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Snakes don't eat fugu, the seafood delicacy prepared from blowfish meat and famed for its poisonous potential. However, should a common garter snake wander into a sushi restaurant, it could fearlessly order a fugu dinner. The snakes have evolved resistance to the blowfish poison, tetrodotoxin (TTX), by preying on rough-skinned newts, which also secrete the toxin. Some newts are so poisonous that they harbor enough TTX to kill a roomful of adult humans. Why would a small animal produce such an excessive amount of poison? The answer lies in the evolutionary back-and-forth between newts and garter snakes. In a new study Charles Hanifin, a postdoctoral scholar at Stanford's Hopkins Marine Station, and his co-authors say that snakes in some areas may have prevailed in the evolutionary arms race between predator and prey.

Most toxic amphibians in the world

Some populations of newts produce enough TTX to kill thousands of mice or 10 to 20 humans. Ounce for ounce, Hanifin said, they are even more toxic than South America's famed poison dart frogs.
"Some populations of these newts may very well represent the most toxic amphibians on the planet," Hanifin said. The poisonous newts have even killed off humans. The Journal of the American Medical Association reports the case of a 29-year-old man who died after swallowing an 8-inch-long newt on a dare. These incidents aside, the newts rarely harm humans. It is safe to handle the newts with bare hands, since the toxin is not absorbed through the skin.

Escaping the arms race

At first glance, the newt and garter snake populations seem to be evenly matched. The most toxic newts are found in the same areas as highly resistant snakes and areas without toxic newts house only non-resistant snakes. Data on the garter snakes came from Hanifin's collaborators, Edmund Brodie Jr. of Utah State University and Edmund Brodie III of the University of Virginia, who measured snake resistance to TTX by injecting the animals with the toxin and measuring how fast they subsequently slithered. To get a closer look at the snake-newt interaction, Hanifin and colleagues tested 383 newts from 28 locations where the Brodies had previously examined garter snake TTX resistance. Hanifin found that snakes were pulling ahead of the newts in several places. In one third of the locations, the most toxic newt could still be eaten by the least resistant snake. This means that all snakes in the population do just as well regardless of their TTX resistance level and there is no evolutionary pressure for the snakes to develop stronger resistance.

Collecting and testing newts

The newts' toxicity means they can afford to be lax about evading rubber-booted researchers and Hanifin caught most of the animals by hand. He said he did not envy the snake collectors, who chased the rapid-slithering animals through grass and underbrush. Future directions of Hanifin's research include learning more about human disease by exploring the genetics of resistant garter snakes. TTX blocks electrical signaling in nerve cells by stopping up a sodium channel and TTX-resistant snakes have a modified channel that the toxin does not recognize. In humans, defects in similar sodium channels can lead to serious illness, including some types of epilepsy and insight into sodium channel biology could help treat these diseases.

Journal reference: Hanifin CT, Brodie ED Jr, Brodie ED III (2008) Phenotypic mismatches reveal escape from arms-race coevolution. PLoS Biol 6(3): e60. doi:10.1371/journal.pbio. 0060060