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University of Nebraska Medical Center

Bats Shrug Off Viruses and Rarely Get Cancer. We’re Trying to Learn From Them.

WSJ

To many people, bats are a terrifying menace, vampirish carriers of dangerous viruses—including, likely, an ancestor to Covid-19

But to researchers and biotech investors, they are a miracle mammal that could help prevent pandemics and reveal blockbuster treatments for deadly human diseases or to slow aging. 

Bats are infected with viruses that kill humans but don’t usually get sick. They rarely get cancer. They are the only mammal that can truly fly and have extraordinarily long lifespans—some the human equivalent of more than 200 years, taking body size into account.  

While the Covid-19 pandemic exposed health risks from bats, it has also made finding out how they crush viral infections and avoid cancer and other diseases more urgent, the scientists said. Mammals have similar genomes, meaning it is possible insights from one could be applied to another. 

“These are really fascinating biological creatures,” said Thomas Zwaka, a stem-cell researcher at the Icahn School of Medicine at Mount Sinai. He is among a group of scientists who are going to bat to decode the winged mammals’ superpowers. 

Bats are “not that different from a human, but the things they can do we can only dream of,” said Linfa Wang, professor in the emerging diseases program at Duke-NUS Medical School in Singapore, who has studied bats for nearly three decades

Paratus Sciences Corp. is putting $100 million into researching bats to target new drugs that could combat viruses as well as, potentially, cancer, diabetes, aging and other conditions. Dr. Zwaka is a founder and Dr. Wang is a founding adviser to the biotech company. 

Working in labs in New York and Singapore, the new company has identified some promising drug targets to address inflammation—which plays a role in many diseases—and aims to have its first product in five years, said Phil Ferro, president and head of global operations. “What we’re doing is using the extreme physiology of mammals to guide us to more effective and efficient drug discovery,” he said. 

The National Institute of Allergy and Infectious Diseases is funding studies into the immune systems of bats, which it said could lead to therapeutics for inflammation and infectious diseases. And a consortium of researchers has a project under way called Bat1K to sequence the genomes of all 1,462 living bat species.

Finding a cure for Covid-19 or cancer in bats might be a long shot and could take years, some scientists said. The study of bat biology is in its infancy. Only a few labs in the world have colonies of live bats for research. “We are in a very pioneering state at the moment,” said Maya Weinberg, a bat researcher in the Yovel bat lab at Tel Aviv University in Israel.

Searching for human disease cures or treatments in animals has a long history. Scientists have probed dog DNA, snake venom and shark antibodies for insights and treatments. What makes bats stand out are their many superpowers, including harboring viruses without getting ill. They can carry Ebola, Nipah—a deadly virus carried by fruit bats that sickens pigs and people in parts of Asia—and viral ancestors to coronaviruses that infect humans, though they haven’t yet been found to carry the Covid-19 virus itself. 

Bats are one of the most diverse groups of animals on the planet, making up more than 22% of mammal species, according to bat conservationists. They range in size from the inch-long bumblebee bat to fruit bats with wing spans of up to 6 feet. Spooky as they seem, they are important to the environment, eating mosquitoes and beetles, pollinating plants and reseeding forests. 

Their ability to get infected and not usually become sick might be linked to adaptations they made over millions of years as they transformed into flying mammals, said Dr. Wang. Some bats fly five to eight hours a night, he said, their hearts accelerating to more than 1,000 beats a minute and their bodies burning lots of calories. 

“The biological pressure and stress is incredible,” he said.

Some species eat their body weight in insects every day; others lap up 1½ times their weight in nectar. Only three species drink blood.

Bats naturally limit inflammation, which occurs from stress or signs of danger. That includes DNA damage caused by the demands of flight or a viral infection, according to research Dr. Wang and his colleagues conducted. Humans become ill when their inflammatory responses kick into overdrive to fight off a virus, but bat immune systems have a more measured response, tolerating the invader. 

“We humans really evolved with our intelligence, with our brain development,” he said. “But in terms of the immune system, I want to be a bat.” He’s now expanding his bat research to metabolic disease and other aspects of the bat’s physiology. 

Bats’ immune systems and response to inflammation also could help them fight off aging, said Emma Teeling, a zoologist at University College Dublin who has spent the past decade studying how long-lived wild bats age. “We found as they age, they increase their ability to repair their DNA,” said Dr. Teeling, who is also a founding adviser of Paratus. 

A breakthrough by Dr. Zwaka is helping virologists and bat biologists accelerate their research. Intrigued when he learned in early 2020 that the new pandemic virus could be linked to a bat, the stem-cell researcher decided to put his expertise to work to create bat “pluripotent” stem cells. This involves reprogramming skin or blood cells back into stem cells that, like embryonic cells, can become any kind of cell. They could be used to make different types of bat tissue for lab studies.  Scientists had failed previously to make these cells from bats. At his lab a few blocks from a makeshift hospital in Central Park where doctors were caring for Covid-19 patients, Dr. Zwaka and his colleagues extracted cells from bat tissue that a researcher in Spain had shipped to them, and spent months trying different recipes until they found one that turned them into pluripotent stem cells.

The cells from Dr. Zwaka’s lab are a step forward for researchers, said Vincent Munster, a virologist at the NIAID who is studying the effects of certain viruses on them. “These novel tools will allow us to do very detailed mechanistic studies,” he said. 

The large, round bat stem cells the researchers produced look very different from other mammalian cells. They have tiny vesicles that contain virus-like structures, and many genes not present in other stem cells that activate when a virus infects a cell, Dr. Zwaka said. Many viral genes are integrated into their genome—further evidence of how bats tolerate viruses, he said. 

“They seem to be genetically wired to support viruses,” he said. 

He and his team are creating bat brain and lung “organoids”—artificially grown clusters of cells that exhibit properties of full organs—as well as blood from the stem cells. While continuing to study viral infection, they plan also to examine how bat tissues respond to cancer genes, how bat stem cells age, and how hibernation helps bats, Dr. Zwaka said.

SHARE YOUR THOUGHTS

What do you think about studying bats to find cures for human diseases and aging? Join the conversation below.

Paratus is collaborating with academic and government scientists to learn more about bats’ physiology, and amassing and analyzing data from genome sequences, stem cells, and other sources. The company is comparing bat cells and human cells to understand the differences in response to stressors. It is also comparing data between bat species—long-lived bats compared with short-lived bats, bats that get cancer and those that don’t, and bats that live on protein-heavy diets of insects compared with those that live on fruit and nectar, said Deborah Slipetz, Paratus’ chief scientific officer, a former drug hunter at Merck & Co. 

“How do they handle a massive glucose load that would cause any of us to have metabolic issues?” she said. “There may be unique insights into that to understand how we might control diseases such as diabetes.” 

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