On January 11, 2020, In Shanghai, just 11 days after the first reports of the outbreak in Wuhan spread globally, a team of scientists led by Yongzhen Zhang of Fudan University has released a draft genome sequence of the new virus via a website called Virological.org. The genome was provided by Edward C. Holmes, a British-Australian evolutionary biologist based in Sydney and Zhang’s colleague on the Genome Assembly Project. Holmes is known among virologists for his work on the evolution of RNA viruses (including coronaviruses), for his original bald head and for his fierce candor. Everyone in the field knows him as Eddie. Posted at 1:05 a.m. Scottish time, by 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 up. He and Holmes composed A brief introductory note to the genome“Feel free to download, share, use and analyze this data,” she said. They knew “data” is the plural, but they were in a hurry.
Immediately, Holmes and a small group of colleagues set about analyzing the genome for clues about the evolutionary history of the virus. They drew on the background of known coronaviruses and their own understanding of how these viruses form in the wild (as reflected in Holmes’ 2009 book, “The Evolution and Emergence of RNA Viruses”). They knew that coronavirus evolution could happen quickly, driven by repetitive mutation (single-letter changes in a genome of roughly 30,000 letters), by recombination (one virus swaps sections of the genome for another, when both reproduce simultaneously in a single cell) and by Darwinian natural selection acting on those random changes. Holmes exchanged ideas with Rimbaud in Edinburgh, a friend of three decades, and with two other colleagues: Christian Andersen at Scripps Research in La Jolla, California. and Robert Jarry at Tulane University School of Medicine in New Orleans. Ian Lipkin, of Columbia University’s Mailman School of Public Health, later joined the gathering. These five would form a kind of far-reaching study group, aiming to publish research on the SARS-CoV-2 genome and its possible origin.
Holmes, Andersen, and their colleagues recognized the virus’s similarity to bat viruses, but upon further study, they saw a pair of “outstanding features” that gave them pause. These traits, two short segments of the genome, make up a very small proportion of the whole, but are potentially of great importance to the virus’s ability to grab and infect human cells. They were technical-sounding elements, familiar to virologists, and now part of Covid-origin slang: a furin cleavage site (FCS), plus an unexpected receptor-binding domain (RBD). All viruses contain RBDs, which help them bind to cells; FCS is a feature that helps some viruses get in. The original SARS virus, which terrified scientists around the world but only caused about 800 deaths, is nothing like the new coronavirus in any respect. How did SARS-CoV-2 come to take this form?
Andersen and Holmes were really concerned, at first, that it might have been engineered. Were these two additional features deliberately inserted into the backbone of the coronavirus by genetic manipulation, intentionally making the virus more transmissible and pathogenic in humans? It had to be considered. Holmes contacted Jeremy Farrar, a disease expert who was at the time a director of the Wellcome Trust, a London foundation that supports health research. Farrar saw the point and quickly arranged a conference call for an international group of scientists to discuss puzzling aspects of the genome and possible scenarios for its origin. The group included Robert Jarry of Tulane and dozens of others, mostly distinguished European or British scholars with relevant expertise, such as 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, director of the National Institutes of Health and, by extension, Fauci’s boss. This is the famous February 1 call that — if you believe some critical voices — convinced Fauci and Collins others to quash any notion that the virus might have been engineered.
“The narrative that goes around is Fauci told us, changed our mind, yada, yada, yada, yada. It’s complete,” Holmes told me. [expletive]. “