Even if the coronavirus did leak from a Wuhan lab, that wouldn't necessarily mean it was engineered

• It's unlikely, but not impossible, that the coronavirus leaked from a Wuhan lab.
• US officials and public-health experts have called for further investigation of the possibility.
• But even if a leak did happen, that wouldn't necessarily mean the virus was engineered in a lab.

Two weeks ago, President Joe Biden asked the US intelligence community to redouble its efforts to find out how the pandemic started: Did the coronavirus jump from animals to people, or did it leak from a Chinese lab?

Any investigation of a potential lab leak - the possibility that a lab worker got infected then spread the virus to other people - must in turn consider two options. One is that a worker was exposed to a raw virus sample collected from bats or other animals, while the other is that the virus was genetically engineered. The evidence for either option remains sparse, so the whole notion is still considered highly unlikely.

So far, much of the discourse about the lab-leak theory has centered on the latter idea: that researchers in Wuhan modified the virus before it escaped a lab. A recent Wall Street Journal op-ed even pointed to one particular piece of the coronavirus' genome as evidence of scientific manipulation. Confirming that the virus was manipulated would, of course, show that it came out of a lab.

But the opposite isn't true: Even if the virus didn't undergo any laboratory manipulation, that wouldn't rule out a lab escape.

A 'smoking gun'?

The starting point nearly all scientists agree on in this debate is that two known bat coronaviruses are a 96% and 97% match for the coronavirus' genetic make-up. A recent study suggests another virus found in bats from southern China could be an even closer relative.

But since scientists have yet to find a bat population harboring an exact match, a lab leak can't be definitively ruled out.

Those who consider the lab theory to be unlikely are quick to point out that the coronavirus's genetic code has no tell-tale hallmarks of being engineered. A March 2020 study analyzed the virus' DNA and concluded that it "is not a laboratory construct or a purposefully manipulated virus."

However, the people who do think the coronavirus might have been engineered focus on a few particular areas of its genome.

Steven Quay, founder and president of biopharmaceutical company Atossa Therapeutics Inc., argued in the Wall Street Journal that investigators should look closely at a part of the coronavirus' spike protein that cleaves in half in order to prep the virus to enter human cells.

Many viruses use an enzyme that chops them up into smaller pieces to help them better invade cells. Different viruses use a variety of types of chops, and some work better than others. One particular chop is called the furin cleavage site. If the virus splits right here, Quay argues, it becomes "supercharged." The new coronavirus' closest known relatives do not have this site, but other coronaviruses have it, and research suggests it can arise naturally.

Quay told Insider, however, that 11 labs around the world "have purposefully put in a furin site to make a virus more infectious."

One of those labs, he said, is the Wuhan Institute of Virology (WIV), where researchers studied bat coronaviruses before the pandemic. Some of that work involved tweaking viruses to make them more lethal and infectious as a way to anticipate future pandemics - what's called gain-of-function research.

David Baltimore, a Nobel Prize-winning biologist, has called the coronavirus' furin cleavage site a "smoking gun" for the lab-leak theory. He told journalist Nicholas Wade last month that the site's presence in the coronavirus poses a "powerful challenge to the idea of a natural origin."

However, Baltimore has since walked back that comment, saying Wade took his quote out of context.

Efficient human-to-human transmission

Quay also points to the coronavirus' highly infectious nature as evidence that it could be man-made.

"Natural viruses don't support human-to-human transmission from the beginning," he said.

Former CDC director Robert Redfield, too, has said the virus could have gotten better at infecting people in a facility like the WIV.

"Most of us in a lab, when we're trying to grow a virus, we're trying to make it grow better," Redfield told CNN in March.

Indeed, scientists sometimes introduce viruses to human cells in a lab over and over again to see if the virus will evolve to become better at infecting those cells.

"But there's a limitation to that approach if your intent is evil," John Doench, a scientist at the Broad Institute of MIT and Harvard, told Insider. "Because the virus is only getting good at what you asked it to do - infecting cells in a dish."

It's another thing, he said, for a virus to do that effectively in the human body, which is protected by the immune system - a luxury not afforded to lab-cultured cells.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, has said he thinks it's more likely that the coronavirus got good at jumping between people while spreading "below the radar" in China in late 2019. Growing evidence suggests COVID-19 was spreading for weeks, if not months, before the first cases were reported.

That's probably what led the virus "to be pretty well adapted when first recognized," Fauci said in March.

Doench said he thinks observational bias may be leading people to incorrectly assume a lab leak is more probable than it really is.

"We're observing the one virus that did break through and cause and pandemic, not the billions of other viruses that failed to do so," he said.

A cancer cell that's incredibly efficient at spreading in the human body "may seem engineered," Doench added, but that's because we're not comparing it to the 40 trillion other cells that didn't turn into cancer.

Accidents do happen

Those who think the coronavirus might have jumped from an unaltered lab sample to a lab worker mostly cite past instances in which that exact thing happened. SARS, another coronavirus, has leaked from labs four times: in Taiwan, Singapore, and China. In 2004, two researchers in Beijing got infected with SARS and passed it to seven other people.

Three years ago, US officials visiting Wuhan sent a pair of memos to the State Department warning of inadequate safety measures there. And a report obtained by the Wall Street Journal suggested three WIV staff were hospitalized with "COVID-like" symptoms in the fall of 2019.

However, it's possible the virus had already started to spread in the city by then, and the World Health Organization team that visited Wuhan to investigate the pandemic's origin said it was satisfied with the WIV's safety protocol.

Peter Ben Embarek, a scientist specializing in animal disease who was on that WHO trip, said it's natural to speculate about a link between one of the labs in Wuhan and the coronavirus outbreak there.

"Even the staff in these labs told us that was their first reaction when they heard about this new emerging disease, this coronavirus: 'This is something coming out of our labs,'" Ben Embarek said in March.

But the WIV seems to have made rigorous changes since the State Department memos, and Ben Embarek said it now houses a "state-of-the-art lab."

That's part of the reason his WHO team thinks it's "very unlikely that anything could escape from such a place."