“Juicing up super viruses is not new. Scientists in the U.S. have long known how to mutate animal viruses to infect humans. For years, Dr. Ralph Baric, a virologist in the U.S., has been collaborating with Dr. Shi Zhengli of the Wuhan Virology Institute, sharing his discoveries about how to create super viruses. This gain-of-function research has been funded by the NIH. … Dr. Fauci, do you still support funding of the NIH funding of the lab in Wuhan?”

— Sen. Rand Paul (R-Ky.), remarks at a Senate hearing, May 11

“Senator Paul, with all due respect, you are entirely and completely incorrect that the NIH has not never and does not now fund gain-of-function research in the Wuhan Institute of Virology.”

— Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, in response.

This fact check has been updated with a statement by the National Institutes of Health

This showdown between Paul and Fauci quickly went viral last week. But the nature of their debate regarding the origins of the coronavirus pandemic may seem obscure to many people. “Gain of function” is one of those insider-y terms that are subject to different definitions. The debate over such experiments predated the pandemic, but it has gained new urgency as scientists investigate the origin of the virus that has killed more than 3 million people around the world.

The core of the dispute is this: Did the virus emerge from nature — “zoonotically” from animals — or was it the result of a lab experiment gone awry?

Last May, the Fact Checker video team reported that the “balance of the scientific evidence strongly supports the conclusion that the new coronavirus emerged from nature.” A joint report by the World Health Organization and China, released in February, said a lab escape of the virus was “extremely unlikely.” But last week, a group of 18 preeminent scientists published a letter in the journal Science saying a new investigation is needed, because “theories of accidental release from a lab and zoonotic spillover both remain viable.”

If the lab leak is found at fault, Paul was suggesting, then the U.S. government was partially responsible.

The Facts

Let’s start with the basics. What is gain-of-function research?

In many ways, it is basic biological research. It’s done all the time with flies, worms, mice and cells in petri dishes. Scientists create novel genotypes (such as arrangements of nucleic acids) and screen or select to find those with a given phenotype (such as trait or ability) to find new sequences with a particular function.

But it’s one thing to experiment with fruit flies and another thing when the research involves genotypes of potential pandemic pathogens and functions related to transmissibility or virulence in humans.

That’s when “gain of function” becomes controversial. The idea is to get ahead of future viruses that might emerge from nature, thereby allowing scientists to study how to combat them. But many believed the research was potentially dangerous.

In a 2011 opinion article published in The Washington Post, Fauci and two co-authors noted that “the question is whether benefits of such research outweigh risks. The answer is not simple. … Safeguarding against the potential accidental release or deliberate misuse of laboratory pathogens is imperative.” In 2014, such research was paused for three years as the government set up a review process to oversee funding, known as the Potential Pandemic Pathogen Care and Oversight (P3CO) framework.

In Wuhan, China, where the first cases of the coronavirus emerged in late 2019, at least two labs studied coronaviruses that originate in bats — the Wuhan Institute of Virology (WIV) and the Wuhan Center for Disease Control and Prevention (WHCDC). Both are close to the seafood market that was originally deemed the source of the outbreak. The WIV is about eight miles away. The WHCDC is right around the corner.

The WIV is where one of the world’s foremost experts on bat viruses, Shi Zhengli, works. The WIV has a biosafety level 4 (BSL-4) laboratory, the most secure, where researchers wear protective suits. But some of WIV’s more controversial experiments on bat coronaviruses are believed to have been done at BSL-2 labs, where researchers wear white lab coats and gloves, as in a dental office.

W. Ian Lipkin of Columbia University had co-authored an influential letter in March 2020 that the coronavirus was “not a laboratory construct or a purposefully manipulated virus.” He recently told former New York Times reporter Donald G. McNeil Jr. that the BSL-2 revelation was significant, even though there still is no direct evidence of a lab leak. “That’s screwed up,” he said. “It shouldn’t have happened. People should not be looking at bat viruses in BSL-2 labs. My view has changed.”

In any case, is there evidence that NIH funded such gain-of-function research at WIV? To some extent, that depends on the definition of gain of function, which, as we noted, is open to dispute.

For instance, in 2017, WIV published a study that said researchers had found a coronavirus from a bat that could be transmitted directly to humans. WIV researchers used reverse genetics to deliberately create novel recombinants of wild bat coronavirus backbones and spike genes, then tested the ability of these chimeric (man-made) viruses to replicate in — not just infect — a variety of cell lines. The article reported the discovery of novel coronavirus backbone and spike combinations that do not exist in nature and are capable of replicating efficiently in human cells with the angiotensin-converting enzyme 2 (ACE2), the protein that provides the entry point for the coronavirus to hook into and infect human tissue.

The article, under its list of funders, included: the National Institutes of Health.

The NIH grant that funded the project said it would study “the risk of future coronavirus (CoV) emergence from wildlife using in-depth field investigations across the human-wildlife interface in China.” The grant description included this line: “Test predictions of CoV inter-species transmission. Predictive models of host range (i.e. emergence potential) will be tested experimentally using reverse genetics, pseudovirus and receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice.”

