Origin of COVID-19: Bat or Lab?

It’s a legitimate question and an exceedingly important one.

Only science will enable us to anticipate, plan for, and defeat future viruses that are certain to antagonize and endanger mankind. Science and our trust in science are the requisites for survival in a world in which known microbes, and microbes yet to be discovered, will threaten human existence.

Because everyone is a potential victim of the next viral pandemic, everyone is entitled to know the feasible causes of the current pandemic and what steps have been taken or will be taken to vastly reduce the likelihood of similar public-health calamities.

Given that conspiracy theories, once concocted, spread about as fast as virulent viruses, solid unvarnished information is the only effective antidote to the mischievous and often dangerous spread of misinformation. For example, a study last July conducted by the Annenberg Public Policy Center found that 66% of those who rely on certain politically oriented, narrative-driven media believe the Chinese government developed COVID-19 as a bioweapon. While reckless and unfounded, that conspiracy theory has a patina of plausibility because, in Wuhan, China, where COVID-19 first erupted, there is an internationally recognized Institute of Virology.

 This column will not dwell on the bioweapon conspiracy theory because it makes no sense and has no credible proponent. It deflects attention away from a critical issue that does raise a serious question that demands a serious answer. Is there reason to believe that safety protocols at the Wuhan Institute of Virology were lacking, given the risk of a highly contagious, deadly virus “escaping” into the general population?

Yes, it appears that safety protocols may have been lacking at the Wuhan Institute of Virology, according to a report recently published in the Bulletin of the Atomic Scientists. The report was written by Nicholas Wade, who, for many years, wrote for the Science Times section of the New York Times and is the author of several books, some controversial, dealing with science and evolution.

While Wade’s report is far too expansive to cover in detail in this column, his bottom line conclusions are serious, and they seem, to me, to be credible and compelling. Any tendency by some to rush to dismiss his conclusions as a conspiracy theory is premature and possibly just plain defensive.

Wade notes that there are two theories regarding the genesis of COVID-19.

(1) an animal (a bat), from which it jumped indirectly after infecting other species to humans or —

(2) a research laboratory in which essential safety protocols were not followed, enabling a highly contagious virus to infect a technician who subsequently and unintentionally introduced the pathogen to the outside world.

While I found Wade’s report to be thorough and impressive, I am not a scientist. So, I forwarded Wade’s report to Dr. Michael Kaback, a well-known geneticist, physician, and academician I have known for many years. While he is not a virologist, he is a thoughtful medical scientist who found Wade’s report to be important and provocative, but concludes that the issue remains unresolved, and demands further investigation and analysis.

 If a consensus evolves among objective, recognized public health authorities, including virologists and infectious-disease experts, that a laboratory failure rather than a species-jumping virus may have been the probable cause of the COVID-19 pandemic, that information should be shared with the general public on a timely basis. The general public needs to be confident that public health authorities are being scrupulously candid if we are to achieve reasonably uniform compliance with the protocols they establish to protect the public.

A dangerous virus possibly “escaping” from a government-operated or funded laboratory makes for sensational news and great fodder for conspiracy theorists, especially when the government operating the laboratory is widely perceived by many to be an enemy of the United States. But here’s the thing; government research laboratories have a long history of relatively rare but serious and dangerous mishaps, and that includes research facilities that are operated or funded by our own government. It happens. It has happened many times in the past, and hopefully, it will happen far fewer times in the future.

These facilities are operated by dedicated men and women who may make mistakes from time to time. Virology research is vital and lifesaving, but it comes at the price of potential and sometimes dangerous human error. That is the price we pay for research that produces life-saving vaccines and treatments for diseases caused by deadly pathogens.

COVID-19 is from a viral family known as beta-coronaviruses. Initially, this suggested that the virus had managed to jump from bats via another animal host to people, as had the SARS 1 (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome) outbreaks a few years ago.

At first blush, COVID-19 also seemed to share another connection with these earlier epidemics; a so-called wet market in which animals are sold to the public for human consumption. However, Chinese researchers soon identified and quickly revealed earlier cases of COVID-19 that had no connection to the Wuhan wet market. That discovery meant that all other credible explanations for the presence of COVID-19 in Wuhan were (and are) on the table. This raised interesting questions because nearly all other cases of COVID-19 were discovered in Wuhan or in other areas in China among people who had recently traveled from Wuhan. Wuhan was the thread that held them all together. So, what other location in Wuhan might a pathogen with the genetic sequence of this particular coronavirus be found?

