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WUHAN, CHINA —In recent months, “gain-of-function” (GoF) research has been a topic of great controversy, the subject of intense and ongoing public disputes. With the origins of the Covid-19 pandemic under a powerful microscope, documents recently obtained through leaks or Freedom of Information Act (FOIA) litigation have purported to show that the Wuhan Institute of Virology (WIV) was engaged in dangerous GoF research. Many people appear, however, to be confused about what the term “gain of function” means and have been driven into mass panic over ordinary scientific research dealing with pandemic preparedness.
I previously investigated for MintPress News popular claims about the WIV, the Chinese research facility at the center of most of the lab-leak speculations, regarding its allegedly subpar safety standards. While these allegations have been uncritically accepted as true by both those who reject and those who subscribe to the hypothesis that Covid-19 originated in a laboratory, I found that there is little evidence for any of them.
Another of the most popular and explosive claims commonly accepted as fact is the charge that the WIV was doing controversial GoF research, lab work that is reasonably anticipated to make viruses more virulent and/or transmissible in people. In this article I will address more specifically the honesty and accuracy of those claims.
Did the NIH fund GoF research at the WIV?
In May, during a highly publicized confrontation between Senator Rand Paul (R-KY) and Anthony Fauci — director of the National Institute for Allergy and Infectious Diseases (NIAID), one of the branches of the National Institutes of Health (NIH) — Paul accused Fauci of being responsible “more than any other single living American” for the pandemic. Paul claimed:
To arrive at the truth, the U.S. government should admit that the Wuhan Virology Institute was experimenting to enhance the coronavirus’s ability to infect humans.
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.”
In response, Fauci denied that the NIH funds GoF research in Wuhan, and claimed that the NIH had funded the New York-based EcoHealth Alliance, which subcontracted part of its grant to the WIV, in order to better understand potential epidemic viruses and how to prepare for them:
Senator Paul, with all due respect, you are entirely and completely incorrect… [T]he NIH has not ever and does not now fund gain-of-function research in the Wuhan Institute of Virology…
The SARS-CoV-1 originated in bats in China. It would have been irresponsible of us if we did not investigate the bat viruses and the serology to see who might have been infected in China.”
From this exchange, it’s clear that Paul and Fauci have different understandings of what constitutes GoF research since they disagree on whether the heavily scrutinized 2015 study led by virologist Ralph Baric — in collaboration with the WIV’s eminent virologist Shi Zhengli — counts as GoF research. However, when one reads many reports by journalists covering the topic, it is clear that they also don’t have a clear idea of what GoF research is.
For instance, when Newsweek’s Fred Guterl fact-checked the Paul/Fauci dispute, he not only reported the allegation that the WIV was conducting GoF research as a fact, he went further and claimed that scientists around the world do the same by collecting viruses and making them more dangerous with GoF research:
Scientists in laboratories all over the world have for the past decade been collecting dangerous viruses and making them even more dangerous by performing “gain-of-function” experiments on them — manipulating the viruses to make them more infectious or deadly or both…
The Wuhan Institute of Virology, under the direction of Dr. Shi Zengli, was clearly doing GOF experiments before the pandemic arose. But GOF work is now commonplace. The real scandal is not that the Wuhan Institute was doing GOF work, it’s that everyone does it. That, and not the Wuhan lab origin theory, is what we should all be arguing about.
Everyone involved with the WIV denies GoF research allegations
To be clear, it’s undeniable that some U.S. funding went to the WIV. What is disputed is whether the research the WIV conducted with that money constitutes GoF research. However, it is crucial to note that all parties involved reject the accusation that the NIH funded GoF research, and scientists who have worked at the WIV also claim not to have performed or seen any GoF research there.
Corroborating Fauci’s claim that the NIH “has not ever and does not now fund gain-of-function research in the Wuhan Institute of Virology,” Francis Collins, director of the NIH, released a statement in support:
…[N]either NIH nor NIAID have ever approved any grant that would have supported “gain-of-function” research on coronaviruses that would have increased their transmissibility or lethality for humans.
In email exchanges, Robert Kessler, a spokesman for the EcoHealth Alliance, told The Washington Post, “The NIH has not funded gain-of-function work… 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.” 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.”
Dr. Shi Zhengli also denied that her laboratory conducted GoF research in an interview with The New York Times.
Dr. Shi, in an emailed response to questions, argued that her experiments differed from gain-of-function work because she did not set out to make a virus more dangerous, but to understand how it might jump across species.
“My lab has never conducted or cooperated in conducting GOF experiments that enhance the virulence of viruses,” she said.
