Are bats carrying the next plague?
A fast-growing cohort of international scientists is studying not only bats but also the viruses they carry, many of which are deadly.
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“Bats do carry a bunch of really nasty pathogens. The kind of big question is . . . why are they emerging from bats and why are they emerging now?”
president of EcoHealth Alliance
The first time Jon Epstein tried to catch a bat, things went awry.
It was the summer of 1998 in Australia, and a grey-headed flying fox had just flown into Epstein’s net. The 24-year-old veterinary student was going through the motions — controlling the bat’s feet and wings, gently securing the jaw — when he suddenly lost his grip. Chomp.
Epstein jerked his arm and the bat “pancaked” on the ground, startled but unhurt. Flustered, he scrambled to pick it up.
“Then, when I looked at his mouth, it turned out it didn’t have any teeth,” Epstein recalls today from New York. “As a first time getting bitten, that was probably the best way it could have happened: a toothless old bat.”
Fifteen years and thousands of bats later, Epstein has perfected his technique, having gone on bat-trapping expeditions everywhere from the suburbs of Australia to Malaysia’s mangrove forests.
The wildlife veterinary epidemiologist is part of a fast-growing cohort of international scientists studying not only bats but also the viruses they carry. Bat research is booming and scientific publications have doubled in the last decade alone, says virologist Linfa Wang with Duke-NUS graduate medical school in Singapore.
“Without exaggeration, every month there is a new paper describing bat viruses,” says Wang, often dubbed the “bat man” by colleagues. “My lab — we’re sitting on 60 new viruses we (found in bats but) haven’t yet published.”
Why the surging interest in bat viruses? One good reason is Ebola. Another is SARS. Then there is Marburg, Hendra, Nipah and, most recently, MERS, plus several other nasty diseases contributing toward a growing body count around the world.
All are viruses that are particularly deadly to humans. All have emerged in the last few decades.
And all of these viruses, it would appear, have come from bats.
New virus emerges
Just a few decades ago, there was really only one bat virus, as far as humans were concerned.
“Up until about 1990, the only thing we cared about with bats was rabies,” says Peter Daszak, Epstein’s boss and the president of EcoHealth Alliance, a conservation group in New York studying emerging infectious diseases.
Then, in September 1994, an Australian horse got sick.
Drama Series, a pregnant mare and retired racing horse, died swiftly and agonizingly. Within weeks, 13 other horses from the same stable succumbed — as did Vic Rail, their 49-year-old trainer.
The virus was named Hendra after the Brisbane suburb where Drama Series died. It was initially thought to be a horse measles-like virus but investigators soon realized it was something different — and new.
They went searching for the source, testing every land animal under the Australian sun: kangaroos, reptiles, bandicoots. When none showed any sign of the virus, investigators started looking up.
“That year, there were two independent (outbreaks). One was in Hendra, one in MacKay, 800 kilometres apart,” says Wang, who worked in Australia at the time and helped investigate the outbreak. “We started to think that maybe it was something that could travel long distances. So we concentrated on birds and bats.”
Once they started looking at bats, the evidence started cascading. In two years, investigators tested more than 1,000 flying foxes, a megabat native to Australia; nearly half had antibodies to Hendra, meaning they had all been infected at some time.
So Hendra was a bat virus. This was shocking news — Australia was considered rabies-free and the country had never worried about bat viruses.
But just two years after Hendra, Australians had yet another virus to worry about.
In 1996, a Queensland woman was scratched by a bat and quickly died from something that looked a lot like rabies. Only, she wasn’t infected with rabies — this virus, although genetically related, was entirely new. They named it Australian bat lyssavirus. In February, it claimed its third and latest victim, an 8-year-old boy from Brisbane.
The world was introduced to yet another bat-borne disease in 1998, one that later inspired the virus that kills Gwyneth Paltrow in the pandemic movie Contagion. A close relative of Hendra, Nipah virus first appeared in Malaysia, causing a massive outbreak that infected more than 250 people, nearly 40 per cent of whom died.
But this outbreak had a twist: most victims worked in the pork industry. They were catching it from sick pigs.
More than 1.1 million swine were culled, but scientists eventually concluded another animal had infected the pigs — bats. Malaysia has been Nipah-free since then, but the virus showed up in India and Bangladesh in 2001 and small but deadly outbreaks have hit the region nearly every year since.
But the virus that really catapulted bats to the top of the world’s priority list was a coronavirus.
Most people have caught coronaviruses; they cause the common cold. But in 2002, a new one popped up in China. Within a year, SARS had spread across 30 countries and killed 800 people, including 44 Torontonians.
Where did SARS come from? Scientists originally suspected the civet cat, a small mammal that looks like a cross between a badger and raccoon. They had found the virus in civets being sold for meat in Chinese wildlife markets.
