--Hal, from 2001, discusses the year 2000 problem. Outstanding Apple quicktime movie!
The vivdly-colored poison dart frogs make up one of the most feared families of the animal kingdom. Although very small, sometimes only as large as a thumb, these amphibians are some of the most poisonous animals that inhabit Earth. One species, Phyllobates terribilis, has enough toxin in its skin to kill up to 20,000 mice, or ten humans. (Heselhaus 29) While other organisms have learned to avoid these tiny frogs, humans have learned to use these frogs for both survival and medicine.
Poison dart frogs, also called poison-arrow frogs or simply poison frogs, belong to the Dendrobatidae family. This family is split into four genera: Epipedobates, Colostethus, Dendrobataes, and Phyllobates. Recent studies have included additional genera, Allobates and Minyobates, however these hew divisions have not been officially accepted as a divison of the Dendrobatidae family. (Summers 6227) While each genera has general distinctions, there are many intraspecific differences, including coloration, habitat, and behavior. Colostethus is also known as the “false poison frog” because it is the least toxic, if at all, of the amphibians. (Heselhaus 13) Phyllobates, on the other hand, is the most toxic genus. Phyllobates terribilis is the most toxic animal on Earth. Simply touching it may potentially cause death.
Poison frogs would be easily overlooked if it weren’t for their vivid colors. These amphibians are very small, ranging in size from a half inch to three inches, many only the size of a thumb. (Moffett 100) Although the miniature-sized frogs appear to be helpless, they rarely have to worry about an encounter with a predator, as they exhibit aposematic coloration. Their brightly colored skin serves as a warning to potential predators, a coloration pattern characteristic of venomous and toxic animals. The basic dorsal color of Dendrobatidae is red, orange, green, blue, or black. The ventral color may be yellow, red, white, or blue, while the limbs are frequently black. In addition, the body may be unicolored, spotted, or speckled. (Daly 970) The intensity of the color, however, is not reflective of the toxicity of the organism. For example, the most toxic species, Phyllobate teribili, is an unassuming yellow while the slightly poisonous Dendrobates silverstonei is an intense red. (Heselhaus 29)
Poison frogs are a Neotropical family, living in the warm and humid rain forests of South and Central America. The frogs live in a variety of environments within the Neotropics, with differences ranging in altitude and proximity to water. While all frog species require water to reproduce, some remain near the water for their entire life span while others only return to small ponds during mating season. (Heselhaus 13) The majority of the Dendrobatidae species live in the valleys, however some inhabit the cooler mountainous forests. Yet others reside in the dryer areas, relying on shade from low vegetation to keep the gound moist. (Heselhaus 13) Dendrobates quitquevittatus is a unique species, as it has acquired flattened fingertips that act as “suckers,” allowing the organism to stick to leaves and trees. It makes its home high in the trees, up to four meters high, and relies on the ponds in water-filled leafy funnels of bromeliad plants. (Heselhaus 34) The geographical distribution is more species specific, as many individual species are isolated to small locations within the Neotropics. Phyllobates terribilis, for example, is isolated to a small area around the Rio Saija in western Columbia. (Heselhaus 90) Other species, such as Dendrobates pumilio, also known as the strawberry poison frog, lives in extended regions throughout Central and South America.
Coloration and toxicity are not the only factors that make poison frogs a unique frog family. Their parental behavior is unique in that they continue to care for their young tadpoles while most frogs abandon the eggs shortly after they are deposited in a body of water. (Heselhaus 36). After a poison frog’s eggs are deposited, the female guards her batch until they hatch. In most species, the male then carries the tadpoles on his back to a safer pool of water. In Dendrobates pumilio it is the female that transports her offspring to pools of water in the leaves of certain plants. ( Moffett 107) After the transportation is complete, the parental care of poison frogs is usually over. In the strawberry poison frog, however, the female returns to the tadpoles every few days to provide unfertilized eggs as nourishment. (Moffett 109) In addition, the tadpoles are scattered around the habitat to increase the odds of survival, since the tadpoles lack the toxic substances used for defense by the mature frogs. (Moffett 109) As a result of this necessity for plenty of space to separate their offspring, poison frogs are territorial organisms. The males will aggressively defend their territory. Keeping two males in the same environment in captivity sometimes will result in the death of one of the frogs, as they try to defend their territory. (Heselhaus 32) These behavioral tendencies demonstrate the intelligence of poison frogs, as they have adapted the common frog’s behavior to ensure the survival of their unique species.