Dr. Shi’s testimony is corroborated by Australian virologist Danielle Anderson, who worked at the WIV’s BSL-4 laboratory (the subject of many irrelevant speculations as the “source” of the pandemic) until November 2019. For Bloomberg, she testified that she never saw any evidence of GoF research being conducted there — while acknowledging that she wasn’t aware of what everyone was researching, owing to the WIV’s size — and supports further investigation into the WIV to rule out the lab-leak theory:
The Wuhan Institute of Virology is large enough that Anderson said she didn’t know what everyone was working on at the end of 2019. She is aware of published research from the lab that involved testing viral components for their propensity to infect human cells. Anderson is convinced no virus was made intentionally to infect people and deliberately released — one of the more disturbing theories to have emerged about the pandemic’s origins.
Anderson did concede that it would be theoretically possible for a scientist in the lab to be working on a gain of function technique, to unknowingly infect themselves, and to then unintentionally infect others in the community. But there’s no evidence that occurred and Anderson rated its likelihood as exceedingly slim.
It is quite striking that all of the parties directly or indirectly involved with the WIV have denied the allegations that the WIV was conducting GoF research, whether it was funded by the NIH or not. These statements should be given more credibility than hearsay or accusatory speculations from those not involved with the WIV, but one common tactic among lab-leak conspiracy theorists is to simply accuse those involved of “lying,” also without any evidence.
Unconfirmed allegations and sloppy reporting on GoF research
It’s not surprising that many people now seem to think they know what GoF research is, and believe that the WIV was performing GoF research, because sloppy reports earlier in the pandemic presented GoF in ill-defined ways, and reported the claims as if they were true.
Journalist Sam Husseini’s report for Salon characterized GoF research as work that “actually seeks to make deadly pathogens deadlier, in some cases making pathogens airborne that previously were not.” Husseini reported that the U.S. government issued a moratorium on GoF research in 2014 for “certain organisms” before lifting it in late 2017, though he stated that “exceptions for funding were made for dangerous gain-of-function lab work.” Husseini falsely claimed that the 2015 study cited by Rand Paul – a collaboration between the University of North Carolina, Harvard and the WIV — was among the exemptions to this “dangerous gain-of-function lab work” ban, when in fact it was not found to be GoF work at all.
An earlier alarmist Newsweek report, “The Controversial Experiments and Wuhan Lab Suspected of Starting the Coronavirus Pandemic,” also reported as fact that the WIV was engaged in GoF research:
… Wuhan Institute of Virology scientists have for the past five years been engaged in so-called “gain of function” (GoF) research, which is designed to enhance certain properties of viruses for the purpose of anticipating future pandemics. Gain-of-function techniques have been used to turn viruses into human pathogens capable of causing a global pandemic…
Some of this research involves taking deadly viruses and enhancing their ability to spread quickly through a population — research that took place over the objections of hundreds of scientists, who have warned for years of the program’s potential to cause a pandemic.
The Post published a report mischaracterizing both the WIV and the 2015 Baric study, while also reporting the claim that the WIV was engaged in GoF research as fact:
More controversial was the Wuhan institute’s 2015 research into creating a chimera, the hybrid virus that combined elements from two bat-borne coronaviruses, including one that causes SARS. The mutated virus that resulted was more easily able to infect human cells, making it more useful for lab experiments. Such “gain of function” experiments — which enhance a pathogen’s natural traits — have been a source of controversy in the West because of the potential for harm if an altered strain escapes the confinement of the lab, experts say.
Explaining relevant GoF terminology
Before attempting to explain GoF research and the Baric/Shi experiments, it is necessary to briefly explain some technical scientific terminology. In numerous reports on this topic, terms like “pathogenic,” “virulent,” “infectivity” and “transmissibility” are frequently misused to create the impression that the WIV was engaged in the controversial kind of GoF research.
Viruses are bits of genetic material and associated proteins that essentially do nothing but replicate themselves by hijacking a host cell to use its cell reproduction workshop to make copies of themselves. “Infectivity” refers to a virus’s ability to infiltrate a host cell and replicate once it does. However, just because cells can be infected doesn’t necessarily mean the host will suffer, as some viruses can infect cells without apparent harm to the host. Thus, some people infected with the virus SARS-CoV-2 are asymptomatic carriers who otherwise appear healthy, with little to no symptoms of the disease Covid-19.
A virus is either pathogenic or not, since “pathogenicity” refers to whether a virus is able to cause disease, whereas ”virulence” refers to the degree of disease caused to the host by the virus — such that lethal viruses like Ebola are very virulent while common colds are less virulent. However, it is important to stress that many people use the terms “pathogenicity” and “virulence” interchangeably.
“Transmissibility” refers to the virus’s ability to pass from one person to another, and it is possible for a virus to be highly infective without also being highly transmissible, as there are viruses that can infect a member of another species without being able to transmit easily between members of that species. An example would be viruses that have limited human-to-human transmission, where outbreaks are primarily triggered by infections from animals but die out soon after infecting a few people, like MERS.
Changing definitions of GoF research over time
Plenty of scientists have already explained that “GoF” research can be a broad and vague term. Regarding GoF research, the Times reported:
“It’s a horribly imprecise term,” said Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security.
