Since the early days of the COVID-19 pandemic there has been a debate about the origin of the SARS-CoV-2 virus, with the two main theories being that it either was a spillover event from wild animals, likely originating in the Wuhan wet market, vs a leak from the nearby Wuhan Institute of Virology. Actually initially there were accusations that the virus was deliberately engineered and released from the lab, but direct examination of the genetics of the virus argued strongly against it being genetically modified. (To be clear, there was debate on this topic as well, but eventually a consensus emerged that the virus is not engineered). The lab-created hypothesis was then replaced with the lab-leak hypothesis – that the virus was still naturally occurring, but it spilled over from the lab to technicians working there who then spread the virus in the community.

Unfortunately, this important scientific question became the subject of politics, with many in the public holding opinions not based on the status of the scientific evidence but their political allegiance. Two years later, what is the status of that scientific evidence? The research has moved steadily in the direction of the wet market origin hypothesis.

There are several types of evidence we can bring to bear. One is simply investigational evidence regarding the activities and events occurring within the Wuhan lab and the Wuhan market. In this respect, the WHO has had teams investigating the lab. They have not found evidence to prove the lab-leak hypothesis, but neither have they been able to rule it out completely, and are calling for still more investigation. This is partly because China has been less than fully cooperative, partly because they are very defensive about the lab-leak theory, which they see as blaming them for the pandemic. Unfortunately this has fueled conspiracy theories and kept the lab-leak idea alive.

A second line of evidence is the genetics of the virus itself. As stated, this has largely ruled out the notion that the virus was genetically modified. It supports the hypothesis that the virus naturally emerged from animal populations and then spilled over into the human population. However, this type of examination has not found the “smoking gun” – the specific species (the intermediate host) or even the individual animal in which the new form of the virus emerged. This is not surprising, and does not call into question the animal spillover hypothesis, although it is often used to do just that. Currently several animals species remain possible intermediate hosts for SARS-CoV-2, including American minks, red foxes, and raccoon dogs, all of which are sold in the Wuhan wet market.

The third type of evidence we can use to address this question is epidemiological, tracking the spread of the earliest cases of COVID. This evidence has always favored Wuhan as the origin, but of course both the wet market and the virology lab are in Wuhan. We needed more precise data to differentiate these two hypotheses. Two studies just published (although released earlier this year as preprints) argue strongly for the wet market theory.

The first study used genetic analysis of the virus in the earliest cases to trace their origin and spread. You can use genetic analysis to trace spread as the virus mutates rapidly, splitting off into branching subtypes identifiable by genetic markers. This analysis finds that there were very likely two distinct spillover events, not just one, although they happened close together in space and time – in Wuhan in late November and early December 2019. The authors conclude:

These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events.

This is a body blow to the lab leak hypothesis. The second study then delivers the knock-out punch. They tracked the earliest cases of COVID, and also looked at environmental DNA samples to track where the virus may have been at the time. They found:

We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.

Their evidence shows the virus was in the market and the first cases likely occurred in the market. Lead author Michael Worobey characterized the data this way:

In a city covering more than 3,000 sq miles (7,770 sq km), the area with the highest probability of containing the home of someone who had one of the earliest Covid-19 cases in the world was an area of a few city blocks, with the Huanan market smack dab inside it.

The data is even visually compelling, as you can see from the main image. This data is almost impossible to align with the lab-leak hypothesis. You would have to believe that there were two lab-leak events, both of which promptly went to the Huanan market and spread the virus. That represents epic-level special pleading, and is not sound epidemiological reasoning.

At this point the lab-leak hypothesis should be scientifically dead. The dominant hypothesis, that COVID resulted from zoonotic spillover events in the Huanan market, has now emerged as a fairly solid conclusion. This is critical to understand, as it relates to our efforts to prevent future spillover events. There were more than 47,000 individual live animals from 38 different species sold in the Huanan market between May 2017 and November 2019 in the market. Further, the conditions were often unhygienic and unsafe. This is exactly the kind of close contact between animals and humans the predispose to zoonotic spillover events.

Author

  • Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.