Where did Covid-19 come from? The case for a natural origin.

Forget talk of "the China virus" and a "lab leak". Bats and the trade in wild animals are a far more likely source of the coronavirus pandemic.

Ever since the assassination of John F. Kennedy, people’s faith in official narratives has been eroding. In their place has come what Don DeLillo in his novel Libra calls “theories that gleam like jade idols”. Employing 20/20 hindsight, these theories are seductive precisely they provide simple, easy-to-understand explanations for seismic political events.

But what happens when these theories go mainstream or, in the case of Covid-19, a quasi-conspiracy theory is adopted by the White House and becomes the official narrative of how the coronavirus pandemic started? This is what happened last week when information about Covid vaccines and testing was deleted from US government sites and replaced withg an image of the 47th president beside the phrase, “Lab Leak: the true origins of Covid-19”.

It was nothing of the sort of course. Instead, the White House made a series of factually inaccurate claims about alleged “gain-of-function” studies at the Wuhan Institute of Virology (WIV), including that the virus possessed a biological characteristic “not found in nature” and that data showed that all Covid cases stemmed from “a single introduction into humans.”

As Adam Kucharski and others have pointed out, both claims are easily refuted (see for instance this paper in Lancet Microbe describing how a supposedly unusual biological characteristic, known as a furin cleavage site, that some experts believe was engineered, has been found in several naturally occurring viruses, and this paper in Science showing that there were at least two separate introductions of the coronavirus).

Peak lab-leak

When an official government site becomes a propaganda platform for a weakly supported theory, we have surely reached peak “lab leak fever”, to co-opt the title of a new book by the Swiss science blogger Philipp Markolin. The problem is that the lab leak theory, like conspiracy theories alleging the coronavirus was the product of a secret Chinese biowarfare experiment, are appealing precisely because they seek to lay the blame on state actors operating behind the scenes.

As the Swiss filmmaker Christian Frei puts it in his new documentary, Blame: Bats, Politics and a Planet out of Balance:

“We have a natural tendency to think that big events must have big causes, a tendency to assume that events with a significant impact are the result of deliberate acts by intentional and powerful agents.”

But, with science, we are always dealing with degrees of probability, and it often takes years for convincing evidence to emerge.

Khao Chong Phran Cave, Ratchaburi Province, southern Thailand. The cave is home to 2.8 millions of bats; guano collectors enter the cave every week. Credit: Adam Dean for Christian Frei Filmproductions

In this week’s Observer News Review, I interview Frei and speak to several of the protagonists in Blame, including Peter Daszak, a close colleague of Shi Zhengli, the Chinese scientist whose research into coronaviruses at WIV triggered the claims of a lab leak [if you value independent journalism please considering buying a copy at our local newsagent).

The former president of the New York-based NGO EcoHealth Alliance, Daszak has suffered a torrid five years being vilified by US politicians and the tabloid press for his supposed part in facilitating gain-of-function studies at WIV. His appearance before Congress last year was nothing short of a witch trial. The result is that rather than being applauded for his role in helping to identify zoonoses with the potential to “spill over” into humans, Daszak has been banned from applying for research grants for five years. None of this makes us safer or better able to respond to the next pandemic.

In what follows, I sketch an alternative scenario of the Covid-19 pandemic. Unlike the lab leak theory, for which there is zero physical evidence, the natural origin scenario is based on direct physical and epidemiological evidence and peer-reviewed scientific papers. To my mind it is a far more compelling scenario than the lab leak, one that starts with the premise that, like every pandemic before it, the virus of Covid-19, emerged from an animal reservoir.

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The natural origin scenario

Perhaps ground zero was a cave in a region of Laos famous for its limestone sinkholes, or perhaps it was a cave in northern Thailand, or Myanmar, or Yunnan in southern China. These regions support an extraordinary diversity of wildlife, including bats which harbour coronaviruses and palm civets which like to feed on bat guano.

Guano collectors, Thailand.

Perhaps sometime in early 2019 a palm civet crept into one of these cavess in search of a snack and a poacher later captured it (civets are considered a delicacy in China). Or perhaps, a farmer visited one of the caves to collect guano with which to fertilise his fields and accidentally became infected with a bat coronavirus with an unusual adaption that allowed it to attach to receptors in the human respiratory tract.