To some experts, that certainly sounds like gain-of-function research, though we should note that, based on what has been disclosed publicly by WIV, none of the virus samples used to conduct these experiments were or could have been transformed to be the new coronavirus that causes the disease covid-19.

“The research was — unequivocally — gain-of-function research,” Richard H. Ebright of Rutgers University, a longtime critic of such research, told The Fact Checker. “The research met the definition for gain-of-function research of concern under the 2014 Pause.”

(Our colleague Josh Rogin reported that this 2017 research article prompted U.S. diplomats and scientists to visit the WIV facility. Afterward, they sent a cable to Washington expressing concern about the safety standards there, intended as “a warning about a potential public-health crisis.”)

But Robert Kessler, a spokesman for the nongovernmental organization EcoHealth Alliance that NIH funded, said claims about funding gain-of-function research are based on a misunderstanding of the grant’s role in the research. He said EcoHealth provided WIV $133,000 a year, except for $66,000 in 2020 (when the grant was terminated by the Trump administration), for a total of about $600,000.

“The NIH has not funded gain-of-function work,” Kessler said in email exchanges. “EcoHealth Alliance was funded by the NIH to conduct study of coronavirus diversity in China. From that award, we subcontracted work with the Wuhan Institute of Virology to help with sampling and lab capacity.” He said the citation in the paper was mainly the result of researchers’ desire to cite any possible research that contributed to the findings, with much of the funding coming from the National Natural Science Foundation of China. (Another funder listed was USAID’s Predict program, which helped collect animal viruses and also funded EcoHealth.)

“As described in the paper, all but two of the viruses cultured in the lab failed to even replicate,” he said. “None of them had been manipulated in order to increase their ability to spread, all the researchers did was insert S [spike] proteins in order to gauge their ability to infect human cells.”

Kessler added that “much of that work [described in the grant] wasn’t done because the grant was suspended. But GoF was never the goal here.” As he put it, “gain of function research is the specific process of altering human viruses in order to increase their ability (the titular gain of function) either to spread amongst populations, to infect people, or to cause more severe illness.”

In a lengthy statement to The Fact Checker, Baric — who signed the letter calling for a new investigation — also pushed back against Paul’s assertions at the hearing.

“The Baric laboratory has never investigated strategies to create super viruses,” he said. “Studies focused on understanding the cross-species transmission potential of bat coronaviruses like SHC014 have been reviewed by the NIH and by the UNC Institutional Biosafety Committee for potential of gain-of-function research and were deemed not to be gain of function.”

“We never introduced mutations into the SHC014 [horseshoe bat coronavirus] spike to enhance growth in human cells, though the work demonstrated that bat SARS-like viruses were intrinsically poised to emerge in the future,” he added. “These recombinant clones and viruses were never sent to China. Importantly, independent studies carried out by Italian scientists and others from around the world have confirmed that none of the bat SARS-like viruses studied at UNC were related to SARS-CoV-2, the cause of the COVID-19 pandemic.”

We gave NIH six days to respond to questions and though we were promised a statement, none was received. That’s fishy. Fauci, speaking to the United Facts of America fact-checking festival on May 11, said Paul’s statement was “preposterous.” He said the research was “a very minor collaboration, as part of a subcontract of a grant, we had a collaboration with some Chinese scientists.”

Update, May 19: The National Institutes of Health issued a statement to The Fact Checker which in part said: “NIH has never approved any grant to support 'gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans. The research proposed in the EcoHealth Alliance, Inc. grant application sought to understand how bat coronaviruses evolve naturally in the environment to become transmissible to the human population.” When gain-of-function research was paused, “this grant was reviewed again and determined by experts to fall outside the scope of the funding pause.”

In a separate statement also issued May 19, NIH Director Francis S. Collins said: “NIH strongly supports the need for further investigation by the World Health Organization (WHO) into the origins of the SARS-CoV-2 coronavirus.”

“Despite Dr. Fauci’s denials, there is ample evidence that the NIH and the NIAID, under his direction, funded gain of function research at the Wuhan Institute of Virology,” said Paul spokeswoman Kelsey Cooper. “In light of those facts, the question Dr. Paul asked was whether the government has fully investigated the origin of the disease, which it clearly has not. This research and the lab should be thoroughly investigated and opened to public scrutiny.”

The Pinocchio Test

There is some smoke here, but we do not yet perceive the fire claimed by Paul. To some extent, all money is fungible. But the EcoHealth funding was not related to the experiments, but the collection of samples. The NIH grant includes language that some say suggests gain-of-function research; NIH says that is a misinterpretation. Paul’s statements about Baric’s research also appear overblown. We wavered between Two and Three Pinocchios, but decided on Two, because there still are enough questions about the work at the Wuhan lab to warrant further scrutiny, even if the NIH connection to possible gain-of-function research appears so far to be elusive.

Two Pinocchios

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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)