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Super bats: What doesn’t kill them, could make us stronger


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Article has some evolutionary concepts .. But an intresting read
 

EMMA TEELING loves bats. She is so keen on them that she has spent the past three summers clambering around Gothic churches in Brittany searching for greater mouse-eared bats under dusty eaves and in dark bell towers. She is aware that others do not share her passion. Bats have been demonised throughout history and across cultures. For most of us, Teeling’s little furry fliers are the crepuscular creatures of folklore, witchcraft and horror stories.

Indeed, the dread instilled by bats has only increased in recent years, with the discovery that they harbour the viruses that cause Ebola, SARS, MERS and other so-called emerging infectious diseases. Often fatal in humans, an outbreak of any of these is likely to cause widespread panic – and bats have paid the price. Although they rarely spread these pathogens directly to humans, whole bat colonies are being killed in the name of public health. But where some see a problem, Teeling, a geneticist at University College Dublin in Ireland, sees an opportunity.

Wang, too, despairs of wanton bat killing. But he is emphatic that bats are unusual. “In the last few decades, the high-profile emerging diseases, especially the highly lethal ones, happen to pop up in bats.” He has no answer as to why this is so, but believes we should not be afraid of bats because the viruses they carry hardly ever transmit to humans. In fact, he says, trying to control emerging diseases by killing bats may be the worst thing we can do, because any remaining bats will be more stressed, and this seems to raise their virus loads, increasing any risk of spillover to other animals. This may explain why in Queensland in 2011, Hendra virus made multiple leaps out of flying foxes into horses, with a steep spike in outbreaks and 24 cases. Although Wang cannot say what stressed the bats, he did note a surge in the levels of Hendra and other viruses they were carrying.

Far from fearing bats, we should welcome them, says Teeling. “Bats have been demonised and misunderstood.” Their nocturnal habits and use of echolocation make them unsettling, almost alien creatures to us, but they are intriguing mammals. “The grassroots conservation organisation I work with in Brittany shows people live bats and they are always shocked at what beautiful furry creatures they are, once seen up close,” she says. They are also useful. Many eat insects and one colony can consume tonnes of crop pests in a single night. Now, it turns out, they could teach us how to live longer, healthier lives too. Teeling is confident that it’s only a matter of time before this research yields therapeutic rewards. “It’s simple. Mother Nature has the answer,” she says.

Wang is keen to know more too. At his lab, researchers are trying to identify the proteins bats use to control inflammation and other processes associated with disease. These proteins, or versions of them, might one day help to treat disorders where inflammation is a problem – everything from rheumatoid arthritis to heart disease. They could also help stop viruses such as MERS and Ebola from killing us. “There is a cliché in the infectious disease field,” says Wang. “Few viruses kill humans. Usually humans kill themselves, because of excessive inflammation.”

Closer scrutiny of bat mitochondria also holds promise for therapeutics. Textbooks describe mitochondria as power generators, but increasingly researchers view them as crucial command centres. “Mitochondria are involved in sensing and deciding whether a cell should fight or self-destruct,” says Wang. “We propose looking at bat mitochondria to see what’s unique about them.”

Despite such enthusiasm, not everyone thinks bats are so extraordinary. Birds are also long-lived, and one theory suggests this is because evolving flight enabled them to evade predators, increasing their chances of living to old age and making it worthwhile to invest in costly mechanisms to reduce cellular damage. The same thinking applies to bats. As for the diversity of viruses they host, that could simply reflect bat diversity, says Tony Schountz, an infectious disease specialist at Colorado State University in Fort Collins. Rodents host at least 15 deadly types of hantavirus, he says. And he wagers that if rodents were scrutinised as bats are, we would find lots of new dangerous viruses in them. Bat conservationist Merlin Tuttle agrees. “Virologists often survey hundreds of bats but few other creatures,” he says. “Colonial bats are the easiest mammals on the planet to catch in large numbers. I invented the trap most virologists use,” he adds ruefully.

Bats aren’t to blame

Schountz believes that any deadly jumps of viruses from bats to people can be explained by humans encroaching on bat habitat and eating bushmeat, and by the movements of domesticated animals. “These viruses have been circulating in bats for hundreds, thousands or perhaps millions of years,” he says. “They are only new to us.” Tuttle also fulminates against the term “emerging infectious disease” as misleading and a PR disaster for bat conservation. These are exceptionally rare diseases, not sinister “emerging” pandemic catastrophes, he says. And bats are unfairly blamed. The recent outbreak of MERS, first detected in the Middle East in 2012, was initially blamed on bats but later traced to camels. There is no proof of bats having passed Ebola to people either, he says. Yet these remarkable mammals, which have lived alongside us since prehistoric times, are suffering from the stigma of being disease-ridden. “I routinely talk to people who destroyed large bat colonies out of fear of bat diseases,” says Tuttle.

You could say that, compared with other animals, bats have a more proportional response to viruses – a live-and-let-live approach. They certainly defy the textbook response to pathogensResearch published last year highlights this. Injecting animals with bacterial toxins normally triggers an immune fight-back in mammals. However, the bats had no fever and no spike in white blood cells – two telltale signs that the immune system is launching an attack – although they did lose some body weight. Wang has found this too. “When you infect bats with a virus, almost uniformly it is hard to make them sick. They don’t even have a fever,” he says. What’s more, give bats tumour-causing drugs and they are far less likely to develop cancer than other mammals. “Bats carry a lot of viruses and that might explain their ability to carry tumours. Without doubt, they are interrelated,” he says.

