‘We made a mistake.’ Omicron origin study retracted after widespread criticism | Science


An article published earlier this month science He claimed that the Omicron variant of SARS-CoV-2 emerged gradually over a large area of ​​Africa before the authors detected it today. In the retraction notice, all 87 researchers involved in the paper acknowledged that the crucial genome sequences on which the study bases its conclusions were the result of contamination. “We made a mistake and it’s a bitter one,” says lead author Felix Drexler of the Charité University Hospital in Berlin.

The paper drew criticism almost from the moment it was published, and some scientists say the problem could have been avoided if the study had been published as a preprint, allowing independent scientists to comment. “This would have died on Twitter within days of being in preprints,” says Aris Katzourakis, an evolutionary virologist at the University of Oxford.

Omicron was first discovered in late 2021 in Botswana and South Africa, quickly spread around the world, and has since dominated the pandemic. Its exact origins have been a mystery, in part because the Omicron is so different from the variants that were circulating before it.

Researchers have put forward several ideas to explain the genetic gap. In one scenario, the virus underwent a long evolution in an animal host and then spilled over into humans. In another, it evolved over a long period of time in a single patient with a chronic infection. A third possibility was that the virus was quietly circulating and mutating in an area of ​​the world where few viruses were being collected and sequenced.

The science the paper seemed to confirm the third possibility. Analyzing thousands of older samples from COVID-19 patients across Africa with a specific Omicron assay, the researchers found evidence of this variant in 25 patient samples from East and West Africa in August and September 2021, months before the outbreak. South Africa The researchers sequenced the genomes of the five samples, all from Benin, and found that there were some features of Delta—the first dominant variant—and some of Omicron, suggesting that they represented an intermediate stage of evolution.

But Kristian Andersen, who studies pathogen evolution at Scripps Research, says the theory of evolution was gradually “off the table” before the paper was published. If Omicron had truly evolved as SARS-CoV-2 slowly spread through a population, it should have had more synonymous mutations, the kind that don’t change viral proteins, Andersen says, because those mutations often become “fixed.” or permanently set in person-to-person transmission. “So when this paper came out … it was an immediate red flag,” he says.

After delving into the paper, Andersen and the other researchers quickly pointed out the inconsistencies on Twitter and directly to the authors. For example, the genome sequence presented as the first ancestor of Omicron had many mutations expected in a progenitor, but also typical of the BA.1 subvariant of Omicron, which evolved later. “That pattern suggested there was a problem with pollution,” says Michael Worobey, an evolutionary biologist. in University of Arizona, Tucson.

Drexler acknowledges that some of the individual reads in the Benin samples—parts of the genome sequenced individually and then assembled together—were the result of contamination. The team concluded that they had essentially sequenced fragments of Omicron and earlier SARS-CoV-2 strains; Then the computer stitched them together into a genome sequence that looked like a virus between Omicron and earlier variants. Attempts to re-sequencing the virus from residual samples did not replicate previous results, Drexler says.

Critics of the paper say the flaws should have been caught up in peer review.

“There are definitely some tough questions to be asked,” Andersen says. Another scientist, he says he asked science who reviewed the manuscript—and asked to remain anonymous—says the paper’s flaws were pointed out during a critical review.

Holden Thorp, Editor-in-Chief science, wrote in an email: “There was more than enough support here to publish the reviewer’s paper,” without elaborating. “But just because we had help getting the paper published doesn’t mean we don’t regret discovering these problems until after publication,” Thorpe added. “We accept responsibility because we didn’t figure that out in the review.” (scienceThe news department is independent of its editorial staff.)

Drexler admits that publishing a preprint would have prevented the paper from being published and retracted. It didn’t seem like he could get the necessary information out quickly because it didn’t answer pressing public health questions, but “in retrospect, I regret it,” he says.

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