In Linfa Wang’s ideal world, all humans would be just a bit more bat-like.
Wang, a biochemist and zoonotic-disease expert at Duke-NUS Medical School, in Singapore, has no illusions about people flapping about the skies or echolocating to find the best burger in town. The point is “not to live like a bat,” Wang told me, but to take inspiration from their very weird physiology in order to boost the quality, or even the length, of human life. They might not look it, but bats, Wang said, are “the healthiest mammals on Earth.”
That thought might be tough to square with bats’ recent track record. In the past three decades—from 1994, when Hendra virus jumped to humans, to 2019, when SARS-CoV-2 emerged—at least half a dozen of the most devastating viral epidemics known to have recently leapt into people from wildlife have had their likeliest origins in bats. But bats themselves rarely, if ever, seem to fall ill. Ebola, Nipah, Marburg, and various coronaviruses don’t appear to trouble them; some bats can survive encounters with rabies, which, left untreated in humans, has a near 100 percent fatality rate. “They’ve evolved mechanisms to limit the damage of disease,” says Emma Teeling, a bat biologist at University College Dublin, who collaborates with Wang.
The creatures’ apparent ability to defy death goes even beyond that. Some nectar-devouring species spend years spiking their blood-sugar levels high enough to send a human into a hyperglycemic coma—and yet, those bats never seem to develop what we’d call diabetes. Others have been documented surviving up to 41 years in the wild—nearly 10 times as long as mammals of their size are generally expected to live—all the while avoiding cancer and fertility dips.
Wang and Teeling, along with several colleagues, were recently awarded a $13 million grant by the European Research Council to try to better understand the biology behind these batty abilities—and how it might help other creatures. (And they’re certainly not the only ones trying to find out.) Wang’s team, as he likes to cheerfully boast, has already put some of his ideas to the test by genetically engineering a healthier, more disease-tolerant “bat-mouse.” He and his colleagues are still years away from creating any sort of bat person, but they are confident that this line of thinking could one day inform new treatments for humans—to combat diabetes, to temper infectious diseases, maybe even to extend the life span.
The key to bats’ health seems to be flight, or at least the effects that evolving flight has had on the bat body. Flight, for all its perks, is one of the most energetically taxing transportation options: When bats fly, their metabolism can rev up to 15 to 16 times above its resting state; their heart rate may soar above 1,000 beats per minute; their body temperature can exceed 105 degrees Fahrenheit, effectively plunging the animals into an epic fever state. Put all of that on virtually any other mammal, and their body would likely be overwhelmed by the blaze of extreme inflammation, the toxic by-products of their metabolism effectively rending cells apart.
To cope with this self-destructive form of locomotion, bats have evolved two essential safeguards. First, they are extraordinarily good at maintaining bodily Zen. Even when pushed into extreme forms of exertion, bat bodies don’t get all that inflamed—maybe in part because they lack some of the molecular machinery that kicks those systems into gear. Which means that bats simply rack up less damage when their bodies get stressed. And for any damage that does occur, bats have a second trick: Their cells appear to be unusually efficient at cleanup and repair, rapidly stitching back together bits of torn-up DNA.
Those strategies, Wang and Teeling told me, haven’t just made flight a breeze for bats. They also mitigate other types of bodily harm. Cancer tends to unfurl after errors appear in particular parts of our genetic code. And, molecularly speaking, aging is basically what happens to the body as it accumulates a lifetime of cellular wear and tear. In a sense, stress is simply stress: The root causes of these chronic health issues overlap with the greatest taxes of flight. So the solutions that keep a bat body running smoothly in the air can address problems throughout its lifetime. While humans get worse at repairing damage with age, bats’ ability improves, Teeling told me.
