Why Gain of Function Study on Viruses was Secretly Authorized by Fauci. Risks and Potential Benefits. Scientific American Repost. 2021-06-14. By Emily Willingham on June 14, 2021

Why Scientists Tweak Lab Viruses to Make Them More Contagious. This is a repost of various soures and I add my edits in as well. Some “gain of function” studies explore how a dangerous pathogen might cross species barriers to start an outbreak. They are not without controversy. Jyrkkanen Comment: [They are in my opinion an enormous threat for two reasons. They can be abused for bioterrorism and biological warfare by covert rogue actors and they can escape the lab by mistake or by design by careless or rogue actors for nefarious purposes.] By Emily Willingham on June 14, 2021 Why Scientists Tweak Lab Viruses to Make Them More Contagious Security suits for a biosafety training lab at Rocky Mountain Laboratories in Hamilton, Mont. Credit: Preston Gannaway Getty Images The microbiology toolbox includes techniques to induce mutations in viruses that give the microbes new powers. Scientists perform these manipulations for many reasons, including wanting to understand how the microbes evade detection by our immune systems. But adding capability to a pathogen carries obvious risks, especially if this “gain of function” involves enhanced virulence or infectiousness. Escape from a lab, by accident or design, is a possibility. So why do it? Some researchers argue the work can offer a peek at what a virus can do before it goes into the natural world and poses a threat to people. Controversy over gain-of-function research has generated academic papers, conferences and even a moratorium in 2014, when the U.S. government paused funding for three years until steps could be taken to ensure the safety of the procedure. Debate about gain-of-function experiments continues in the latter phases of the pandemic as thoughts turn to the “next one” or a possible second act for COVID-19. Science policy makers must wrestle with defining the rare instances in which the benefits of experiments that enhance a virus’s capacity to survive and flourish in human hosts outweigh any risks. Densely technical discussions often bog down over the very definition of gain of function. Recently, semantics were front and center in the debate over whether National Institutes of Health–funded work at the Wuhan Institute of Virology (WIV) in China constituted gain-of-function research, a contention denied by the U.S. agency. The WIV has also been the focus of a revived dispute over whether SARS-CoV-2, the virus that causes COVID-19, escaped from its facility. Advertisement Here are a few basic answers to questions about why an obscure technical term now receives so much attention. What is gain of function research? Techniques to enhance some aspect of an organism’s functioning are commonplace in research and applied to everything from mice to measles. One typical application of this approach is tweaking mouse genes to generate more of a protein that limits fat deposition. But that is not the kind of gain-of-function study that raises fears among scientists and regulators. The high-risk practices are those that create mutations to examine whether a pathogen becomes more contagious or lethal as a means of estimating future threats. Some experts acknowledge the critical differences between the two types of studies. One proposed term to represent the more threatening subset of this research is “potential pandemic pathogens,” says Marc Lipsitch, a professor of epidemiology at the Harvard T. H. Chan School of Public Health. That phrase “singles out the name and reason for being concerned,” he adds. It has not caught on in common usage, however, returning only about 8,500 results in a Google search, compared with 13.4 million for “gain of function.” Advertisement Making this distinction is important for a few reasons, Lipsitch says. When the U.S. government placed the 2014 moratorium on “gain of function research,” some of the studies that were affected carried no obvious risk of setting off a pandemic. What is the purpose of this research? Knowing what makes a microbe more dangerous enables preparation of countermeasures, says Lipsitch, who is one of 18 signatories to a May 14 letter, published in Science, that calls for the investigation of a SARS-CoV-2 lab spillover as one of several possible explanations for the origins of the COVID-19 pandemic. He points to the difficulties of studying viruses for the development of vaccines and treatments without doing experiments in a mouse or in other nonhuman animals. There is, Lipsitch says, a “direct path from doing that research to gaining public health benefits,” enabling a balancing of risks and potential benefits. newsletter promo Sign up for Scientific American’s free newsletters. The riskier version of gain-of-function research creates viruses with abilities they do not have in nature. In two separate studies in 2011, scientists