Dendrobatidae is perhaps one of the most toxic families of organisms, as its species include some of the most poisonous animals known to man. A poison is any substance that produces disease conditions, tissue injury, or otherwise interrupts natural life processes when in contact with the body. Toxins are poisonous substances produced by living creatures, including amphibians, bacteria, insects, plants, and reptiles. (Plotkin 6) Although the chemicals and toxins vary among the different species, they are all used for a single reason: survival. Some simply produce a bitter taste, some cause a burning sensation, and a few are potent enough to kill a predator, including humans. (Adamson) The toxins are stored in granular glands below the frog’s skin and are released when the animal feels threatened or stressed. The glands are dispersed among mucous glands and are distributed over the entire surface of the frog’s skin. (Heselhaus 30) The chemicals are afferent, having the ability to affect a nearby predator. Snakes that mistakenly attempt to eat these frogs have been seen to bury their open mouths in the dirt in an attempt to decrease the unpleasant taste or burning sensation. (Adamson)
The most potent toxin of the Dendrobatidae family is batrachotoxin, produced only by the Phyllobates species. Batrachotoxin is a steroidal alkaloid toxin, and the most potent of all naturally occurring nonprotein poisons know for vertebrates. (Bartram 810) It is a strong cardio- and neurotoxin, which results in irreversible depolarization of nerves and muscles. The nervous system functions via depolarization and polarization of ion channels, which sends signals to tell the organs and skeletal muscles to contract or relax. An irreversible depolarization will cause the muscles to lose the ability to relax, resulting in a permanently excited state. (Karp 172) This can have detrimental affects, including paralysis and death, with death occurring form muscular and respiratory paralysis. (Heselhaus 31) The minimal lethal dose of batrachotoxin when injected into mice is about 0.05 microgram per kilogram of the mouse’s weight. (Patocka) A single Phyllobates terribilis produces about 1100 micrograms of batrachotoxin, which is enough poison to kill over 20,000 mice. The anticipated lethal dose of batrachotoxin for humans is only 2.0 to 7.5 micrograms when administered by injection. (Patocka) Observed symptoms of mice injected with the toxin included locomotor difficulty with partial paralysis of the hind limbs, salivation, convulsions, and finally death. (Daly 970)
Another group of toxins, pumiliotoxins, occur in all species of Dendrobates and Phyllobates. The pumiliotoxins classes A and B are the second most toxic class of alkaloids produced by the poison frogs. (Summers 6229) Although the specific action of the pumiliotoxins is unknown, it probably involves calcium and sodium-dependent processes in nerve and skeletal muscle mechanisms. (Patocka) Sodium and calcium are ions that control the activation and depolarization of nerve cells, which ultimately results in the sending of electrical signals by the nervous system and in muscle contraction. (Karp 166) An injection of one hundred grams in mice caused locomotor difficulties, partial paralysis of the hind limbs, salivation, extensor movements, and clonic convulsions and death in lest than ten minutes. (Patrocka)
An important question in recent studies has been that of toxin origin. Recent studies have demonstrated that some species of poison frogs accumulate and sequester some of their toxins from dietary sources. (Summers 6230) This is most evident by the differences in toxicity levels between native and captive frogs. Frogs in captivity lose their toxicity, and it was found that a difference in diet played a role. Dednrobatid frogs raised on a diet of insects from forest leaf litter continued to accumulate toxins in their skins, while those raised on fruit flies did not. (Summers 6230) Their natural diet includes ants, beetles, and small millipedes, which are all possible sources of the alkaloids that are the basis of the toxins. Genetic differences are likely to control the ability of a species’ ability to accumulate specific toxins, as Phyllobates contain batrachotoxins while Dendrobates do not. (Summers 6231) Differences in synthetic abilities are also probably genetic in origin, as some compounds isolated from the toxins are not found in the frogs’ dietary sources. (Summers 6231)
