Last year was indeed a remarkable year for science. The world faced a devastating pandemic and there were far more questions than answers on almost every aspect of COVID-19. There were successes such as the rapid development of mRNA vaccines, along with evident failures such as unproven cures and the continuing inability to ascertain how the pandemic started. The abundance of questions but not answers has unsurprisingly triggered waves of speculation and hand-waving in the media and among scientists themselves.
Novel viruses that infect humans usually jump from other animals. They make it to humans through contact with the reservoir animals directly or contact with intermediate species, such as farm animals. Identifying how a virus first appeared in human populations is a difficult and costly endeavor that involves extensive sampling of viruses from animals known to host related viruses and serological testing of exposed human populations to identify earlier clusters. There are still many missing pieces in SARS-CoV-2’s origins and source stories, as is the case with many other viruses like Ebola and hepatitis; many of those pieces may never be found.
In the particular case of COVID-19, the earliest known clusters occurred in the city of Wuhan, which happened to host two virology labs that sampled thousands of coronaviruses from the area where SARS-CoV-2’s nearest known progenitors are found, over 1,200 miles away from Wuhan. The city of Wuhan has roughly 0.8% of the population of China, but being an urban area, it is not particularly known for consumption of wildlife. This has given rise to the idea that the pandemic started as a result of a lab leak that was sustained by the population density in Wuhan. Early in 2020, I wrote two articles that explained the possibility of a lab leak was not an improbable conspiracy theory, as large media platforms then seemed intent on declaring it based mostly on straw-man arguments. Both articles were written in collaboration with an expert virologist working on biorisk and global security issues who preferred to remain anonymous, and were reviewed by several other experts.
The lab-leak theory is a collection of ideas that aim to explain the emergence of SARS-CoV-2 in human populations within the context of a laboratory or laboratory-related release. It is effectively not a single “theory” in the sense that it branches out into six different ones: (a) the accidental leak of a natural coronavirus through infection of a lab worker during lab experiments, (b) the accidental lab leak of a natural coronavirus through improper disposal and infection of a nonlaboratory individual or animal in a dense city, (c) the infection of a field worker with a coronavirus during sampling and collection activities, (d) the lab leak of a chimeric (laboratory-modified) coronavirus through accidental infection of a worker, (e) the intentional release by a malicious lab worker or unknown entity, (f) state-sponsored activity (not necessarily from China). There is no known evidence to support (e) and (f); therefore, I’ll focus this discussion on the first four theories, which are more credible in light of the available knowledge.
After more than a year and a half of intense debate, there is still no definitive evidence that resolves the lab leak discussion. This is not unexpected, as the pandemic started in China, a totalitarian state in which information flow is tightly controlled. From the beginning, the Chinese government has objected to and impeded investigations of the lab leak theory that would normally be conducted through independent serological testing of lab workers, access to hospital records, inspection of laboratory records and pre-outbreak collections, etc. Nevertheless, little pieces of evidence have emerged here and there that lend credence to both the natural-origin zoonotic jump and natural-origin lab leak theories as plausible causes of the pandemic.
Regardless of how COVID-19 started, the premature suppression of the discussion of the lab leak theory highlights a new and unhealthy relationship between the mainstream media and science. It is alarming that journalists were labeling the lab leak hypothesis with all its different branches a “debunked” conspiracy theory as early as February 2020 based on studies that simply said that the virus was likely not engineered. Reframing this partial answer as a much broader and more definitive one, the press then cherry-picked comments from scientists who had collaborated extensively with the lab and whose apparent conflicts of interest were ignored in order to present their statements as proven facts.
The narrative in the media changed after the extensive efforts of Alina Chan, a postdoctoral researcher at the Broad Institute of MIT and Harvard, to advocate for nonexclusion of the lab leak hypothesis, and after a letter from 18 scientists that included distinguished virologists and biologists such as Jesse Bloom, Ralph Baric, Pamela Bjorkman, Marc Lipsitch, Tim Stearns, David Relman, and others appeared in Science magazine calling for a rigorous investigation into the origins of COVID-19 including the lab leak hypothesis, which they considered to be plausible given the available evidence.
It may seem counterintuitive that distinguished scientists would publish a letter urging others to investigate something instead of investigating it themselves. The issue of COVID-19 origins, however, is not one that could be solved by science alone. Science aims to explore nature and explain natural observations relying on data and evidence that no one controls or restricts. However, in the particular case of COVID-19, China controls access to lab personnel, data, and records that could be studied to arrive at a firm conclusion. What we are left with so far are unavoidably speculative conclusions that lack the certainty that media organizations and political types have sought to enforce.