famously and controversially did just that with the H5N1 influenza virus, or “bird flu,” resulting in a version capable of airborne transmission among ferrets. The naturally occurring virus does not have this ability. Making mammal-to-mammal transmission easier set off alarm bells and triggered discussion of a U.S. moratorium. In 2015 researchers engineered a hybrid pathogen that combined features of the original SARS virus (SARS-CoV) that infected humans in the early 2000s with that of a bat coronavirus. Most bat coronaviruses cannot infect the cells lining the human respiratory tract. This experiment was intended to mimic what would happen if a third species served as a mixing vat for the bat and human viruses to exchange genetic material. The result was a pathogen that could enter human cells and also cause disease in mice. Reactions to this work were polarized, as demonstrated by experts quoted in a 2015 article in Nature: one said that all the research did was create a “new, non-natural risk” among the multitude that already exist, while another contended that it showed the potential for this bat virus to become a “clear and present danger.” Advertisement Experts in the latter camp argue that gain-of-function virus studies can presage what will eventually happen in nature. Speeding things up in the lab gives researchers firsthand evidence about how a virus might evolve. Such insights could drive predictions about future viral behaviors in order to stay a step ahead of these pathogens. That calculation must be made on a case-by-case basis, Lipsitch says. “There is not one-answer-fits-all,” he adds. But the key question to address in this complex computation is “Is this work so valuable for public health that it outshines the risk to public health in doing it?” Lipsitch was “very outspoken,” as he puts it, about the influenza-ferret study, and he led the effort for the 2014 moratorium on similar gain-of-function work. “I did that because I thought that we need to have a real accounting of the benefits and risks,” he says. “I had a view that the benefits were very small, and I still have that view.” The moratorium was lifted in 2017. A U.S. government review panel later approved a resumption of funding for more lab studies involving gain-of-function modifications of bird flu viruses in ferrets. Conditions of the approvals, according to reports, included enhanced safety measures and reporting requirements. As for SARS-CoV-2, the virus of most urgent interest right now, the NIH released a statement on May 19 that neither the agency nor its National Institute of Allergy and Infectious Diseases has “ever approved any grant that would have supported ‘gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans.” Advertisement What are the risks? Predictions based on gain-of-function studies may be hypothetical, but lab breaches in the U.S. are not. Serious violations are uncommon and have almost never resulted in a pathogen being released into the community. But 2014 showed why human error may prove to be the biggest wild card in planning these experiments. Several lab accidents that year endangered researchers and set off waves of uneasiness. These incidents were not gain-of-function mishaps, but they demonstrated the potential threats posed by a biosafety lab—whether from negligence or malfeasance. In 2014 about 75 Atlanta-based employees at the U.S. Centers for Disease Control and Prevention learned about their potential exposure to anthrax after safety practices were ignored. Also, several long-forgotten vials of freeze-dried smallpox—a pathogen long thought to be stored in only two places, one in Russia and one in the U.S.—turned up during a cold-storage cleanup at the NIH that year. And the CDC made news again a month later, after it sent out vials of a relatively benign influenza virus contaminated with the much more deadly H5N1 avian flu virus. The possible reason, as reported in Science, was that a researcher was “overworked and rushing to make a lab meeting.” Michael Imperiale, a professor of microbiology and immunology and associate vice president for research and compliance at the University of Michigan, co-authored a 2020 editorial about gain-of-function studies that said that the key to planning them is to have proper mechanisms to ward off the threats of accidental or intentional harm. “If proper biosafety procedures are in place and proper containment is used, the risks can be mitigated substantially,” he says. Biosafety level 4 (BSL-4) labs have the highest containment precautions in place, and the U.S. currently has 13 or more such facilities planned or in operation. Research on the novel coronavirus is handled in labs one notch down: BSL-3. In their editorial, Imperiale and his co-author Arturo Casadevall, editor in chief of mBIO, wrote that even predicting the threat level of an accidental release is difficult. After publication of the studies of ferret-to-ferret transmission of