A short history of SARS-CoV-2 Origins

In 2011, Ron Fouchier said “hold my beer” and performed a stunt for the history books. Ron took a strain of the bird flu and infected a series of ferrets with it. By serially passaging bird flu through ferrets, Ron harnessed the power of evolution to create a mammalian infectious variant of the bird flu capable of causing a pandemic that could kill millions. Ron thought his stunt was cool and could aid the development of vaccines that prepare the world for a possible bird flu pandemic. Others disagreed.

For years, scientists argued about the ethics of such dangerous research. Many argued that it is unreasonably dangerous, that if such research were funded indefinitely it would only be a matter of time until a research-related accident caused a pandemic resulting in historic loss of life and undermining the delicate reputation of science and scientists as trustworthy, capable of managing risks and helping civilization. Others argued that gain of function research will help us understand the evolutionary pathways that could create a pandemic, enabling us to block those pathways and/or prepare for such a pandemic.

The pendulum of power swayed back and forth. First, Ron performed his reckless stunt. Then, there was a moratorium on gain-of-function research. More recently, two staunch advocates of this research - Anthony Fauci and Francis Collins - overturned the moratorium by attempting to redefine gain-of-function research so that what they wanted to fund would not fall under the moratorium. Oh, to have the unbridled power of an executive agency and the arrogance to not only risk millions of lives, but to undermine the trust of Chevron deference that enables such esoteric mismanagement of scientific systems.

Fauci and Collins split hairs on the definition of a “potentially pandemic pathogen” (PPPs) as pathogens that are “‘likely’ highly transmissible and capable of wide, uncontrolled spread in human populations and highly virulent”. Additionally, Fauci & Collins split hairs by unilaterally declaring that research enhancing the virulence or transmissibility of PPPs would not be considered “gain-of-function” research if the research was intended to make vaccines. That’s like saying a nuclear test is not considered a nuclear test if it’s intended to make better bunkers or shields - clearly, any other parties on the nuclear test ban treaty would find such a redefinition absurd. As evidenced by a pandemic that resulted in 20 million dead, the bat SARS coronaviruses engineered to have enhanced transmissibility in humans are potentially pandemic pathogens such that, even by Fauci & Collins’ definition, enhancing the transmissibility of these pathogens is gain-of-function research.

SARS-CoV-2 began infecting humans sometime in the fall of 2019. On December 1 2019 there was a surge in the use of “SARS” on the Chinese social media app Weibo, coinciding with the date of an early reported case that had no connection a wet market. There were earlier reported cases, such as a November 17th case, but the Chinese government ordered the destruction of all earlier cases - why did they do that? Can we trust the early cases that result from such a sampling procedure?

The SARS-CoV-2 genome was shared with the world in January 2020 around the same time by Chinese scientists and Eddie Holmes, an Australian scientists. In addition to being close enough to Chinese researchers to have the genome of SARS-CoV-2 before the rest of the world, we would later learn that Eddie was studying novel bat SARS coronaviruses with researchers in China since 2018, a conflict of interest to note.

Weeks later, the closest known relative to SARS-CoV-2 was published. Of all the places in the world to have unpublished genomes of the closest relative of SARS-CoV-2, RaTG13 would be in the possession of the leading institute for gain of function research on bat SARS coronaviruses in the exact same city where SARS-CoV-2 emerged, highly transmissible and highly virulent, far more so than most bat SARS coronaviruses. In fact, the early versions of SARS-CoV-2 had spike proteins that were better at binding humans than bats. Odd. Anyways, the novel sequence RaTG13 was not discovered in January 2020 but rather had been in the possession of the Wuhan Institute of Virology since 2013. Never before in human history have zoonotic diseases had unpublished closest-known-relative genomes in the same city in which they emerged. In every lab accident, a lab in the same city where the virus emerged had the closest known relative to the virus. Incidentally, after the animal trade outbreak of SARS-CoV-1 in 2002, there were 6 additional outbreaks of SARS-CoV-1, all of which were lab leaks in which the closest known relatives of the virus were in labs in the same city where the first infections occurred.