Wuhan Institute of Virology

The Wuhan Institute of Virology is a respected internationally recognized research facility that works closely with leading medical research institutes worldwide, including top research facilities in the United States, such as our own National Institutes of Health and various universities. The Institute, like similar research facilities throughout the world, employs serious and dedicated professional workers.

Nonetheless, Wade makes a rather convincing case that safety protocols at the Wuhan Institute of Virology were, at least on occasion, lacking, and that reality was the probable culprit that introduced COVID-19 to the world. While the Wuhan Institute of Virology had a new BSL4 laboratory (the highest safety level), its state of readiness considerably alarmed the US State Department inspectors who visited it in 2018. “The new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” the inspectors wrote in a cable dated January 19, 2018, about a year before the COVID-19 pandemic outbreak.

In BSL4 labs, researchers wear the equivalent of space suits, conduct operations in closed cabinets, and settle for every function taking twice as long. Before the pandemic, Wade writes, the rules followed by virologists in China and elsewhere required experiments with the SARS1 and MERS viruses to be conducted in BSL3 conditions, with all other bat coronaviruses studied in BSL2 labs, the next level down.

BSL2, according to Wade, requires taking fairly minimal safety precautions, such as wearing lab coats and gloves.

Another troubling aspect of research at the Wuhan Institute of Virology that Wade cites is that the Institute has used an investigative technique known as Gain-of-Function (GOF) research. GOF is an extraordinarily effective (but potentially risky) technique for studying the transmissibility or virulence potential of potential new pathogens. This is done by creating laboratory alterations of existing viruses that could, in nature, evolve into a serious threat to humans. The benefit of GOF research is that it can enable science to be better prepared to defend against previously unseen pathogens that are likely to evolve. In other words, to get ahead of a future viral outbreak in nature. The risk is that GOF research that is not subject to meticulous safety protocols could result in a new (novel) pathogen escaping from a laboratory and infecting the greater population.

Given the risks of conducting GOF research, the Obama Administration in 2014 halted direct funding (and other research involving US Government funding) of Gain-of-Function experiments involving several diseases, including SARS, a variation of which causes COVID-19.

Wade writes that researchers at the Wuhan Institute of Virology were doing Gain-of-Function experiments with coronaviruses whose RNA was specifically altered (designed) to evaluate the newly modified virus’s ability to infect human cells. These experiments were carried out in humanized mice in which human DNA has been introduced into the mouse genome and in cultures of human airway cells grown in lab dishes. Such research is conducted to, hopefully, provide valuable insight into the best way to defeat a new SARS-like outbreak.

This is, Wade alleges, precisely the kind of experiment from which a SARS2-like virus could have emerged. So, the escape of such a virus would not be at all surprising if the highest level of security demanded for this type of research wasn’t uniformly and scrupulously followed.

According to Wade, the researchers at Wuhan were not vaccinated, nor could they have been, against the newly created viruses under study. To compound the problem, Wade writes, although he provides no evidence, that they were working in the minimal safety conditions of a BSL2 laboratory. So, Wade conjectures, the escape of a virus would not be at all surprising. Wade notes that in all of China, the pandemic broke out on the doorstep of the Wuhan institute, and the new virus, having been grown in humanized mice, was already well adapted to humans.

“Proponents of natural emergence have a rather harder story to tell,” Wade writes. “The plausibility of their case rests on a single surmise, the expected parallel between the emergence of SARS2 (sort of a first cousin to COVID-19) and that of SARS1 and MERS. But none of the evidence expected in support of such a parallel history has yet emerged. No one has found the bat population that was the source of SARS2 if indeed it ever infected bats. No intermediate host has presented itself, despite an intensive search by Chinese authorities that included the testing of 80,000 animals. There is no evidence of the virus making multiple independent jumps from its intermediate host to people, as both the SARS1 and MERS viruses did. There is no evidence from hospital surveillance records of the epidemic gathering strength (elsewhere) in the population as the virus evolved. There is no explanation of why a natural epidemic should break out in Wuhan and nowhere else…”

There is probably no one who could shed more light on the mystery of the origins of COVID-19 than Dr. Shi Zhengli, Director of the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology. Dr. Shi Zhengli led several expeditions to the bat-infested caves of Yunnan in southern China to collect bat coronaviruses.