Many gain-of-function experiments could never pose an existential threat; instead, they have provided huge benefits to humanity. In 1937, researchers found that when they passed the yellow fever virus through chicken cells, it lost the ability to cause disease in humans — a discovery that led to a vaccine for yellow fever. Likewise, herpes viruses have been engineered to gain a new function of their own: attacking cancer cells. They’re now an approved treatment for melanoma.
When Poynter reported on the spectacle between Rand Paul and Anthony Fauci in May, it cited biologist Alina Chan, one of the most prominent boosters of the lab-leak hypothesis, to make several important clarifications. She clarified that the lab-leak theory is “distinct from the hypothesis that gain-of-function research created the new coronavirus,” and that the lab-leak theory can be “as simple as a researcher being infected by an animal or even another infected person in remote areas, and then bringing it into one of the most densely populated cities on Earth.” She also explained that the definition of GoF changed over time, with the original definition including “any selection process involving an alteration of genotypes and their resulting phenotypes,” which is why subsequent definitions were narrowed to target obviously dangerous experiments that enhance the transmissibility and virulence of “potential pandemic pathogens,” as the broader definition “covers a ton of research that doesn’t even come close to risky pathogen research.”
The Post’s fact-checker, Glenn Kessler, is one of the few journalists who came closest to defining what GoF research is, according to the official 2017 definition under the P3CO framework (issued after years of deliberation on the risks and benefits of GoF research), which is research that is reasonably anticipated to enhance the virulence/pathogenicity or transmissibility of viruses in humans. In Kessler’s words:
“Gain of function” is one of those insider-y terms that are subject to different definitions… 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.
Deflating ‘Gain-of-Function’ fearmongering
The popularized notion of all GoF research being “dangerous” stems from scientific illiteracy regarding how uncontroversial it is to do many experiments. The original definition was so broad that it covered many genetic modifications that pose no threat. This is why the NIH used a more narrow definition to capture only experiments with potential harm in its 2014 moratorium, and why entire panels were created to review whether an individual experiment qualifies as GoF. Some experts have proposed different names to distinguish between the potentially dangerous and safe kinds of GoF research because some of the studies affected by the 2014 moratorium on GoF research had no risk of setting off a pandemic.
However, many fearmongering reports on GoF research ignore the fact that many GoF experiments (including many of the most feared experiments alleged to be GoF) “often also lead to loss of function.” For instance, Husseini’s report erroneously described virologist Ron Fouchier’s experiments passaging the H5N1 virus through ferrets to make it more transmissible, as having made it “more virulent,” when the opposite was true. When one actually reads the study, although the H5N1 virus became airborne transmissible when it previously wasn’t, it also became less lethal, and therefore less virulent, which is why “[n]one of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses.” However, these crucial details are omitted from Husseini’s report.
Microbiologist Stanley Perlman at the University of Iowa explained to me that, under the broader definition of GoF research, certain aspects of the WIV’s research could appropriately be characterized as “GoF” even if scientists there weren’t trying to make viruses more virulent or transmissible. But he clarified that it is “nothing in the worrisome category” because “making a virus better able to infect mice while losing the ability to infect human cells is a gain of function of sorts.”
NIH grant was funding basic research, not GoF research
One of the most frequently cited bits of “evidence” for whether the WIV was engaged in GoF research are sections from grants for the fiscal years 2018 and 2019 referenced by the disgraced science writer Nicholas Wade, found in his influential Medium blog post, which was later reprinted by the Bulletin of the Atomic Scientists:
Test predictions of CoV interspecies 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.
We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential.
According to Wade’s fearmongering presentation of these selective quotes:
What this means, in non-technical language, is that Shi set out to create novel coronaviruses with the highest possible infectivity for human cells.
It is admittedly difficult for nonscientists to interpret what these grants mean, so I reached out to experts like virologists James Duehr at the University of Pittsburgh and Stephen Goldstein at the University of Utah to help interpret their language.
Dr. Duehr explained why Wade’s characterization of Dr. Shi’s work as trying to create the “highest possible infectivity for human cells” is ridiculous, and stated that it’s more accurate to say Dr. Shi was trying to test when an animal virus’s spike protein (“S protein sequence”) becomes sufficiently compatible with human ACE2 receptors (“receptor binding,” the cellular doorway that allows SARS-CoV-2 to bind to host cells). He confirmed that “% divergence thresholds” as described in the grant are actually about trying to figure out what is the smallest % change (the “threshold”) needed at the genetic level for an animal virus to diverge into becoming a human virus capable of starting a pandemic. Claiming that Dr. Shi was trying to create coronaviruses with the “highest possible infectivity” is not only false, but also pointless because it doesn’t answer any relevant questions described in the grants designed to predict when an animal virus becomes capable of starting an epidemic in humans (“spillover potential”).
Most importantly, Duehr specified:
[Shi] wasn’t trying to make the viruses more infectious, she was just trying to figure out how infectious they already were. That’s why it isn’t “gain-of-function” research in my eyes.”
