Did SARS-CoV-2 Originate in the Laboratory?

It's Likely

The SARS-CoV-2 virus was the pathogen behind the COVID-19 pandemic, which is estimated to have killed 25 million people around the world. An understanding the origin of SARS-CoV-2 is of critical importance because it will help us predict, plan for, and prevent future epidemics and pandemics.

Until recently, laboratory manipulation wasn’t possible and all viruses originated in the wild. The virus existed in an animal population, was transmitted from animals to humans, and then eventually was transmitted from humans to humans. Because close contact between humans is far more common than close contact between wild animals and humans, for a pandemic to commence, this last step of effective transmission between humans is essential.

Given that the great majority of viruses originated in the wild—called zoonotic origin—it is reasonable to consider the case that the SARS-CoV-2 (often shortened to SARS2) virus originated in the wild. The zoonotic theory is considered in a sister article. This article considers the theory that SARS2 virus originated in the laboratory.

Once a virus has infected many humans, scientists will characteristically investigate its origins. Even if there is no witness providing direct evidence, viruses that have been manipulated in a laboratory will leave many fingerprints for scientists to discover. Let’s consider the strength of the forensic evidence for a laboratory origin of SARS2:

Past occurrences of lab leaks

·      Leaks of highly contagious pathogens from laboratories are not rare. A USA TODAY investigationconcluded that there were “more than 1,100 lab accidents involving dangerous pathogens or toxins in the U.S. alone between 2008 and 2012.”

·      “The smallpox virus escaped three times from labs in England in the 1960’s and 1970’s, causing 80 cases and 3 deaths.”

·      “The most notable lab leak known is the 1977 H1N1 lab escape from China that caused a worldwide pandemic.” The H1N1 virus, released during the testing of a vaccine, killed 700,000. It has killed peoplefor the years 1977 through 2009.

·      “The SARS [SARS1]virus escaped from research labs in the early 2000s and caused minor outbreaks in Beijing, Taiwan, and Singapore…”

·      “Nearly every SARS [SARS1] case since the original epidemic has been due to lab leaks — six incidents in three countries, including twice in a single month from a lab in Beijing.”

·      “In 2020 more than 6,600 people in Lanzhou, China, tested positive for brucellosis, a bacterial disease, after a leak from a vaccine factory the previous year.”

·      Ralph Baric’s lab at the University of North Carolina has had infected mice escape. “Between April 2013 and September 2014, eight individual mouse escapes were reported at the University of North Carolina-Chapel Hill. Several of the mice were infected with either SARS or the H1N1 flu virus.”

·      Research suggests that lab accidents are not always reported.

Problems at the Wuhan Institute of Virology (WIV)

·      The Wuhan Institute of Virology (WIV) was known to have safety issues. In 2018, U.S. diplomats in China warned of “a serious shortage of appropriately trained technicians and investigators needed to safely operate” the facility. Chinese experts have also expressed concerns, such as, “lab trash can contain man-made viruses, bacteria or microbes” and that “some researchers discharge laboratory materials into the sewer after experiments without a specific biological disposal mechanism.” American scientists have also raised safety concerns about WIV.

·      WIV is a BSL-4 laboratory, the highest level of safety conditions. Shi Zhengli, sometimes referred to as the “bat woman” because of her extensive experience studying coronaviruses found in bats, has been an important researcher at WIV. In an interview, Shi reported that, “[t]he coronavirus research in our laboratory is conducted in BSL-2 or BSL-3 laboratories.” BSL-3 is less rigorous than BSL-4, and BSL-2 is equivalent in safety protocols to a local dentist’s office. “In 2016 the Wuhan institute reported experimenting on a live bat coronavirus that could infect human cells in a BSL-2 lab…” Stanford’s Michael Lin said this admission was “an actual scandal, recorded in print.”

·      Even Yuan Zhiming, then director of WIV’s biosafety level 4 lab, expressed concerns about the safety of the lab.

Geographical evidence of SARS2

·      The earliest surge in hospital activity related to COVID-19 happened at the hospitals closest to WIV.

·      China’s two most advanced biological research laboratories, both in Wuhan, the Wuhan Institute of Virology and the Wuhan Center for Disease Control and Prevention, were involved with collecting live bats from caves across China to study viruses. This can explain how the virus could have traveled 1,000 miles from a cave in southern China to Wuhan.

·      The closest viruses identified, in the bats in southern China, are not geographically close to Wuhan. Not only are the caves in question far from Wuhan, but also the topology, flora, fauna, and weather are very different between the two places. It would have been unlikely that the bats themselves traveled from the southern caves to Wuhan.

