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3D printing of a spike protein from SARS-CoV-2, the virus that causes COVID-19 – before 3D printing a SARS-CoV-2 virus particle. The spike protein (foreground) enables the virus to enter human cells and infect them. On the virus model, the virus surface (blue) is covered with spike proteins (red) that enable the virus to penetrate human cells and infect them. Photo credit: NIH

Eighteen scientists from some of the world’s most prestigious research institutions are calling on their colleagues to dig deeper into the origins of the coronavirus, which is responsible for the global pandemic.

In a letter published Thursday in the journal Science, they argue that there is not enough evidence yet to rule out the possibility that the SARS-CoV-2 virus escaped from a laboratory in China, calling for a “proper investigation” of the matter.

“We believe this question deserves a fair and thorough science-based investigation and that any subsequent assessment should be made of the available data,” said Dr. David Relman, Professor of Microbiology and Immunology at Stanford University, who wrote the letter.

The short letter was inspired in part by the publication on March 30 of a report commissioned by the World Health Organization attempting to trace the origin of the virus, which killed more than 3.3 million people worldwide.

The authors of this report, credited to both WHO and China, rated each of the four possible scenarios on a scale from “extremely unlikely” to “very likely”.

After reviewing the information, data and samples submitted by the Chinese team members, the authors concluded that the likelihood of the virus jumping from a parent animal to an intermediate species and then to humans was “likely very likely” while due to introduction from An accidental laboratory leak was rated “extremely unlikely”.

Other possible avenues the researchers considered were a direct jump from animal to human with no intermediate host (“possible to likely”) and transfer from the surface of frozen products (“possible”).

However, Relman and his co-authors said their colleagues who worked on the WHO study did not have enough information to draw these conclusions.

“We are reasonable scientists with expertise in relevant areas,” said Relman, “and we don’t see any data that says this must be of natural origin.”

Ravindra Gupta, a professor of clinical microbiology at Cambridge University who signed the letter, said he would like to review laboratory notes from scientists working at the Wuhan Institute of Virology, a research center that studies coronaviruses. He would also like to see a list of the viruses that have been used at the institute over a five year period.

The WHO report documents a meeting between its investigators and several members of the institute, including laboratory director Yuan Zhiming, who gave the joint team a tour of the facility.

During the meeting, representatives from WIV disproved the possibility that the coronavirus that causes COVID-19 may have leaked from the laboratory, noting that none of the three SARS-like viruses cultivated in the laboratory are closely related to SARS-CoV-2 is.

They also pointed out that blood samples from workers and students from a research group led by Shi Zhengli, a WIV virologist who studies SARS-like coronaviruses derived from bats, did not contain SARS-CoV-2 antibodies that target a stream would indicate past infection.

But Relman said that as a scientist, he needed more than this third-party report to rule out the possibility of an accidental lab leak. (He and his colleagues did not suggest that a potential leak was intentional.)

“Show us the test you used: what was the method? What were the results and the names of the people tested? Did you test a control population?” Said Relman. “In any case, it was not an adequately detailed way of presenting data that would allow an outside scientist to come to an independent conclusion.”

Tedros Adhanom Ghebreyesus, WHO Director General, expressed a similar opinion when the report was first published.

“Although the team has concluded that a laboratory leak is the least likely hypothesis, it requires further investigation, possibly with additional missions involving specialists who I am willing to deploy,” he said in an address WHO member states on March 30th. “Let me be clear that all hypotheses remain on the table for WHO.”

Michael Worobey, who studies viruses at the University of Arizona to understand the origin, creation and control of pandemics, also signed the letter. Since the beginning of the pandemic, he had considered two ways it could have started – either as an escape from a laboratory or as a natural transmission from animals to humans.

Fifteen months later, he’s still open to both options.

“There just wasn’t enough definitive evidence,” he said, “so both stay on the table for me.”

In his own laboratory, Worobey works with a student collecting viruses from bats in the wild, and he has put a lot of thought into how this research could create an ecological way to introduce a new pathogen to humans.

“As someone who does this, I am very aware of the opening up that is causing new viruses to get close to people, and so I think this is another reason I take this seriously,” he said. “I worry about this in my own work.”

Other scientists have convincingly shown that SARS-CoV-2 is not a genetically engineered laboratory construct to make it more transmissible to humans, Worobey said. However, this does not rule out the possibility that an unmodified virus collected by scientists in the field and taken to a laboratory could have entered humans.

“I haven’t seen any evidence that I can look at them and say, ‘Oh, OK, this undoubtedly refutes the lab’s random origin and makes virtually 100% sure it was a natural event,'” he said. “By the time we’re on stage, both options are feasible.”

Scientists said there was conclusive evidence that the virus did indeed spread to humans through a natural event – the discovery of the wildlife from which the virus originated.

Akiko Iwasaki, professor of immunobiology and epidemiology at Yale University, noted that the WHO report mentioned testing of more than 80,000 animal, animal and poultry samples from 31 provinces in China. None of these tests revealed a SARS-CoV-2 antibody or an excerpt from the genetic material of the virus before or after the SARS-CoV-2 outbreak in China.

“It is possible, however, that an animal reservoir was overlooked and further investigation reveals such evidence,” said Iwasaki, who also signed the letter.

David Robertson, head of the viral genomics and bioinformatics division at the University of Glasgow, was not among the signatories of the letter. He said he didn’t get the point.

“Nobody says a laboratory accident is impossible – there is just no evidence that the Wuhan Institute of Virology is in Wuhan,” he said.

Robertson said viruses naturally migrate from animals to humans all of the time, and SARS-CoV-2 could have been one of them.

Although he agreed with the letter’s authors that it was important to find the origins of SARS-CoV-2 in preparation for the next pandemic, “wasting time examining laboratories is a distraction,” he said .

Relman doesn’t see it that way.

“If it turns out to be of natural origin, we will have a bit more information on where this natural reservoir is and how we can be more careful with it in the future,” he said. “And if it’s a laboratory, then we talk about it, thinking much more seriously about what kind of experiments we’re doing and why.”

The letter’s authors noted that during this time of anti-Asian sentiment in some countries, it was Chinese doctors, scientists, journalists and citizens who shared vital information with the world about the spread of the virus.

“We should show the same determination to promote dispassionate, science-based discourse on this difficult but important topic,” they wrote.

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More information:
Jennifer Sills et al. Investigate the origins of COVID-19, Science (2021). DOI: 10.1126 / science.abj0016

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