January 11, 2020, Just 11 days after the first reports of the Wuhan outbreak circulated globally, in Shanghai, a team of scientists led by Yong-Zhen Zhang at Fudan University released the draft genome sequence of the new virus through 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 construction project. Holmes is well-known among virologists for his work on the evolution of RNA viruses (including coronaviruses), his clean baldness, and his mediated candor. Everyone on the set knows him as Eddie. The post was posted at 1:05 am Scottish time, at which point the site’s curator in Edinburgh, Andrew Rambeau, a professor of molecular evolution, was alarmed and ready to rush things.he and Holmes composed A brief introduction to the genome: “Please feel free to download, share, use and analyze this data”. They knew “data” was plural, but they were in a hurry.
Soon, Holmes and a small group of colleagues set out to analyze 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 such viruses form in the wild (reflected in Holmes’ 2009 book, The Evolution and Emergence of RNA Viruses). They knew that coronavirus evolution could occur rapidly through frequent mutations (single-letter changes in a genome of about 30,000 letters), recombination (one virus swaps genome sections with another when both are replicated simultaneously in a single cell), and Darwinian natural selection acting on those random changes. In Edinburgh, Holmes conversed with Rambo, a friend of 30 years, and two other colleagues. Christian Andersen of the Scripps Research Institute in La Jolla, California. and Robert Garry of the Tulane University School of Medicine in New Orleans. Ian Lipkin of Columbia University’s Mailman School of Public Health also joined the rally later. The five will form a sort of long-distance research group, aiming to publish a paper on the genome of SARS-CoV-2 and its possible origin.
Holmes, Andersen, and their colleagues recognized that the virus had similarities to bat viruses, but further research found a pair of “notable features” that stopped them. These features, her two short blips in the genome, represent a very small proportion of the total but are potentially very important for the virus’ ability to trap and infect human cells. These were technical elements familiar to virologists, but are now part of the jargon of the origin of the novel coronavirus. a furin cleavage site (FCS) and an unexpected receptor binding domain (RBD). All viruses have an RBD that helps them attach to cells. FCS is a feature that helps certain viruses get inside. Although the original SARS virus terrified scientists around the world, it only killed about 800 people, dissimilar to the new coronavirus in either respect. How did SARS-CoV-2 come to look like this?
Andersen and Holmes were genuinely concerned at first that it was engineered. Were these two features, he said, intentional add-ons inserted into the coronavirus backbone through genetic engineering, intentionally making the virus more transmissible and pathogenic among humans?It needed to be considered. Holmes called Jeremy Farrar, a disease expert who was then on the board of the Wellcome Trust, a London foundation that supports health research. Farrar saw the point and quickly arranged a conference call between an international group of scientists to discuss the puzzling aspects of the genome and possible scenarios for its origin. This group included Robert Garry of Tulane and a dozen others, most of whom were eminent European or British scientists with relevant expertise, such as Rimbaud of Edinburgh, Marion Koopmans of the Netherlands and Christian Drosten of Germany. Also present on the conference call were Anthony Fauci, then director of the National Institute of Allergy and Infectious Diseases, and Francis Collins, then director of the National Institutes of Health and Fauci’s boss. In that famous Feb. 1 conference call, if critics are to be believed, Mr. Fauci and Mr. Collins persuaded other lawmakers to suppress any idea that the virus could have been engineered.
“The prevailing story was that Fauci told us, ‘Change your mind, yada, yada, yada, yada. We have been rewarded,” Holmes told me. “It was completed [expletive]”
