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Read more: “Amphibian planet: Six of the strangest“

AN UNKNOWN disease springs out of nowhere and sweeps across the globe, leaving millions of dead bodies strewn in its wake. Even worse, the disease strikes not just one species, but hundreds. Nothing can check the epidemic, which threatens to drive many species to extinction.

It sounds like a movie plot, but it’s real and it’s happening today to the world’s frogs and salamanders. “Maybe people don’t care about amphibians, but imagine if this kind of pathogen had gotten into mammals,” says Vance Vredenburg, an ecologist at San Francisco State University. Although mass die-offs of amphibians have been happening since the 1980s, we only discovered that a fungus was to blame in 1999. Back then, no one knew where the disease came from, what made it so deadly or how it had spread so rapidly around the world. But now, thanks to genetic detectives, we are starting to find clues to the mystery of its sudden, devastating emergence.

Even if there were no killer fungus running amok, amphibians would be in trouble. We are draining the wetlands and cutting down the forests in which frogs and salamanders live, leaving many species with nowhere to go.

The fungus, though, adds an ominous extra dimension to the problem. “We can’t simply protect habitat and stop the decline – we’re losing species even from protected habitats,” says Vredenburg. “That’s really alarming. We can think of creative ways not to chop down the rainforest and not put parking lots on wetlands. But if we can’t even save stuff that’s in the pristine areas…”

As a result of this multiple onslaught, nearly half of all amphibian species are declining in numbers, hundreds of species are endangered and many have already gone missing. Species are estimated to be going extinct up to 40,000 times faster than the normal rate over the 360 million years since the first amphibians crawled out of the water. No one knows what the long-term consequences will be, but the world will undoubtedly be poorer without them. We are losing extraordinary species such as the gastric brooding frogs of Australia, with their unique habit of swallowing their eggs and raising their young in their stomachs. These frogs have not been seen since the 1980s and are almost certainly extinct.

The killer, in many cases, is a single-celled fungus called Batrachochytrium dendrobatidis (Bd). It infects the skin of amphibians and spreads by releasing spores into the water (see diagram). Severe infections alter the fluid balance within the body, causing heart failure.

The Bd fungus is an unlikely suspect for a frog-killer. The other members of the group to which it belongs, the chytrids, are an obscure group of aquatic microbes that feed on decaying plant matter. “It’s very strange for a chytrid to attack vertebrates,” says Erica Bree Rosenblum, an evolutionary biologist at the University of California, Berkeley, and even stranger for it to kill them. “It’s like learning that humans started dying from athlete’s foot,” she says.

“These fungi are usually harmless. It’s like learning that people started dying from athlete’s foot”

Bd has turned out to be no ordinary chytrid, though. It has , and when Rosenblum recently compared its genome with that of its closest known relative, she found that it has hundreds of unique genes. Many of them code for enzymes that digest proteins – in other words, that allow Bd to eat meat (). “Those features didn’t just arise overnight,” she says. Rather, Bd‘s ability to feed on frog skin seems to have evolved over many millennia. So why is it killing amphibians en masse now? “That’s what we’re all trying to understand. Where was this thing 30 years ago, when we weren’t seeing amphibian declines?” says team-member Jason Stajich, an evolutionary biologist at the University of California, Riverside.

Biologists have suggested two main explanations. The first is that Bd only turns nasty in certain situations – the Jekyll and Hyde hypothesis. Soon after the discovery of Bd, it became clear that in some places, low numbers of the fungus live on the skins of frogs without causing any obvious harm. One idea is that , turning a mild infection into a deadly plague. Another is that factors such as pollutants are making frogs vulnerable to the fungus, perhaps by weakening their immune systems.

The second explanation is that Bd itself has changed, turning into a monster that is sweeping across the world, wiping out populations that have never encountered this new strain before. So, are we dealing with Jekyll and Hyde or some new monster? This, it turns out, is a case for the genetic detectives. If Bd has been around for a long time and is killing only because conditions have changed, there should be lots of differences between the strains causing mass die-offs in different parts of the world. If a new strain is spreading around the globe, the killer should be pretty much the same everywhere.

When Timothy James, a mycologist now at the University of Michigan in Ann Arbor, and colleagues first sequenced small parts of Bd‘s genome nearly a decade ago, they found that the 35 samples they gathered from three different continents all looked remarkably similar to one another. In a larger follow-up study of 59 strains in 2009, the team found much the same – samples from Africa and Colorado looked just like those from California and Queensland ().

More recently, some teams have discovered other strains with clear genetic differences. James has found one in Brazil, details of which are about to be published. (Andrias japonicus). But these strains don’t seem to cause mass die-offs, and may be local ones that have long existed.

Perhaps the clincher comes from a study led by Matthew Fisher, an epidemiologist at Imperial College London. His team sequenced the entire genomes of 20 samples of Bd from around the world. Sixteen of the fungal samples – including all of those taken from regions where swathes of amphibians are dying – were identical ().