Dr. Shi worked with coronavirus researcher Ralph S. Baric, at the University of North Carolina to study the ability of bat viruses to attack humans. In November 2015, according to Wade’s report, they created a novel virus that was able to infect the human airway cells, at least when tested against a lab culture of such cells. But Wade contends that no connection between bats and COVID-19 has been found, nor has Wade’s contention been refuted.

Dr. Shi, who probably has the most insight to share regarding the origin of COVID-19 has had relatively little to say publicly. However, Dr. Shi did pen an editorial in a recent issue of Infectious Diseases & Immunity in which she refers to various sources who opine that a laboratory lapse is a “highly unlikely” cause of COVID-19. That having been said, however, Dr. Shi acknowledges that “one year after the start of the pandemic, the origin of the virus remains unresolved.”

As might be expected, Nicholas Wade’s report has drawn heavy incoming fire from various sources, including some of the most notable and outspoken advocates of the type of research being pursued in Wuhan and other research facilities around the world. That anyone would be dismissive of a laboratory origin of COVID-19 without carefully investigating the possibility is, to this writer, rather curious.

However, a growing number of eminent authorities have begun to caution against prematurely ruling out any viable explanation of the possible origin of COVID-19. Specifically, 18 infectious disease experts, immunologists, and epidemiologists signed their names to a letter in the current issue of the journal Science stating that “there still isn’t enough known to determine whether the coronavirus jumped directly from animals to people or whether it was released from a research laboratory in China.”

“Public health agencies with information on those early cases and research laboratories studying similar viruses need to open their records to the public,” said Akiko Iwasaki, an immunologist at Yale University and one of the authors of the letter.

Lawrence Gostin, the faculty director of the O’Neill Institute for National & Global Health Law at Georgetown University, minced no words. “China has not allowed a full, independent, and rigorous examination of its territory…every single moment from the initial reporting of the pandemic, there has been catastrophic failure,” he said.

 Even WHO (World Health Organization) Director-General Tedros Ghebreyesus acknowledged that the WHO team was unable to give sufficient consideration of a laboratory origin of COVID-19, and he even offered to provide additional resources to fully evaluate the possibility of a laboratory origin of the virus.

 “A proper investigation should be transparent, objective, data-driven, inclusive of broad expertise, subject to independent oversight, and responsibly managed to minimize the impact of conflicts of interest…” the open letter in Science declared.

“The lack of information,” the signers of the letter wrote, “feeds conspiracy theories and prevents scientists and policymakers from taking steps to prevent the next deadly pandemic.”

Jesse Bloom, who studies viral evolution at the Fred Hutchinson Cancer Research Center in Seattle, and is very skeptical of a laboratory origin, nonetheless, said there is not enough evidence yet to draw such a conclusion.  Bloom said he couldn’t rule out another possibility: that someone in a lab in Wuhan, China, was studying the virus and accidentally released it.

“Finally, in this time of unfortunate anti-Asian sentiment in some countries, we note that at the beginning of the pandemic, it was Chinese doctors, scientists, journalists, and citizens who shared with the world crucial information about the spread of the virus—often at great personal cost. We should show the same determination in promoting a dispassionate science-based discourse on this difficult but important issue,” the letter concludes.

I, of course, do not presume to know what caused COVID-19. Neither does anyone else. Therefore, every reasonable possibility must be thoroughly investigated. Declaring that any plausible causal event is either highly likely or highly unlikely is, at this point, poor science. What we do know as a certainty is that we don’t know.

 My point is not to cast stones at anyone working in glass research laboratories but simply to plead for thoroughness and candor by those who have a well-founded understanding of how this horror could, or could not, have occurred.

All comments regarding these essays, whether they express agreement, disagreement, or an alternate view, are appreciated and welcome. Comments that do not pertain to the subject of the essay or which are ad hominem references to other commenters are not acceptable and will be deleted.