Dr. Goldstein clarified that the portions of the grants Wade cites are actually describing standard and classical methods of doing biology and virology. Goldstein stated that it’s “ridiculous” to say that Dr. Shi or Dr. Baric were trying to create “superviruses” because they were “trying to see if different coronaviruses are able to infect humans, not make them more infectious.”
This is why virologist Kristian Andersen pointed out that news outlets like Fox are confusing “Gain of Function Research” and “Basic Research.” He explained:
The bat research performed at the Wuhan Institute of Virology [of which] EcoHealth was a part, was basic research – and in fact, was instrumental in our ability to respond quickly when SARS-CoV-2 emerged.”
This is also why microbiologist Robert Garry stated that attempting to shut down basic research by confusing potentially dangerous GoF research with basic virology, where scientists “swap bits and pieces of viruses,” could backfire by endangering the world’s ability to study viruses that could be harmful to humans.
Why Rand Paul is wrong
With regard to the 2015 Baric experiments, in which chimeric viruses were created, both Dr. Goldstein and Dr. Perlman agreed with Dr. Baric’s statement denying that his study counts as GoF research, and confirmed that it is a misrepresentation to portray it as a nefarious attempt to create “superviruses,” as Rand Paul did in his confrontation with Fauci in May. Goldstein confirmed that it is “completely normal” for virologists to create chimeric viruses in a lab, and Perlman stated that the Baric experiments have no relevance to the Covid-19 pandemic because SARS-CoV-2 is not a chimeric virus.
Reading Dr. Baric’s study, one also discovers that the experiments were conducted in North Carolina, not China, with pseudoviruses that can’t cause pandemics, and that Dr. Shi had only provided the genetic sequence used in Dr. Baric’s experiments, as confirmed by an MIT Technology Review report.
Dr. Duehr explained that the Baric experiments also don’t count as GoF because taking bat virus spike proteins to facilitate the infection of human cells “isn’t increasing the infectivity of any virus, and indeed what they found is that it was very similar to the ability of the virus to infect the cell to begin with. None of their chimeras had increased ability to infect compared to the natural virus, which is why I wouldn’t characterize it as gain-of-function work.”
Although creating chimeric viruses may sound scary to some, Duehr, in a Reddit post for non-scientists, explained why virologists conduct this basic research:
If you want to show that a certain part of a virus is what allows it to infect a certain type of cells, you take that part, and you put it on a virus that, right now, can’t infect those cells.
Then, when you make the chimera, you try and infect the cells with it. If you’re successful, you’ve shown that the part you spliced in (the “spike” in this case) was sufficient for infection! And you can also go to the original virus, the one you stole the spike from, and trade its spike for the new one that couldn’t infect. And if, now, the old virus with the new spike can’t infect, then you’ve also shown the spike was “necessary.” Necessary and sufficient.
Along the way, you’ve demonstrated that part of the virus (the spike) would be a great target for a vaccine! And that drugs that inactivate this part of the virus could be very useful.
When one understands the science, it is clear why all the parties involved with the WIV deny that U.S. money was funding GoF research there, why WIV scientists claim they haven’t performed GoF research, and why there’s no evidence they’re “lying.”
It is also how we can confirm that Anthony Fauci is correct to say that Rand Paul is lying and doesn’t know what he’s talking about when he claimed that “all the evidence is pointing that it came from a lab,” when Paul falsely accused Fauci of lying about GoF during their second publicized confrontation in July.
— Marc Lipsitch (@mlipsitch) May 13, 2021
Numerous scientists defended Fauci’s statements and explained that the 2017 paper Paul was citing in that confrontation does not count as GoF research because the viruses retained function: they were already capable of infecting human cells, and didn’t become any better at doing so afterwards.
GOF research on known viruses couldn’t create SARS-CoV-2
It should be deeply disturbing that much of the popularized evidence-free lab-leak speculations depended on the major premise that the WIV was engaged in GoF research, which is yet another set of evidence-free speculations. However, a much more potent argument is that GoF research couldn’t have created SARS-CoV-2 even if WIV scientists had tried.
There is a credulous belief among lab-leak theorists that GoF research can serve as some kind of deus ex machina to explain why their pet conspiracy theory can be true, but this is demonstrably false because such GoF experiments also have their limitations.
Novelist Nicholson Baker has published a lengthy speculation in New York Magazine arguing that SARS-CoV-2 was “designed,” and cites methods like “no-see’m” as ways for scientists to manipulate viruses without “any signs of human handiwork.” In contrast, prominent scientists like microbiologist Susan Weiss and virologist Linfa Wang have argued that they couldn’t create SARS-CoV-2, even if they tried.
Sam Husseini criticized virologists like Kristian Andersen for supposedly not considering “other lab methods” that could have created coronavirus mutations without leaving behind any laboratory signatures in an influential Nature study, which concluded that they “do not believe that any laboratory-based scenario is plausible” for the Covid-19 pandemic. Husseini argued, implying Dr. Andersen’s naivete, that “other forms of lab manipulation” besides bioengineering — such as “serial passage,” where one passages a virus through animals (rather than cell culture) to induce mutations — could have created SARS-CoV-2.
