A paper published earlier this month by Science claiming the Omicron variant of SARS-CoV-2 arose gradually, across a broad area of Africa, before it was detected was retracted today by its authors. In a retraction notice, all 87 researchers involved in the paper acknowledged that crucial genome sequences on which the study based its conclusions were a result of contamination. “We made a mistake and that is bitter,” says senior author Felix Drexler of 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 posted as a preprint first, allowing independent scientists to comment. “This would have been slaughtered on Twitter within a few days of being on 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 across the world, and has dominated the pandemic since. Its exact origin has been a mystery, in part because Omicron is so different from the variants circulating before it.
Researchers have put forth several ideas to explain the genetic gap. In one scenario, the virus went through an extended bout of evolution in an animal host and then spilled back 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 had been quietly circulating and mutating in an area of the world where few viruses were being picked up and sequenced.
The Science paper seemed to confirm the third option. By screening thousands of older samples from COVID-19 patients from across Africa with an Omicron-specific assay, the researchers found evidence of the variant in 25 patient samples from East and West Africa as early as August and September 2021, months before it exploded in southern Africa. The researchers sequenced genomes from five of the samples, from Benin, and found they had some characteristics of Delta—the previously dominant variant—and some of Omicron, suggesting they represented an intermediate stage of evolution.
But Kristian Andersen, who studies the evolution of pathogens at Scripps Research, says the gradual evolution theory was already “off the table” 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 type that does not lead to changes in viral proteins, Andersen says, because such mutations often become “fixed,” or permanently established, during transmission between people. “That’s why when this paper came out … it was immediately a red flag,” he says.
After digging into the paper, Andersen and other researchers quickly pointed out inconsistencies on Twitter and directly to the authors. For instance, the genome sequences presented as early ancestors of Omicron had many mutations expected in a precursor, but also some that are typical of the Omicron subvariant BA.1, which evolved later. “That pattern suggested there was an issue with contamination,” says Michael Worobey, an evolutionary biologist at the University of Arizona, Tucson.
Drexler acknowledges that some of the individual reads in the Benin samples—snippets of genome that are sequenced individually and then put together—appeared to be the result of contamination. The team concluded it had essentially sequenced bits of Omicron and earlier SARS-CoV-2 strains; the computer then stitched them into one genome sequence that masqueraded as a virus halfway between Omicron and the earlier variants. An attempt to sequence the viruses again from residual samples did not replicate the earlier results, Drexler says.
The paper’s critics say the mistakes should have been caught in peer review.
“Some hard questions certainly need to be asked,” Andersen says. Another scientist, who says they were asked by Science to review the manuscript—and who asked to remain anonymous—says they pointed out the paper’s flaws in a critical review.
Holden Thorp, editor-in-chief of Science, wrote in an email that “There was more than enough support here to publish the paper from the reviewers,” without elaborating. “But just because we had the support to publish the paper doesn’t mean that we don’t regret the fact that these problems were only discovered after publication,” Thorp added. “We accept responsibility for the fact that we didn’t figure that out during review.” (Science’s News department is independent from its Editorial side.)
Drexler agrees that posting a preprint would have avoided the publication and retraction of the paper. It didn’t seem necessary to rush the information out because it didn’t answer urgent public health questions, but “I do regret that in retrospect,” he says.
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