COVID-19 and the Lab Leak

Today we're going to engage in what to many science communicators is the most distasteful part of our job: try to answer a science question that's become infected with divisive party politics. Scientists can say one thing, and when loud pundits say something different, the general public often never hears the science-based conclusion. And they don't have to just be pundits: they can be investigators, intelligence agencies, government officials, and even scientists with strong political beliefs. By no means should any reasonable person expect that a general public that gets its information through the media, online or otherwise, is likely to get the unvarnished scientific perspective. Today our question is the lab leak hypothesis for the origin of the COVID-19 pandemic. Was COVID-19 triggered by a virus leaked from the Wuhan Institute of Virology in China? It's a view held by almost nobody in the relevant sciences, but if you get your news from anywhere outside of top virology journals, you've almost certainly come to believe something very different. We are in the unfortunate position of witnessing a political fight to answer a science question.

There is really only one point upon which everyone agrees — scientists and politicians — and that's that SARS-CoV-2 (the version of the coronavirus responsible for the COVID-19 pandemic) has its ultimate origin in a population of horseshoe bats from a cave in Mojiang County in Yunnan province. As early as 2017, two years before COVID-19, an article in the journal Nature published that this bat population contained all the genetic building blocks of SARS (Severe Acute Respiratory Syndrome). From 2002 to 2004, a SARS outbreak occurred which infected 8,000 people in 30 countries, resulting in 774 deaths, and it was finally traced to this same cave. Researchers warned in that 2017 article another similar outbreak could be possible.

I should say that it's not entirely accurate to say "everyone agrees" on this. There is always what Theodore Roosevelt called the "lunatic fringe" — conspiracy theorists and alternate reality aficionados who insist upon outlandish claims that cannot be reconciled with established facts. Simple genetics show beyond any reasonable doubt that this horseshoe bat population is the origin of the virus, to the point that not even the staunchest of lab leak hypothesizers dispute it. Where the conflicting claims begin is upon what happened next.

That's where people start to split up into camps. The strongest dividing line is between scientists in the relevant fields and everyone else; the other primary dividing line is — unfortunately — political parties. And the camps they fall into are defined by their answers to two basic questions:

1. SARS-CoV-2 is a naturally evolved coronavirus, vs. it had a natural origin but was genetically manipulated by humans; and
   
   
2. SARS-CoV-2 was transmitted to humans by animals, either in nature or in markets, vs. it was leaked from the Wuhan Institute of Virology, either accidentally or on purpose.

The first question, whether it was manipulated or not, is purely a science question and is easier to answer. Virology labs all over the world have been studying coronaviruses for a long time, with the basic goal of being most effectively able to fight the inevitable outbreaks. We've had the genomes for all the variants. When COVID-19 broke out, its genome was quickly published and shared worldwide, and an international team of virologists published the seminal article "The proximal origin of SARS-CoV-2" in the journal Nature Medicine in March 2020. Its introduction concludes:

We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

You're free to read the paper, but the oversimplified, simplified version is that SARS-CoV-2 bears all the characteristics of natural selection, and none of the markers of human manipulation.

This is a good place to introduce "gain-of-function" research. This is when we take a pathogen, and manipulate it to make it more deadly. I.e., more transmissible, more virulent, and able to infect a broader range of hosts. We have to be prepared for possible future variants of a pathogen that might cause another pandemic, so we create variants of our own. This is an absolutely crucial step in pandemic preparedness. And, it's perfectly rational to suspect that that's what the Wuhan Institute of Virology might have been doing.

When we do this kind of research, we start with the genetic backbone of a virus known to infect humans. We insert gene sequences from other viruses with the desired properties. All of these steps are familiar and easily recognizable to virologists. But SARS-CoV-2 didn't have the familiar backbone or the known inserted sequences. Its method of infecting humans was novel; its spike protein which empowers it to bind to and enter human cells was new. Yet its overall molecular structure closely matches that of coronaviruses found in bats and pangolins, indicating a zoonotic spillover event. It was not the hodgepodge of chunks all virologists are familiar with. This was something that evolved in nature. Since the paper was published, this basic finding has been overwhelmingly accepted by the relevant scientific community, despite a tiny but vocal minority of virologists claiming to have found suspicious traits or whatnot. Is there room for doubt? Absolutely. Room for doubt, exploiting it, and finding evidence for an alternative is what science is all about.

But so far that hasn't happened. In February 2024, the journal Science reported the results of of a worldwide survey of virologists and epidemiologists. Its main finding was:

The study's experts overall stated that the COVID-19 pandemic most likely originated via a natural zoonotic event, defined as an event in which a non-human animal infected a human, and in which the infection did not occur in the course of any form of virological or biomedical research. The experts generally gave a lower probability for origin via a research-related accident, but most experts indicated some chance of origin via accident and about one fifth of the experts stated that an accident was the more likely origin.

And this is supported by a pretty important paper, published in the journal Nature in 2023, that reported on the results of sampling at the Huanan Seafood Wholesale Market in Wuhan. The market closed in January 2020, basically as soon as China determined that that's where everything began. 923 samples were collected from the environment and 457 samples from animals in refrigerators, freezers, and fish tanks. SARS-CoV-2 was found in 73 of the samples.

