The Shift in Hypotheses

The dominant theory from last year suggested that the virus originated zoonotically, suggesting a transmission from bats (natural carriers of coronaviruses) to humans, possibly through an intermediary host. However, due to the rarity of direct contact between bats and humans, the involvement of another animal host was proposed.

This year, however, perspectives have evolved.

During a briefing on March 30, 2021, Dr. Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization (WHO), emphasized that all hypotheses regarding the virus's origin remain under consideration following the review of a comprehensive investigation report. This stance demonstrated commendable integrity from him. Jamie Metzl, a noted geopolitical analyst and science writer, remarked, “Tedros risked his entire career to uphold the credibility of the WHO.”

Before delving deeper, it is crucial to clarify that the lab origin hypothesis encompasses two interpretations, the first of which is more plausible:

• Coronaviruses from nature, which may or may not have undergone gain-of-function (GOF) experiments, could have accidentally escaped from a laboratory setting. GOF refers to the intentional enhancement of microbes to assess their potential dangers in nature. There is ongoing debate regarding whether GOF research pertains solely to human-affecting microbes or includes all species, which is why the U.S. has denied funding for GOF research at the Wuhan Institute of Virology (WIV) focused on animal coronaviruses.
• Another interpretation suggests bioengineering from scratch to create a bioweapon that could have leaked, whether intentionally or by accident. Bioengineering involves the creation of new organisms, while gain-of-function refers to modifications of existing ones.

This briefing marked a transition toward more open discussions about the lab origin hypothesis, a topic previously deemed taboo and linked to anti-Asian sentiments. Surprisingly, this dialogue has gained traction and acceptance.

The Growing Recognition

For instance, in April 2021, I authored an article summarizing the WHO-China joint investigation report, highlighting its weaknesses and criticisms, and discussing arguments for and against the lab origin theory, along with future steps needed to unravel this mystery.

However, it wasn't until the following month that two significant events brought widespread attention to the lab origin hypothesis. The first was a detailed article by Nicholas Wade, an experienced science writer, presenting circumstantial evidence supporting the lab origin theory from both political and scientific angles. The second was an open letter signed by 18 prominent scientists, including Prof. Akiko Iwasaki, Prof. Ralph S. Baric, and Prof. David A. Relman, published in the journal Science, advocating for further investigation into the lab origin theory.

Even Dr. Anthony S. Fauci, the U.S. President's chief medical advisor, who had previously dismissed the lab origin theory, has reevaluated his stance.

When asked if he still believed SARS-CoV-2 developed naturally, Dr. Fauci responded, “No, actually, I am not convinced about that. We should continue to investigate what occurred in China until we can ascertain what happened... Although investigators suggest it likely emerged from an animal reservoir, it could have been something else, and we need to uncover that.”

Despite being circumstantial, the evidence supporting the lab origin theory is considerable and persuasive, as noted by various writers, including Wade, Yuri Deigin, Donald McNeil, and others. Here are the key points:

1. The WHO-China investigation did not find any evidence of SARS-CoV-2 in nature. Over 80,000 animal samples were tested in China, all returning negative results. Only a few non-animal samples from market surfaces tested positive, indicating infections occurred but not through animals. Notably, no samples from Wuhan laboratories, where the initial outbreak began, have been formally examined.
2. Accidental lab leaks of dangerous pathogens have happened numerous times, even in high-security labs like the U.S. Centers for Disease Control and Prevention (CDC). For instance, the prior SARS outbreak experienced at least six lab leaks post-2003.
3. Current gain-of-function research has advanced to a level indistinguishable from natural evolution, making it difficult to determine if a microbe like SARS-CoV-2 has been enhanced in a lab. The WIV has conducted gain-of-function studies on coronaviruses in biosafety level 2 and 3 labs, which are not stringent enough for certain pathogens.
4. The U.S. Intelligence Community reported that three WIV staff members exhibited symptoms resembling Covid-19 in November 2019, prior to the outbreak. This contradicted earlier claims by Dr. Shi Zhengli, head of the WIV, who stated there were no infections among staff before January 2021.
5. The WIV's database containing a vast collection of coronavirus genomes was locked in September 2019 and taken offline in spring 2020 to supposedly protect against cyberattacks during the pandemic. However, this database was not scrutinized during the WHO-China investigation.
6. If SARS-CoV-2 originated in nature, specifically among bats, then Yunnan should be the epicenter. Bat caves are located there, and bats do not migrate to Wuhan, the outbreak's initial site. In Wuhan, there are labs and markets selling wildlife products, yet bats were not sold in the market when the outbreak began. As mentioned earlier, no traces of SARS-CoV-2 were discovered among the tens of thousands of tested animal samples.
7. Although contentious, the political context may also serve as circumstantial evidence. China's secretive nature is well-documented, as it has historically suppressed journalists and scientists investigating sensitive issues. For example, China downplayed case counts and restricted WHO researchers from accessing the site of the 2002 SARS outbreak, repeating this behavior in 2020 regarding SARS-CoV-2. Therefore, the possibility of cover-ups related to accidental lab leaks cannot be dismissed. Additionally, researchers who quickly dismissed the lab origin theory may have conflicts of interest, as their careers depend on coronavirus research.