Although there is good reason to suspect that the pandemic could have been a result of a lab leak or lab-related accident, the available circumstantial evidence for some version of the lab leak theory does not automatically lend credence to the lab-manipulation hypothesis: The nature of the virus and how it appeared in humans are separate questions. We do know through recent investigations that certain features of the SARS-CoV-2 virus make it harder for it to have emerged as a result of laboratory manipulation. The SARS-CoV-2 virus loses a critical region known as the furin cleavage site (FCS) that gives it the ability to infect human cells after passaging in typical cell-culture experiments. This loss of FCS, however, only occurs after extended passaging, and scientists who intentionally want to preserve the FCS may limit the passaging, as Alina Chan has stated.
The Wuhan Institute of Virology (WIV), like several other labs around the world, conducted some research on chimeric coronaviruses, but there is no evidence that it possessed viruses that could have feasibly resulted in SARS-CoV-2 when combined in a laboratory. Such evidence, as leading coronavirus expert Ralph Baric has explained, can only be obtained through information within the Wuhan laboratories such as the pre-outbreak collections and records of experiments conducted. Recent grant proposal documents obtained by the Intercept from the NIH further confirmed that the lab had the capability to modify coronaviruses but revealed no evidence of manipulation of SARS-CoV-2-like bat coronaviruses. Based on the NIH documents and published works of the lab, we only know that it worked with a few chimeric coronaviruses that do not resemble SARS-CoV-2. On the other hand, it is well known that it sampled thousands of natural bat coronaviruses from the same geographical area where SARS-CoV-2 likely originated. Chimeric-origin theories, although not impossible, remain speculative and lacking in evidence compared to natural-origin lab leak theories.
Luigi Warren, an mRNA pioneer whose 2009 mRNA reprogramming experiment at Harvard with Moderna’s co-founder Derrick Rossi, according to a 2013 Boston magazine article, led to the foundation of Moderna, explained in a recent short opinion article:
I believe the COVID-19 pandemic is the result of a lab accident, likely involving a precursor virus brought back to Wuhan wittingly or unwittingly by Shi Zheng-Li from the infamous Mojiang mineshaft. From where I am standing, I still see no smoking gun that it was the result of “engineering”—e.g., by insertion of the FCS or mix-and-match replacement of the hACE2 RBD—although it’s reasonable to consider that possibility. It’s also reasonable to entertain the idea that gain-of-function techniques such as serial passage through humanized mice were applied at WIV to enhance the infectivity of a precursor virus harvested on one of Shi’s many sampling expeditions to Southern China. Still and all, no smoking gun has emerged.
Warren had been a leader in the natural-origin lab leak movement since May 2020 after he directed attention to the 2013 mineshaft in Mojiang, Yunnan, China, from which the WIV extensively sampled coronaviruses. An anonymous Twitter user, “The Seeker,” had found and translated a master’s thesis on the miners’ strange pneumonia cases in 2013. Warren exposed the obfuscation in the WIV’s published research, which did not explicitly point out that it was studying coronaviruses from that particular area motivated by the unexplained death of miners due to a severe respiratory disease. The WIV itself confirmed this theory in an addendum to its original January, 2020 Nature paper that had released the genome and key information on SARS-CoV-2. In the addendum, it stated that:
Between 1 July and 1 October 2012, we received 13 serum samples collected from 4 patients (one of whom was deceased) who showed severe respiratory disease. These patients had visited a mine cave in Tongguan town, Mojiang County, Yunnan Province, China, to clean bat faeces in order to mine copper before being admitted to the First Affiliated Hospital of Kunming Medical University on 26–27 April 2012.
It also stated that:
We suspected that the patients had been infected by an unknown virus. Therefore, we and other groups sampled animals including bats, rats and musk shrews in or around the cave, and found some alphacoronaviruses1 and paramyxoviruses2. Between 2012 and 2015, our group sampled bats once or twice a year in this cave and collected a total of 1,322 samples.
During these expeditions, the WIV sampled the closest-known bat coronavirus relatives of SARS-CoV-2 including RaTG13, which is 96.2% similar to SARS-CoV-2. To be clear, the RaTG13 and the SARS-CoV-2 viruses diverged more than a decade ago (2003-13 95% HBD limit). This distance in evolution is short enough to indicate that the more proximal ancestors of SARS-CoV-2 likely come from the same geographical region in Yunnan province and the surrounding area where the RaTG13 virus was collected. The WIV released the whole RaTG13 genome in 2020 not out of transparency but because it had already publicly released part of it, namely the RdRp segment, in 2016. In late May 2020, after questions about its authenticity, the WIV released its raw amplicon sequences, which demonstrated the veracity of the RaTG13 genome published in January 2020.