engineered H5N1, two groups tried to predict what would have happened if this virus had escaped into the human population. One team, Imperiale and Casadevall wrote, predicted an “extremely high level” of transmission. The other, from one of the labs involved in the ferret-influenza work, concluded otherwise. Advertisement In the context of the COVID-19 pandemic, the authors of the editorial wrote, the source of a pathogen—whether from nature or a lab—does not change how the world should prepare to respond to it. But gain-of-function experiments should be governed by transparency in planning the research, a “rededication” to biosafety and a strong surveillance program to capture breaches. What alternative techniques are available to test a potential viral threat? If a virus has already moved from an animal host to humans, gain-of-function research may be unnecessary, Imperiale says. “In these cases, there may be animal models that serve as useful surrogates for humans” in testing the virus’s effects, he says. Researchers can also test the capacity of virus proteins to engage with different kinds of cells. Software can predict how these proteins might interact with various cell types or how their genetic sequences could be associated with specific virus features. Also, if the researchers use cells in a lab dish, the viruses might be designed not to replicate. Another option is loss-of-function research. Using versions of a virus with less pathogenic potential is another way to unlock that microbe’s secrets. Still, highly pathogenic forms can be quite different from their less threatening counterparts—for example, they may differ in how often they replicate—possibly limiting the usefulness of such studies. Fauci Coverup

‘Bombshell’ New Emails Reveal Dr. Fauci was Part of NIH and WHO Conspiracy to Silence Wuhan Lab Leak Theory Dr. Anthony Fauci, once considered America’s ‘top Covid doc,’ conspired with influential scientists around the world, including at the World Health Organization, to quell concerns that SARS-CoV-2 may have leaked from the Wuhan Institute of Virology, newly unredacted emails show. The newly released emails raise questions about Dr. Fauci’s motives in dispelling public scrutiny over the potential the novel coronavirus had escaped from the Wuhan laboratory. Fauci had misled Congress over the extent that the National Institutes of Health had funded the Wuhan lab as a subcontractor of EcoHealth Alliance. The Wuhan laboratory was also funded by the Pentagon, contract awards show. The unredacted NIH emails show how public questioning that SARS-CoV-2 may have escaped from a laboratory was a concern for the group’s scientists lest it become a “conspiracy theory.” Emails were exchanged among Dr. Anthony Fauci, the National Institute for Allergy and Infectious Diseases chief; Sir Jeremy Farrar, a top scientist at the World Health Organization; Kristian Andersen, a leading immunologist and microbiologist with Scripps Research; Professor Edward Holmes, a biologist at the University of Sydney; Dr. Francis Collins, former Director of the National Institutes of Health; Chris Elias of the Bill & Melinda Gates Foundation; George Fu Gao of the Chinese Center for Disease Control and Prevention; Viktor J. Dzau of Duke University; and various other influential scientists and philanthropists around the world. An academic paper, “The Proximal Origin of SARS-CoV-2,” published on March 17, 2021, had definitively propped up the rival theory to the lab leak theory that SARS-CoV-2 had natural origins. But the final form of the paper was far afield of its initial stages, as shown by the NIH emails. The influential academic paper evolved from its early stages seriously entertaining three rival hypotheses (the bioengineered theory, the lab leak theory, and the natural origins theory) to one that attempted to close the book on public inquiry into the possibility that SARS-CoV-2 had escaped from the Wuhan laboratory. "*" indicates required fields Who's your favorite former President?* Trump Obama Email* This poll gives you free access to our premium politics newsletter. Unsubscribe at any time. This evolution was due in no small part to the feedback from Dr. Anthony Fauci, Dr. Francis Collins, and Sir Jeremy Farrar, the unredacted emails show. The academic paper upon publication was soon weaponized by the mainstream press to attack critics of the Wuhan laboratory as “conspiracy theorists”; but behind-the-scenes the authors themselves were taking the possibility that the virus escaped from a laboratory more seriously. (Recent insights into the strong probability that SARS-CoV-2 originated in a laboratory bears out that the authors’ inclination to take the lab leak theory seriously was justified, as will be briefly covered below.) The Intercept, the publication that obtained the unredacted emails, gives an overview of the paper’s influence on the national debate. Drawing on “comparative analysis of genomic data,” the