In mid January 2020, Kristian Andersen looked at the genome of SARS-CoV-2 compared to RaTG13 and noticed a weird furin cleavage site - a perfect sword-in-the-stone insertion of exactly the niche feature virologists had been fascinated by for decades. Combined with the geographic evidence and high transmissibility, Andersen consequently suspected SARS-CoV-2 may have been the result of gain of function research. He contacted Dr. Holmes (who still knew of unpublished SARS CoVs from his work with Chinese coronavirologists) and then both Andersen & Holmes wrote to Dr. Fauci and Jeremy Farrar that they believed SARS-CoV-2 may be a laboratory escape, noting that the virus’ genome was “inconsistent with evolutionary theory” and consistent with the gain of function research conducted by the Wuhan Institute of Virology.

Early the next morning, Dr. Fauci wrote Hugh Auchincloss an email, attaching a paper by Ralph Baric conducting gain of function research on bat SARS CoVs, research funded by Dr. Fauci’s NIAID and enabled thanks to Dr. Fauci’s actions overturning the moratorium on gain of function research. Fauci said Hugh would have urgent responsibilities and they would need to jump on a call. We don’t know what happened on that call. Neither Dr. Fauci nor Dr. Auchincloss will tell us.

The next day, Fauci, Collins, and Farrar organized a call between Kristian Andersen, Eddie Holmes, and some of the most vociferous proponents of gain-of-function research including Ron Fouchier, the person who pulled the “hold my beer” stunt with bird flu, endangering the lives of millions for his own ambitions with exactly zero known benefits on human health, medical countermeasures, etc.

On the call, the proponents of gain-of-function research reportedly shouted at Andersen & Holmes. The funders of gain-of-function research, agency heads who overturned the moratorium on this research, whose signatures decorate grants subcontracting to the WIV, whose email addresses received progress reports on gain-of-function research in Wuhan, and who were the final judges of Andersen’s $9 million NIAID grant - Fauci & Collins - sat beside the coliseum they organized and watched Andersen & Holmes get excoriated by gain of function proponents for their misfortune of discovering SARS-CoV-2 most likely came from a lab.

At some point during the call, Eddie Holmes says privately on the Slack channel with Andersen et al. “Big Ask!” We don’t know what the “big ask” was. Dr. Holmes won’t say.

Andersen replies, “Destroy the world based on sequence data. Yay or nay?” We don’t know why Andersen said this. Dr. Andersen won’t say.

After the call, there are reports of Andersen and Farrar discussing who-knows-what on burner phones, and there are emails revealing how Andersen, Holmes, Robert Garry, and Andrew Rambaut became aware of the “shit show” of political consequences of anyone serious accusing China of even an accidental release. With this exact motivation and context, the authors advocate saying that a natural origin and lab origin are indistinguishable and so therefore they favor a natural origin. They proceeded to look and present only for evidence favoring a natural origin. While they had private doubts and reasons to believe a lab origin was highly likely, they made public claims to have “debunked” a lab origin.

As Andersen et al. mislead reporters and follow their motivated reasoning towards Proximal Origins, Dr. Fauci met with Ralph Baric to discuss chimeras and reverse genetics systems for quite some time. After the call, Ralph was reportedly very beat and taking jokes about a lab origin very seriously, not-funny. We don’t know what happened at that meeting - Dr. Fauci even later testified under oath that he doesn’t ever remember meeting Ralph Baric, despite immediately thinking of Ralph Baric upon hearing Andersen’s email and sending Hugh Auchincloss Ralph Baric’s paper the very next morning.

The same week Andersen says a lab origin is “so friggin likely”, he receives emails from reporters like Don Neil that “pretty much nailed” the lab origin hypothesis… but Andersen goes on to tell journalists that a lab origin is “conspiracy theory” that has been “debunked”. Over the course of a long trail of motivated reasoning and toxic shit-talking, peppered with insulting images of Peter Daszak and jabs about Daszak’s “EgoWealth Alliance” likely creating a pandemic they sought to preempt, failing to predict the pandemic they caused, etc., the scientists finalize the language of their paper to say “we do not believe any type of laboratory-based scenario is possible”, not even the types that the authors admit are indistinguishable from a natural zoonosis. How could they possibly rule out a scenario that they admit is indistinguishable from the scenario they chose to advocate? Their critically flawed paper was shepherded to Nature Medicine with the help of Jeremy Farrar who contacted the editors for these authors. I wish Jeremy Farrar could contact editors for me sometime, but I suppose it’s naive to wish for a meritocracy in science when the old boy’s club benefits these gentlemen so handsomely.

