Why We Will Never Know the Real Origins of SARS-CoV-2

COVID-19 slashed red tape and poured in government funding to spark giant leaps forward in scientific innovation, most prominently in vaccinology but also behind-the-scenes in genetic sequencing to track a fast-evolving virus generating new variants. These developments set the stage for promising new strategies for a range of infectious disease threats, from malaria to influenza. In contrast, it should be lost on no one what minuscule progress has been made in figuring where the virus came from in the first place — and why.

Decades from now, when we sit the dinner table, regaling our grandchildren with sordid tales of the great Pandemic of 2020, we will recount the fear of touching doorknobs, the great run on toilet paper, and finally the joy of receiving the miracle vaccine that saved everyone and let kids go back to classrooms. But when our descendants ask where the virus came from and how it got into people, we will just have to take a long, slow swig of beer and admit that some things, like who shot JFK, are just never known.

We will list the various theories that got batted around, filling the airwaves with media fodder. Pangolin soup. Lab accidents in Wuhan. In contrast to other unsolved mysteries of science – why did the dinosaurs vanish? – the absence of a proven COVID-19 origins story presents a real practical problem going forward. The next pandemic virus is already out there, somewhere, circulating in an animal. The next global pandemic could blow in twenty years, or twenty months. Any global strategy for preventing future pandemics hinges on knowing whether to invest in shoring up lab vulnerabilities worldwide or massively expanding disease surveillance of ‘viral chatter’, which refers to the thousands of viruses that pass between animals and humans every year but in most cases never establish in humans. The absence of a resolved origins story saps the political will to do either.

As a scientist with a decade of experience studying how pathogens transmit between animals and humans I have a strong hunch about where SARS-CoV-2 came from, at least in principle. Strong enough to bet my career on. But science is not about hunches, and there is no point dissecting the conjectures, coincidences, and scraps of evidence that provide little more than tea leaves at the moment.

Tragically, it need not be this way. Conspiracy theories about global pandemics caused by scientists mishandling pathogens rise and recede every time an outbreak occurs, like a tide. When the 2009 H1N1 pandemic broke an Australian scientist propagated a theory that the virus contained genetic signatures that suggested it arose during an error in commercial production of influenza vaccines for US swine. A decade earlier, a Rolling Stone article outlined the evidence that HIV jumped to humans by way of a contaminated oral polio vaccine campaign in central Africa in the 1950s. The theory was researched in more detail in another journalist’s compelling 1000-page book. The page-turner was eloquent and a great read. The only problem: it was dead wrong. After a period of capturing the media’s attention, the theories were eventually put to rest by accruing scientific evidence.

It is a great deal easier to draw together a compelling lab origins theory based on conjectures and coincidences than it is to debunk one with hard scientific evidence. Tracking down the real source of HIV required arduous expeditions deep into Congolese jungles to sample viruses from apes. The team of Oxford researchers had to navigate rebel forces and swarms of mosquitoes (one famous professor died of malaria) during a needle-in-a-haystack search for simian viruses related to HIV. The search for the origins of the 2009 H1N1 pandemic in Mexico’s swine herds was tame by comparison. But my collaborators and I spent seven years painstakingly swabbing the noses of tens of thousands of pigs from farms to extract and sequence the genetic material of disease-causing pathogens to resolve the virus’s perplexing origins. An unusual amount of detective work was required to trace how swift globalization of swine farming in the 1990s led to pigs being moved across continents via commercial air travel that spread influenza viruses found in pigs in Europe, Asia, and the United States into Mexican farms, creating a new hotspot for influenza virus evolution and eventually a virus that could jump to humans.

The fact that the lab origins theories of the 2009 H1N1 pandemic and HIV did not hold up does not mean that human error never plays a role in disease outbreaks. One of my first scientific papers as a graduate student included genetic evidence that the 1977 H1N1 ‘Russian flu’ pandemic had been a lab escape (although it was not the focus of the paper). The H1N1 virus had circulated in humans from 1918 – 1957 before vanishing, only to surprisingly reappear twenty years later and cause a pandemic that mostly infected children, since most adults had already been infected when they were younger. The 1977 pandemic virus was nearly genetically identical to the virus that had circulated in the 1950s, a pattern that would not be seen if the virus had just been circulating in nature unobserved in humans or an animal reservoir.  Combined with knowledge that Soviets had been conducting experiments with a vaccine that included a live H1N1 virus that may not have been properly attenuated, we concluded that the 1977 pandemic was caused by human error and was a lab virus, which was supported by subsequent analyses. The lab-escaped virus caused recurring epidemics worldwide for forty years before it vanished a second time, replaced by a newer strain during the 2009 pandemic.

