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Amphibian Skin: Toxic Chemicals to Medical Marvels

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Illustration by Adelaide Tyrol

I was eating breakfast when I noticed a black duck quietly feeding on our small pond. It would occasionally “tip-up” — head underwater, tail skyward — in typical puddle duck fashion. Suddenly, the peaceful scene was interrupted as the duck began spinning wildly in circles, one wing flapping frantically as water splashed in all directions. Ten seconds later and just as suddenly, all was calm, including the duck, which was now floating belly-up. I searched for signs of an underwater predator, perhaps an otter or the Loch Ness Monster, but saw nothing. A little shocked, I carefully fished the duck out and brought it to the office where a colleague and I conducted a quick necropsy. Not really expecting any answers, we were quite surprised when we opened the gizzard and found it stuffed with at least a dozen undigested adult eastern newts. I was aware that newt skin contained toxins, but wondered if it was potent enough to kill a 3-pound duck so quickly.

At first glance, amphibians appear rather defenseless. Most are quite small, move relatively slowly, lack any protective armor or claws, and have tiny teeth that are incapable of providing meaningful defense. However, all amphibians have glands that, in addition to keeping their skin moist and improving respiration, also cause them to be slippery. While this in itself can aid in defense, they also have glands that produce toxic secretions, the potency of which is highly variable, ranging from distasteful, to a mild irritant, to deadly. In the case of the eastern newt (as well as all North American newts), it’s deadly.

Newts contain a powerful poison called tarichatoxin, which is biochemically very similar to tetrodotoxin, or TTX, found in pufferfish. A highly potent neurotoxin, TTX is the most poisonous non-protein substance known to science. Once it enters the bloodstream, TTX acts quickly by blocking the conduction of nerve signals to the muscles, causing blood vessels to relax, leading to a sudden drop in blood pressure. Basically, the toxin blocks the signals from your brain that tell your heart to beat and your lungs to breathe. There have been several cases of human poisoning from newts, including at least one death, but ordinary handling is not dangerous, as the poison must enter the digestive tract or the bloodstream. The bright orange, immature, terrestrial stage of the eastern newt, known as the red eft, contains ten times as much TTX as the drab-colored adults.

In many cases, it’s not the potency of the toxic secretion, but the stickiness or disagreeable taste that provides the amphibian with an opportunity to escape a potential predator. In many salamanders, including the spotted and Jefferson salamanders, poison glands are concentrated in the tail. When a predator is encountered, salamanders assume a defensive posture, often elevating or “waggling” their tail toward the attacker, while a sticky, whitish substance is secreted. If the predator “takes the bait” and gets a mouthful of noxious salamander “goo,” it often decides to seek more palatable prey elsewhere.

In most of our local frog species, including the American bullfrog, green, mink, and wood frogs, poison glands are uniformly distributed over the entire skin surface. While the toxicity of the secretions is relatively mild in these species, it is apparently distasteful to some mammals and birds.

Toads in the genus Bufo, on the other hand, including the widespread American toad, have poison glands concentrated in “warts” on their backs, and in two large paratoid glands behind their eyes. When grabbed by a predator (including dogs and cats), the paratoid glands release a whitish, foamy secretion consisting of three substances: bufogenin and bufotoxin — which affect the adrenal and cardiovascular systems — and bufotenin, an alkaloid which is a powerful hallucinogen also found in some mushrooms. In most cases, the toad is quickly released due to the repulsive taste of the toxins. Then, for the next several hours, as a lingering reminder of the encounter, the predator is left with a variety of symptoms — including salivation, nausea, vomiting, heart arrhythmia, and hallucinations. If an entire toad is ingested, the symptoms range from convulsive seizures, to paralysis, neurological disorders, and even death.

Amphibian secretions are not all bad, however. More than 200 chemical toxins considered to be beneficial in medical research have been isolated from just a small percentage of the world’s amphibian species. One alkaloid produced by a tropical poison dart frog is a highly effective painkiller, 200 times stronger than morphine without being addictive. Skin secretions from the Australian green treefrog stimulate activity in the human pancreas and intestine, and commercial drugs are now available based on these compounds. Some amphibian skin secretions, like those of the African clawed frog, also have powerful antibiotic properties that help heal cuts and bruises, which may provide doctors with a whole new class of antibiotics in the years ahead.

Discussion *

Oct 31, 2011

Hi Rock,
Thanks for your comment.  It would be fascinating to know how those experiments turned out—any effect on the frogs?

Steve Faccio
Oct 31, 2011

Hi Kit,
Thanks, I’m glad you enjoyed the article.  To the best of my knowledge, wading birds don’t have any special adaptations for dealing with amphibian toxins. But, as I mentioned in the article, skin secretions from frogs are not very toxic, just distasteful apparently (I haven’t tried them myself!).  Toads on the other hand, are presumably avoided by experienced wading birds, since eating one would make them quite sick.  Many snakes however (including Garter and Hognose snakes) appear to be immune to most amphibian toxins, including those from American Toad.  However, when garter snakes were experimentally fed tropical poison arrow frogs (Dendrobates spp.) they had convulsions and one individual died.  Seems like a pretty clear indication that some snakes evolved with certain amphibians.

Steve Faccio
Oct 21, 2011

Nice reminder, Steve, of 40 years ago when I was doing research at UB Med school with TTX and one of its cousins BTX.  In a bit of turn about, we were exposing frog skin to TTX and BTX, both in live specimens and in isolated frog skin chambers, to explore the impact on the short circuit current.

Rock Termini
Oct 21, 2011

Steve,

I enjoyed the article on the toxicity of amphibian skin.  Since many wading birds and some snakes eat toads and frogs, do they have a way of neutralizing the effects of the secreted skin chemicals?

kit hood

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