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The Origin of the COVID-19 Outbreak in Wuhan

We don’t know yet. But contrary to recent reporting, science does not rule out a lab accident or even bioterrorism.

Khaled Talaat
April 07, 2020
Kevin Blumenthal
Kevin Blumenthal
Kevin Blumenthal
Kevin Blumenthal
Editor’s note: This article first appeared in Tablet on April 6, 2020. 

After the exponential growth in coronavirus (SARS-CoV-2) infections, it is no surprise that the internet is full to the brim with all sorts of conspiracy theories regarding its origin. Strong claims often trigger similarly strong responses, such as accusations by conspiracy theorists of malicious intent and claims that the virus could not have been leaked from a laboratory. Loud voices from both sides overshadow calls to investigate a spectrum of plausible scenarios.

Recent studies suggested that the virus is not bioengineered. However, bioweapons and genetically engineered viruses are not equivalent, as the latter are used in peaceful applications in order to understand potential threats in the environment. These include studying the natural gain of function that happens in nature as viruses evolve or recombine, and their potential for use in drug delivery and vaccine development. On the other hand, a bioweapon used by a nonstate actor (i.e., a bioterrorist) could be an entirely natural virus, although a malicious state might be likely to seek a more effective weapon through bioengineering.

Given the novelty of SARS-CoV-2, it’s unlikely to be a bioweapon. Recent research suggests that the virus is likely natural in origin, although the immediate natural reservoir of the virus is yet to be identified. Additionally, it would seem improbable that a bioterrorist would use an unknown natural virus as a weapon, unless they were involved in experiments that ascertained that such a virus or one of its ancestors could effectively bond to human receptors and efficiently infect human cells.

Coronaviruses, as well as flu and other viruses that pose a moderate health hazard, are studied at biosafety level 2, which is not very strict, with protective equipment only worn as needed. It is unclear whether SARS-CoV-2 was known to any of the Chinese virology labs before the outbreak, but its close relatives, like RaTG13, have been known and studied since 2013.

Contrary to the preponderance of recent media claims, studies that aim to trace the origin of the SARS-CoV-2 are not conducted with the intent to verify whether the virus is a bioweapon or not, but rather contribute toward identifying its natural reservoir. It is important to understand how the virus jumped from animals to humans, as this might happen again with the same or a different strain. By identifying related viruses, researchers also inform other studies that work toward identifying known molecules that may inhibit bonding between the virus’ S protein and human protein receptors, or even ones that could potentially block the RdRp binding pocket. This could help identify drugs that could cure the disease or inhibit infection.

Recently, the authors of a much-reported-on Nature Medicine correspondence expressed their personal beliefs and speculations at the end of the correspondence. This is rather unusual in research, where only supported facts are typically presented. The authors stated: “Since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.”

This conclusion is a logical leap and an unsupported generalization. There is no doubt that the correspondence provided useful analysis of the mutations from RaTG13, which was found in another study to exhibit 96% similarity to SARS-CoV-2. This 96% similarity suggests that SARS-CoV-2 is related to RaTG13, although the 4% could account for significant functional differences. The nature of the mutations suggests a natural origin of the virus but doesn’t prove that a laboratory-based scenario is impossible, as the authors then claimed. A lab scenario may involve either a fully natural virus that is related to SARS-CoV 2, or even a chimeric virus which could have acquired random mutations due to being released into the environment a long time ago.

Kevin Blumenthal

For the conclusions by the authors of the correspondence (Andersen et al.) to be acceptable, they would have needed to identify the immediate natural reservoir of the virus and study how it evolved in that population and later spread to humans. This is a much more complex task than a genomic comparison that suggests a natural origin but does not explain how the virus jumped from animals to humans. Another study published in Nature showed that SARS-CoV-2 exhibits greater similarity to Malayan pangolin coronaviruses in the receptor region, but exhibits greater similarity to RaTG13 in many other segments. The pangolin virus, however, is not the same as the human SARS-CoV 2-virus, but rather only a relative, just like RaTG13. The natural reservoir of the SARS-CoV-2 virus has yet to be identified.

However, malicious intent at the individual level is far less predictable than at the state level. Individuals, possibly even lab workers, could use sophisticated strategies to obscure the origin of the virus. At this point, whether the present outbreak is a result of bioterrorism or not is unsettled, and if it is, it is as of yet unclear when or how the release might have happened.

One compelling argument against the bioterrorist hypothesis for the COVID-19 outbreak that began in Wuhan is that malicious actors would have other options with much more predictable damage levels to suit their desired damage targets and political goals. Further, they would likely have introduced it far from Wuhan, which is the site of a lab known to study coronaviruses, to avoid attention. Nevertheless, these arguments assume we are dealing with somewhat rational thinkers, which might also not be the case. They may have even worked at another lab and introduced the virus in Wuhan to falsely implicate the lab located there. The psychology of terrorists is a sophisticated topic beyond microbiology studies. However, there is no hard evidence at this point that suggests an intentional release of the virus, and this claim remains an unsupported hypothesis. In my opinion, it is too early to make a conclusion, but I speculate that it is unlikely that the present outbreak is a result of an intentional release.