Their paper - The Proximal Origin of SARS-CoV-2 - gets published by Nature Medicine and amplified by its editors, Jeremy Farrar, the Wellcome Trust, and more as “definitive evidence” that “disproves” and “debunks” the “conspiracy theories” and “misinformation” that SARS-CoV-2 might have come from a lab. A censorship campaign is born.

Anthony Fauci uses his position as “America’s Doctor” and head of NIAID to tell the whole world that a team of ‘independent’ experts has shown SARS-CoV-2 did not originate from a lab. Francis Collins does the same. Jeremy Farrar and the Wellcome Trust do the same. Together, these funders of gain-of-function research at the Wuhan Institute of Virology, who directly manage the majority of health science funding in the world, call a lab origin a “conspiracy theory” without revealing their own role in driving the authors away from their early, truly independent conclusions that a lab origin is “so friggin likely”. Meanwhile, Peter Daszak and Jeremy Farrar write a letter to The Lancet calling any type of lab origin theory a “conspiracy theory”. Altogether, these authors and health science funders with major conflicts of interest manipulated an entire field of busy scientists, scientists too busy focusing on outbreaks and pandemic public health policy to read every paper closely. Scientists slowly incorporate through osmosis the vague dislike of a lab origin theory and associate the theory with Donald Trump. Many call it a “conspiracy theory” without ever having considered the evidence or read the papers themselves.

FOIA’s later reveal some of the intentions to manipulate. Specifically, we now know that Daszak conspired with Ralph Baric, Linfa Wang, and others to organize The Lancet’s letter but not sign it themselves, to maximize the appearance of an independent voice. Daszak helped organize this letter calling a lab origin, which may implicate him, a “conspiracy theory” and he intended to use the letter not to make a scientific point for which he had strong evidence, but as a piece of propaganda that could be shouted more productively from megaphones not in his hand to manipulate public opinion, mislead people into thinking some independent consensus of scientists all believes Daszak had no role in the pandemic, and engineer a toxic discourse in science whereby people who face potential criminal liability from a scientific theory can call that theory a “conspiracy theory”, if only they get enough friends to parrot their words. Jeremy Farrar, a ghost-writer of Proximal Origins, is a co-author of The Lancet paper as well.

While a coterie of conflicted scientists conspired to mislead the world with publications declaring lab origin theories “conspiracy theories”, a team of internet sleuths called DRASTIC, unconnected and uninfluenced by the funders of gain of function work, investigated the possibility of a lab origin. In the course of their work, DRASTIC members learn of the Wuhan Institute of Virology’s surveillance of bat viruses, including bat SARS coronaviruses that caused serious illness in Mojiang miners. Not only did they entertain other unpublished sequences collected over the years during which RaTG13 was unpublished, but they also found the Wuhan Institute of Virology had collected and published sequences of bat alphacoronaviruses in 2017 that had very similar furin cleavage sites to that found in SARS-CoV-2. It was the furin cleavage site which raised alarm bells in Andersen’s mind and made him believe SARS-CoV-2 emerged from a lab. What would Andersen think if he knew the Wuhan Institute of Virology had in their possession in 2019 a furin cleavage site exactly like that found in SAR-CoV-2?

As DRASTIC sleuths investigated the research activities of coronavirus research in Wuhan, the WHO appointed Peter Daszak to be the US emissary for their COVID origins investigation, a fruitless endeavor that gave all the pomp & appearance of an “investigation” but never actually set foot inside the Wuhan labs. Peter Daszak was also appointed by Jeffrey Sachs to lead The Lancet’s COVID origins investigation. Daszak appointed his friends to help him lead The Lancet’s investigation, but apparently both Daszak and many of the friends he appointed all had something in common: they all had conflicts of interest in their prior work with the Wuhan Institute of Virology, the exact labs at the heart of this investigation. When Jeffrey Sachs learned of these pervasive, undisclosed conflicts of interest and unearthed a pattern of lies designed to hide these conflicts of interest, he ultimately concluded that the Lancet investigation had been irreparably compromised and dispanded it. Daszak’s presence and undisclosed conflicts of interest obstructed impartial investigations into COVID origins

While Daszak obstructed formal investigations, DRASTIC marched on.