Or perhaps the event that ignited the chain of infections was a bat defecating on a pen near a cave where a breeder was raising racoon dogs and ferret badgers for the wild animal trade. And perhaps both the animals and the farmer – or the drivers that transport the animals to market – were infected.

Any one of these scenarios could have led to SARS-CoV-2, or a progenitor virus, spilling over to mammals and infecting people. In all likelihood, such events occur all the time across Southern China and Southeast Asia, a region known for its biodiversity and for being a hotspot for bats that viruses such as SARS and Nipah.

Serological surveys suggest that up to four percent of people living in the vicinity of bat caves possess antibodies to bat coronaviruses. In Laos, where the current closest ancestor of SARS-CoV-2 was found in 2022, the odds of infection are even higher, with one in five people who’ve had direct contact with bats and other wildlife found to have antibodies. In all, it is estimated that 66,000 people every year are infected with SARS-like coronaviruses harboured by bats.

What is more, coronaviruses that circulate in bats that roost in caves in the limestone karstic region of northern Laos, close to the border of Yunnan, have the same ability as SARS-CoV-2 to bind to cells in the respiratory tract. Some of these coronaviruses are more genetically similar to SARS-CoV-2 than a virus known as RaTG13 recovered by researchers at the Wuhan Institute of Virology from a disused mineshaft in Yunnan, that was previously thought to be the closest relative to the pandemic virus (see graphic below).

Bat caves in Southeast Asia containing the closest relatives of SARS-CoV-2.

However, while these viruses possess similar spike proteins to SARS-CoV-2, they lack a furin cleavage site - a feature that occurs naturally in many viruses with mosaic genes and which allows the spike protein of SARS-CoV-2 to be cut so that it can enter human cells more efficiently.

However, it is worth bearing in mind that even a virus that is well-adapted to humans would die out most of the time because there would not be enough people to sustain the chains of transmission. In other words, it’s a lottery. Sooner or later, a virus that makes the jump will find itself in possession of a winning ticket. To spark a pandemic, however, it must possess two winning tickets: it must infect a human and it must find itself in a densely populated urban area.

There are several ways this could have occurred. Perhaps a driver from a wild animal farm in Yunnan or another Chinese province, such as Guangxi or Guangdong, stopped at a roadside café close to Wuhan or a restaurant in the city and infected other diners there. Or perhaps, after delivering the animals to a market in Wuhan, they visited a busy train station.

However, we know that the likely epicentre of the outbreak was the Huanan seafood market because scientists have traced two distinct sub-lineages of the virus, known as “A” and “B”, to a stall in the market’s southwest corner. This suggests that the crucial spill-over event occurred on at least two occasions at the market (there may also have been other occasions but even a pathogen as infectious as SARS-CoV-2 will go extinct 70 percent of the time, meaning that it would not infect enough people to establish a transmission chain that could later be detected by genomic analysis).

This infection could have been introduced by someone employed in the wild animal trade who in turn infected animals at the market, or a customer who visited the market. Or it could be that an infected animal ntroduced the virus to the market. In the latter scenario, the spill over event could have occurred when the animal was slaughtered and its blood and entrails discarded.

Perhaps the vendor who performed this task was already coughing and running a fever. Or perhaps a speck of animal blood got in the vendor’s or customer’s eyes. Either way, one or both would now be infected, initiating a chain that spread from the market to the rest of Wuhan and beyond.

Another key piece of evidence supporting this scenario is that the animals on sale at the Huanan market included racoon dogs, Asian and hog badgers, marmots, foxes, and bamboo rats, all of which are known to be susceptible to SARS-CoV-2 and which, in the case of racoon dogs, were implicated in the emergence of the first SARS epidemic in 2003.

Additionally, environmental samples taken from the market show that the highest areas of viral contamination were concentrated in the southwest corner close to a stall that sold racoon dogs. Swabs taken from the cages and sewers under the cases all tested positive for SARS-CoV-2. Moreover, an Australian virologist who visited the market in 2014 took photographs of a stall in exactly this part of the market full of live animals, including racoon dogs and muskrats. In the photograph, the animals are stacked in cages, one on top of the other, making it likely that a virus harboured by one animal would have infected others in adjacent cages. This scenario makes it likely there were several spill-over events, two of which resulted in separate viral lineages.