However, I also disagree with media assertions that it has been “proven” that the virus is not a bioweapon. To prove this, one would need to know exactly how patient zero was infected—not whether the virus is natural or bioengineered in origin. Given the overall significance of the problem, even unlikely scenarios should not be dismissed offhand and should be investigated.

A much less echoed, although less radical, scenario is that the current outbreak is related to a lab accident involving disease transmission experiments intended for peaceful purposes. As mentioned earlier, coronaviruses are generally studied at biosafety level 2 and sometimes 3, including the 2003 SARS-CoV. Coronaviruses are not typically highly hazardous—the dangerous ones are not highly infectious and the highly infectious ones are not deadly. SARS-CoV-2 happens to be an exception, although it is not extremely fatal, as many other viruses are.

The Wuhan Institute of Virology has been extensively studying coronaviruses since the SARS outbreak of 2002-03 in order to prevent a similar outbreak and potentially develop vaccines. A key challenge was identifying the natural reservoir of the SARS-CoV virus. Unlike what the public may imagine, scientists don’t go around in the wild sampling millions of random animals to identify a natural reservoir. In actuality, a much more efficient approach is to sample a few animals from species that are known to host related viruses and investigate whether the human virus would bond to their protein receptors and cause infection or not.

For an animal to be a natural reservoir of a human virus, the virus must be infectious to both species. If the virus does not transmit efficiently in the animal, then it is unlikely that a particular population of that animal is the natural reservoir. Bats carry many different types of coronaviruses including RaTG13, which is closely related to SARS-CoV-2. The incredible diversity in bat ACE2 receptors complicates the search for the natural reservoir as sampling more bats and bat species becomes necessary. Bat coronaviruses typically do not bond to human ACE2 receptors. For this reason, there were concurrent searches at the Wuhan lab for an intermediate species. Civet cats were found to carry closely related viruses to the 2003 SARS-CoV such as the SZ16, civet007, and PC4_13 viruses.

The type of infectious disease transmission experiments mentioned in the previous paragraph were carried extensively in research published by the Wuhan lab using both natural strains of coronavirus and chimeric coronaviruses, which can simulate recombination scenarios in nature. Similar research on coronaviruses was also carried out in the United States and Europe, although the Wuhan lab studied coronaviruses more extensively than other labs after the SARS-CoV outbreak of 2003 and the MERS-CoV outbreak of 2012 in East Asia. This research is necessary in order to prevent outbreaks, as the incident of transmission from animals to humans can happen multiple times. These experiments involve a little risk but can reduce the overall risk of an outbreak as natural threats can be identified. The lab’s work may also contribute to the future development of vaccines.

Ideally, any animals or cells used in these experiments are cremated post-experiments to prevent a leak of the virus to the environment. Introducing the virus to a new species in a lab can result in the emergence of new strains. The virus can recombine with a related virus during coinfection of the host cell and exchange genetic segments, leading to an accelerated natural gain of function.If safety protocols aren’t properly followed, the virus may leak into the environment and potentially infect other animals. Different animals have different immune systems, which can again result in the emergence of more aggressive strains of the virus with human infection capabilities in densely populated cities like Wuhan. China’s widespread use of wildlife as a food source in “wet markets” amplifies the risk of transmission to humans.

The Wuhan Institute of Virology used RaTG13, a close relative of SARS-CoV-2, as evidence that the SARS-CoV-2 is natural in origin in order to respond to state-sponsored bioengineered weapons claims. The RaTG13 virus, a close relative of SARS-CoV-2, was discovered in 2013 in bats in Yunnan province, some 1,200 miles away from Wuhan city. It is unclear what experiments were conducted using the virus and other viruses related to SARS-CoV-2, such as the pangolin viruses. While the intent would not be to blame China in case of an accident scenario, releasing records that detail how RaTG13 was handled and what experiments were conducted using the RaTG13 virus and related viruses could help accelerate the search for the natural reservoir and prevent another wave of infections. It would also help establish better safeguards in similar laboratories to prevent an accident or an intentional leak scenario.

In closing, I would like to emphasize that it is possible that the virus could have fully originated or evolved in nature without human intervention in the transmission. My article in no way intends or attempts to serve as evidence of an accident scenario and should not be used for that purpose. My intention is to explain the debate as well as my view that an accident scenario not involving malicious intent should not be prematurely dismissed. In fact, I think a lab accident scenario is more benign than a completely natural emergence. If the virus emerged naturally without connection to lab experiments, it may be harder to identify and isolate the natural reservoir and reemergence of the virus or similar viruses becomes likely.

While the COVID-19 crisis is unlikely to be a case of bioterrorism, the extent of the damage caused by the virus calls for stronger safeguards against bioterrorism, especially given continued advances in biotechnology. The advances in detection and testing capabilities need to be on par with the advances in bioengineering technology. I call on world leaders to implement additional safeguards against bioterrorism that are up to the same quality standards of the nuclear nonproliferation safeguards. This may include building statistically informed monitoring stations for infections at travel hubs, moving labs that deal with dangerous pathogens outside of densely populated cities where wild animals are consumed, and working toward banning the sale of live animals that could potentially be used as carrier vehicles to deliver viruses that would otherwise not be easily transmitted to humans.

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.

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