As scientists obstructed formal investigations by false claims of having “debunked” a lab origin theory, including in writings to US government officials in OSTP and HHS and the National Academies of Science, and as NIH leaders sent Proximal Origin and nothing more (not even the 2018 progress reports from Wuhan) to the State Department when asked for all information about research funded in Wuhan and the possibilities of a lab escape, the unyielding DRASTIC team produced the biggest bombshell of SARS-CoV-2 origins: the DEFUSE grant.

The DEFUSE grant proposed in 2018 to insert a furin cleavage site in a bat SARS coronavirus infectious clone. The PI’s of the DEFUSE grant include none other than Daszak, who obstructed COVID origins investigations left and right, called a lab origin a “conspiracy theory”, and did not disclose DEFUSE when asked to lead investigations on SARS-CoV-2 origins. Other PI’s include Ralph Baric, who authored the paper Anthony Fauci sent to Hugh Auchincloss and who Fauci talked with for quite some time in February 2020 about reverse genetic systems before Fauci seemed to forget Baric ever existed, and Shi ZhengLi, the lead bat SARS coronavirus researcher at the Wuhan Institute of Virology who led the collection of RaTG13 and had many other unpublished bat SARS coronaviruses in her possession, including some that were pre-COVID collaborations with Eddie Holmes. Scientists also found evidence of unpublished MERS coronaviruses docked inside BAC clones in Wuhan, evidence suggesting unpublished gain of function work with unpublished infectious clones was happening in Wuhan in 2019.

Truly independent scientists, not the Proximal Origin crew or the funders of gain of function work, found evidence that RaTG13 may not be what it appears to be. RaTG13 was reportedly a bat fecal sample, but fecal samples often have 80% of their reads as bacterial reads because there’s a lot of bacteria in poop. RaTG13 has only 10% of its reads mapping to bacteria, and it turns out there are strange issues and inconsistencies with the other close relative genomes being produced by the Wuhan Institute of Virology and the Chinese Academy of Sciences (and Eddie Holmes).

Andersen, Holmes et al. continued to publish papers broadcasting conclusions that were unsupported by their methods. Worobey et al. published a paper claiming to have found “dispositive” evidence “disposing” of a lab origin theory, but their paper finding cases centered around the wet market relied entirely on cases provided by the Chinese government who, we recall, selectively destroyed early cases including the December 1 and November 17th cases. Worobey et al. also failed to account for documented biases of how early cases were obtained via contact & location tracing, failed to account for market samples prioritizing sampling of animal vendors, and ignored completely cases preceding the wet market outbreak with no connection to the wet market. Worobey’s flawed paper led to overconfident claims in mainstream outlets from the New York Times to The Atlantic, and at every opportunity to engage with scientists who had solid reasons for disagreement, Michael Worobey instead claimed we didn’t know what we were talking about.

Pekar et al. (including Andersen, Holmes, Rambaut, and Garry) claimed the early outbreak evolutionary tree’s two-big-branches could only be explained by two-spillovers, but that’s not true. Their conclusions are unsupported by their methods - they excluded intermediate sequences that undermine their “two-big-branches” observation, they also ignore how cases were preferentially obtained by contact tracing (and how this impacts the structure of the evolutionary tree), and the claim a single lab origin is unlikely is a direct result of them using an HIV model for viral transmission and evolution as opposed to a SARS-CoV-2 model for viral transmission and evolution. Pekar, too, is frequently cited in major media outlets without any acknowledgement of the scientific counterarguments, including the intermediate sequences that completely undermine the entire paper.

The DEFUSE grant had one additional piece of its proposal. The DEFUSE grant proposed to insert a furin cleavage site in a bat SARS coronavirus in Wuhan, all properties which are anomalous among an emergent SARS coronavirus and yet are all exactly the geographic, phylogenetic, and genomic features of the emergence of SARS-CoV-2. To insert a furin cleavage site, the PI’s of DEFUSE proposed to use a “reverse genetics system”, a special system used to cut & paste viral genomes together, stitching together chimeric viruses like Frankenstein’s arms. Much like Frankenstein’s arms have stitching sites at the joints, reverse genetic systems often left a trace in the viral genome.