·      Natural spillovers of diseases from bats to humans are rare.

·      If the virus infected a researcher at the caves in southern China, and then that researcher traveled back to Wuhan, why is there no record of anyone becoming sick near the caves or on the trip back?

Evidence that scientists can manipulate viruses

·      Scientists now can create and manipulate viruses in laboratories. For example, in February 2020, scientists in Switzerland used the known genomic sequence of the novel coronavirus as a recipe to construct copies of the SARS2 virus from synthetic DNA.

·      For decades, bat coronaviruses have been thoroughly studied and genetically modified.

·      Scientists have shown the ability to create and manipulate viruses at will. They have recreated the 1918 flu virus, synthesized the polio virus from its published DNA sequence, and inserted a smallpox gene into another virus. In 2000, Dutch researchers modified the spike protein of a mouse coronavirus so that it would infect cats instead.

Evidence that gain-of-function experiments on bat coronaviruses were performed at WIV

·      Laboratory research on coronaviruses originating in bats was conducted at the Wuhan Institute of Virology. WIV was studying the closest known relative of SARS2 when the pandemic started. Accordingto former FDA commissioner Scott Gottlieb, “We know that that Wuhan laboratory was doing a lot of experimentation. It had a big repository of coronaviruses.”

·      The spike protein part of SARS2 locks onto a receptor called the angiotensin-converting enzyme 2, or ACE-2, receptor. Scientists at WIV reported working with a virus that “contained a ‘spike protein’ that was particularly good at grabbing on to a specific receptor in human lung cells known as an ACE2 receptor. That means the viruses were potentially very dangerous for humans…”

·      “The Wuhan Institute of Virology had openly participated in gain-of-function research in partnership with U.S. universities and institutions. But the official told me [Josh Rogin] the U.S. government had evidence that Chinese labs were performing gain-of-function research on a much larger scale than was publicly disclosed, meaning they were taking more risks in more labs than anyone outside China was aware of.”

·      In July 2020, “[t]hese [WIV] scientists said they had created a new model for studying SARS-CoV-2 by creating mice with human-like lung characteristics by using the CRISPR gene-editing technology to give the mice lung cells with the human ACE2 receptor — the cell receptor that allowed coronaviruses to so easily infect human lungs.” The State Department alleges that WIV has been doing such classified research on behalf of the Chinese military since at least 2017.

·      Shi Zhengli was working with Ralph Baric, an eminent coronavirus researcher at the University of North Carolina to enhance the ability of “bat viruses to attack humans so as to ‘examine the emergence potential (that is, the potential to infect humans) of circulating bat CoVs [coronaviruses].’”

·      According to Nicholas Wade, a science writer, “It’s documented that researchers at the Wuhan Institute of Virology were doing gain-of- function experiments designed to make coronaviruses infect human cells and humanized mice. This is exactly the kind of experiment from which a SARS2-like virus could have emerged. The researchers were not vaccinated against the viruses under study, and they were working in the minimal safety conditions of a BSL2 laboratory. So escape of a virus would not be at all surprising. In all of China, the pandemic broke out on the doorstep of the Wuhan institute. The virus was already well adapted to humans, as expected for a virus grown in humanized mice. It possessed an unusual enhancement, a furin cleavage site, which is not possessed by any other known SARS-related beta-coronavirus, and this site included a double arginine codon also unknown among beta-coronaviruses. What more evidence could you want, aside from the presently unobtainable lab records documenting SARS2’s creation?”

·      “Baric had developed, and taught Shi, a general method for engineering bat coronaviruses to attack other species. The specific targets were human cells grown in cultures and humanized mice. These laboratory mice, a cheap and ethical stand-in for human subjects, are genetically engineered to carry the human version of a protein called ACE2 that studs the surface of cells that line the airways.”

·      Partly funded by National Institute of Allergy and Infectious Diseases (NIAID) and managed by Peter Daszak of the EcoHealth Alliance, Shi “set out to create novel coronaviruses with the highest possible infectivity for human cells.” “From June 2014 to May 2019, Daszak’s EcoHealth Alliance had a grantfrom the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to do gain- of-function research with coronaviruses at the Wuhan Institute of Virology.”

·      The NIH gave a $3.3 million contract to EcoHealth Alliance to study bat coronaviruses. EcoHealth Alliance then gave $599,000 [another source says $815,000] to WIV.

·      Shortly before the pandemic began, after saying in an interview how easy it was to manipulate coronaviruses in the lab, Daszak told how WIV had successfully “reprogramm[ed] the spike protein and generat[ed] chimeric coronaviruses capable of infecting humanized mice.”

