When Carlos Jared picked up a little frog hiding in the scrublands of the Brazilian Caatinga, he didn’t expect to be hurt.

And he didn’t expect an intense pain radiating up his arm for the next five hours.

A single gram of the toxic secretion would kill more than 300,000 mice or 80 humans

“It took me a long time to realise that the pain had a relationship with the careless collection of these animals,” he recalls.

Now he understands why. The little frog he collected is known as a Greening’s frog  (Corythomantis greening). Its head is covered in deadly spines, and Jared’s research has revealed it is capable of injecting its victims with toxins more potent than those produced by Brazilian pitviper snakes.

Another frog that lives in the rainforest of Brazil, known as Bruno's casque-headed frog, has spines capable of producing venom 25 times more potent than the pitvipers. Calculations by Jared and his colleagues suggest that a single gram of the toxic secretion from a Bruno's casque-headed frog would be enough to kill more than 300,000 mice or about 80 humans.

Frogs have found ways to transmit their toxic skin secretion into the blood of a predator

Both species are the first known frogs to be venomous, scientists report in the journal Current Biology.

Most frogs and toads are poisonous. They sequester distasteful or poisonous compounds, and secrete them onto their skin to deter predators from gulping them down.

For an animal to be considered venomous, it needs to do more than sit around and secrete a bunch of chemicals. It needs to deliver the toxins into the bloodstream of the predator.

Both Greening’s frog and Bruno's casque-headed frog (Aparasphenodon brunoi) do it using a series of killer spines on their head.

These bony spines grow out of the frogs’ skulls, and are rooted in glands that secrete the toxic mucous.

“The fact that frogs have found ways to transmit their toxic skin secretion into the blood stream of a would-be predator is definitely remarkable,” says Egon Heiss from the University of Vienna, Austria, who was not involved in the study.

Amphibian skin toxins are harsh and irritating if they contact the mucous membranes in a predator’s mouth or eyes. But injecting them directly into an enemy’s’ blood stream becomes exponentially more potent, and potentially deadly, he says.

We were astonished at the level of toxicity of these frogs

The chemical composition of secretions from both the species were very similar.

When the frogs’ secretions were analysed, the researchers found hyaluronidase, a protein usually found in venomous snakes. The protein is non-toxic, but aids in the spread of toxins. The presence of hyaluronidase was a clue to the researchers that these species could actually be venomous. This is the first report of the substance from amphibian skin secretions.

“We do not know for sure, but because of the toxins we see, we strongly suspect the frogs produce their own toxin,” says Edmund Brodie, of Utah State University in the US, who led the research into the venomous frogs.

There may even be other more venomous frogs out there

The toxicity of secretions from Bruno's casque-headed frog is a stunning 25 times as much as the toxicity of the venom of the deadly Brazilian pitviper genus, Bothrops. Greening’s frog is not as toxic as A. brunoi, but it is still twice as toxic as the pitviper; on the other hand, it has better developed spines, and larger glands which produce more secretion.

“We were astonished at the level of toxicity of these frogs. I think Carlos is lucky it was C. greeningi that spined him and not A. brunoi,” said Brodie. The researchers also think that there may be predators in the same environment that are resistant to these toxins.

“During all these years that I've lived with this animal in its environment, I’ve never seen any sign of predation or aggression by predators or other aggressors,” said Jared, who is based at the Butantan Institute in São Paulo, Brazil. A predator trying to swallow one of these frogs might be similar to trying to swallow a cacti, he says.

Further, Greening’s frog’s helmet shaped, cactus-like head also mimics the surrounding environment.

These animals have a curious behaviour: they live in holes on rocks or trees, and they close the hole with their body (the head), to maintain humidity inside and reduce water loss from the body.

“The appearance of the top of the head is very similar to the barks of trees, making very difficult for a predator to see them. But in case the disguise is identified, it's almost impossible for the predator to grab the animal by the head trying to pull it out of the hole,” says Jared. The spiny helmet head thus has two uses. Bruno's casque-headed frog lives in holes among bromeliad stems, and also uses its head to keep cool and safe.

There may even be other more venomous frogs out there.

“It is certainly interesting that these frogs have a delivery system for their toxins,” says Jerrold Meinwald, a professor of chemical biology at Cornell University in the US. He thinks we may yet discover other species that inject venom even better than the two frogs just discovered.