Despite technological revolutions in disease surveillance driven by advances in genomic sequencing and mobile phones, it is possible that we will know even less about the origins of SARS-CoV-2 than we know about influenza pandemics that occurred 10-40 years ago, or even a HIV pandemic that began a century ago. It is obviously not a a question of scientific capacity, but of access to samples. And not just samples from the Huanan Seafood Market where the pandemic was first detected in humans. The lack of SARS-CoV-2 virus detected in animals at the seafood market has been cited as evidence for a lab leak, but the argument is specious. The market is not where the original animal-to-human transfer occurred. The market merely amplified transmission in humans because many people congregate there, providing easy routes of human-to-human transmission. Certainly, a wet market presents an environment that is conducive to zoonotic transmission because humans and densely packed animals intermingle. But the first human case of SARS-CoV-2 was detected weeks before the major Huanan market outbreak. The original jump from animals to humans likely occurred 1-2 months before the Wuhan outbreak. Sampling from animals from a larger swathe of China would be helpful in piecing together where the virus traveled prior to the Wuhan explosion.

There is a long history of sensitivity about specific countries being blamed for pandemic pathogens that emerged within their borders. For that reason the 2009 H1N1 pandemic was termed ‘Swine Flu’ instead of ‘Mexican Flu’, breaking a centuries-old tradition of naming ‘Spanish Flu’, ‘Russian Flu’, and ‘Hong Kong Flu’ after the locations of origin (although there was equal backlash from swine farmers after a panicking public stopped buying bacon). During COVID-19 there has also been resistance against naming variants after the country where they are first detected (e.g., South Africa variant, India variant), which disincentivizes countries from performing rigorous surveillance so another country detects the variant earlier. Early references to the COVID-19 pandemic as ‘China flu’ had the same scapegoating effect that incentivizes plausible deniability when it comes to whether the pandemic originated in a specific country. Heroically brave Chinese scientists released early SARS-CoV-2 genome data in January 2020 to alert the international community when the pandemic was rapidly unfolding and authorities were still scrambling. The Chinese government is no longer on its heels.

Chinese authorities seized control of the COVID-19 outbreak in a way no Western government could, extinguishing the spiraling epidemic with a lockdown of fabled intensity. By February 2020, just as the Wuhan outbreak was winding down, the Chinese government turned its attention to the practice of farming of wildlife for food. Farming exotic wildlife had been promoted by the government for decades to advance the economy of the country’s southern rural regions. In a single edict the authorities wiped out the $70 billion industry and transferred the 14 million employees to new ventures. The destruction of all wildlife on the farms eliminated the potential for pathogen exchange between animals and humans that could spawn future pandemics. Tangentially, it also eliminated an entire vast ecosystem of hosts and pathogens that might have left a valuable paper trail of clues into the origins of SARS-CoV-2. Modern methods of genetic analysis can powerfully reconstruct decades of transmission and evolutionary events in the past from present-day data, as shown by our studies of pandemic H1N1 evolving on Mexican swine farms using data collected 4-5 years following the pandemic. There is no need for a time machine, but there is a need for live animals to sample. The lack of answers about SARS-CoV-2’s origins is no shortcoming of science, only a lack of access to samples in an age where it can be politically expedient to leave some scientific questions unanswered. It is clear by now that China answers to no one on the international stage.  

Agnosticism on the question of where SARS-CoV-2 came from seems logical in the absence of irrefutable scientific evidence to the contrary. But the overwhelming human predilection towards lab origins stories, as observed repeatedly over the history of pathogen outbreaks, particularly for HIV but also for the 2009 H1N1 pandemic, makes pure agnosticism a fiction. It is worth pointing out the enormous public health costs when people believe false lab origins theories. The contaminated oral polio vaccine theory for HIV set back the global campaign to eradicate polio by decades. America is at a juncture where the country desperately needs to shore up confidence in the COVID-19 vaccine, particularly as the campaign expands to younger children. The COVID-19 lab origins theory may seem unconnected to vaccine uptake, but it’s not. They all trace to a deep-rooted fear of government cover-ups, corruption, and arrogant scientists who ignore risks and take advantage of people’s blind trust. Being agnostic on the origins of COVID-19 may seem innocuous, but it’s not. I wish I had the data to prove otherwise. Sadly, I don’t think I ever will. And I dread the day I have to explain that to my grandchildren.

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