·      According to Steven Quay, “[s]ince 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory. At least 11 gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”

Suspicious activities at the Wuhan Institute of Virology

·      WIV’s viral pathogen database and tracking system was changed and then removed entirely in May 2020.

·      U.S. intelligence claims it has evidence that the first three people infected with SARS worked at WIV. “…State Department confirmed that people had fallen mysteriously ill [with Covid-like symptoms] at WIV in fall 2019…” “Three people working at a BSL3 lab at the institute fell sick within a week of each other with severe symptoms that required hospitalization.” These individuals were sick “with symptoms consistent with both Covid-19 and common seasonal illness.” One of the WIV researchers was later identified as Ben Hu, who was one of the three key scientists employing U.S. funding to research coronaviruses and conduct gain-of-function studies.

·      Shi Zhengli was an important researcher at WIV. In a May 2020 interview, “she described frantically searching her own lab’s records after learning of the coronavirus outbreak in Wuhan. ‘Could they have come from our lab?’ she recalled asking herself.”

·      Shi Zhengli had acted suspiciously before SARS2 caused a viral pandemic. She was dodgy about a coronavirus that had been renamed and whether that virus had or had not infected and killed some miners. Further, a genomic database at WIV, with information about thousands of bat samples and at least 500 recently discovered bat coronaviruses, went offline in September 2019. The official explanation was hacking. But the database never reemerged and never was shared with researchers in other ways. Shi also changed her story and removed a blog post when questioned about how dangerous it was for researchers to work with wild bats. Shi and Daszak argued that WIV never housed live bats, even though there’s ample evidence that WIV did keep live bats in cages. Daszak has since changed his story.

·      Shi Zhengli was fearful, upon learning of SARS2, that it came from her lab. She said she didn’t sleep for days. “I had not slept a wink for days.” She relaxed after, she claims, she found that “none of the sequences matched those of the viruses her team had sampled from bat caves.”

·      WIV had a bat coronavirus, RaTG13, that was found in a cave that was 96% the same as SARS2. While that encouraged some looking for a zoonotic source, 96% isn’t very close. It is estimated that, if RaTG13 and SARS2 are relatives, their evolutionary path diverged about 40 years ago. Shi’s credibility was damaged when it was revealed that RaTG13 was the same virus as RaBtCoV/4991, which she had been studying since 2016 and which came from a mineshaft and may have caused the deaths of some miners. The fact that Shi didn’t mention this connection and name change was disturbing. Shi’s credibility was further damaged when she claimed that there was “zero infection” among WIV’s stuff and students. This is unlikely given the prevalence of community acquired infections at the time.

·      The U.S. government has evidence that WIV has been collaborating with the Chinese military on classified viral research.

·      Based on an analysis of 500 documents from the WIV website, including Chinese Communist Party dispatches, the “WIV dispatches did indeed signal that the institute faced an acute safety emergency in November 2019; that officials at the highest levels of the Chinese government weighed in; and that urgent action was taken in an effort to address ongoing safety issues.”

Suspicious activities by the Chinese Communist Party

·      The Chinese government has destroyed massive amounts of evidence, failed to provide evidence, such as tissue samples from patients, and has refused to make available people who could provide other evidence.

·      “…the PLA [People’s Liberation Army] dispatched a general to take over the facility soon after the outbreak in Wuhan…”

·      “Xi Jinping’s first speech on the outbreak highlighted ‘lessons learned’ about ‘shortcomings’ and ‘leaking holes’ in China’s management of biological material and biological-security system. He demanded that ‘a new biological-security law’ be made part of the ‘national-security system.’”

·      The Chinese government, which has a lot to lose if the virus was indeed released by WIV, has destroyed evidence and has stonewalled. The Chinese government also arrested whistle-blowers.

·      The Chinese government, which contends that the virus originated zoonotically, “spent three to six weeks telling the world that the virus was not contagious.” Further, satellite photos show empty parking lots at WIV three months before the Chinese Communist Party acknowledged the virus’ existence. During this time, WIV “put out requests for more than $600 million for a new ventilation system.” The Chinese government then pushed the wet-market theory, which has since been discredited and dropped, even by Beijing. Li Wenliang, who first warned colleagues of coronavirus infections, was denounced as a “rumor monger” by Wuhan police. Even though the mayor of Wuhan knew about the epidemic, he still approved a “Ten Thousand Family Banquet,” which 40,000 families joined. His hand was forced; he didn’t have the government’s permission to disclose the outbreak. The CCP mapped the genome of SARS2 at least two weeks before that genetic code was reported to the world, delaying a response to the unfolding pandemic.