Husseini credulously cites biologist Richard Ebright’s claim:
Very easy to imagine the equivalent of the Fouchier’s “10 passages in ferrets” with H5N1 influenza virus but, in this case, with 10 passages in non-human primates with bat coronavirus RaTG13 or bat coronavirus KP876546.
Plenty of things, however, are “very easy to imagine” without being plausible, as scientists like Dr. Garry and Dr. Perlman have clarified that in order to construct SARS-CoV-2 with GoF experiments one would need a virus backbone that matches at least 99% of its genome, if not as high as 99.9%. This is why Dr. Goldstein told me that the odds of someone creating SARS-CoV-2 from RaTG13 (previously the closest known relative to SARS-CoV-2, with a 96% genome match, until Laotian and French scientists published a preprint this month, a study yet to be peer-reviewed, reportedly finding three bat viruses that are the closest relatives to SARS-CoV-2 in Laos) are “zero percent.”
A review in a peer-reviewed journal by over twenty of the world’s eminent virologists argues that the 4% genetic distance between the SARS-CoV-2 and RaTG13 genomes (equivalent to approximately 1,150 mutations) reflects decades of evolutionary change, and that the discovery of other bat viruses — not collected by the WIV and sequenced after the pandemic began — which share a more recent common ancestor with SARS-CoV-2 than RaTG13, demonstrates “beyond reasonable doubt that RaTG13 is not the progenitor of SARS-CoV-2, with or without laboratory manipulation or experimental mutagenesis.”
Dr. Perlman also explained that passaging a virus through non-human primates or humanized mice to make a virus more virulent or transmissible to those species doesn’t necessarily mean it would be capable of infecting humans, as many animal viruses aren’t capable of infecting humans.
This demonstrates that those claiming that GoF research on viruses like RaTG13 is capable of creating SARS-CoV-2 are either misrepresenting the capabilities of GoF research or are simply unaware of its limitations.
The Intercept’s dodgy reporting on “gain-of-function” research
In light of all this information, it becomes obvious why The Intercept’s latest reporting detailing research by the WIV based on an NIH grant to the EcoHealth Alliance, obtained through Freedom of Information Act litigation, is so misleading. I previously reported that The Intercept did not understand the significance of their own documents when they tried to misleadingly present them as “new” information that “raise[s] additional questions about the theory that the pandemic may have begun in a lab accident,” when it is actually evidence against a lab leak.
The grant confirmed what we have already known since the beginning of the pandemic: that the WIV was merely doing research on viruses related to SARS-CoV-1, not SARS-CoV-2. SARS-CoV-1 is even more genetically distant from SARS-CoV-2 than is RaTG13, sharing only ~80% of its genome, which means that SARS-CoV-1-like viruses are even further removed than the minimal 99% genetic similarity required for a virus to plausibly serve as the backbone for SARS-CoV-2 being created from GoF experimentation. This may be why The Intercept clarified in a later incoherent and contradictory report, “NIH Documents Provide New Evidence U.S. Funded Gain-of-Function Research in Wuhan,” that the experiments with transgenic mice, which it cites as “new evidence” that the WIV was conducting GoF research, “could not have directly sparked the pandemic:”
None of the viruses listed in the write-ups of the experiment are related to the virus that causes Covid-19, SARS-CoV-2, closely enough to have evolved into it.
However, when one reads the report carefully, it is clear that the documents don’t in fact provide “new” evidence that the WIV was engaged in GoF research. The Intercept actually notes that the experiments being discussed were already reviewed twice by the NIH and deemed not to be GoF, and even cites their explanations. The NIH argued that WIV research published in 2017 showed that in cells in a laboratory, similar chimeric viruses reproduced less effectively than the original, making it more appropriate to describe it as “loss of function,” not a “gain of function.” Yet another reason the NIH gave was that although the differences in the rates of viral reproduction were particularly pronounced two and four days after the mice were infected with the virus, the amount of virus produced by the parent and chimeric strains “evened out” by the end of the experiment.
In other words, the NIH’s rationale is that experiments with chimeric viruses created with WIV1 as the parent virus (a virus that hasn’t been shown to cause disease in humans) between 2017 and 2018 resulted in either a loss of function or retained function by the experiments’ conclusion. The Intercept actually cites the EcoHealth Alliance’s argument that the NIH grant being renewed in 2019 — despite being informed twice about the WIV transgenic-mice experiment briefly passing the official virus growth benchmark, where scientists have to cease experiments and inform relevant authorities, before subsiding below it by the end of the experiment — is evidence the organization did nothing wrong procedurally. Both Dr. Perlman and Dr. Duehr agreed that the EcoHealth Alliance was “following the rules.” Virologist Angela Rasmussen at the University of Saskatchewan added: “There’s no evidence of malfeasance here; this is evidence that they were reporting the work they were doing to program, exactly as they are supposed to.”