paper’s authors wrote that “our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated construct.” Toward the end of the paper, they added, “we do not believe that any type of laboratory-based scenario is plausible” in explaining the origin of the virus. Instead, the scientists strongly favored a natural origin, arguing that the virus likely spilled from bats into humans, possibly by way of an intermediate animal host. The peer-reviewed paper proved to be hugely influential. Dr. Francis Collins, then the director of the National Institutes of Health, or NIH, announced its findings in a post on the agency’s website in late March 2020. When asked during an April 17 press briefing at the White House about concerns that SARS-CoV-2 had come out of a lab in China, Dr. Anthony Fauci, who recently stepped down as head of the National Institute of Allergy and Infectious Diseases, referenced the paper, describing its conclusions and calling its authors “a group of highly qualified evolutionary virologists.” The paper has been accessed online more than 5.7 million times and has been cited by more than 2,000 media outlets. ABC News, for instance, ran an article on March 27 titled “Sorry, Conspiracy Theorists. Study Concludes Covid-19 ‘Is Not a Laboratory Construct.’” In that article, one of the paper’s authors, Robert Garry, is quoted saying, “There’s a lot of speculation and conspiracy theories that went to a pretty high level, so we felt it was important to get a team together to examine evidence of this new coronavirus to determine what we could about the origin.” The author of the Intercept’s article, Jimmy Tobias, explains that the pre-published version of the academic paper had provoked pushback from the group led by Fauci, Collins, and Farrar. What that quote didn’t quite convey was that Garry and several of the paper’s other co-authors were themselves initially suspicious that SARS-CoV-2 may have emerged from a lab. They communicated their suspicions to Fauci, Collins, and others in late January and early February 2020, and what ensued was a period of intense and confidential deliberation about the origin of the virus. Two of the paper’s authors, Edward C. Holmes and Kristian Anderson, had seriously enterained the “lab side” of the Covid origins investigation. But Dr. Francis Collins and Farrar “nudged” them incrementally away from the lab leak theory and toward the natural origins theory — including with information that would later prove to be inaccurate. After reviewing the summary document from Holmes and his team, Collins responded: “Very thoughtful analysis. I note that Eddie is now arguing against the idea that this is the product of intentional human engineering. But repeated tissue culture passage is still an option—though it doesn’t explain the O-linked glycans.” Dr. Collins and Farrar steered the authors away from even entertaining the notion that SARS-CoV-2 was “engineered” in a laboratory. Farrar replied to the thread: “Being very careful in the morning wording. ‘Engineered’ probably not. Remains very real possibility of accidental lab passage in animals to give glycans.” “Eddie would be 60:40 lab side,” Farrar added. “I remain 50:50.” “Yes, I’d be interested in the proposal of accidental lab passage in animals (which ones?),” Collins wrote. “?? Serial passage in ACE2-transgenic mice,” Fauci responded. “Exactly!” Farrar replied. “Surely that wouldn’t be done in a BSL-2 lab?” Collins asked, referring to biosafety level 2 labs. “Wild West…” was Farrar’s response. This is a particularly damning phrase, given Dr. Fauci’s funding of gain-of-function research at the Wuhan Institute of Virology. Intentional or not, the sensitive research has bioweapons implications. And nothing in China is beyond the reach of the Chinese Communist Party. On February 7, Farrar notified Fauci and Collins with data that proved to be inaccurate about the presence of coronaviruses in pangolins. “Reports coming out overnight that Chinese group have pangolin viruses that are 99% similar,” Farrar wrote. “This would be a crucially important finding and if true could be the ‘missing link’ and explain a natural evolutionary link.” “That will be VERY interesting,” Collins responded. “Does it have the furin cleavage site?” As Tobias notes, the pangolin data did not provide an explanation for the scientists’ central concerns about the furin cleavage site. “The viruses isolated from some pangolins were not 99 percent similar to SARS-CoV-2, but the data did show that coronaviruses circulating in pangolins shared other key features with the pandemic virus,” Tobias explains. “This seems to have played an important role in shifting the scientists’ thinking away from the lab hypothesis.” Holmes, who had been “60:40 lab side,” shifted his position: “Personally, with the pangolin virus possessing 6/6 key sites in the receptor binding domain, I am in favour of the natural evolution theory.” Christian Drosten, a scientist from