How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus

Editor ’ sulfur Note ( 4/24/20 ) : This article was in the first place published on-line on March 11. It has been updated for inclusion in the June 2020 return of Scientific American and to address rumors that SARS-CoV-2 emerged from Shi Zhengli ’ s lab in China .
The mysterious patient samples arrived at the Wuhan Institute of Virology at 7 P.M. on December 30, 2019. Moments late Shi Zhengli ’ mho cell telephone call. It was her emboss, the establish ’ s director. The Wuhan Center for Disease Control and Prevention had detected a fresh coronavirus in two hospital patients with atypical pneumonia, and it wanted Shi ’ randomness renowned testing ground to investigate. If the find was confirmed, the modern pathogen could pose a serious public health threat—because it belonged to the same family of viruses as the one that caused austere acute respiratory syndrome ( SARS ), a disease that plagued 8,100 people and killed closely 800 of them between 2002 and 2003. “ Drop whatever you are doing and deal with it now, ” she recalls the director saying .
Shi, a virologist who is much called China ’ randomness “ bat womanhood ” by her colleagues because of her virus-hunting expeditions in bat caves over the past 16 years, walked out of the conference she was attending in Shanghai and hopped on the next discipline back to Wuhan. “ I wondered if [ the municipal health agency ] got it wrong, ” she says. “ I had never expected this kind of thing to happen in Wuhan, in cardinal China. ” Her studies had shown that the southerly, subtropical provinces of Guangdong, Guangxi and Yunnan have the greatest hazard of coronaviruses jumping to humans from animals—particularly bats, a known reservoir. If coronaviruses were the perpetrator, she remembers thinking, “ Could they have come from our lab ? ”
While Shi ’ s team at the Wuhan institute, an affiliate of the chinese Academy of Sciences, raced to uncover the identity of the contagion—over the following week they connected the illness to the novel coronavirus that become known as SARS-CoV-2—the disease spread like wildfire. By April 20 more than 84,000 people in China had been infected. About 80 percentage of them lived in the province of Hubei, of which Wuhan is the capital, and more than 4,600 had died. Outside of China, about 2.4 million people across 210 or so countries and territories had caught the virus, and more than 169,000 had perished from the disease it caused, COVID-19.

Scientists have retentive warned that the rate of emergence of newfangled infectious diseases is accelerating—especially in developing countries where high densities of people and animals increasingly mingle and move about. “ It ’ s fabulously authoritative to pinpoint the source of infection and the chain of cross-species infection, ” says disease ecologist Peter Daszak, president of EcoHealth Alliance, a New York City–based nonprofit research organization that collaborates with researchers, such as Shi, in 30 countries in Asia, Africa and the Middle East to discover newly viruses in wildlife. An evenly crucial job, he adds, is to hunt down other pathogens to “ prevent alike incidents from happening again. ”
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OUTSIDE A BAT CAVE in China’s Guangxi province in 2004, Shi Zhengli releases a fruit bat after taking a blood sample. Credit: Shuyi Zhang

