Questions raised on tinkering with viruses

CHENNAI: In mid-2020, a team of scientists catching bats in Laotian caves discovered coronaviruses that were strikingly similar to the one that had begun wreaking havoc around the world. In the months since, some of those researchers have been studying one of these mysterious bat viruses in a high-security laboratory in Paris, hoping to discover clues about how its cousin, SARS-CoV-2, went on to become a global threat that has killed an estimated 15 million people.

Their work has been scientifically fruitful. Last year, the scientists discovered that the bat virus was capable of latching on to human cells, at least in Petri dishes. Last month, the team reported more reassuring news: that the virus is not particularly harmful to lab animals. The finding suggests that SARS-CoV-2 evolved its abilities to spread quickly and cause deadly disease only after the two lineages branched apart on the viral evolutionary tree.

If the Laotian virus were to ever jump from a bat to a person, the new research suggests, it might cause a mild stomach bug rather than a life-threatening pneumonia. Nevertheless, lab experiments like these rekindle a longstanding debate among scientists about the wisdom of tinkering with viruses that are so closely related to a known pathogen.

Proponents argue that this kind of data is crucial for understanding — and preventing — pandemics. For example, the new studies have tested whether bat viruses could evolve a “furin cleavage site,” a feature of SARS-CoV-2 that allows it to efficiently infect human cells. “Our motivation was to try to give some insight regarding the origin of Covid,” said Marc Eloit, a virologist at the Pasteur Institute in Paris who is leading the effort.

But critics say that scientists should not run experiments that might make viruses better able to spread among people, given the small but real chance that these altered pathogens might infect lab workers and escape into the outside world. “For me, the benefits of this work are outweighed by the risks,” said Dr. David Relman, a microbiologist at Stanford University.

The bat virus at the center of Dr. Eloit’s experiments came to light on an expedition to limestone caves in northern Laos in the summer of 2020. A team of Laotian and French researchers caught bats flying out of the caves and took samples of their saliva, blood, urine and faeces. The scientists found genetic material from five coronaviruses closely related to SARS-CoV-2. In the faeces from a Marshall’s horseshoe bat, they found whole viruses of a strain they named BANAL-236 (a code indicating the virus came from a bat anal swab).

Once back in their lab, the scientists found that BANAL-236 can infect human cells by binding tightly to the same protein that SARS-CoV-2 uses to gain entry. In February, the researchers published these findings in the journal Nature. Last month, they released a second wave of results, now under review by a scientific journal, in which they investigated the virus’s behavior in laboratory mice and monkeys.

In one experiment, the scientists injected the virus into genetically engineered mice commonly used to study Covid. SARS-CoV-2 replicates quickly in their lungs, just as it does in people, causing them to lose weight and die. BANAL-236, by contrast, struggled to take hold in the animals’ lungs, producing only about 1 percent of the viruses created in a SARS-CoV-2 infection. This shape-shifting region of the spike — known as the furin cleavage site — is crucial to the success of SARS-CoV-2. When scientists have engineered viruses lacking this site, the mutants struggle to replicate in the lungs of lab animals or spread to new hosts.

Zimmer is a science reporter with NYT©2022