'Synthetic' virus? COVID origin paper sparks backlash, author sees minefield in peer review

Scientists are entertaining the possibility that SARS-CoV-2 not only leaked from a lab but had been genetically modified, based on new research into the "peculiar pattern of unique restriction endonuclease recognition sites" in the virus.

This pattern allows "efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses," according to the Oct. 20 preprint by mathematical biologist Alex Washburne, Duke University pharmacologist Antonius VanDongen and University of Wurzburg molecular immunologist Valentin Bruttel.

The "fingerprint" of this "stitching" and the "pattern of mutations generating them are extremely unlikely in wild coronaviruses and nearly universal in synthetic viruses," the researchers wrote.

"The BsaI/BsmBI restriction map of SARS-CoV-2 is unlike any wild-type coronavirus, and it is unlikely to evolve from its closest relatives."

The paper, which has not been peer-reviewed, is drawing polarized responses from scientists, according to The Economist. University of Sydney virologist Edward Holmes said every feature of the virus had been found in other bat viruses and cited "a whole range of technical reasons why this is complete nonsense."

"The study is a clear example of motivated reasoning with a heavy dose of technobabble to make it sound legitimate — but it's nothing more than poppycock dressed up as science," according to Scripps Research Institute immunologist Kristian Andersen.

He claimed the paper couldn't pass "kindergarten molecular biology," which prompted a satirical response from Duke's VanDongen.

Andersen had a very different view in early 2020, telling National Institute for Allergy and Infectious Diseases Director Anthony Fauci that the virus looked "potentially" engineered.

Fauci's official work calendar from November 2019 to March 2020 suggests he feared the virus didn't have natural origin, according to Open the Books, which recently obtained the document through a Freedom of Information Act lawsuit.

It shows Fauci had several previously unreported "top-secret" and "restricted" meetings with the National Security Council in January and February 2020, in venues including the White House Situation Room. Do these meetings "give the impression people-in-the-know thought the virus had a natural origin?" Open the Books founder Adam Andrzejewski wrote.

"We're waiting to hear back from colleagues on where we might be able to find a fair trial" in a peer-reviewed journal, given the "extreme reactions" the preprint has elicited, corresponding author Washburne told Just the News. He runs the microbiome startup Selva and formerly worked on virological modeling at Montana State University.

"In the hands of the wrong editor, a fair peer-review could be slow-walked and take years, or it could have our paper be reviewed by researchers exposed to reputational risk from our findings," he said. "Nearly every correspondence I've had with scientists has included explicit or implicit discussion of their fear of discussing our paper publicly and non-anonymously."

They could face not only removal from academic committees but loss of grant funding and opportunities for appointments and awards "because they took a controversial stance," he said. 

"I tried to poke holes in this study, really hard, and I hate its findings," University College London Genetics Institute Director Francois Balloux wrote in a tweet thread that concluded the preprint "looks solid both conceptually and methodologically."

Balloux said he was "able to replicate the key findings" and called the paper "by far the strongest piece of evidence to date against a simple scenario of strict zoonotic origin." He predicted "Covid twitter will combust in an implosion of rage and fury over this preprint." 

He took down his account before reappearing Sunday to promote a different analysis that denounced the "grandstanding" against the paper while summarizing "legitimate criticism." 

Rutgers University molecular biologist Richard Ebright, known for accusing Fauci of repeated "untruthful" statements on gain-of-function research, described the paper as "noteworthy" but not "decisive." 

China's Wuhan Institute of Virology used "directional cloning" in 2016 and 2017 to construct infectious clones of coronaviruses, and "it would be implausible" if they didn't use the same procedure to do so in 2018-2019, given "their NIH and DARPA grant proposals from 2018," Ebright wrote in a tweet thread.

"It has been clear since early 2020 that the [COVID origin] issue should have been understood as, investigated as, and adjudicated, as a forensic and legal issue, rather than as a basic-science issue," Ebright told Just the News when asked for his response to criticisms of the paper, pointing to his statements from January 2020 and April 2020.

"I left academia because of the toxicity of COVID science communication," Washburne wrote after the paper's publication in a long essay explaining how the research was done and rebutting personal attacks and claims of "fraud, misconduct, deception."

Washburne provided Just the News his point-by-point response to various criticisms, one of which stemmed from "a miscommunication on my part" about a genomic assembly procedure. 

"While it's possible to assemble genomes and not leave type IIS restriction enzymes in place, the common practice amongst those making infectious clones of coronaviruses pre-COVID was to leave the type IIS sites in place," which "allows further modifications of the infectious clone," he wrote.

"We ran a meta-analysis of infectious clones of coronaviruses made with type IIS enzymes over the period from 2000-2019, and almost all of them retained the type IIS sites as recommended for efficient reverse genetic systems."

While it's correct that "recombination is common in RNA viruses," Washburne said, responding to another criticism, their paper found that "no other coronavirus had such a regular-spacing of sites" as the researchers observed in SARS-CoV-2.

"Some have claimed another, distant sequence — RpYN06 — disproves our results because it, too, is missing highly conserved BsaI sites," but the researchers included many coronaviruses "that were missing this highly conserved site, and that genome RpYN06 is a midpoint in the wild type distribution in terms of the even-spaced-ness of its restriction sites," he said.