We know now from Shi Zhengli’s interview with Science that the WIV team sequenced the whole genome in 2018. This reveals interest in SARS-CoV-2-like bat coronaviruses shortly before the pandemic. However, we don’t know if they indeed encountered SARS-CoV-2 itself or a closer progenitor than RaTG13 during their expeditions. There is also evidence of Wuhan lab scientists admitting to being bitten by bats and evidence of scientists at the Wuhan CDC not wearing protective equipment or taking proper safety measures during similar expeditions to bat caves. Given what we know about the research at the WIV and the Wuhan CDC and the interest in SARS-CoV-2 like bat coronaviruses shortly before the pandemic, and as SARS-CoV-2 easily loses furin cleavage site when cultured, the most likely route for a lab leak is therefore infection of a lab worker during field activity.
So what is the significance of a lab-related leak caused by negligent field workers? It is important to note that although humans outside of laboratories come into contact with animals more frequently than scientists overall, researchers are interested in viruses with human infection potential—and therefore they are much more likely than the average person interacting with animals to come across a bat coronavirus with human infection capabilities. The miners’ story provides context that explains why Wuhan scientists were interested in SARS-CoV-2-like bat coronaviruses, and may well have accidentally brought it to a population-dense city and started a global pandemic. If it is confirmed that the pandemic emerged as a result of accidental infection of a lab worker during an expedition, that would raise the question of whether it is a good idea to construct major virology labs in a population-dense city with thousands of people traveling in and out every day.
The U.S. Department of State published a fact sheet in 2020 noting that the U.S. government had reason to believe that workers at the WIV fell sick with symptoms consistent with COVID-19 in the autumn of 2019. Later, it was more specifically revealed that U.S. intelligence identified three lab workers that fell ill in November 2019 and sought hospital treatment.
A report released by the World Health Organization in March was inconclusive with regards to the role of the Huanan live animal market. It stated: “No firm conclusion therefore about the role of the Huanan market in the origin of the outbreak, or how the infection was introduced into the market, can currently be drawn.” The researchers found the circulation of the virus preceded the initial detection of cases by several weeks based on the variation of SARS-CoV-2’s genome in early subjects.
Data collected by the World Health Organization revealed that two distinct genomic lineages of SARS-CoV-2 were associated with individuals who visited different Wuhan wildlife markets. According to analyses by Robert F. Garry, a virologist and professor at Tulane University, this would suggest natural origin as it points to multiple zoonotic jump events at the markets due to animals infected with different lineages being sold at different locations. This, however, remains a hypothesis that is not uncontested. The viruses differ by mutations at only two sites and, according to Trevor Bedford, a leading phylogenetics expert, divergence from the first lineage at other markets to the second lineage at the infamous Huanan live animal market could have feasibly occurred in humans. Alina Chan had proposed in May 2020 that the Huanan live animal market merely amplified the transmission and was not necessarily where the virus first jumped into human populations based on the genetic similarity of the market samples to human SARS-CoV-2 isolates.
Yet despite China’s suspicious responses, which include tightly controlling investigations on SARS-CoV-2’s origins, genomic database takedowns, and pressuring the World Health Organization to dismiss the lab leak hypothesis, it nevertheless also remains plausible that the pandemic was the result of a zoonotic jump that is unrelated to lab activity. In case a lab or lab-related accident did occur (e.g., infection of a field worker), one should not assume that the Chinese government or even the lab’s staff would have necessarily known of the accident—but they could also choose not to know one way or the other, which appears to be the case.
Many of the discussions that have shaped our responses to the COVID-19 pandemic were inherently multifaceted, involving questions not only about health and science but also philosophies of personal freedom, political decision-making, economics, and foreign policy. Bias often follows from attempting to support one’s own philosophy or attachments in one of those areas with wishful thinking that the same ideas are sound in other areas. Journalists and individuals who lack any rigorous scientific training may be tempted to claim little pieces of a large puzzle as conclusive evidence to support their favored conclusions in other areas. The consequences of these repeated behaviors, which can be innocently or unconsciously motivated, are not easy to undo.
The media throughout 2020 reported a “scientific consensus” that the pandemic was a result of a zoonotic jump that is unrelated to lab activity without providing information on what questions the scientists it surveyed were asked, how many scientists were surveyed, and whether or not these scientists conducted investigations into the origin of COVID-19. It is clear that journalists have a powerful tool through which they are able to declare a scientific consensus before a matter is rigorously investigated.
Amplifying ignorance and absolutism in order to enforce unproven opinions as unquestionable “facts” is the opposite of how the scientific method functions. Irresponsible reporting and nonfactual declarations of scientific consensus on developing matters endanger public health just like a virus does, by undermining public trust in science. We should learn something from the boys who cried wolf.
Khaled Talaat is a postdoctoral scholar in nuclear engineering at the University of New Mexico. He has conducted research on multiple subjects including aerosols, radiological protection, and Generation IV lead-cooled fast reactors.