THE CAVES

To Shi, her first virus-discovery expedition felt like a vacation. On a breezy, cheery spring day in 2004, she joined an external team of researchers to collect samples from cream colonies in caves near Nanning, the capital of Guangxi. Her inaugural address cave was distinctive of the area : large, rich in limestone column and—as a popular tourist destination—easily accessible. “ It was spellbinding, ” Shi recalls. Milky-white stalactites hung from the ceiling like icicles, glistening with moisture .
But the holidaylike standard atmosphere soon dissipated. many bats—including several insect-eating species of horseshoe bats that are abundant in southerly Asia—roost in deep, specialize caves on steep terrain. Often guided by tips from local villagers, Shi and her colleagues had to hike for hours to potential sites and edge through tight rock crevasses on their stomach. And the flying mammals can be elusive. In one frustrating week, the team explored more than 30 caves and saw merely a twelve cricket bat .
These expeditions were contribution of the attempt to catch the perpetrator in the SARS outbreak, the first major epidemic of the twenty-first century. A Hong Kong team had reported that wildlife traders in Guangdong first base caught the SARS coronavirus from civets, mongooselike mammals that are native to tropical and subtropical Asia and Africa .
Before SARS, the worldly concern had only an inkling of coronaviruses—so named because their peaky come on resembles a crown when seen under a microscope, says Linfa Wang, who directs the emerging infectious diseases program at Singapore ’ s Duke-NUS Medical School. Coronaviruses were largely known for causing common colds. “ The SARS outbreak was a game changer, ” Wang says. It was the first emergence of a baneful coronavirus with pandemic potential. The incident helped to jump-start a global search for animal viruses that could find their manner into humans. Shi was an early enroll of that feat, and both Daszak and Wang have been her long-run collaborators .
With the SARS virus, fair how the civets got it remained a mystery. Two former incidents were telling : Australia ’ sulfur 1994 Hendra virus infections, in which the contagion jumped from horses to humans, and Malaysia ’ second 1998 Nipah virus outbreak, in which it moved from pigs to people. Wang found that both diseases were caused by pathogens that originated in carpophagous bats. Horses and pigs were merely the average hosts. Bats in the Guangdong market besides contained traces of the SARS virus, but many scientists dismissed this as contaminant. Wang, however, thought bats might be the source .
In those first virus-hunting months in 2004, whenever Shi ’ second team located a bat cave, it would put a net at the open before twilight and then wait for the nocturnal creatures to venture out to feed for the nox. Once the bats were trapped, the researchers took blood and saliva samples, angstrom well as faecal swab, often working into the small hours. After catching up on some sleep, they would return to the cave in the dawn to collect urine and faecal pellets .
But sample after sample turned up no trace of familial material from coronaviruses. It was a heavy blow. “ Eight months of unvoiced work seemed to have gone down the drain, ” Shi says. “ We thought possibly bats had nothing to do with SARS. ” The scientists were about to give up when a research group in a neighbor lab handed them a diagnostic kit for testing antibodies produced by people with SARS .
There was no guarantee that the test would work for bat antibodies, but Shi gave it a run anyhow. “ What did we have to lose ? ” she says. The results exceeded her expectations. Samples from three horseshoe cricket bat species contained antibodies to the SARS virus. “ It was a turn point for the visualize, ” Shi says. The researchers learned that the presence of the coronavirus in bat was ephemeral and seasonal—but an antibody reaction could last from weeks to years. The diagnostic kit, consequently, offered a valuable arrow as to how to hunt down viral genomic sequences .
Shi ’ mho team used the antibody test to narrow down the number of locations and bat species to pursue in the quest for genomic clues. After roaming cragged terrain in most of China ’ sulfur dozens of provinces, the researchers turned their attention to one smudge : Shitou Cave, on the outskirts of Kunming, the capital of Yunnan, where they conducted acute sampling during different seasons over five consecutive years .
The efforts paid off. The pathogen hunters discovered hundreds of bat-borne coronaviruses with incredible familial diversity. “ The majority of them are harmless, ” Shi says. But dozens belong to the same group as SARS. They can infect human lung cells in a petri serve and cause SARS-like diseases in mouse .
In Shitou Cave—where painstaking scrutiny has yielded a natural genetic library of bat-borne viruses—the team discovered a coronavirus striving that came from horseshoe bats with a genomic sequence about 97 percentage identical to the one discover in civets in Guangdong. The discover concluded a decade-long search for the natural reservoir of the SARS coronavirus .
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ON THE SAME 2004 trip, a group of researchers prepare bat blood samples that they will screen for viruses and other pathogens. Credit: Shuyi Zhang

A DANGEROUS MIX

In many cream dwellings Shi has sampled, including Shitou Cave, “ changeless shuffle of different viruses creates a great opportunity for dangerous new pathogens to emerge, ” says Ralph Baric, a virologist at the University of North Carolina at Chapel Hill. In the vicinity of such viral melting pots, Shi says, “ you don ’ t need to be a wildlife trader to be infected. ”
Near Shitou Cave, for exemplar, many villages sprawl among the lush hillsides in a region known for its roses, oranges, walnuts and hawthorn berries. In October 2015 Shi ’ s team collected lineage samples from more than 200 residents in four of those villages. It found that six people, or closely 3 percentage, carried antibodies against SARS-like coronaviruses from bats—even though none of them had handled wildlife or reported SARS-like or other pneumonialike symptoms. lone one had traveled outside of Yunnan anterior to the sample, and all said they had seen bats flying in their village .
Three years earlier Shi ’ mho team had been called in to investigate the virus profile of a mine shaft in Yunnan ’ s mountainous Mojiang County—famous for its ferment Pu ’ erbium tea—where six miners suffered from pneumonialike diseases and two died. After sampling the cave for a year, the researchers discovered a diverse group of coronaviruses in six cream species. In many cases, multiple viral strains had infected a individual animal, turning it into a flying factory for new viruses .
“ The mine shot reek like hell, ” says Shi, who, like her colleagues, went in wearing a protective disguise and invest. “ Bat guano, covered in fungus, littered the cave. ” Although the fungus turned out to be the pathogen that had sickened the miners, she says it would have been only a count of time before they caught the coronaviruses if the mine had not been promptly shut .
With growing homo populations increasingly encroaching on wildlife habitats, with unprecedented changes in nation use, with wildlife and livestock transported across countries and their products around the world, and with sharp increases in both domestic and external travel, pandemics of new diseases are a mathematical near certainty. This had been keeping Shi and many other researchers awake at night long before the cryptic samples landed at the Wuhan Institute of Virology on that ill even last December .
More than a year ago Shi ’ s team published two comprehensive examination reviews about coronaviruses in Viruses and Nature Reviews Microbiology. Drawing attest from her own studies—many of which were published in top academician journals—and from others, Shi and her co-authors warned of the hazard of future outbreaks of bat-borne coronaviruses.