The Intercept tried to argue that the NIH was wrong not to deem the experiments GoF, such evidence notwithstanding, by citing the majority opinion among 11 scientists they selected to opine on their documents, which considers the experiments to be GoF based on two main arguments:
Scientists working under a 2014 NIH grant to the EcoHealth Alliance to study bat coronaviruses combined the genetic material from a “parent” coronavirus known as WIV1 with other viruses. They twice submitted summaries of their work that showed that, when in the lungs of genetically engineered mice, three altered bat coronaviruses at times reproduced far more quickly than the original virus on which they were based. The altered viruses were also somewhat more pathogenic, with one causing the mice to lose significant weight. The researchers reported, “These results demonstrate varying pathogenicity of SARSr-CoVs with different spike proteins in humanized mice.”
However, The Intercept’s journalists don’t demonstrate a clear understanding of the significance of the “reasonably anticipated” clause in official definitions of GoF — or the significance of the fact that human beings are different animal species from transgenic mice — when they cite seven out of 11 scientists claiming the transgenic mice experiments meet the NIH’s criteria for GoF research, without including how each scientist defined GoF research.
The biggest clue showing The Intercept’s journalists don’t understand either of these crucial concepts is when they cite the sole dissenting scientist, Dr. Rasmussen, arguing that the experiments don’t meet the NIH’s criteria for GoF research (three out of the 11 scientists stated they didn’t have enough knowledge about U.S. policies to determine whether the WIV experiments met the NIH’s criteria), without ever explaining why they believe she’s wrong. Dr. Rasmussen argued that the experiment “absolutely does not meet the bar” for GoF research because “[y]ou can’t predict that these viruses would be more pathogenic, or even pathogenic at all, in people,” and since WIV scientists “did not study transmissibility at all in these experiments.”
Examining Dr. Rasmussen’s logic, it’s clear that reasonable anticipation of the viruses studied becoming more virulent or transmissible in humans is an essential component of her definition of GoF research, as she rejects that these experiments constitute GoF because WIV scientists weren’t studying transmissibility, and could not anticipate whether these chimeric viruses would be pathogenic or more virulent in people. This precludes the intentionality required to make viruses “more pathogenic or transmissible” in The Intercept’s own stated GoF definition.
Dr. Perlman (who does a lot of research with humanized mice) confirmed that The Intercept’s report contained “essentially no new information” and stated that “everything depends on how one defines gain of function,” and that one could potentially receive different answers depending on “whom you ask.” He stated that if one defines GoF as making something more virulent or transmissible in mammals like mice, then it “would technically count as gain-of-function.” But Perlman ultimately agreed with Dr. Rasmussen and the NIH’s rationale for not deeming those experiments GoF, and stated that “it’s gain-of-function for mice, but not for people” because making viruses more virulent or transmissible in mice doesn’t necessarily mean they would be in humans, since humanized mice aren’t humans.
As did Rasmussen, Perlman questioned the relevance of whether the WIV’s transgenic mice experiments constituted GoF research, and stated that a virus becoming more virulent or transmissible “in humans” is an essential component of his GoF definition, and clearly also a part of the NIH’s definition cited by The Intercept. The NIH told The Intercept that they never approved “any research that would make a coronavirus more dangerous to humans,” and that the changes to the chimeric viruses “would not be anticipated to increase virulence or transmissibility in humans.”
Perlman also cited The Intercept’s inclusion of microbiologist Vincent Racanellio’s statement that “[y]ou can do some kinds of gain-of-function research that then has unforeseen consequences and may be a problem, but that’s not the case here,” as evidence that some of the seven scientists arguing that the transgenic mice experiments constitute GoF research may not consider making a virus more virulent or transmissible in humans an essential part of their GoF definition.
Yet The Intercept omits the critical distinction between humans and mice as different species in their definition of GoF as merely “intentionally making viruses more pathogenic or transmissible.” They try to make it seem as if differing definitions of GoF aren’t important when they cite Jacques van Helden, a professor of bioinformatics at Aix-Marseille Université, arguing that debate over defining GoF “has been too much focused on technical aspects,” when those “technical aspects” could determine everything.
Dr. Duehr agreed with the NIH and Dr. Rasmussen’s arguments because he also considers “reasonable anticipation” of the viruses becoming more virulent or transmissible “in humans” to be essential components of his GoF definition. However, he does not consider the transgenic-mice experiments to be GoF, even for mice, because he argued “the most important part” to consider is that WIV scientists “weren’t passaging the virus in mice,” and “only infected them once” to measure the chimeric viruses’ effects on mice, not to intentionally make them more virulent (p. 298). Duehr explained that in order for a virus to reliably gain a function for a species, one would need to passage a virus multiple times through different individual members of that species, like Fouchier’s ferret experiments, because “one round of replication does not adaptation make,” since there’s “variation among members of animal species.”
