Why the coronavirus puzzle still hasn't been solved

On a hot August evening in 1854, the tailor at 40 Broad Street in London's Soho district felt a strange rumble through his stomach. A growling portent of doom. Over the next 24 hours, his skin turned a dark blue, stiffened and dried out. Within two days, he was dead. 

The tailor -- Mr. G, as history has dubbed him -- was one of the first to fall victim to a terrifying epidemic of cholera that ripped through Soho in the mid-19th century. 

The disease, caused by a pill-shaped bacterium, wreaks havoc on human intestines. Hours after Mr. G died, a dozen more Soho residents followed. A week later, 500 were dead but it wasn't clear how cholera found its way to London's west end.

The mighty task of uncovering the origins of the Soho outbreak fell to a man named John Snow (not that Jon Snow). After conducting interviews with family members of the deceased in collaboration with a local priest, Snow, a respected anesthetist, plotted a map of cholera cases around the neighborhood. His dashboard of cases helped pinpoint the source of Soho's misery: a contaminated water pump installed just outside the tailor's house. 

Nearly 170 years later, the world is grappling with SARS-CoV-2, the coronavirus that causes COVID-19. The disease has resulted in a worldwide health calamity on a scale completely unseen on the streets of west London. Over 5 million people have been infected, with global deaths topping 350,000. But as in 1854, one of the greatest mysteries of the coronavirus pandemic is where, exactly, it began. 

If the pandemic were a book, we'd be missing a whole chapter, right at the start. But a league of scientists-turned-detectives have assumed the role of John Snow, studying the genetic sequence of SARS-CoV-2 to understand how it may have evolved and where it surfaced. Their search has been made more urgent as countries slowly begin to ease restrictions and hope life can get back to normal.  

"The search for the origin is incredibly important to prevent reemergence of SARS-CoV-2-like viruses," says Alina Chan, a scientist at the Broad Institute of MIT and Harvard.

Without knowing the origin of disease, there's a likelihood it could strike again, wreaking more havoc.

So far, two opposing hypotheses sit at the center of the virus' origin story. The first and most widely accepted posits that the coronavirus evolved naturally, jumping from bats to humans, possibly via an intermediate species. The second, which scientists deem impossible to rule out, is the notion that SARS-CoV-2 escaped from a laboratory in the city of Wuhan, China, where the first COVID-19 cases were discovered. 

The how and why of SARS-CoV-2's emergence looms over the pandemic, amplified by politicking, fear, social media speculation and xenophobia. In the absence of solid evidence for a source or a COVID-19 "patient zero," conspiracy theories and unfounded rumors have readily filled the knowledge vacuum. Some point to China's secrecy and obfuscation as evidence of a cover-up. Others have taken it a step further, making baseless claims that the virus is a bioweapon or a smokescreen enabling the rollout of harmful next-gen 5G technologies. 

Science has been railroaded for speculation, politics and quick, clickable headlines. In this atmosphere, the origin story is being constantly rewritten, scribbled over and erased.

A virus seen 

Coronaviruses are eons older than human beings. The infectious particles have made their homes within the respiratory and intestinal tracts of bats for millions of years, living in relative harmony. As humans have encroached on bats' natural habitat, circumstance and luck have given coronaviruses a chance to move house. This is known as a "spillover event."

There have been seven times in history when a coronavirus -- an unthinking, unfeeling strand of genetic information, known as RNA, wrapped in a spiky ball of protein -- has made the leap into humans. Four of these coronaviruses circulate year-round and cause symptoms of the common cold. The other three cause potentially fatal disease. 

Coronaviruses don't choose who or what to infect. They have no brains, no heart and no eyes. The only way they can replicate is by hijacking the machinery of other other living cells.

The medical detectives tracing the origins of disease today have a major advantage over John Snow: They're spoiled with technologies that can help find the causative agent of an outbreak disease by examining the virus's RNA. By studying the genetic sequence, scientists have shown SARS-CoV-2 is a relative -- a distant cousin -- of the virus that caused the SARS epidemic in 2002-2003.

In late December 2019, three Chinese patients with a respiratory infection of unknown origin presented to the Wuhan Jinyintan Hospital, a hulking utilitarian building of cement and glass about three miles north of the Yangtze river.

Scientists took samples of fluid from their lungs and examined the genetic material. They discovered a jumbled mix of DNA from the patients and RNA from an unknown infectious agent. Sifting through the data and recompiling where the genetic sequences fit together, the sleuths detected a sequence left by an unknown virus that looked remarkably similar to the one that caused SARS. 

