Wisconsin Sea Grant: Frogs
From Medieval Magic to Modern Medicine

reprinted with permission from the Shedd Aquarium

When Shakespeare's witches stirred their stew of "Eye of newt, and toe of frog," in the fourth act of Macbeth, they were using folk knowledge nearly as old and widespread as humankind: Amphibians are strong medicine.

Traditional Chinese medicine treats heart ailments with a powder made of dried toad toxin that acts in the same way as digitalis to strengthen heart contractions. The Choco Indians of Colombia recognized the toxic properties of the brightly colored little frogs hopping around the rainforest floor, using them to make poison blowdarts for hunting. South American Indians knew other species of frogs had healing properties in their skin secretions and rubbed the animals across cuts and wounds.

On the other hand, European traditions attributed everything from warts to witchcraft to toads and their kin. The Western world's revulsion of these amphibians was epitomized by the sentiments of Carolus Linnaeus, the 18th-century Swedish taxonomist: "These foul and loathsome animals are abhorrent because of their cold body, pale color, cartilaginous skeleton, filthy skin, fierce aspect, calculating eye, offensive smell, harsh voice, squalid habitation, and terrible venom...."

In the last 30 years, scientists in the United States and elsewhere have discovered in the "venoms" (actually skin secretions) of a variety of frog and toad species hundreds of chemical compounds that could redefine the concept of "miracle drugs" - everything from potent painkillers to potential treatments for the most deadly cancers.

It's in the skin

All frogs and toads have two types of glands in their skin. The mucous glands, which occur all over the body, continuously secrete a clear, viscous - or slimy - coating that keeps the animal moist and enables it to absorb both water and oxygen through its permeable skin. The granular, or poison, glands are distributed across the body, often with the heaviest concentration around the head or neck, where a frog or toad is most likely to be grabbed by a predator.

The granular glands are among frogs' and toads' most important defense mechanisms, along with escape and camouflage. When activated by stress or injury, the glands secrete a milky substance that varies by species from slightly noxious to extraordinarily toxic. The ooze also has antimicrobial properties that combat bacteria, fungi and parasites that might find moist skin an inviting environment.

The granular-gland secretions make frog skin a veritable pharmacopoeia, with some of the best pharmaceutical promise found among the most potently toxic frogs. Batrachotoxin, unique to Phyllobates frogs - among the most toxic creatures in the animal kingdom - is a particularly powerful steroid-like alkaloid that behaves in a unique, lightning-fast way. Batrachotoxin introduced into an animal's bloodstream via a poisoned blowdart immediately halts all nerve and muscle function, causing cardiac arrest.

Research into the way this toxin works clarified to scientists how electrical messages are transmitted across the nervous system. Discovery of the sodium channels may lead to insights into severe neurological disorders such as Lou Gehrig's disease.

Not all frogs being studied are toxic. Little African clawed frogs (Xenopus laevis) are as much a staple in research labs as white mice, as well as being popular pets. A few years ago, a researcher noticed that his lab frogs quickly recovered from a surgical procedure even though they were returned to their aquariums without treatment. His scientific curiosity aroused, he discovered that the frogs' skin secretes a remarkable antimicrobial compound that disinfects everything it touches.

The secret of the secretion is a peptide, one of a family of small proteins that kill bacteria by rupturing their cell membranes. Potential applications of a synthetic derivative of the peptide, named magainin, seem to be limitless, from a plaque-fighting toothpaste additive to a nontoxic glue for human organ surgery. Among the most exciting possibilities are drugs to treat ovarian cancer and malignant melanoma, the deadliest form of skin cancer.

These pharmaceutical discoveries have occurred at the same time that many frog and toad species are jeopardized by habitat destruction, particularly tropical rain forest species. All Dendrobates and Phyllobates species are classified as threatened. Scientists are concerned that other species harboring chemicals with the potential of epibatidine or magainin will disappear before they can be studied - or perhaps even before they are discovered.

Australia's gastric brooding frog (Rheobatrachus silus) offered hope to people suffering from stomach ulcers. Discovered only in 1973, the species' females confounded zoologists by swallowing their fertilized eggs and incubating them in their stomachs. While the tadpoles were developing, the females did not eat and somehow shut off the production of gastric acids. The tiny froglets "hatched" by being spit up. Researchers speculated that whatever function enabled the frogs to brood their young without digesting them might have applications in treating stomach ailments.

In the spring of 1980, as researchers pursued the mysteries of the species' digestive mechanisms, the gastric brooders and another frog native to the same area did not make their annual appearance in the streams to breed. They have not been seen since and apparently are extinct. The search for a new medicine came to a dead end.

- article copyright the Shedd Aquarium

copyright 2001 University of Wisconsin Sea Grant Institute