NIGHTMARE SCENARIO

On the train back to Wuhan on December 30 stopping point year, Shi and her colleagues discussed ways to immediately start testing the patients ’ samples. In the following weeks—the most intense and the most nerve-racking prison term of her life—China ’ s bat woman felt she was fighting a battle in her worst nightmare, evening though it was one she had been preparing for over the past 16 years. Using a technique called polymerase chain reaction, which can detect a virus by amplifying its genic fabric, the team found that samples from five of seven patients had genic sequences present in all coronaviruses .
Shi instructed her group to repeat the tests and, at the same clock, sent the samples to another facility to sequence the entire viral genomes. meanwhile she madly went through her own lab ’ sulfur records from the past few years to check for any botch of experimental materials, particularly during disposal. Shi breathed a sigh of relief when the results came spinal column : none of the sequences matched those of the viruses her team had sampled from bat caves. “ That truly took a load off my beware, ” she says. “ I had not slept a blink of an eye for days. ”
By January 7 the Wuhan team had determined that the fresh virus had indeed caused the disease those patients suffered—a decision based on results from analyses using polymerase chain reaction, full genome sequence, antibody tests of blood samples and the virus ’ s ability to infect homo lung cells in a petri smasher. The genomic sequence of the virus, finally named SARS-CoV-2, was 96 percentage identical to that of a coronavirus the researchers had identified in horseshoe bats in Yunnan. Their results appeared in a newspaper published on-line on February 3 in nature. “ It ’ south crystal clear that bats, once again, are the natural reservoir, ” says Daszak, who was not involved in the analyze .
Since then, researchers have published more than 4,500 genomic sequences of the virus, showing that samples around the universe appear to “ share a common ancestor, ” Baric says. The datum besides point to a single presentation into humans followed by free burning human-to-human transmittance, researchers say .
Given that the virus seems fairly stable initially and that many infect individuals appear to have balmy symptoms, scientists suspect that the pathogen might have been around for weeks or even months before severe cases raised the alarm. “ There might have been miniskirt outbreaks, but the viruses either burned out or maintained low-level transmittance before causing havoc, ” Baric says. Most animal-borne viruses reemerge sporadically, he adds, therefore “ the Wuhan outbreak is by no means incidental. ”
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IN YUNNAN PROVINCE, CHINA, scientists from EcoHealth Alliance, an international group that searches for diseases that can jump from animals to people, hunt for pathogens in a bat cave. Credit: EcoHealth Alliance

MARKET FORCES

To many, the region ’ south burgeoning wildlife markets—which sell a wide scope of animals such as bats, civets, pangolins, badgers and crocodiles—are perfect viral melting pots. Although humans could have caught the deadly virus from bats directly ( according to respective studies, including those by Shi and her colleagues ), autonomous teams have suggested that pangolins may have been an intercede host. These teams have reportedly uncovered SARS-CoV-2-like coronaviruses in pangolins that were seized in antismuggling operations in southern China .
On February 24 China announced a permanent bachelor of arts in nursing on wildlife consumption and trade except for research, medicative or display purposes—which will stamp out an industry worth $ 76 billion and put approximately 14 million people out of jobs, according to a 2017 report commissioned by the chinese Academy of Engineering. Some welcome the enterprise, whereas others, such as Daszak, worry that without efforts to change people ’ s traditional beliefs or to provide alternative livelihoods, a blanket ban may merely push the business underground. This could make disease detection even more challenge. “ Eating wildlife has been part of the cultural tradition ” in China for thousands of years, Daszak says. “ It won ’ thymine deepen overnight. ”
In any case, Shi says, “ wildlife trade and pulmonary tuberculosis are only separate of problem. ” In late 2016 pigs across four farms in Qingyuan County in Guangdong—60 miles from the site where the SARS outbreak originated—suffered from acute vomit and diarrhea, and about 25,000 of the animals died. local anesthetic veterinarians could not detect any acknowledge pathogen and called Shi for help. The cause of the illness—swine acuate diarrhea syndrome ( SADS ) —turned out to be a virus whose genomic sequence was 98 percentage identical to that of a coronavirus found in horseshoe bats in a nearby cave .
“ This is a good induce for refer, ” says Gregory Gray, an infectious disease epidemiologist at Duke University. Pigs and humans have very like immune systems, making it easy for viruses to cross between the two species. furthermore, a team at Zhejiang University in the chinese city of Hangzhou found that the SADS virus could infect cells from many organisms in a petri dish, including rodents, chickens, nonhuman primates and humans. Given the scale of swine farming in many countries, such as China and the U.S., Gray says, looking for novel coronaviruses in pigs should be a top priority .
The current outbreak follows respective others during the past three decades that have been caused by six different bat-borne viruses : Hendra, Nipah, Marburg, SARS-CoV, MERS-CoV ( Middle East respiratory syndrome ) and Ebola. But “ the animals [ themselves ] are not the problem, ” Wang says. In fact, bats promote biodiversity and ecosystem health by eating insects and pollinating plants. “ The problem arises when we get in contact with them, ” he says .