They then placed their samples under a powerful microscope, magnifying the contents up to a million times. This gave them a window into the nanoworld where they could look inside cells for signs of infection. Against a gray, static background, white blobs with a faint, blurry halo appeared in view. It was the first time this new coronavirus was seen with human eyes. 

A bat found

Seven years earlier, its closest ancestor was found in a bat cave, 1,200 miles from Wuhan. 

The ancestral coronavirus, known as RaTG13, was discovered in a fecal sample retrieved from a horseshoe bat living in caves near Kunming, in southwest China. Its discovery is intricately tied to Shi Zhengli, a member of the Wuhan Institute of Virology, one of the world's leading hubs for studying coronaviruses.

Shi's work over the last two decades has focused on cataloging the diverse range of coronaviruses that infect bats. Colleagues call her the "bat woman." Her research after the 2002-2003 SARS epidemic in China helped solidify the hypothesis that bats were the starting point for the disease. 

Before SARS-CoV-2 flipped the world on its head, Shi's work at the institute was essentially unknown to the public. But Shi has been publishing articles in the virology community -- including acclaimed journals like Nature and Science -- for the past 15 years. Her studies now seem incredibly prescient, warning of spillover events and the increasing likelihood of bat coronaviruses leaping into humans and causing new disease.

In February, her team published a paper in the journal Nature showing the genetic sequence of RaTG13 is 96% identical to SARS-CoV-2. Though the virus was found 1,200 miles away, it was studied at the Wuhan Institute of Virology. Theories abound that it was manipulated in the lab or accidentally leaked.

"There is some unfounded speculation that this virus was the origin of SARS-CoV-2," said Edward Holmes, a virologist at the University of Sydney who has published extensively on the novel coronavirus, including with Shi. Holmes suggests the genetic sequence separates it from SARS-CoV-2 by about 20 years of evolution. 

A paper published in Nature in March provides two scenarios for how the novel coronavirus could have emerged naturally, writing "It is improbable that SARS-CoV-2 emerged through laboratory manipulation." But still, for many, it was too hard to ignore the links between a Wuhan lab and the reported birthplace of the new disease: the Huanan Seafood Wholesale Market. 

A market closed

In the early days of the pandemic the Huanan Seafood Wholesale Market, a wet market in the urban core of Wuhan, was ground zero for COVID-19. A cluster of the earliest cases were linked to the site, which was known to sell live wildlife such as crocodiles, civet cats and snakes. 

As a result, the market was quickly shuttered on Jan. 1, 2020. Samples were taken from the site by China's Center for Disease Control and Prevention, looking for signs of coronavirus RNA. A total of 585 samples were collected, with 515 from the environment and 70 collected from wild animal vendors. Thirty-three showed evidence of the virus. In January, Gao Fu, director-general of China's CDC, told a news briefing the new disease had originatedin wildlife sold at the market. 

But as the pandemic unfolded, it became clear the market was not the origin of the disease. Instead, it played the role of the Broad Street pump: It was a place where people gathered, giving the virus a chance to move through market-goers. One-third of the first cohort of patients with COVID-19 in Wuhan had not visited the market before presenting with symptoms. On May 26, Gao Fu noted samples from the market "failed" to show links between the virus and animals sold there. Someone, unknowingly, must have brought the virus into the market in late 2019. 

Speculation grew in early February that some of the wildlife sold at the market may have enabled SARS-CoV-2 to spread through Wuhan. The pangolin, a scaly, ant-eating mammal highly prized in Asia for its meat and scales, was fingered as a suspect, though there is no evidence the animal was sold at Huanan. A handful of studies have found coronaviruses like SARS-CoV-2 lurking in a batch of smuggled Malayan pangolins, but the sample size is small and the evidence not definitive. 

There's also a possibility the pangolins contracted the virus from other animals during the animal trafficking process. Chan, the scientist from the Broad Institute, points to two reports showing pangolins smuggled with palm civets and bats. 

"The focus on pangolins is actually biasing the scientific community and reducing the motivation to sample other species," she says. 

The seafood market lies around eight miles from the Wuhan Institute of Virology and another laboratory, known as the Wuhan Center for Disease Control and Prevention. At a glance, it's easy to suggest someone from these labs or an escaped research animal accidentally leaked the coronavirus into the marketplace. Shi even asked herself whether her laboratory might be responsible in December, according to a March interview in Scientific American. She's adamant that's not the case, but US President Donald Trump has previously claimed he has evidence suggesting the virus originated in a Wuhan lab. During an interview on May 23, the director of the Institute, Wang Yangi, called the claims "pure fabrication" but the theory has continued to proliferate.

