Lipkin, of Columbia University’s Mailman School of Public Health, joined the huddle later. These five would form a sort of long-distance study group, aimed toward publishing a paper on SARS-CoV-2’s genome and its likely origin.

Holmes, Andersen and their colleagues recognized the virus’s similarity to bat viruses but, with more study, saw a pair of “notable features” that gave them pause. Those features, two short blips of genome, constituted a very small percentage of the whole, but with potentially high significance for the virus’s ability to grab 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; an FCS is a feature that helps certain viruses get inside. The original SARS virus, which terrified scientists worldwide but caused only about 800 deaths, didn’t resemble the new coronavirus in either respect. How had SARS-CoV-2 come to take this form?

Andersen and Holmes were genuinely concerned, at first, that it might have been engineered. Were those two features deliberate add-ons, inserted into some coronavirus backbone by genetic manipulation, intentionally making the virus more transmissible and pathogenic among humans? It had to be considered. Holmes called Jeremy Farrar, a disease expert who was then director of the Wellcome Trust, a foundation in London that supports health research. Farrar saw the point and quickly arranged a conference call among an international group of scientists to discuss the genome’s puzzling aspects and the possible scenarios of its origin. The group included Robert Garry at Tulane and a dozen other people, most of them distinguished European or British scientists with relevant expertise, like Rambaut in Edinburgh, Marion Koopmans in the Netherlands and Christian Drosten in Germany. Also on the call were 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 Feb. 1 call on which — if you believe some critical voices — Fauci and Collins persuaded the others to suppress any notion that the virus might have been engineered.

“The narrative going around was that Fauci told us, Change our mind, yada, yada, yada, yada. We were paid off,” Holmes said to me. “It’s complete [expletive].”



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