While many people enjoy keeping these beautiful animals as pets in terrariums, native tribes of Columbia have been using poison frogs for a more practical use. The Choco tribe learned to use the toxins produced by Phyllobates terribilis, Phyllobates aurotaenia, and Phyllobates bicolor for poisoning their blowgun darts. (Bartram 810) They catch the frogs and then keep them in a piece of hollow sugar cane until they are needed. When they are ready to prepare the darts, they impale the frog with a sharp stick, causing it to produce a white foam that the most effective toxins produced by the frog. The Indians dip the tips of their darts into the foam, which then retain their lethal properties for a year. (Heselhaus 30) The southern Chaco Indians learned how to collect the batrachotoxins of Phyllobates terribilis without causing harm to the animal. Instead of impaling it, they simply pass the arrowhead along the back of a live specimen. The frogs are so highly toxic that the simple contact is sufficient. (Heselhaus 30) The natives then use these darts to hunt for food. When an animal is impaled with the toxin-covered arrow, the toxin causes paralysis followed by death in the prey. Oral contact with these toxins does not cause death in humans, so the natives can eat the animals caught with their darts without risk of being effected by the poison. (Patocka)
Recently, we have learned how to utilize the toxin of Epipedobates tricolor for medicinal purposes. In 1974, John Daly discovered that epibatidine, extract from the skin of this frog, blocked pain in rats more effectively than morphine. (Cameron) This new finding resulted in research to reduce the toxicity of the extract in an attempt to make it safe for human use. With new technology twenty-five years after the discovery of epibatidine, the structure of the toxin was analyzed using nuclear magnetic resonance and gas chromatography-infrared spectroscopy. (Plotkin 5) The structure was found to be similar to that of nicotine, which blocks pain by targeting acetylcholine receptors. Daly and his colleagues began synthesizing compounds with structures similar to epibatidine, hoping that one would retain the pain-killing effects but lack the toxicity of the natural toxin. (Plotkin 6) After hundreds of molecules were devised and tested, Abbott Laboratories selected ABT-594 for further testing. Its structure resembles both nicotine and epibatidine and proved effective against several types of pain. (Cameron) It even blocked against pain caused by a nerve damage, for which opiates such as morphine are ineffective. (Plotkin 6) In addition to its unparalleled pain-killing properties, ABT-594 did not cause the serious side effects of morphine, such as lung depression, constipation, and physical dependence. (Cameron) With increasing improvements in technology, the pharmaceutical industry will continue to advance, and may even include new compounds isolated from other poison frog toxins.
Vividly colored, the species of Dendrobatidae are a fascinating group of animals. Despite its miniscule size the poison frog is one of the most lethal organisms known, some having to ability to kill thousands of mice. One genus even contains the most potent naturally occurring toxin. Its geographical distribution stretches across the Neotropics through Central and South America, with habitat detail specific to each particular species. The poison frogs are rapidly losing their habitats, as deforestation of the tropical forests is increasing. (Adamson) More species of poison frogs are becoming extinct as sections of forest are destroyed, and with the extinction of these animals we also lose the potential for new medicines.
1. Adamson, Andrew. “Turning to poison-dart frogs to save lives.” Accessed via the web address http://ww.exn.ca/Stories/1998/05/22/57.asp Viewed May 7, 2003.
2. Bartram, Stefan and Boland, Wilhelm. “Chemistry and Ecology of Toxic Birds.” Chembiochem. 2 (2001): 809-811
3. Cameron, John and Brawley, Kathleen. “ABT-594.” Accessed via the web address http://www.abdn.ac.uk/chemistry/abt/ Viewed May 4, 2003.
4. Clough, M. and Summers, K. “Phylogenetic systematics and Biogeography of the poison frogs: evidence from mitochondrial DNA sequences.” Accessed via the web address http://core.ecu.edu/biol/summersk/summerwebpage/Research/PoisonFrogPhylogeny/PoisonFrogPhylogeny.htm Viewed May 7, 2003.
5. Daly, John W. and Myers, Charles W. “Toxicity of Panamanian Poison Frogs (Dendrobates): Some Biological and Chemical Aspects.” Science. 156 (1967): 970-973
6. Karp, Gerald. Cell and Molecular Biology. 3rd ed. New York: John Wiley & Sons, Inc., 2002.
7. Moffett, Mark W. “Poison-Dart Frogs: Lurid and Lethal.” National Geographic. May 1995: 98-111
8. Patrocka, Jiri, et al. “Dart Poison Frogs and Their Toxins.” The ASA Newsletter. 1999. Accessed via the web address http://www.asanltr.com/ASANews-99/995frogs.htm Viewed May 4, 2003
9. Plotkin, Mark J. Medicine Quest. New York: Viking Penguin, 2000.
10. Summers, Kyle and Clough, Mark E. “The evolution of coloration and toxicity in the poison frog family (Dendrobatidae).” PNAS. 98 (2001): 6227-6232.
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