So most biologists now agree that the killer is a new strain of Bd that is spreading around the world; Fisher calls it the global panzootic lineage. And it is clear how it is spreading – with the help of people. “I don’t know that anybody doubts that trade is getting this thing from continent to continent, because it doesn’t survive in salt water, and as far as we know there’s no airborne stage. How else would you get from continent to continent except by human means?” says Karen Lips, an ecologist at the University of Maryland in College Park who was among the first to sound the alarm about amphibian declines.

Circumstantial evidence

In particular, many experts point to the trade in two species, the African clawed frog (Xenopus laevis) and the North American bullfrog (Rana catesbeiana). Both are relatively resistant to Bd, so they can carry the fungus around and pass it on to other animals. The clawed frog is used in labs around the world for research (see “Dying to know”), and the bullfrog is grown for meat. Originally restricted to the eastern US, the bullfrog was exported for growing for frog legs and is now found across the world.

The first case of Bd in wild frogs in the UK, in 2004, was in a lake where escaped North American bullfrogs had established a breeding colony. The first known Bd outbreak in Asia is just downstream of a bullfrog farm in the Philippines. This is only circumstantial evidence, of course, but it is nevertheless pretty compelling. Vredenburg is working to make the case even stronger.

Recently, his team developed a way to detect Bd‘s DNA on amphibians preserved in jars on museum shelves. Vredenburg has now begun taking samples from specimens that were preserved before and just after known shipments of clawed frogs and bullfrogs to see whether Bd shows up right after the shipment.

Meanwhile, Fisher’s work suggests that the killer strain of Bd is not the only one being carried around. Of the samples he sequenced, 4 out of 20 did not belong to the killer strain. Of these, one was found only in a pond in Switzerland. The other three samples were identical – yet one of these was from the Cape region of South Africa and two from the Mediterranean island of Mallorca. In 1991, endangered clawed frogs from the Cape (Xenopus gilli) as local midwife toads being bred for release on Mallorca. It seems that this is how the Cape strain of Bd came to be present on the island.

Fortunately, the Cape strain kills only occasionally. “The same animals, if infected with [the global lineage], are all dead within a short time,” says Fisher’s student Rhys Farrer, who has tested its virulence.

So more than one strain of Bd is being spread by the trade in amphibians. Fisher thinks this is significant. “It’s impossible they’re not meeting,” he says. And when different strains meet and mix in places such as airport holding centres or zoos, new hybrids can arise – and fungal hybrids are sometimes far more dangerous than the parent strains.

Fisher thinks this is how the killer strain of Bd came into being. Not only does his team’s analysis point to it being a hybrid, there are also so few genetic differences among the 16 samples he sequenced that it may have arisen within the past century or so – in other words, after the global trade in amphibians began.

Captive frogs could have played yet another role in the emergence of the killer strain. In the wild, natural selection tends to make diseases less virulent, because pathogens that rapidly kill their hosts have less chance of spreading. In crowded conditions, however, evolution favours the nasty. In the high-density environment of aquaria where salamanders are raised for bait, some viruses that infect salamanders have evolved higher virulence, says Andrew Storfer, a population geneticist at Washington State University in Pullman. “The same probably is going on in these bullfrog farms. You might again see artificial selection for higher virulence,” he says, although there is no direct evidence of this with Bd.

So all the clues point to the killer strain of Bd being our very own Frankenstein’s monster. We can say with certainty that the worldwide spread of the strain is due to the trade in amphibians. What’s more, it seems highly likely that we inadvertently created this killer by creating conditions in which different strains could mingle to create hybrids, and also which favoured the most virulent strains.

The case could be closed by finding the two parental strains that gave rise to the killer strain. That could reveal exactly where and how the strain arose. It could also reveal what makes it so nasty, and how some amphibians have evolved tolerance – both of which may yield clues to ways to tame the epidemic. “There are a lot of people swabbing frogs right now,” says Cherie Briggs, an ecologist at the University of California, Santa Barbara.

There are obvious places to look. Amphibians that have been exposed to the parental strains or strain for a long time should be most resistant to the killer lineage. “There hasn’t been a single reported occasion of a mass die-off in [mainland] Asia. Same with Africa,” says Vredenburg. “I think those would be the two most likely areas.”

Nothing has turned up yet. “I’m beginning to think we’re going to have to look quite hard for these putative parental lineages,” says Fisher. In the meantime, if the clues discovered by genetic detectives like Fisher are anything to go by, it is not just the frogs we should be worrying about. We could be spawning other monsters right now, as we spread diseases around the world, give them opportunities to mingle and hybridise, and provide them with crowded farms – and cities – that favour the most virulent.

“We’re seeing a breakdown in global biosecurity that’s having a profound impact on natural environments,” says Fisher. “We’re seeing it in plant systems, we’re seeing it in animal systems, and we’re seeing it in human systems as well. It’s pretty terrifying.”

“We’re seeing a breakdown in global biosecurity that’s having a profound impact on the environment”