TOWARD PREVENTION

When I spoke to Shi in late February—two months into the epidemic and one calendar month after the government imposed hard movement restrictions in Wuhan, a megacity of 11 million—she said, laughing, that life felt about normal. “ possibly we are getting used to it. The worst days are surely over. ” The establish staffers had a special base on balls to travel from base to their lab, but they could not go anywhere else. They had to subsist on clamant noodles during their long hours at oeuvre because the establish ’ second canteen was closed .
New revelations about the coronavirus kept coming to light. The researchers discovered, for case, that the pathogen enters human lung cells by using a sense organ called angiotensin-converting enzyme 2, and they and other groups have since been screening for drugs that can block it. Scientists are besides racing to develop vaccines. In the long ladder, the Wuhan team plans to develop broad-spectrum vaccines and drugs against coronaviruses deemed hazardous to humans. “ The Wuhan outbreak is a wake-up call, ” Shi says .
many scientists say the populace should move beyond merely responding to baneful pathogens when they arise. “ The best room forward is prevention, ” Daszak says. Because 70 percentage of emerging infectious diseases of animal origins come from wildlife, a top precedence should be identifying them and developing better diagnostic tests, he adds. Doing so would basically mean continuing on a much larger scale what researchers such as Daszak and Shi had been doing before their financing ended this year .
such efforts should focus on bad viral groups in mammals prone to coronavirus infections, such as bats, rodents, badgers, civets, pangolins and nonhuman primates, Daszak says. He adds that developing countries in the tropics, where wildlife diversity is greatest, should be the front man line of this battle against viruses .
Daszak and his colleagues have analyzed approximately 500 human infectious diseases from the past hundred. They found that the emergence of newly pathogens tends to happen in places where a dense population has been changing the landscape —by build roads and mines, cutting down forests and intensifying department of agriculture. “ China is not the lone hot spot, ” he says, noting that other major emerging economies, such as India, Nigeria and Brazil, are besides at capital risk .
once electric potential pathogens are mapped out, scientists and public health officials can regularly check for possible infections by analyzing blood and swab samples from livestock, from wild animals that are farmed and traded, and from bad human populations such as farmers, miners, villagers who live near bats, and people who hunt or manage wildlife, Gray says. This access, known as “ One Health, ” aims to integrate the health management of wildlife, livestock and people. “ lone then can we catch an outbreak before it turns into an epidemic, ” he says, adding that the strategy could potentially save the hundreds of billions of dollars such an epidemic can cost .
back in Wuhan, where the lockdown was last lifted on April 8, China ’ s bat woman is not in a celebratory mood. She is stressed because stories from the Internet and major media have repeated a flimsy suggestion that SARS-CoV-2 by chance leaked from her lab—despite the fact that its genetic sequence does not match any her lab had previously studied. other scientists are agile to dismiss the allegation. “ Shi leads a first lab of the highest standards, ” Daszak says.

Despite the disturbance, Shi is determined to continue her work. “ The mission must go on, ” she says. “ What we have uncovered is good the tip off of an iceberg. ” She is planning to lead a national undertaking to systematically sample viruses in bat caves, with much wider setting and saturation than previous attempts. Daszak ’ second team has estimated that there are more than 5,000 coronavirus strains waiting to be discovered in bats globally .
“ Bat-borne coronaviruses will cause more outbreaks, ” Shi says with a tone of brooding certainty. “ We must find them before they find us. ”
Read more about the coronavirus outbreak from scientific American here. And read coverage from our external network of magazines here .

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