All of this can also help explain why bats are such hospitable hosts for pathogens that can kill us. Many of the most dangerous cases of infectious disease are driven by the body’s overzealous inflammatory response; that reaction can pose a greater threat than any damage that a pathogen itself might do to cells. Many of our defenses are like bombs set off on our home turf—capable of killing invaders, yes, but at great cost to us. Bats have such a high threshold for igniting inflammation that many viruses seem able to inhabit their tissues without setting off that degree of destruction. In laboratory experiments, bats have been dosed with so much virus that their tissues end up chock-full—clocking some 10 million units of Ebola virus per milliliter of serum, or 10 million units of the MERS coronavirus per gram of lung——and researchers were still unable to discern serious problems with the bats’ health. Bats and their viruses have, in effect, struck “an immunological detente,” says Tony Schountz, a bat immunologist at Colorado State University.
Such astronomical levels of virus aren’t a bat’s preferred state. Bat bodies also happen to be very good at tamping down viral replication up front. Part of the reason seems to be that, in certain bat species’ bodies, parts of their antiviral defense system “are always on,” Wang told me. “I call them ‘battle ready.’” So when a pathogen does appear, it knocks up against a host that is already teeming with powerful proteins, ready-made to block parts of the viral life cycle, hindering the microbe from spinning out of control.
The catch here is that the viruses have wised up to bats’ tricks—and evolved to be more forceful as they attempt to infiltrate and replicate inside of, and then spread between, those well-defended cells. And that bat-caliber offense can be excessive in a human that lacks the same shields, says Cara Brook, a disease ecologist at the University of Chicago. That might help explain why so many bat viruses hit us so hard.. Couple that show of force with our difficulties reining in our own inflammation, and what might have been a trivial infection for a bat can turn into utter chaos for a person.
One of Wang’s primary ideas for dealing with this kind of host-pathogen mismatch is to use drugs to make our inflammatory responses a bit more muted—that is, a bit more bat-like. That option is especially intriguing, he told me, because it could also lower the risk of autoimmunity, maybe even forestall aging or certain kinds of chronic metabolic disease. His bat-mouse, which was engineered to express a particular inflammation-suppressing bat gene, is an experiment with that principle, and it seemed to fare better against flu, SARS-CoV-2, even gout crystals.
But the idea of muffling inflammation isn’t exactly new: Our medical armamentarium has included steroids and other immune-system-modulating drugs for decades. All have their limits and their drawbacks, and a treatment specifically inspired by bats would likely be subject to the same caveats, says Arinjay Banerjee, a virologist and bat immunologist at the University of Saskatchewan. Inflammation, as damaging as it can be, is an essential defense. Any drug that modifies it—especially one taken long-term—must avoid the hurt of too much while skirting the risk of not enough. And ultimately, humans just aren’t bats. Plop a bat’s defense into a human body, and it might not work in the way researchers expect, says Hannah Frank, a bat immunologist at Tulane University. To truly see bat-like benefits in people, chances are, we’d need more than one treatment turning more than one physiological dial, Banerjee told me.
As much as researchers are learning about bats, the gaps in their knowledge are still huge. What’s observed in one of the more than 1,400 species of bats may not hold true for another. Plus, bat physiology is distinct enough from ours that no one really can precisely say what optimal health for them looks like, Frank told me. Although bats rarely die from their viruses, those infections may be still taking a toll in ways that researchers have yet to appreciate, Brook told me. Bats aren’t the only intriguing virus-carriers, either. Rodents, too, haul around a lot of deadly pathogens without falling sick, as Schountz points out. Nor are they the only mammals that live at extremes. Naked mole rats withstand low-oxygen conditions underground; seals must cope with organ-crushing pressures when they dive. Like flight, those adaptations may have rejiggered immunity in yet untold ways.
Certainly, though, bats have more to offer us than many people give them credit for. In the aftermath of a Hendra virus outbreak in Australia, years ago, “we even had a politician say, Let’s bomb the bats,” Wang told me. The start of the coronavirus pandemic, too, ignited calls for bat cullings; some animals were even reportedly burned out of roosts. “I still don’t want a bat as a pet,” Wang told me. But if his findings keep panning out, maybe someday people will associate bats less with the diseases we don’t want to get from them, and more with the healthy traits we do.
Katherine J. Wu
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