Germany, then provided an observation about the email exchanges: “Can someone help me with one question: didn’t we congregate to challenge a certain theory, and if we could, drop it?” “Who came up with this story in the beginning?” he added. “Are we working on debunking our own conspiracy theory?” Holmes replied: “Ever since this outbreak started there have been suggestions that the virus escaped from the Wuhan lab, if only because of the coincidence of where the outbreak occurred and the location of the lab. I do a lot of work in China and I can you [sic] that a lot of people there believe this and believe they are being lied to.” Kristian Andersen, one of the authors of “Proximal Origin,” chimed in on February 8. “The fact that Wuhan became the epicenter of the ongoing epidemic caused by nCoV [novel coronavirus] is likely an unfortunate coincidence, but it raises questions that would be wrong to dismiss out of hand,” he wrote. “Our main work over the last couple of weeks has been focused on trying to disprove any type of lab theory, but we are at a crossroad where the scientific evidence isn’t conclusive enough to say that we have high confidence in any of the three main theories considered.” “As to publishing this document in a journal,” he added, “I am currently not in favor of doing so. I believe that publishing something that is open-ended could backfire at this stage.” Andersen suggested that the scientists wait and collect more evidence so they could publish some “strong conclusive statements that are based on the best data we have access to. I don’t think we are there yet.” But the inconclusive evidence supporting any one theory had persuaded the five authors to come out with a definitive conclusion in support of the natural origins theory by the next month. On March 6, Andersen wrote to Farrar, Fauci, Collins, et al. informing them that “Proximal Origin” had been accepted for publication. “Thank you for your advice and leadership as we have been working through the SARS-CoV-2 ‘origins’ paper,” he wrote. “We’re happy to say that the paper was just accepted by Nature Medicine and should be published shortly (not quite sure when).” “Thanks for your note,” Fauci replied. “Nice job on the paper,” he added, approvingly. David Relman, a professor of microbiology, immunology, and medicine at Stanford University, told the Intercept that the paper rested on “flawed assumptions and opinion” and it didn’t properly address the possibility of a lab-associated origin for Covid-19, which he believes is as plausible as the natural origin thesis. “When I first saw it in March 2020, the paper read to me as a conclusion in search of an argument,” he said. “Among its many problems, it failed to consider in a serious fashion the possibility of an unwitting and unrecognized accidental leak during aggressive efforts to grow coronaviruses from bat and other field samples. It also assumed that researchers in Wuhan have told the world about every virus and every sequence that was in their laboratories in 2019. But these [unredacted emails] actually provide evidence that the authors considered a few additional lab-associated scenarios, early in their discussions. But then they rushed to judgment, and the lab scenarios fell out of favor.” “It appears as if a combination of a scant amount of data and an unspoken bias against the [lab origin] scenario diminished the idea in their minds,” he added. The Intercept added that “several academic scientists who were asked to comment for this article expressed their gratitude that these documents are now public but declined to speak on the record given the rancor surrounding this subject.” There is new cutting-edge research into the origins of SARS-CoV-2, replicated by Dr. Francis Balloux, strongly supports the laboratory origins theory. Princeton researcher Alex Washburne in October 2022 announced the pre-print publication of the study, which some skeptics are now crediting with changing their mind on the issue. “We examined whether SARS-CoV-2 was synthesized in a lab,” Washburne wrote. “We studied a common method for synthesizing CoVs in the lab. This method was thought to not leave a fingerprint. We found the fingerprint. That fingerprint is in the SARS-CoV-2 genome.” Professor Francois Balloux, a world renowned expert on Covid-19, gave his assessment of the study. Professor Balloux said that he could replicate its key findings. “This is an important piece of work,” Balloux said. “To me, it looks solid both conceptually and methodologically. I was given advance warning and was able to replicate the key findings. To the best of my knowledge, I confirm the reported patterns are genuine.” Dr. Anthony Fauci and other top scientists are expected to be called before the new GOP-led House of Representatives to account for misleading the public on Covid-19. These newly unredacted NIH emails will provide more ammunition for critics of the U.S. government’s Covid-19 pandemic response.