The Intercept’s flawed methodology
Out of the 11 scientists The Intercept claims to have contacted, only six of them are identified, and their report omits critical information such as how each scientist defines GoF. We don’t know, for instance, whether The Intercept asked these scientists whether those experiments could be reasonably anticipated to enhance virulence or transmissibility of those viruses for humans. If some or all of the seven scientists who argued that the WIV experiments constitute GoF for mice would reject that they constitute GoF for humans, then that dramatically changes how worried people should be about those experiments, and raises the question of why The Intercept would omit such necessary information.
Even if one concedes, for the sake of argument, that the WIV experiments are GoF in mice, The Intercept doesn’t explain what relevance that would have for humans. If animals like transgenic/humanized mice could serve as perfect predictors for how viruses and drugs would behave in humans, then there would be no need for human research after animal research.
There’s reason to suspect that The Intercept’s methodology of arguing that the NIH’s decision was wrong — based merely on tallying up the opinions of the scientists they contacted, without refuting Dr. Rasmussen and the NIH’s arguments — is unreliable. Their first bad-faith report on the grant asked only scientists who have been promoting the lab-leak theory, Richard Ebright and Alina Chan, to opine on their documents — hinting that the lab-leak theory is a predetermined narrative for the report’s authors Sharon Lerner and Mara Hvistendahl — and it’s possible that The Intercept is engaged in similarly biased source selection with this report too. Dr. Duehr stated that if reporters really want to argue that the NIH was wrong by merely tallying the opinion of scientists instead of making their own argument, then the proper approach would be to “ask an unbiased large sample of people with relevant expertise, not just people who already agree with you, or [a] few people.”
The fact that Intercept journalists credulously cite biologist Stuart Newman’s irrelevant statements like “making chimeric coronaviruses, mixing and matching RBDs [a part of the virus that allows it to attach to receptors] and spike proteins” being “exactly the scenario imagined” by lab-leak theorists is proof that they don’t understand basic information about SARS-CoV-2 not being a chimeric virus, with no signs of human manipulation, acknowledged even by lab-leak boosters like Richard Ebright.
Even RaTG13, which shares a 96% genome match with SARS-CoV-2, has over a thousand nucleotide differences spread throughout its genome like raisins in a pudding, not just in the receptor binding domain and spike protein sequences, which means scientists can’t just “mix and match” RBDs and spike proteins, like cutting and pasting paragraphs of an essay, to create SARS-CoV-2 with chimeric experiments. If Intercept journalists don’t even understand basic information about SARS-CoV-2’s genome, what reason is there to trust their judgment on which scientists to contact or believe?
When I reached out to Dr. Rasmussen for comment, she confirmed that The Intercept’s Sharon Lerner and Mara Hvistendahl were explicitly informed that their methodology of presenting people like Richard Ebright and Alina Chan as experts equivalent with actual virologists like herself, or experts on dual-use research, is flawed because they don’t have the relevant expertise to assess whether a study presents an undue risk. Rasmussen also confirmed that they were explicitly informed that it is a mistake to call the hACE2 transgenic mice used in the WIV experiment “humanized mice” in their report (even if the grant itself referred to them as “humanized mice”) because “[e]xpressing a single human gene” does not “render a mouse analogous to a human,” and that they had the critical distinction between the “fundamentally different physiology” of different animal species explained to them. This means that they were not merely ignorant, but deliberately omitted critical information by creating the misimpression to a general audience that mice are analogous to humans and insisting on erroneously using the term “humanized mice” throughout their report despite correction.
After examining their email correspondence, I confirmed that Dr. Rasmussen was asked only general questions like “Did the work described below fit NIH’s definition of GoF research at the time?” instead of more precise questions referencing specific NIH documents containing definitions for GoF. She also clarified that her understanding of GoF research being lab work that’s reasonably anticipated to enhance the virulence and/or transmissibility of viruses in humans is not an arbitrary or idiosyncratic one. She answered the question of whether the 2017-2018 transgenic mice experiments met the NIH’s criteria for GoF according to the 2017 P3CO framework that defines potential pandemic pathogens, which was drawn up by the NIH, and even referenced by The Intercept in their own article.
If other scientists contacted by The Intercept were asked similarly vague questions like Dr. Rasmussen, this left more room for scientists to answer whether the transgenic mice experiments qualify as GoF in open-ended ways. Rasmussen also stated that criticisms of the U.S. government’s oversight process are a “separate question” from how GoF is “defined currently by the U.S. government.”
None of the other five named scientists explain why the NIH and Dr. Rasmussen’s arguments related to reasonable anticipation or relevance to humans are wrong and thus there is no logically necessary reason for readers to conclude that the NIH and Dr. Rasmussen are wrong. Certainly not based on a mere tally of a small and apparently arbitrary selection of scientists by The Intercept, especially when they omit necessary context such as how each scientist defines GoF.
