Stanley Perlman, who has been studying coronaviruses for 39 years, got a nasty email June 4: “Dr. Frankenstein just wants more public money and wants to research things he shouldn’t be messing with. THANKS A LOT FOR CORONA LOSER.”

Perlman, a mild-mannered, grandfatherly virologist at the University of Iowa, didn’t know the author of the dyspeptic email and had nothing to do with the emergence of the coronavirus. But he had co-signed a letter to the Lancet in February 2020 saying SARS-CoV-2 was not a bioengineered virus and condemning “conspiracy theories suggesting that COVID-19 does not have a natural origin.”

That remains the consensus of many scientists — but the “lab leak” theory has never gone away and has become louder than ever. It is not a theory so much as a constellation of scenarios that imagine how the virus may have emanated from a laboratory in China, ranging from the accidental to the sinister.

It dominates news coverage and public discussion of the origin of the pandemic, shoving aside the natural zoonosis hypothesis — which asserts that, like so many previous infectious pathogens, the novel coronavirus most likely jumped unassisted into the human population from a still-unidentified animal host.

Scientists haven’t found that animal, however. Some virologists, including Perlman, have said they can’t rule out some kind of unintentional laboratory accident.

In the absence of crucial evidence of how the new coronavirus began comes many theories — one is that the virus accidentally escaped from a lab in Wuhan, China. (Sarah Cahlan, Meg Kelly/The Washington Post)

It’s possible, for example, that researchers studying coronaviruses in Wuhan did not even know they had SARS-CoV-2 in their facility. The new openness to such scenarios culminated last month when the journal Science published a letter from 18 prominent scientists calling for a more robust probe of the virus’s origin and criticizing a World Health Organization report that called a lab leak “extremely unlikely.”

This is a fraught moment not only for virologists, but for scientists broadly. They have had to deal with some version of the “Frankenstein” meme for generations. Now, they’re faced with suspicion that somehow they are responsible for a plague that has killed millions of people.

The situation has exacerbated long-standing tensions within the sprawling and often cantankerous scientific community. The lab-origin possibility has reignited debate over “gain of function” experiments that, in an effort to anticipate future pandemics, may alter the potency of viruses in secure laboratory settings. Scientists have clashed repeatedly over the risks and rewards of that kind of research for the past decade.

“There’s sniping going on in all directions,” said Marcia McNutt, president of the National Academy of Sciences.

Her message to everyone: cool it. She doesn’t think a scientist who is open to the possibility of a laboratory accident should be labeled a conspiracy theorist. And some people are proclaiming certainties about the origin of the virus despite having limited knowledge or expertise, she said.

“If anyone is going to come out strongly on one hypothesis or another, the scientific method says that there should be evidence to back it. I worry when some people are very willing to be firm about one origin or the other but fail to either have the evidence or the expertise to back it up,” McNutt said.

McNutt and the presidents of the national academies of medicine and engineering published a letter Tuesday staking out a neutral position amid all this rancor. It advocated for a probe “guided by scientific principles” that would consider multiple scenarios for the origin of the pandemic. It called on China to share information about research there. And it defended scientists.

“[M]isinformation, unsubstantiated claims, and personal attacks on scientists surrounding the different theories of how the virus emerged are unacceptable, and are sowing public confusion and risk undermining the public’s trust in science and scientists, including those still leading efforts to bring the pandemic under control,” the letter said.

Francis S. Collins, director of the National Institutes of Health, said in an interview that “it’s deeply disheartening to see this terribly difficult worldwide situation that has taken almost 4 million lives and somehow turned into a motivation to demonize some of the scientists who have done the most to try to get through this.”

He cited Anthony S. Fauci, the director since 1984 of the National Institute of Allergy and Infectious Diseases. Fauci has managed to serve seven presidents by avoiding political quagmires, but in recent weeks he has been excoriated in the right-wing news media and by some prominent Republican officials for his institute’s past funding of virus research at the Wuhan lab. Peter Navarro, who served as Donald Trump’s trade representative, went so far as to declare in March that “Tony Fauci is the father of the virus.”

Fauci this month fired back.

“It’s very dangerous, because a lot of what you’re seeing as attacks on me, quite frankly, are attacks on science. Because all of the things that I have spoken about consistently from the very beginning have been fundamentally based on science,” he said on MSNBC. “Science and the truth are being attacked.”

There is more noise than signal here. The lab-leak hypotheses lack direct evidence. Chinese scientists deny they had SARS-CoV-2 or its immediate ancestor in-house. The leak conjectures are fashioned around unknowns, missing information, inconsistent statements by scientists and a lack of transparency among Chinese officials. Suspicion and speculation fill holes in the narrative.