In an attempt to find out what’s going on, Wang and his colleagues compared the genomes of two species of bat – a fruit bat and an insect-eater – with those of other mammals. They discovered that genes involved in DNA repair have been reconfigured during bat evolution. “They are very efficient at dealing with DNA damage,” says Wang. He notes that key genes in DNA damage repair are also involved in tumour development and immunity. But that’s not all– bats have also lost an entire branch of the immune system made up of inflammasomes, receptors and sensors that induce inflammation. In other words, they have evolved to turn down their inflammatory response to various threats, including infection by viruses.

Wang believes the key to understanding these evolutionary changes is flight. Bats are the only mammals capable of powered flight, which is demanding in terms of energy and tough on metabolism. A bat’s heart can beat over 1000 times a minute. When in the air, their metabolic rate increases some 34-fold, compared with an eight-fold increase in exercising rodents. This ramped up metabolism spews out free radicals – energetic particles that can damage cells, kick-starting inflammation. Bats needed to evolve adaptations to cope with flight. “If they had the same inflammation system as land mammals, they would get sick more easily,” says Wang. So their ancestors re-engineered the system to cope with the harmful metabolites produced by flying and this, in turn, allows them to avoid overreacting to viral infections.

Support for the idea that flight has fundamentally changed bat physiology comes from their mitochondria – the cellular powerhouses. DNA comparisons reveal that bat mitochondria have undergone more evolutionary changes than mitochondria in other mammals. Intriguingly, individual bats have an assortment of mitochondria, rather than carbon copies as most other organisms do. And bat mitochondria seem to have evolved mechanisms to help them mop up the damaging free radicals produced during flight, which researchers at Princeton University think could explain their long lives, tumour avoidance and more. Others, including zoologist Thomas O’Shea at the US Geological Survey, have speculated that bats’ revved-up metabolism allows them to raise their temperature and power a faster immune response, a sort of daily fever. “[This] might promote natural selection for the evolution of lower virulence in viruses,” he says.

There’s still plenty to be discovered. To that end, last summer Teeling took blood and wing samples from the church bats to track genes and gene expression as bats age. She should be able to tell whether gene regulation becomes gradually disrupted as it does in other animals. If not, that might help explain bats’ exceptional longevity. Teeling believes such knowledge will lead to the development of drugs to improve human health and lifespan. Alternatively, she says, we could use new gene-editing technology to make the human genome a little more like that of bats.

The thing is, bats are weird. They don’t just carry headline-grabbing viruses, they are also renowned for the huge number and diversity of pathogens they host. In other mammals these would result in sickness or death, but bats hardly ever succumb to viral diseases. They almost never get cancer, too. In fact, they generally live between three and 10 times longer than other mammals of their size – one male Brandt’s bat tagged in Siberia in 1962 was recaptured 41 years later, still sprightly enough to catch prey and dodge predators. In the past, researchers have put these peculiarities down to bats’ hibernation, a type of suspended animation in places with few predators, and usually at chilly temperatures not ideal for virus replication. Now Teeling and others have found something far more surprising going on. As a result, they believe bats hold secrets that could not only improve our health but also help us live longer.

With more than 1200 species, bats are one of the most diverse groups of mammals – second only to rodents – so it’s hardly surprising that they carry many different pathogens. But diversity alone cannot explain why almost every family of virus has been found in bats. Their habit of roosting in large, dense colonies and the ability to fly long distances also play a part. “The way bats live in terms of their mixing patterns and life history will contribute to the way viruses persist,” says epidemiologist James Wood at the University of Cambridge, who found that bats host more viruses per species than rodents.

What’s really extraordinary, however, is their ability to live with viruses. Working in Ghana, Wood found that between 60 and 80 per cent of fruit bats aged 10 years and older had antibodies for lyssavirus, indicating that they had been in contact with the pathogen, which causes rabies. Nevertheless, the bats were in rude health. The same is true for bats carrying Ebola virus. Kate Baker at the Wellcome Trust Sanger Institute in Cambridge, UK, studied fruit bats in West Africa before the latest Ebola outbreak. In common with many bat species, fruit bats live jam-packed in huge colonies of perhaps a million individuals – perfect for passing on viruses. They can also fly thousands of kilometres, delivering viruses to kin as far away as Uganda and Tanzania. Yet one bat studied by Baker’s group lived with Ebola virus for more than a year, showing no ill effects. What is their secret?

Living with the enemy

It’s well known that pathogens tend to become less virulent as they coexist with a host over millennia of evolution. But there seems to be something more going on here. Virologist Linfa Wang at Duke-National University of Singapore found one clue. He spent almost two decades in Australia studying flying foxes and Hendra virus, which can jump to horses and then humans, in whom it is often fatal. Around 30 to 70 per cent of these bats in any given colony had antibodies to the virus – revealing they had been infected in the past – with some 3 per cent carrying the virus at any given time. However, the infected individuals had very low levels of the pathogen, indicating they were able to keep it at bay. This probably explains why Hendra very rarely jumps from bats to horses. “It is purely contained by a threshold of virus levels in bats,” says Wang. This might be true for other bat viruses too, and could explain why, during the recent Ebola outbreak in West Africa, amid thousands of human-to-human transfers, there was just one presumed bat-to-human transfer.


Edited by Lance
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