"There is no evidence for this, just speculation and perhaps a correlation between a laboratory being in Wuhan and the epicenter of the pandemic being in this location," says Hassan Vally, an epidemiologist at Australia's La Trobe University. "Correlation does not equal causation."

There is also no evidence definitively ruling out the lab leak theory and there may never be. Can the lab be cleared of wrongdoing? At this stage, the answer is no -- and it's this gray area between plausibility and scientific speculation where other theories have taken hold. 

A conspiracy born

Pick 10 people out of a crowd and ask them how they think the coronavirus pandemic began. It's likely you'll hear the routinely debunked, racist theory that this all began with a sip of bat soup (it didn't), or that China unleashed this on the world to crash economies (it didn't), or that it's actually a virus that was made in the US (it isn't). And surveys by the Pew Research Center showed eight in ten Americans distrust coronavirus information coming from the Chinese government. 

This isn't the first time in history we've seen infectious diseases lead to conspiracy. Plagues and pestilence are notorious for giving far-fetched beliefs room to breathe.

"These massive illnesses do destabilize society in a way that accentuates our desire to find culpable parties," says Chris Fleming, senior lecturer in the school of humanities at Western Sydney University in Australia. "Historically speaking, this just plays out with monotonous regularity."

Around the time of Snow and the Broad Street pump, cholera epidemics swept across the world, often leading to waves of distrust in physicians, health authorities and government officials. Wherever the disease appeared, the pages of the daily papers were filled with quack tinctures and treatments to "cure" patient ills. A stark class divide appeared, with the poor and the working class believing that they were being lied to and that cholera was a tool created to eliminate them.

Similar narratives are playing out again in 2020. A potent confluence of events has allowed speculation and conspiracy to flourish around SARS-CoV-2 in the five months since it first appeared. Spurred by reports, such as the cables leaked to the The Washington Post in April suggesting there were safety issues at the Wuhan Institute of Virology and a 15-page dossier prepared by "Western governments" obtained by The Daily Telegraph on May 4 claiming China deliberately destroyed evidence of the outbreak in January, the tendency to feel suspicious is all too easy. 

It's even easier to turn to conspiratorial plots when the science underpinning the coronavirus origin story is complex and constantly changing. Science is usually a slow, methodical process. Discoveries are made over months, years or even decades. But during the pandemic, science has been moving at light-speed. Yesterday's discoveries can be quickly rebuked and rebutted -- or spun out of control in the 24/7 news cycle.

In science, there's always room for the origin story to change based on new evidence. 

But in the meantime, it becomes far simpler to find a scapegoat, or point to potential lab outbreaks instead of trusting that the convoluted intermingling of evolution, RNA mutations and luck can give rise to new disease. 

"There is very little room in the conspiracy theorists' world for 'shit happens,'" says Fleming.

A story written 

In 1854, once John Snow had identified the water pump at 40 Broad Street as the source of the cholera outbreak, he had the handle removed. No one in Soho could access the pump. With the contaminated supply cut off and the epidemic slowing, the outbreak began to peter out. 

But cholera hadn't spontaneously appeared in the water supply. In a sad twist of fate, a 5-month-old infant who lived at 40 Broad Street contracted cholera in late August 1854. Its mother had soaked the babies' soiled diapers in water and then thrown the water into a cesspool in front of the house. Little did she know, the water housed thousands of cholera-causing microbes and the cesspool was leaking into the Broad Street pump's supply.

Will we ever be able to write a similar origin story for coronavirus? Scientists I spoke with suggest the highly politicized back-and-forth is making it difficult. Mary-Louise McLaws, an epidemiologist at the University of New South Wales, called the politicization surrounding the source of the pandemic "unprecedented."

In an example of how volatile the situation has become, the Australian government pushed in early May for an independent inquiry to investigate the origins of COVID-19, but was rebuffed by China. The proposal led to a prickly war of words between the two nations, before trade tensions escalated and China imposed tariffs on Australia's barley exports. China denies the action has any link to the coronavirus inquiry. 

But if we're to prevent a pandemic of this scale from happening again, we simply must go back to the start. 

"Without knowing where SARS-CoV-2 came from, we are less informed to take action and enact policies to minimize the risk of future outbreaks," says Chan. She notes that it also leaves us wide open for a reemergence that could kick-start another outbreak or the possibility of similar viruses jumping from bats (perhaps through an intermediate host) to humans in the future.

On May 18, the World Health Organization pledged it would launch an independent evaluation of the global response to the pandemic. Once the pandemic is under control, an investigation into the origins of SARS-CoV-2 will get underway. It has received backing from China's president, Xi Jinping. 

And so the origin story will be rewritten, scribbled over and changed once more.