Reconstructing the mutations in the SARS-CoV-2 via molecular clock analysis shows that lineage B was the first to jump to humans, followed, perhaps a few weeks later, by lineage A. These events are estimated to have occurred no earlier than late October 2019, meaning that claims that the virus was spreading before this date can be discounted.

Unfortunately, we do not know exactly which animals were involved in the transfer of SARS-CoV-2 to humans because traders removed the animals before Chinese officials arrived to inspect the market on January 1, 2020. Although some traders had certificates allowing them to sell wild animals, it is likely that many did not, so to avoid fines and possible imprisonment they culled the animals and/or removed them from the scene of the crime.

It is also worth pointing out that the Huanan seafood market is a far more likely place for a spillover event to occur than a scientific research institute. Before it was closed, an estimated 10,000 people a day passed through the market, navigating narrow corridors and floors covered in faeces and guts. Few, if any of these people, would have been wearing masks, much less biohazard suits. By contrast, the WIV had around 500 employees spread across two campuses, both several kilometres from the market. Of this number, approximately a dozen studied bat coronaviruses and three to four worked closely with these viruses in the lab. All would have been wearing gloves, masks and Tyvek suits. This makes it highly unlikely that, even if a lab worker had been infected in an accident, they could have introduced the virus to the Huanan market on not one but two separate occasions.

Why difference does it make where Covid came from?

We know that every pandemic in history prior to Covid-19 originated in an animal reservoir. Analysis of the genome of the H1N1 influenza virus responsible for the 1918-1919 influenza pandemic shows it is descended from an avian virus that jumped from birds to humans or some other mammal, such as pigs, in around 1917. Similarly, HIV/AIDs began as a simian immunodeficiency virus of wild chimpanzees and gorillas in west Africa. No one can be sure when or how the virus first spilled over to humans but the most likely route is via the consumption of wild bush meat. As with coronaviruses, cross-species transmissions of simian viruses happen all the time but most end in dead ends. However, molecular clock analysis suggests that HIV-1, which is the principal cause of AIDS, dates to 1921 when a chimpanzee infected a bush meat hunter somewhere in Cameroon. However, it was only when the virus reached a major city and was amplified by medical practices, such as the sharing of hypodermic needles, and the sex trade, that it began to spread more widely.

Or take Ebola. We can infer from the fact that bats have antibodies to Ebola that they are the likely reservoir host. However, despite more than a dozen Ebola outbreaks across central and west Africa, so far no one has succeeded in recovering live Ebola virus from bats. And what applies to Ebola also applies to other emerging and re-emerging infectious diseases. Sine 1940, scientists have identified 335 new human infectious diseases. Nearly two thirds are of animal origin, and of these 70 percent originated in wildlife, with bats harbouring a higher proportion than any other mammal. This is not surprising when you consider that bats make up a fifth of all mammals on the planet and that a single cave in southern China can contain as many as two million bats. Indeed, Daszak estimates that for every species of bat there may be 17 viruses out there waiting to be discovered, and ten more in the cases of each species of rodent and primate. As he told me when I interviewed him for Going Viral_the podcast:

“If you got to Malysia and sit by the edge of a river with a street-light nearby, all night long you’ll see bats of different shapes and sizes flitting past and eating insects. They’re extremely abundant, extremely diverse, and so are their viruses.”

The cancellation of EcoHealth’s grant and the suspension of similar virus-sampling research following the furore over gain-of-function studies, means we are in a far worse position to anticipate the next emerging infectious disease than we were in 2019. And all the while, the odds of another spill-over event are increasing as climate change, deforestation and modern farming practices contribute to the further disruption to animal habitats.

The result is that rather than living in equilibrium with wild animals, we are continually creating new opportunities for their viruses to recombine and transfer to new hosts, including us. As Daszak put it an editorial for EcoHealth Alliance shortly before his organisation was wound up:

‘Behind every global pandemic is a humble origin—often a single person infected by an animal virus—an event that brings an unfortunate mix of the right type of virus affecting the right person at the right time to spread across communities, landscapes and countries. Identifying exactly where and when this critical spillover happens is surely the key to preventing future pandemics.”

Nature, in other words, is the most dangerous laboratory of all. Our failure to recognise this fact, while blaming the scientists who have devoted their careers to studying these viruses, makes us less, not more, safe.