·      A Chinese military scientist, Zhou Yusen, who patented a vaccine for SARS2, must have started working on his vaccine no later than 2019, according to Robert Kadlec, former Assistant Secretary of Health and Human Services (Preparedness and Response). When this information, and the speculation that Zhou may have started the COVID-19 pandemic, became public, he was subsequently found dead under suspicious circumstances.

Was WHO’s investigation of the origin of SARS2 thorough?

·      The World Health Organization, which is heavily influenced by the Chinese government, conducted a superficial investigation of the origin of SARS. The head of WHO, Director-General Tedros Ghebreyesus, was skeptical of his own organization’s efforts, calling for further investigations; Beijing rejected the idea. The Biden Administration had “deep concerns” about the WHO’s efforts. The State Department has alleged a Chinese government cover-up and asserted that “Beijing continues today to withhold vital information that scientists need to protect the world from this deadly virus, and the next one.”

Genetic evidence that SARS2 was manipulated in a laboratory

·      The genetic code (codons) around the furin cleavage site is also suspicious, taking on a structure preferred by human cells over that of coronaviruses. Nobel laureate David Baltimore, an eminent virologist and former president of Caltech reported, “[w]hen I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2.”

·      SARS2 has some interesting features that suggest laboratory manipulation. There are six different genetic combinations of genes that biological beings can use to produce arginine. To make two arginine amino acids in a row, those six combinations turn into 36 (six squared). The combination used by SARS2 is CGG-CGG, which is one of 36 possible combinations. In the entire class of coronaviruses that includes SARS2, CGG-CGG has never before been found. Viruses can pick up new genetic code by recombination with other viruses. How could SARS2 pick up CGG-CGG from another coronavirus if no other coronavirus has CGG-CGG? Interestingly, of the 36 possible ways for code for arginine, CGG-CGG is the preferred genetic code for lab-manipulated viruses.

Conflicts of interest

·      Francis Collins and Anthony Fauci, heads of the two government agencies most responsible for the funding of EcoHealth Alliance’s research in China, argued against a moratorium on gain-of-function research, used an exception in the moratorium to continue funding gain-of-function research, and then didn’t properly report this research, as required, under the Potential Pandemic Pathogens Control and Oversight (P3CO) Framework.

·      Some of the individuals and groups that have most strongly argued for a zoonotic origin for SARS2 have extreme conflicts of interest, sometimes not reported, and many of them have been shown to have acted less than honestly. Their behavior is consistent with a cover-up.

a.        Peter Daszak, who was behind DEFUSE (the research proposal) and the work of EcoHealth Alliance, did not disclose this conflict of interest upon being elected to be a member of WHO’s COVID origins investigation in Wuhan.

b.        Daszak did not disclose his conflict of interest when he was chosen to lead the Lancet’s COVID-origins investigation.

c.        Daszak apparently ghost wrote—but distanced himself from, to not appear self-serving—the letter in the Lancet saying the virus came from zoonotic sources and smeared the lab origin theory as “a conspiracy theory.”

d.        When the NIH terminated a grant to study bat coronaviruses, Daszak purposefully hid some genetic sequences from Genbank, because these sequences would have brought "very unwelcome attention."

e.        Daszak claimed that the coronavirus research would be conducted at University of North Carolina’s BSL-3 laboratory, but he intended early on to conduct the research at WIV’s BSL-2 labs.

f.           Anthony Fauci has been one of the biggest advocates of gain-of-function research. According to Robert Kadlec, former Assistant Secretary of Health and Human Services (Preparedness and Response) and technically Fauci’s superior, he was pressured by Fauci to help him downplay the lab leak theory. As Kadlec understood it, Fauci’s actions were intended to take the attention away from U.S. government involvement and to protect Fauci’s reputation because of his involvement in the matter.

g.         Emails from David Morens, Fauci’s former top advisor, indicate that NIH and NIAID were circling the wagons to protect Fauci, Daszak, and colleagues.

h.        Morens also claimed to have employed techniques to avoid FOIA requests. In other words, he violated the law to destroy important evidence. For instance, he wrote to an outside collaborator that he “had deleted all his emails related to the Covid origin ‘when the s— started hitting the fan.’”

A coverup?

·      Kristian G. Andersen of the Scripps Research Institute, claimed, “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully [sic] manipulated virus.” However, in emails released under freedom-of-information requests, Andersen wrote to Fauci saying the virus had “unusual features” that suggested laboratory manipulation. “[O]ne has to look really closely at all the sequences to see that some of the features (potentially) look engineered.”