In 2022, an epidemiological study published in Science found that that same market was indeed the original epicenter of the pandemic, even localizing the earliest cases to "one section where vendors of live wild animals congregated and where virus-positive environmental samples [were] concentrated." These findings, published in Science and Nature, are basically undisputed. It was the unknowable events prior to the spread from the market that later disagreement built upon. The paper even states "There is insufficient evidence to define upstream events, and exact circumstances remain obscure."

Then, this question appeared to be clarified with events reported in early 2024. Virtually every news agency in the world reported that a new study found that the lab leak was more probable than a natural origin. This all stemmed from an online pre-publication of an article titled "Use of a risk assessment tool to determine the origin of severe acute respiratory syndrome coronavirus 2" written by four Australian epidemiologists who specialize in bioterrorism.

There are a few things about this new study finding the lab leak more probable that were not often reported. First of all, it was not in a medical journal; it was published in the journal Risk Analysis. It was not an epidemiological analysis, nor was it even an analysis of investigation done. The paper presented the results given by something called the modified Grunow-Finke assessment tool, which is a protocol for studying a bioterrorism attack. Rather than considering any actual evidence, the framework takes inputs from things like the rate and spread of the disease, the population affected, clinical presentation, the public health response, and the historical and intelligence context of the outbreak. The result is a statistical analysis, and in this case, the tool gave SARS-CoV-2 41 out of 60 points, or a 68% chance that it had an unnatural origin compared to a 32% chance that it was natural. News outlets trumpeted that the mystery had been solved.

But the authors themselves noted that this was not really an appropriate way to assess the origin of SARS-CoV-2, saying:

This study has several limitations that need to be considered. First, the mGFT tool was previously applied to smaller outbreak scenarios, and this is the first time it has been applied to a pandemic. Secondly, the tool was originally designed to detect biowarfare, not laboratory leaks or accidents… Therefore, this interpretation may require further testing and training of the tool.

And the paper also didn't say what all the world headlines reported it said, which was that a new study has found SARS-CoV-2 came from a lab. Instead, the authors carefully articulated "Our analysis indicates that both theories of origin are equally plausible."

However, this somewhat exaggerated reporting on this new study was also bolstered with some rehashing of big news from March 2023, which was that two US agencies, the FBI and the DOE (Department of Energy), had both concluded that the lab leak hypothesis was the most likely source of the pandemic. Taking all this together, a lot of news outlets began reporting that the lab leak was now generally agreed as the most likely cause. And this wasn't just crackpot fringe news outlets such as the typical ones known for reporting COVID-19 misinformation, like taking hydroxychloroquine or Ivermectin or calling for the prosecution of Dr. Anthony Fauci. No, many mainstream and centrist news outlets reported this as well.

What a lot of these left out was what was published in June 2023, which was a report from the Office of the Director of National Intelligence in response to the President's request that the Intelligence Community (IC) update its previous judgments on the origins of COVID-19. This report opens with a few clearly-worded findings on which the IC has "broad agreement":

• The virus was not developed as a biological weapon.
  
  
• The virus was not genetically engineered.
  
  
• China's officials did not have foreknowledge of the virus before the outbreak of COVID-19.

That finding that it was not genetically engineered is a synthesis from six intelligence agencies, four of which assessed with low confidence that it was not genetically engineered, and two of which found insufficient evidence to assess either way. In other words, the FBI and DOE findings are outliers, in that six other agencies disagree with them. So if we're doing science by minority vote, then yes, you can say the government thinks it came from a Chinese lab leak. But if you want to accurately characterize the government's consensus assessment, then it has to go the other way.

The IC report does not, however, actually name any of those other agencies, referring to them simply and cryptically as "IC elements". And importantly the report also clarifies what the lab leak hypothesis is actually saying. It posits that one or more workers inside the lab accidentally became infected during their work at the Wuhan Institute of Virology, and then went out into the community and infected other people, probably at the Huanan Seafood Wholesale Market. Nobody in the IC is claiming that anything was deliberately released, and certainly not that SARS-CoV-2 was ever being looked at as a bioweapon.

And so we can now return to our two original questions given at the top of the show, and answer them:

1. Was SARS-CoV-2 naturally evolved or engineered in a laboratory?
   Among scientists, the answer is nearly universally that it was naturally evolved; the intelligence community concurs but with lower confidence. Both groups have fringe outliers that loudly make claims the virus was engineered, contradicting the clear consensus.
   
   
2. Did SARS-CoV-2 jump to humans naturally or via a lab leak?
   The majority of epidemiologists agree that it jumped naturally, the rest of the community is split or says there's insufficient evidence either way. The intelligence community is more split, with a slight majority agreeing with the consensus view that it jumped naturally. Accidental infection in a lab setting remains plausible.

And there we have it. It's important to maintain an open mind, although the likelihood of any new evidence coming to light grows decreasingly probable with each passing year. We will probably never have proof either way; until then, if you want to be more likely right than wrong, use the majority consensus as your starting assumption. And when you hear a news story make any kind of strong declaration against the consensus view, remember to always be skeptical.

By Brian Dunning
Follow @BrianDunning