But scientists who support a natural origin have yawning gaps in their own story. They have not identified the intermediate animal host carrying SARS-CoV-2.

So where did this awful thing come from? That is a legitimate scientific mystery. The stakes are high, and crucial pieces of information are absent. As a result, the quest to understand the origin of the pandemic has been caught up in political battles and ideological maelstroms. There’s a hunt for villains before the crime has been fully documented.

“This discussion has just gotten so acerbic. It’s just been terrible,” Perlman said.

'Horses and zebras'

Collins and Fauci have called for Chinese scientists to open their records to inspection. President Biden echoed that this month, saying China should let investigators have access to the laboratories: “We have not had access to determine whether or not this was the consequence of the marketplace of animals and environment . . . or an experiment gone awry in the lab.”

Biden has ordered his intelligence agencies to sort through all possibilities and report back no later than August.

The main argument in favor of natural zoonosis — one that unfolded beyond the walls of a lab — is that this has happened before with countless viruses, including coronaviruses. SARS, the coronavirus that caused a deadly outbreak in 2002 and 2003 but was throttled before it became a pandemic, first passed through an intermediate animal sold in markets — Himalayan palm civets. Scientists believe this new coronavirus probably passed through an intermediate host as well.

For many scientists, the lab-leak hypotheses remain a classic example of an extraordinary claim that requires extraordinary evidence.

Susan R. Weiss, a virologist at the University of Pennsylvania who has studied coronaviruses for 40 years, invokes the adage about what people should expect to see coming if they hear hoofbeats.

“You know the thing about horses and zebras,” she said. “Zoonosis is the horse, and the lab leak is the zebra.”

There are many variations on the lab-leak theory, some requiring scientific subterfuge — a conspiracy, in other words, to hide what was being done in the lab. Such hypotheses, built on suspicions of missing information and deception, are hard to disprove. Scientists adhering to the natural origin hypothesis are unlikely to embrace a rival hypothesis that requires, as a fundamental assumption, an impenetrable wall of deceit.

They are more likely, however, to be open to the possibility of an accident at a lab, one without nefarious intent, perhaps involving a virus that slipped into the facility under the radar amid legitimate research efforts.

But the Wuhan Institute of Virology remains something of a black box. Critics say the WHO investigators who delivered a report on the virus origin did only a cursory investigation of the institute. They also note that the WHO investigators included Peter Daszak, president of the EcoHealth Alliance, an organization that directed a grant from Fauci’s institute to the Wuhan lab. Daszak also signed the 2020 Lancet letter denouncing conspiracy theories about a lab origin.

Even the director general of the WHO, Tedros Adhanom Ghebreyesus, distanced himself from the WHO report’s dismissal of the lab theory and called for a more thorough investigation.

That was followed by calls from scientists to probe more deeply into lab-leak scenarios. The letter to the journal Science, in particular, helped put the imprimatur of mainstream science on an idea previously marginalized as a conspiracy theory.

Perlman said he would not have signed the letter if asked, because of “false balance.”

“It made it sound like all possibilities are equal, which I don’t think is true,” Perlman said.

“There isn’t any balance of plausibility,” Columbia University epidemiologist W. Ian Lipkin said.

Stanford University microbiologist David A. Relman, one of the organizers of the letter to Science, said the political climate last year made many scientists hesitant to express openness to the lab-leak idea. They did not want to align themselves with a theory closely associated with Trump and his allies, who referred to the coronavirus as “the China virus.”

Relman took the leap, though: In November, he published an essay in the Proceedings of the National Academy of Sciences discussing possible origins of SARS-CoV-2, including laboratory manipulation: “Even though a definitive answer may not be forthcoming, and even though an objective analysis requires addressing some uncomfortable possibilities, it is crucial that we pursue this question.”

Relman said two scientists who were asked to sign the letter to Science expressed concern that it could contribute to anti-Asian bigotry. Only one signed. Relman noted that the letter concluded with an affirmation of support for Chinese scientists fighting the pandemic.

Relman said he goes back and forth on whether a natural or laboratory origin of SARS-CoV-2 is more likely. He is open to the possibility that Chinese officials haven’t been forthcoming about their laboratory experiments.

“It seems more likely that either the virus was grown unknowingly and produced an asymptomatic infection, and none of that was recognized, or a laboratory worker infected themselves unknowingly during collection of samples from a natural viral reservoir, like a cave with bats,” Relman said.

“It is also theoretically possible there was some engineering going on there with some recent ancestor viruses that haven’t been talked about, that haven’t been published,” he said. “That would then suggest there has been a deliberate effort to not talk about some work that was going on there.”