But the real source emerged in 2005 with the publication of two studies, one by Linfa Wang and his team, including Daszak and Epstein. The paper’s title said it all: “Bats are natural reservoirs of SARS-like coronaviruses.”
“I think the emergence of SARS in China — and the work that Peter, Jon and others published in 2003 — really helped to spur this bat-viral craze, I guess you could call it,” says Kevin Olival, a senior research scientist with EcoHealth. “Interest really started to peak around that time.”
And with the discovery of more viruses, the interest has remained. In the last five years alone, scientists have found evidence for about 250 new bat viruses, according to Olival.
Shortly after the SARS discovery, evidence also emerged implicating bats as the “reservoir” for two particularly horrifying diseases: Marburg, first detected in 1967, and Ebola, which has decimated gorilla populations and caused its first known human outbreak in 1976. Both rank among the world’s most feared diseases — victims are often dispatched with devastating speed, sometimes with blood leaking in and from their bodies.
In April 2012, a strange hospital outbreak in Jordan killed two people, one of them a nurse. The mysterious incident would have gone unnoticed by history books but two months later, a businessman in Saudi Arabia died, too.
A new coronavirus was soon discovered and dubbed MERS, or Middle East respiratory syndrome. To date, it has infected at least 130 people and nearly half have died. Public health officials are now wringing their hands over the prospect of the next SARS, especially as the upcoming Hajj season brings millions of pilgrims to Saudi Arabia, the epicentre of MERS.
The animal origin for MERS remains unknown but, once again, fingers are pointing at the bat. A recent study published by Saudi scientists, EcoHealth and respected virologist Dr. Ian Lipkin — Columbia University’s famed “microbe hunter” — found a tiny fragment of virus RNA in an Egyptian tomb bat that perfectly matched the MERS virus that killed the first Saudi victim.
By scientific standards, this is does not prove MERS came from bats. But we do know MERS is closely related to other coronaviruses found in bats and for EcoHealth’s Daszak, he is “pretty confidant” they are the source.
Even if the MERS link is never conclusively made, there is no denying: bats cannot be ignored.
“Bats do carry a bunch of really nasty pathogens,” Daszak says.
“The kind of big question is . . . why are they emerging from bats and why are they emerging now?”
A numbers game?
Shortly after the SARS-bat connection emerged, a virologist named Charles Calisher asked himself this same question.
He decided to start answering it by posing another one: what has science already learned about bats and their viruses? Calisher assembled a team to scour the scientific literature and in 2006 they published a review paper called “Bats: important reservoir hosts of emerging viruses.”
Almost immediately, Calisher’s phone was “ringing off the hook” with hundreds of requests for the paper, according to Spillover, a book about animal diseases that jump into humans.
“It’s the classic in the field,” says Lipkin, who has discovered more than 600 viruses, a “large number” in bats. “This is the one that inspired everyone to start looking in this way.”
Calisher’s paper begins by pointing out bats are perhaps the world’s “most abundant, diverse, and geographically dispersed vertebrates.” They roam every continent except Antarctica and boast nearly 1,200 known species — meaning bats represent about 20 per cent of all mammals. Every fifth mammalian species is a bat.
Perhaps, then, it is just a numbers game; more bats equal more bat viruses.
“They’re as diverse as rodents,” Daszak says. “And we know that rodents carry all sorts of nasty diseases.”
Many bats also live in dense colonies. Imagine, for example, a crowded elementary school — but one where the kids all poop on the floor and lick each other a lot.
“You have all kinds of social contact and, for a virus, that’s really what you need,” says Epstein. “If the virus is shed in saliva or urine or feces and bats are grooming by licking each other’s fur . . . there’s plenty of opportunity for viruses to pass from individual to individual.”
Some bats hibernate or enter daily torpor, a kind of short-term hibernation state where the body temperature plummets. One theory raised by Calisher’s paper is that “perhaps colder temperatures suppress immune responses that might otherwise control (virus in the blood).” The paper also points to a 1972 study that found the rabies virus in mucus scraped from bats’ nostrils — one of the orifices used in echolocation.
“Many (bats) do communicate by ultrasonic signal,” Lipkin says. “That results in a loosening of upper respiratory tract secretions and aerosols that pass these infectious agents widely within colonies, even amongst different subtypes of bats.”
But the bat’s most remarkable characteristic, perhaps, is hinted at in the Greek roots of its scientific name: Chiroptera, or “hand wing.”
Bats are the only mammals capable of sustained flight. Hitchhiking viruses can therefore spread themselves far and wide — the Mexican free-tailed bat, for one, can migrate at least 1,200 kilometres, roughly the distance between Toronto and North Carolina.