In October of 2022, Valentin Bruttel, Tony VanDongen and I published our findings that SARS-CoV-2 is an anomaly among wild CoVs in just how perfect it resembles and efficient reverse genetic system. Our finding is noteworthy because our finding was a prediction one would make from the theory that SARS-CoV-2 was a research product of the DEFUSE research program. Under a zoonotic origin, our effort to find a reverse genetic system would be fruitless. It is a prediction because it wasn’t known in January 2020 or even when DEFUSE was revealed by DRASTIC - the cryptic pattern of scars left in the genome of a reverse genetic system is not obvious, yet with careful quantitative microscopes it can be seen.

We tested this theory that DEFUSE provides the blueprint for SARS-CoV-2 and found that the DEFUSE grant was able to tell us things about the SARS-CoV-2 genome that had been hidden in plain sight for nearly 3 years. Not only does SARS-CoV-2 appear to be an outlier among wild coronaviruses in exactly the way it is a midpoint of infectious clones bred from reverse genetics systems, but the precise mutations that generated this modified restriction map of SARS-CoV-2 are silent mutations - the exact mutations bioengineers use for such modifications - and there is a 9x higher rate of silent mutations in these restriction sites than the rest of the SARS-CoV-2 genome. There is less than 1 in 10 million chance of seeing such a high concentration of silent mutations in these restriction sites if silent mutations were equally distributed inside vs. outside these sites. DEFUSE helped us predict this 1 in 10 million feature of SARS-CoV-2 hidden in broad daylight.

Hidden in plain sight: The BsaI/BsmBI map of SARS-CoV-2 is an anomaly among wild coronaviruses and consistent with a reverse genetic system. This improbable feature, and the silent mutations producing it, is a prediction of the SARS-CoV-2 genome made by the 2018 DEFUSE grant and research at the WIV.

Andersen et al. were livid. They called our work “poppycock” and claimed that it wouldn’t pass “kindergarten molecular biology”, yet our findings come from detailed examination of the molecular biological protocols for making reverse genetic systems. Slack communications from 2020 reveal that Andersen himself privately knew that reverse genetic systems were easy to make and commonly used to make coronavirus infectious clones, yet when we produce evidence that the SARS-CoV-2 genome may be a reverse genetic system Andersen tries to discredit us. Holmes calls our work “confected nonsense”. The whole time they were trying to discredit us, they knew that reverse genetic systems were commonly constructed and easy to make.

Now, we have FOIA’s in which Fauci, who met Ralph Baric in February 2020 to discuss chimeras and reverse genetic systems, testified that he doesn’t think he ever met Ralph Baric. Dr. Fauci also testified under oath that he never funded gain of function research at the Wuhan Institute of Virology, yet we have progress reports of Daszak thanking NIAID for overturning the moratorium on GoF work, allowing him to proceed with engineering bat SARS coronaviruses. In a 2018 progress report, Daszak reports to Fauci & others at NIAID that he succeeded in engineering bat SARS coronaviruses capable of producing 100-10,000x higher viral titers than wild type strains in the lungs of humanized mice. In other words, Daszak revealed to NIAID that bat SARS coronaviruses engineered in Wuhan were capable of high transmissibility in humans, a revelation that should’ve immediately triggered a halt to the experiments under even Fauci & Collins’ definition of gain of function research. Combined with their high virulence of SARS coronaviruses (that’s the main reason there was such a fixation over this clade of coronaviruses) it was clear in 2018 that the bat SARS coronavirus were enhanced Potentially Pandemic Pathogens.

Now, we have the slack communications in which Andersen, Holmes, Garry, and Rambaut conspire to mislead reporters by claiming that a lab origin was “debunked” while privately acknowledging it was highly likely. Andersen & Holmes, backed up by Daszak, Farrar, Collins & Fauci calling a lab origin a “conspiracy theory”, proceeded to marginalize scientists, including myself and my colleagues, who produced papers indicating why we can’t conclude a wet market origin and uncovering unbiased evidence consistent with a lab origin. Many scientists appear to be trapped in a bubble of credulity, stuck in the narrative cement laid by conflicted scientists in 2020. These scientists who never read the papers yet called a lab origin “conspiracy theory” now claim Andersen’s words are taken out of context without reading the Slack communications and learning the words are even worse in context.

