We made a mistake. Omicron Origin Study Retracted After Much Criticism | Science

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A paper published earlier this month by Science claiming that the Omicron variant of SARS-CoV-2 emerged gradually, across a large region of Africa, before it was detected, was retracted today by its authors. In a retraction notice, the 87 researchers involved in the paper acknowledged that the crucial genome sequences on which the study based its conclusions were the result of contamination. “We made a mistake and it’s bittersweet,” says lead author Felix Drexler of Charité University Hospital in Berlin.

The article drew criticism almost as soon as it was published, and some scientists say the problem could have been avoided if the study had first been published in preprint form, allowing independent scientists to comment. “It would have been butchered on Twitter within days of being posted,” 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 across the world and has dominated the pandemic ever since. Its exact origin is a mystery, in part because Omicron is so different from the variants that circulated before it.

Researchers have put forward several ideas to explain the genetic gap. In one scenario, the virus went through a long period of evolution in an animal host and then spread to 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 quietly circulated and mutated in an area of ​​the world where few viruses were detected and sequenced.

The Science article seemed to confirm the third option. By examining thousands of older samples from COVID-19 patients from across Africa with an Omicron-specific test, researchers found evidence of the variant in 25 patient samples from East and South Africa. West as early as August and September 2021, months before it explodes in South Africa. The researchers sequenced the genomes of five of the samples, from Benin, and found they had some features of Delta – the previously dominant variant – and some of Omicron, suggesting they represented an intermediate stage in evolution.

But Kristian Andersen, who studies the evolution of pathogens at Scripps Research, says the theory of gradual evolution was already “out of place” before the paper was published. If Omicron had really evolved as SARS-CoV-2 gradually spread through a population, it should have had many more synonymous mutations, the kind that don’t lead to changes in viral proteins, Andersen says, because those mutations often become “fixed”. or permanently established, during transmission between people. “That’s why when this document came out…it was immediately a red flag,” he said.

After digging through the article, Andersen and other researchers were quick to point out inconsistencies on Twitter and directly to the authors. For example, the genome sequences presented as early ancestors of Omicron had many mutations expected in a precursor, but also some that are typical of the BA.1 subvariant of Omicron, which evolved later. “That pattern suggested there was a contamination problem,” says Michael Worobey, an evolutionary biologist at the University of Arizona, Tucson.

Drexler acknowledges that some of the individual reads in the Benin samples — genome snippets that are individually sequenced and then put together — appeared to be the result of contamination. The team concluded that they had essentially sequenced fragments of Omicron and earlier strains of SARS-CoV-2; the computer then assembled them into a single genomic sequence that masqueraded as a virus halfway between Omicron and previous variants. An attempt to re-sequence viruses from residual samples did not replicate previous results, says Drexler.

The journal’s critics say the errors should have been caught during peer review.

“Some tough questions definitely have to be asked,” Andersen says. Another scientist, who says he was invited by Science to review the manuscript – and who asked to remain anonymous – says he pointed out the paper’s flaws during a critical review.

Holden Thorp, Science editor, wrote in an email that “there was more than enough support here to publish the reviewers’ paper,” without giving further details. “But just because we had the support to publish the article doesn’t mean we don’t regret the fact that these issues weren’t discovered until after publication,” Thorp added. “We accept responsibility for the fact that we did not understand this during the review.” (The science news department is independent of its editorial side.)

Drexler agrees that publishing a preprint would have avoided publication and retraction of the article. It didn’t seem necessary to rush the information out because it didn’t answer pressing public health questions, but “I regret that in retrospect,” he says.

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