But for Wang, he suspects that flight has given the bat another evolutionary advantage: a more robust immune system.
Bats are persistently infected with viruses — but they rarely get sick. Perhaps bat immune systems have evolved to find a kind of sweet spot, Wang proposes: the ability to keep viruses at bay without also going overboard and self-destructing.
“That’s the thing we’re interested in,” Wang says. “A lot of viruses kill humans but it’s not necessarily because of the virus doing damage to you . . . it’s actually your body’s defence that goes overboard.”
In a recent study, Wang and several international collaborators published the first two bat genomes ever sequenced. When they compared them with genomes from other mammals, they discovered one key difference: the genes involved in DNA damage and repair.
When cells metabolize, a toxic byproduct is produced, which can damage DNA, Wang explains. We have built-in DNA damage repair systems, however — systems that also “cross-talk” with the immune system.
Bats, however, need huge bursts of metabolism to fly. So Wang’s theory is that they have also evolved to develop more robust DNA damage repair and immune systems — and a byproduct of that is their ability to tolerate more viruses.
EcoHealth’s Olival sees promise in Wang’s research on bat immunology. But he cautions it is too early to tell whether bats truly are unique as an animal source of viruses.
There seems to have been an uptick in bat virus spillovers but, for all we know, they may have been infecting people for centuries — only we lacked the surveillance and technology to detect them.
The scrutiny on bats right now could also be distorting the data, he adds.
“The more we start looking in bats, the more viruses we’re going to find in bats,” Olival says. “In order to answer the question ‘Are bats special?’ we can’t have a very myopic view . . . we need to be also looking at primates and ungulates and other types of mammals.”
But a new study published in January did compare bats with rodents and found that bats — although far outnumbered by rodents — seemed to host more viruses on a per-species basis.
And there is no denying the momentum right now is behind bats. Wang and his team recently received $10 million to study bat immune systems — an “unthinkable” sum just 10 years ago, he says.
The enthusiasm is partly due to the hope that bats will teach us about more than just viruses — they also have low cancer rates and exceptionally long lives (on average, bats live three to 10 times longer than other similarly sized mammals).
Could bats also be harbouring secrets for fighting cancer and living longer?
“The explosion of bat virus research in the last 20 years has really led us to a position where we have no choice but to study bats,” Wang says. “Everything is pointing to something that is unusual.”
One might be tempted, at this point, to raise the uncomfortable question: if we already know bats have viruses that can kill us, why not just get rid of them?
After Hendra “in Australia, some politicians just said bomb the bats, kill the bats,” Wang recalls. “But obviously that’s a silly way of (dealing with) it.”
For one, bats are incredibly important to the environment. They are major pollinators and seed dispersers; Epstein points out that they are responsible for about half of the world’s tropical rainforests.
They have huge economic importance, too. Their guano is sold as fertilizer in many countries and insectivorous bats provide an important source of pest control — one study published in the journal Science estimated that the extinction of bats in North America could result in agricultural losses amounting to more than $3.7 billion per year.
Finally, when it comes to the phenomenon of bat virus spillover, another mammal is largely to blame: people.
“The most important thing to know is that these viruses emerge because of human activities,” Epstein says. “This is not the bat’s fault.”
It has become widely accepted within the scientific community that human behaviour is hastening the emergence of new infectious diseases. Take Nipah, for example. The outbreak in Malaysia might never have happened if massive pig farms hadn’t been built next to fruit trees, where bats like to roost and eat their meals.
In Bangladesh, most people get Nipah from drinking date palm sap, which is often collected in buckets hung from trees. “We have plenty of evidence that bats do drink from date palm sap trees and pots,” Epstein says. “We even have infrared camera work showing these bats defecating and urinating in these pots.”
The solution, then, is not to destroy bats but to understand them better and recognize their connection to us, says Simon Anthony, an associate research scientist with both Columbia University and EcoHealth.
“Bats could very well have a direct impact on your own health,” he says. “That’s true whether you are working on a wet market in Asia or . . . sitting in an apartment in New York City.”
It is also true if you are Arlene Edwards, a 62-year-old retired schoolteacher from Pickering. In March 2003, Edwards’ mother suffered a heart attack and was brought to Scarborough Grace hospital — just days after one of Toronto’s first SARS patients was also admitted there.
SARS spread through the hospital and both Edwards and her mother became infected. Her mother eventually died from circumstances arising from her battle with SARS.
For Edwards, she never could have imagined that her life would be forever changed by a tiny microbe that emerged from some furry, flapping mammal halfway across the world.
“To think that a bat is the actual source of what ultimately killed my mother and many other people,” she marvels. “That is so incredible. Just incredible.”
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