Flying Blind on the Origin of a Pandemic

Ruth Etzioni, Full Member, Division of Public Health Sciences, Fred Hutch Cancer Center

I was always curious. 

An early elementary school memory is my mother returning from a parent-teacher conference to report that my teacher thought I had “an enquiring mind.”

Curiosity is what led me to a life of research, as a biostatistician and population scientist. Because in research, the questions you ask are just as important as their answers. The questions I ask have to do with the inevitable gaps in evidence that get in the way of making well-informed medical decisions. 

So I am having a hard time fathoming why people around me are not more curious about how on earth this pandemic began. Without knowing where the SARS-CoV-2 virus came from or how it began to infect people, it’s hard to be strategic about preventing the next pandemic.

The standard explanation is that the virus started in a bat, a bat transmitted the virus to another animal, and then at some point the virus began to infect humans. Scientists call this a zoonotic event, transmission of a pathogen from animals to humans.

But there are gaps in the evidence.

A recent New York Times article by Thomas Friedman titled, “One Year Later, We Still Have No Plan to Prevent the Next Pandemic,” focuses squarely on the illicit wildlife trade and how it facilitates the leap of viruses from wildlife to humans. While Friedman interviews some wildlife veterinarians, the prevailing zoonotic explanation involves an intermediate animal host.

Virologists believe an intermediate species is critical, because bat viruses need to have an opportunity to adapt so that they are able to infect and transmit between non-native species such as humans.

But natural zoonosis is not the only possible explanation. 

Another explanation is that the SARS-CoV-2 virus could have accidentally escaped from a laboratory. This was posited by former CDC director Robert Redfield in an interview with CNN’s medical correspondent, Dr. Sanjay Gupta. It’s his view, Redfield said, the virus escaped from a lab in Wuhan where genetic research was being done on coronaviruses.

Although Redfield is not alone in suggesting lab escape, the newly published WHO report termed this possibility “highly unlikely.” And CNN immediately labeled his comments as “a controversial theory without evidence.” Other media outlets were quick to jump in to the fray, dismissing Redfield’s assertion as “baseless.”

Since theory, evidence and likelihood are my bread and butter, I started thinking about whether CNN’s characterization was appropriate. What is a theory? What is evidence? And how would one even begin to assess how likely any explanation might be when thinking about how the pandemic began?

My goal is not to try and convince you about what happened, because I don’t know. Rather, I hope to convince you that the question is important, that the evidence about every explanation is lacking, and that healthy curiosity is warranted. 

Like many of you I spent hours every day last year reading news stories and research articles about the coronavirus, yet I saw relatively little about the question of its origins, at least in the mainstream media. 

That may be changing. More voices are clamoring for answers. In addition to CNN’s reporting, CBS just aired a 60 Minutes segment, “What happened in Wuhan? Why questions still linger on the origin of the coronavirus.” (Watch segment here).

According to Merriam-Webster, a theory is “a hypothesis assumed for the sake of argument or investigation,” or “an unproved assumption.” But both zoonosis and lab escape are more than assumptions. Rather, they are potential explanations that are made plausible by our experience in other settings.

Avian influenza viruses have been definitively isolated from animals, shown via genetic sequencing to be the source of human infections among exposed individuals such as poultry workers, and then implicated in human-to-human transmission as household members and other contacts of these workers have fallen ill.

Lab escape, even from supposedly secure facilities working with dangerous and highly contagious pathogens, has been documented in labs across the globe. As it turns out, there was a lab — the Wuhan Institute of Virology — doing genetic research on bat coronaviruses just a few miles away from the wet market originally suspected to be the site where the zoonotic leap happened. 

Evidence, on the other hand, is defined by Merriam-Webster rather vaguely, as, “something that furnishes proof.” The Oxford Dictionary is more specific here, defining evidence as, “facts, signs, or objects that make you believe that something is true.”

Here things get fuzzy. 

While bats are known to harbor coronaviruses, the original bat virus that was the definitive source has not been found, there is no clear sequencing trail that matches what has informed our understanding of avian influenza, and there is no identified intermediate host. Civet cats were implicated as the source of the 2002 SARS-CoV-1 outbreak, and were immediately considered suspects this time around, along with pangolins, mink, and ferrets. 

More than a year into this pandemic, none of the extensive sampling of animals at the market has yielded any useful “facts, signs or objects” that would have confirmed the market to be ground zero. So far, that natural zoonosis generated the pandemic seems therefore to be largely an argument of precedent — it happened before so it could happen again.

Records from the Wuhan lab and its collaborators have been blocked from the scientific community so any evidence that might confirm a lab escape as being the source of the pandemic is missing. Documentation of the types of bat viruses being held in the Wuhan Institute of Virology and the experiments being conducted there would be useful “facts, signs or objects” that could discredit or support this explanation.

We just don’t know, because these data are being kept away from the international scientific community. While lab escape has precedence in other settings, in this case the argument seems to be largely one of mechanism — the existence of such a lab could have led to a chain of events that could have seeded a pandemic.

When evidence is lacking, uncertainty reigns, and it becomes natural to start thinking in terms of probabilities. The new report from the WHO calls the lab escape explanation highly unlikely and dismisses it as the least plausible of four possible explanations. (The report finds natural zoonosis to be most likely despite the evidence gaps.) But whether something is likely or unlikely is an assessment of probability.

To know the probability of lab escape would require meticulous documentation of the number of times per year such escapes happen – in labs like the the one in Wuhan and, more specifically in the Wuhan lab itself.  The number of escapes would need to be normalized by the number of pathogens being handled or experiments being carried out, further complicating the calculation. There is no register of lab escapes and there likely never will be.

And to know the probability of a zoonotic event seeding a coronavirus pandemic like the one we are still living through would require identifying all possible encounters of humans with animals carrying such viruses and counting the ones that succeeded – not only in infecting humans but infecting humans in a manner that makes them contagious to one another. It’s hard to imagine getting any idea of this probability.

In summary, we have at least two origins for the pandemic that are more than theories. One seems to rest largely on precedent, the other on mechanism. Both are lacking definitive evidence.  And the likelihood of either is impossible to assess. 

Are you curious yet?

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