Despite these points, the lab origin hypothesis is not without its criticisms. Donal G. McNeil, a veteran science and health journalist, and others have outlined significant shortcomings. Here are the main critiques:

1. While both lab and natural origins are plausible, the latter is generally considered more likely. A lab leak relies on a single event—a mistake—while zoonotic spillover can happen through numerous animal-human interactions in various settings across China.
2. The lab leak scenario hinges on the assumption that researchers were working with live SARS-CoV-2 (or its ancestor) and that higher authorities were aware. However, Dr. Shi has claimed they had not studied any viruses similar to SARS-CoV-2 prior to the outbreak.
3. Although the destruction of potential SARS-CoV-2 samples by Chinese authorities may seem like a cover-up, it could also be a public health measure to avoid further outbreaks. Moreover, China's lack of cooperation during the initial pandemic phase may stem from defensiveness rather than malicious intent.
4. While some unusual elements in the SARS-CoV-2 genome might suggest manipulation, this is just one interpretation. Another view is that these peculiarities are products of natural evolution.
5. Historically, large-scale outbreaks have typically originated from natural sources. Examples include SARS and MERS, which jumped from bats to intermediate hosts before infecting humans. Other viruses like Ebola and influenza also have natural origins.
6. Although China did not find SARS-CoV-2 in extensive animal testing, it may be premature to conclude absence. More thorough sampling, potentially beyond China, may be necessary. Identifying origins for previous outbreaks, like SARS and HIV, took years.

In conclusion, neither the natural nor lab origin hypotheses have been definitively proven. This is why they remain hypotheses rather than established theories. At this juncture, rather than questioning the true origin, we should focus on what it would take to obtain a clearer answer.

The Path Forward

An independent, impartial investigation into the Wuhan labs is necessary to either validate or refute the lab origin hypothesis. This would require examining lab records, data, samples, and equipment. However, such investigations may never occur due to the sensitivity of the information involved, especially given the WIV's alleged connections to the Chinese military, which Dr. Shi has denied.

Even if an independent inquiry were permitted, nearly two years have elapsed since the initial Covid-19 outbreak in Wuhan. This duration provides ample opportunity to eliminate potential evidence. Therefore, skepticism may persist even if future investigations dismiss the lab origin theory.

The only way to assuage doubts would be for Chinese authorities to either acknowledge a lab leak or provide evidence of SARS-CoV-2 in a natural reservoir. However, without independent investigations, many will remain unconvinced, suspecting that China may fabricate evidence to divert attention from the labs.

To restore faith in China, the lab origin hypothesis must be disproven. The circumstantial evidence supporting this theory has become increasingly compelling. However, disproving it may be an insurmountable challenge, as the possibility of evidence being destroyed cannot be ruled out. The window for sending independent investigators to the Wuhan labs may have closed, and expectations for conclusive results are low.

“I doubt we will ever uncover definitive proof, especially if it was indeed a lab accident. The stakes are enormously high now. It would be alarming to be held accountable for millions of Covid-19 cases and potentially a million deaths if the pandemic spirals out of control,” stated Alina Chan, Ph.D., a molecular biologist at the Broad Institute of MIT and Harvard.

David A. Relman, M.D., professor of medicine and immunology at Stanford University, emphasized, “As time passes, the types of information that could prove crucial will likely diminish and fade away.”

Ultimately, the true origin of SARS-CoV-2 may remain shrouded in mystery, leaving many perpetually skeptical regardless of the outcome. Without clarity on how this pandemic began, we lack the knowledge to prevent future ones. We are left to navigate the uncertainties and prepare for the unknown.

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