Leaked EcoHealth Alliance grant not evidence of GoF research in Wuhan
Many of the same points made above apply to the latest Intercept report on a grant proposal from the EcoHealth Alliance rejected by the Defense Advanced Research Projects Agency (DARPA) in 2018, which was leaked by DRASTIC, a group of internet activists pursuing the lab-leak theory. Assuming the documents are authentic, the grant proposed things like creating full-length infectious clones of SARS-CoV-1-like coronaviruses and inserting a “proteolytic cleavage site” into bat coronaviruses. One type of cleavage site was able to interact with furin, an enzyme expressed in human cells, and has drawn attention because SARS-CoV-2’s furin cleavage site has never been seen before among sarbecoviruses (the category of viruses to which SARS-CoV-2 belongs), which is why some lab-leak theorists suspect it doesn’t have natural origins.
However, The Intercept omits that furin cleavage sites are “commonplace in other coronavirus spike proteins,” such as MERS and other endemic human coronaviruses. Virologist Stuart Neil’s Twitter analysis on the leaked documents noted that although the EcoHealth Alliance proposed what could appropriately be called GoF research, the important thing to note is that the SARS-CoV-1-like coronaviruses are too genetically distant and “can’t possibly be the source” of SARS-CoV-2.
14. So the nature of the recombinant viruses that would accept the spikes id’d by WIV – more of the same. Using WIV1, and the 2 other SARS CoV1 related viruses. GoF or not, these (a) can’t possibly be the source of SARS2 and (b) would have been done in the US not China
— Stuart Neil (@stuartjdneil) September 23, 2021
He also noted that the proposal (which was never funded), would have been carried out in the U.S., not China, since the WIV’s major role in the proposal was to sample and sequence viruses, not do any molecular virology, consistent with the division of labor in previous collaborations with Dr. Baric. This is why Dr. Goldstein told The Intercept that it’s “hard to assess any bearing” the documents have on pandemic origins. SARS-CoV-2 is also not a chimeric virus, and inserting a furin cleavage site into SARS-CoV-1-like coronaviruses that haven’t been shown to cause disease in humans wouldn’t be able to create SARS-CoV-2 anyways.
The Intercept notes that scientists have argued that there’s “no logical reason” why an engineered virus would utilize such a “suboptimal” furin cleavage site, which would just be “an unusual and needlessly complex feat of genetic engineering,” since scientists can just insert furin cleavage sites known to be more efficient, and as there was “no evidence of prior research at the WIV involving the artificial insertion of complete furin cleavage sites into coronaviruses.” However, it still implied that the WIV could have found other ways to “pay for the experiments” and do the work on their own, despite how unusual, or ethically out of character, that would be for someone like Dr. Shi Zhengli, who, according to Dr. Rasmussen, is “by all accounts [a] good collaborator.” Thus far, although the leaked documents may raise legitimate questions about transparency from the EcoHealth Alliance, there is no evidence the WIV was engaged in GoF research that is reasonably anticipated to enhance the virulence or transmissibility of pathogens in humans — only a lot of innuendo.
The ‘Lying Chinese’ redux
Ultimately, lab-leak conspiracy theorists resort to these ever-shifting appeals to possible explanations like “no-see’m” and “serial passage” (without arguing for a specific scenario), and reject the credibility of scientists, because there is no evidence for a lab leak or laboratory manipulation of SARS-CoV-2. Some even go so far as to speculate that Chinese scientists have been using U.S. grant money to conduct GoF research in secret, as when Senator John Kennedy (R-LA) questioned Anthony Fauci on whether “the Chinese” would “lie” to him, since the grants typically cited as “evidence” don’t prove that the WIV was doing GoF research.
GoF research is subject to intense government scrutiny and oversight and is hard to do under the radar. But even if it were true that the WIV was conducting GoF research, it has no relevance to the Covid-19 pandemic unless it can be shown that it possessed SARS-CoV-2, or an undisclosed virus that is genetically closer to it than is RaTG13, prior to the pandemic. GoF research on known viruses being unable to create SARS-CoV-2 may be why some accuse the WIV of possessing an undisclosed virus and hiding research on it from international scientists with whom they collaborate. However, Dr. Shi has denied that she conducted or collaborated on any GoF experiments on coronaviruses that weren’t published, and many scientists have also pointed out there’s “no evidence that the WIV sequenced a virus that is closer to SARS-CoV-2 than [is] RaTG13, and no reason to hide research on a SARS-CoV-2-like virus prior to the COVID-19 pandemic.”
These neverending accusations and assumptions that Chinese scientists are lying, without evidence, are rooted in Orientalist tropes of the “dishonest Chinese” based on centuries of Western Yellow Peril propaganda, which is why some equate lack of evidence for a lab leak with evidence of a “coverup.”
Dr. James Duehr assisted with fact checking this article, and Dr. Diana Lu provided research assistance.
Feature photo | A view of the Wuhan Institute of Virology’s P4 lab after a visit by a WHO team on Feb. 3, 2021. Ng Han Guan | AP
Joshua Cho is a Korean-American writer based in New York.