·      In another FOIA email, Daszak wrote to Fauci to thank him for his help denigrating the lab leak theory. “I just wanted to say a personal thankyou [sic] on behalf of our staff and collaborators, for publicly standing up and stating that the scientific evidence supports a natural origin.”

·      Andersen and Daszak, who were involved in gain-of-function research with WIV and launched unscientific attacks on those who considered the lab-leak theory, were given a large grant from NIAID in August 2020, possibly as a reward for their service covering up evidence.

·      The U.S. Energy Department and FBI have concluded that the COVID-19 pandemic most likely arose from a lab leak. The CIA, on the other hand, favored the zoonotic explanation. However, a whistleblower has claimed that of the seven-member CIA team, only the senior member believed the zoonotic explanation. “The whistleblower further contends that to come to the eventual public determination of uncertainty, the other six members were given a significant monetary incentive to change their positions.”

The assessments of experts

·      According to Richard Muller and Steven Quay, “[b]ased on experience with SARS-1 in 2003 and MERS in 2012, we know that many people are infected by a host animal long before a coronavirus mutates to the point where it can jump from human to human. An extensive data set from late 2019—more than 9,000 hospital samples—is available of people exhibiting flulike (thus Covid-like) symptoms in China’s Hubei and Shaanxi provinces before the epidemic started. Based on SARS-1 and MERS, the natural zoonotic theory predicts 100 to 400 Covid infections would be found in those samples. The lab-leak hypothesis, of course, predicts zero. If the novel coronavirus were engineered by scientists pursuing gain-of-function research, there would be no instances of community infection until it escaped from the laboratory. The World Health Organization investigation analyzed those stored samples and found zero pre-pandemic infections. This is powerful evidence favoring the lab-leak theory.”

·      “SARS-CoV-2 emerged in Wuhan with a furin cleavage site never before seen in a sarbecovirus. It needs to be emphasized that, to the best of our global knowledge, ‘sarbecovirus with furin cleavage site’ did not exist in nature before 2020, but it did exist in a grant proposal to make something not found in nature, and that biological novelty was proposed to be made in Wuhan. The exact furin cleavage site found in SARS-CoV-2 is found in another protein, a protein called alpha-ENaC found in humans and studied heavily at the same university (UNC) as one of the PI’s [principal investigators] of DEFUSE [the research proposal from EcoHealth Alliance].” “Finally, and most importantly, the authors [of the DEFUSE grant] propose a specific location in the genome where they will insert these furin cleavage sites: the S1/S2 boundary, a narrow window in a 3,600 nucleotide gene, and SARS-CoV-2 has its furin cleavage site at exactly the location proposed in these grants.”

·      “The most likely origin of COVID-19, of the Wuhan virus…was a lab leak at the Wuhan Institute of Virology,” according to former United States Director of National Intelligence John Ratcliffe. He went on to say, “[t]he people that had access to the most data—the most intelligence—will all tell you the same thing, that this is really, most likely, what happened. It's more than just a possibility. It's certainly a probability and it's probably a certainty.”

·      Based on information collected by reporter Nicholas Wade, all the pieces for the scenario where SARS2 was constructed in a WIV lab have fallen into place:

a.        In March 2018, American and Chinese virologist applied to DARPA to manipulate viruses related to SARS1.

b.        The proposal for Project DEFUSE specified that the viruses’ infectivity would be enhanced by the introduction of the genetic element known as the furin cleavage site.

c.        Three biologists independently speculated that if SARS2 had been created using the methods specified in the DEFUSE proposal, that it would have certain attributes. While these predictions were derided by some prominent virologists, the SARS2 virus does show evidence of all the attributes specified by the three biologists, primarily:

i.         SARS2 appears to be assembled from six sections of DNA using an enzyme known as the BsmBI restriction enzyme.

ii.         The genetic code to specify the cleavage site is something that is seen in human DNA, not that of coronaviruses.

The lab leak theory is a “conspiracy theory”?

“I have no data yet. It is a capital mistake to theorise before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts.” — Sherlock Holmes

The lab leak theory has been attacked by some who claim it was not true, misinformation, a conjecture, a conspiracy, false information, implausible, something out of a comic book, extremely unlikely, already debunked, and repeatedly disproven. They said those advocating the lab leak theory were finger pointing, being racist, contributing to discrimination and violence against Asian Americans, and claiming a “major conspiracy theory.”

The most generous interpretation of what the critics were saying is that we, the people investigating evidence of a possible lab leak, had reached a conclusion before we had all the facts. Fair enough. However, instead of offering platitudes and attacking the motives of those who suspected a lab leak, they should have argued that we needed to get the facts straight before arriving at conclusions. This paper is an attempt to do just that.