From the Slack communications, Andersen doesn’t just know a lab origin is likely, he also knows that reverse genetics clones are easy to make - “these guys did it in a week.” In other words, he knew that our finding of a reverse genetics system was not ‘poppycock’, certainly not ‘kindergarten molecular biology’, yet that didn’t stop him from trying to discredit our research and derail our scientific careers.

We are living through historical crises, from a pandemic likely caused by gain of function research to propaganda campaigns by scientists and science funders themselves who burn the reputation of all of science by intentionally deceiving the world on SARS-CoV-2 origins (as opposed to sacrificing the reputations of the few who funded & conducted this work).

The Proximal Origin authors were right about two things. (1) A lab origin was so friggin likely even before DEFUSE and the restriction map evidence we uncovered; now, with new evidence, a lab origin is even more likely. (2) The consequences of a lab origin are extreme. 20 million people died. Indeed, this is the exact scenario that opponents of gain of function research warned about. The Cassandras of Virology warned that gain of function research runs the risk of causing a pandemic, killing millions of people, and embroiling the field - and perhaps all of science - in a controversy so profound that it may result in a revolution in the organization of scientific systems and the relationships between science and society.

The funders of gain of function work at the Wuhan Institute of Virology paid little attention to the possible geopolitical consequences, such as the possibility that gain of function work could be misinterpreted as a bioweapon and lead the world to nuclear war. The Chinese government could perceive accusations of a lab origin as a threat to their national security, and thus the truth could provoke China as Australia calling for investigations of a possible lab origin led to immediate retaliation from China. Yes, the stakes are high, but that doesn’t excuse the mismanagement by scientists who ignored risks to fund the risky work that brought us here, nor does it excuse the misconduct of scientists who used their positions as experts to lie to the world and attempt to squash the careers of scientists who uncovered the truth.

There’s no way to know the history of the COVID-19 pandemic without considering the long arc of scientific mismanagement and misconduct that brought us to where we are today. Only by acknowledging the mistakes and misconduct can we begin the process of repairing our scientific institutions and rebuilding the trust that binds science and society.

Once we’ve dealt with the scientists who have undermined science in the West, we’ll need to turn our attention to the Chinese Communist Party that funded the labs and played the largest role of any entity in the world in the creation & cover-up of SARS-CoV-2’s probable lab origins. To make matters complicated, State department cables suggest there were ties between the People’s Liberation Army and Wuhan labs, including possible Bio-Warfare Research Institutes. The presence of the Chinese military in the Wuhan labs doesn’t imply SARS-CoV-2 is an offensive bioweapon, in fact the research trail most strongly suggestive of a lab origin was for the purpose of defensive capabilities - vaccines. However, the prioritization of Bio-Warfare research by the PLA and a Chinese general discussing his interest in ethnic bioweapons does suggest, as horrific as it may seem, the possibility that COVID-19 could be just the beginning of a biologically armed future.

The efforts by scientists to sow doubt about the attribution of SARS-CoV-2 origins are providing our adversaries with a playbook for how to sow confusion should they cause a pandemic and wish to obscure the fact. The actions of western scientists further undermine our safety by depriving the world of the scientific insights and moral clarity managers need at this pivotal moment to pull the world back from a biological arms race. Rather than pull back, we are seeing a proliferation of BSL-4 labs in cities around the world. If we go down this road of unaccountable biological agent development, where ambitious scientists can make the most dangerous pathogens so long as they propose it is for making a vaccine against these nonexistent horrors, where scientists connected to labs at the epicenter of a pandemic can lie with impunity to obscure the origins of a virus, our civilization will forever live one cracked vial or punctured glove away from disaster. All it takes is one accident to release an invisible disease that overwhelms our hospitals, kills millions to billions of innocent people, and introduces engineered infectious diseases that would’ve never otherwise evolved in this world.

As a biologist, my guide to a healthy human civilization is to not go down this road. To see the path ahead more clearly, we have to see how the obvious high likelihood of a lab origin has been obscured, and we have to tell the history of SARS-CoV-2 origins as those who fail to learn the lessons of history are doomed to repeat it.