'We may never know'

Some scientists are dismayed by what they’re reading and hearing. They think the case for natural zoonosis remains strong. A significant fraction of early coronavirus infections were linked to a sprawling Wuhan market where, according to the WHO report, traces of SARS-CoV-2 were found in drains and other surfaces near animal stalls.

A report published this month in the journal Nature said the Wuhan markets in the 2½ years before the pandemic sold more than 47,000 animals from 38 species, including raccoon dogs, weasels, badgers, hedgehogs, marmots, minks, bamboo rats and flying squirrels. SARS-CoV-2 has been shown to be a highly precocious virus that can infect many different kinds of animals. It has been found in domesticated and stray cats across Wuhan.

Although tens of thousands of animals have been tested in China in the search for the intermediate host, researchers have not found a precursor strain of SARS-CoV-2. The animal origins of many zoonotic diseases, including Ebola, have never been conclusively established. Surveillance of viruses capable of jumping into the human species remains spotty.

“Somewhere it’s out there, and there’s a ton of it, and we just haven’t flipped over enough stones yet,” said Benjamin Neuman, a virologist at Texas A&M University who, like Perlman, was one of the scientists who gave SARS-CoV-2 its name in early 2020.

He is irritated that some fellow virologists have lent weight to the lab-leak idea.

“This is distressing,” he said. “I feel like they’re taking the lab coat off when they say these things.”

Robert F. Garry Jr., a Tulane University virologist who co-authored an influential Nature Medicine paper in March 2020 saying SARS-CoV-2 was not engineered, is similarly emphatic that a natural origin outside of a lab remains most likely. He said the virus has genetic features that “scream” natural evolution. He noted the clustering of early cases linked to the market and pointed out that the virus has mutated into more transmissible variants — a sign, he said, that the virus is still adapting to the human species.

“I think people are frustrated, and a lot of people are looking for somebody to hang this on,” he said. He added, “You can’t get over the fact that the outbreak started in Wuhan and there’s a large institute of virology that studies coronaviruses there.”

A fact sheet posted by the State Department on Jan. 15, during the final days of the Trump administration, said several people who worked at the Wuhan Institute of Virology were hospitalized in fall 2019 with symptoms consistent with covid-19 or seasonal influenza. There has been no public documentation of who these workers were, their medical diagnoses or any illnesses among their close contacts.

The controversy put a spotlight on earlier documented instances in which a laboratory accident led to an infection. For example, nine SARS infections in 2004 were traced to laboratory research in Beijing that came after the original outbreak of SARS. And in 1977, Russian research on influenza may have led to the escape of a flu strain that became pandemic.

At the center of the Wuhan lab controversy is Shi Zhengli, a world-renowned coronavirus researcher who has collaborated with U.S. scientists. Shi has said she scoured records in her lab and found no evidence that SARS-CoV-2 was ever present. In an interview with the journal Science last year, she said Trump’s allegations jeopardized the academic work and personal lives of her team, adding, “He owes us an apology.”

Although they may be skeptical about a colleague’s research findings, scientists generally assume their colleagues in the international scientific community are honest. But there are lab-leak scenarios that do not require deception. Accidents can happen unknowingly.

Lipkin, the Columbia epidemiologist, was a co-author of the Nature Medicine paper saying the virus was not engineered, and he hasn’t changed his mind. But he has hedged his assessment in recent months, as first noted in a Medium post by science journalist Donald G. McNeil Jr. Lipkin said it’s possible that the Wuhan scientists had the coronavirus in-house and simply didn’t realize it.

“If they’ve got hundreds of bat samples that are coming in, and some of them aren’t characterized, how would they know whether this virus was or wasn’t in this lab? They wouldn’t,” Lipkin said.

Lipkin said two scientific papers co-authored by Shi indicated bat coronaviruses were handled in biosafety level 2 laboratories, rather than more secure BSL-3 or BSL-4 labs. That raises the possibility of sloppy handling of a dangerous virus, he said.

An accidental infection in a lab with an undocumented virus would be nearly impossible to distinguish from one that occurred outside the lab, he said.

“We may never know where this thing came from,” Lipkin said.

Science is not a list of knowns so much as a process of exploring the unknown, and scientists by nature are comfortable with uncertainty, ambiguity and provisional conclusions. But the pandemic is a global catastrophe that has killed and sickened millions of people, and there are demands for definitive answers about how this happened. Scientists may never be able to provide answers that satisfy everyone.

“On both sides, there’s really a lack of information. That’s why we have such extensive discussions and, in some cases, vituperative discussions,” Perlman said. “There’s really no data. It’s really just opinions.”

Yasmeen Abutaleb contributed to this report.