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Poisons Ol Ancienl Pem Poisons ol ancienl Pem A climbing plant, a fish, a frog-these natural sources of toxins long known to the early peoples of Peru have already contributed significantly to neurophysiology and the study of nerve impulses by Fernando Cabieses ven before the structure of the Theo in 1907, using curare in inner­ ongm. Even today, when the patient tissues of the nervous system was vated or denervated muscles, J. Langley research of Dermot Taylor and the emi­ Ediscovered, many of the poisons established the basis for the physiology nent botanist Ramon Ferreyra has pro­ present in nature were known to have a of the · motor end-plate, or myoneural duced detailed information on its source neurotoxic action. Sorne of these toxins junction. lt was not until 1936 that H. and preparation, people still daim it is were discovered and put to use by the Dale demonstrated that the production an unknown mixture of various sub­ ancient civilisations of Peru; they were of acetylcholine, which had already been stances of obscure and unexplained ori­ used mainly on the arrows and spears identified as the chemical intermediary gin. This is simply not true. Basically, used for hunting, fishing and warfare. in the end-plate, is not inhibited by curare is an extract from a climbing Their continuous use down to the pre­ plant of the Amazonian region, with sent day, references to them in the 16th the scientific name Chondodendron century chronicles of the Spanish Con­ tomentosum. quest, and their appearance in pre­ The indigenous collectors of this Columbian art are not just a remarkable plant, whose daily efforts are unfortu­ historical and archaeological curiosity; nately contributing to its extinction, they also represent an interesting cul­ fetch from the forest small bundles of tural link between students of the past stems of varying thickness, which they and present-day neurophysiologists. boil in large pans. This extraction by Claude Bernard, the French scientist boiling is not a simple process ; it lasts who is regarded as the creator of mod­ several days, until a smooth, sticky paste ern physiology, deduced that there must is obtained. The paste undergoes a be some connecting organ between The puffer fish-Spheroides spengleri number of tests that have been in use nerve and muscle: a myoneurallink. He -origin of the lethal poison tetrodo­ since time immemorial, and suggest the arrived at this conclusion through his toxin. existence of sophisticated biological investigations into curare, a hunting Photo WHO/F. Cabieses knowledge among the ancient peoples. poison used by the natives of Amazonia. Quality, for example, is determined by In Bernard's experiments, both the the ability of a specified dosage of the nerve fibre and the muscle fibre were curare unless the latter acts after the paste to paralyse a toad in a given time. stimulated at two points, A or B, by an myoneural junction, that is, in the mus­ From the two main types obtainable in electrical current. Normally, stimulation cle receptors themselves. the forest, "calabash curare" ( curare C) at A produces a muscular response al­ Three years la ter, A. Hodgkin and and "pipe curare", modern scientists most identical to that obtained by stimu­ A.F. Huxley took a tremendous step have managed to purify C-curarine and lation at B. Over a century ago, in one of forward by studying electrical potentials tubocurarine, whose use in' modern the earliest attempts to use poisons for and ion exchange in the isolated axon of medicine as a muscle relaxant is well the study of physiology, Bernard proved the squid. From that time onward, known. that under the effect of curare the natural neurotoxins of different origins stimulus at A could not reach the mus­ have been essential for advanced re­ A hundred legends have been woven around cle, even though the muscle remained search on neurophysiology. curare-the poison used on the spears and excitable; thus the discovery was made A great deal has been written about arrows of native hunters and fishermen that the toxin does not cause muscular curare, and a hundred legends have throughout the Amazonian region. problems. been woven around the mystery of its Photo WHO 18 Anyone who eats the offal of the are the same as those shown on N azca puffer fish, especially the liver or roe, pottery. feels a numbness and tingling of the lips, The genera Dendrobates and Phylo­ tangue and cheeks after a few minutes. bates contain a number of species whose This presently becomes complicated by skin produces a secretion regarded as debility and progressive paralysis of all the most patent non-proteinic poison the muscles, vomiting, low blood existing in nature. A small frog two pressure, tachycardia and respiratory centimetres long can provide enough paralysis ; death ensues within half an poison to kill 50' adults. hour. Of all the non-proteinic natural If a fraction of a milligram of the toxin poisons, therefore, the two most effec­ is administered intravenously to a dog, tive are those that were already used within seconds it causes cardio-respirat­ as arrow poisons by the ancient Peru­ Above : The coi-coi, a brightly coloured frog ory death and incapacity of all the used in preparing the most patent non­ vians : one from the puffer fish and one proteinic poison existing in nature. muscles to respond to electrical stimuli. from the frog popularly known as the An extensive series of neuro-phy­ coi-coi-tetrodotoxin and batracotoxin. Below : The same frog figures on the pottery They are fatal in a dosage of one­ of the Nazcas, who knew its useful properties siological experiments initiated by many centuries ago. Fusao Ishihara in 1918 and recently millionth of a gram per kilo gram of body weight. Photo WHO/F. Cabieses completed by Toshio Narahashi, showed that tetrodotoxin mainly and initially Batracotoxin is a steroid which has affects the axon of the motor nerve ; been exhaustively studied by Bernard only at a later stage does it directly Witkop and others. Unlike tetrodotoxin affect the muscle. which is hydrophilic (moisture-absorb­ Today tetrodotoxin, the poison of the ing), batracotoxin is lipophilic (having puffer fish which terrorised the Con­ an affinity for body fats) and acts in the quistadors of Peru, has become a tool opposite way to the former within the for the electro-chemical study of the sodium ion pathway in the axonal mem­ conduction of nerve impulses. lt has brane. Whereas tetrodotoxin blacks the made possible, for instance, the discov­ movement of the sodium ion, batracoto­ ery that the channels for sodium inter­ xin selectively increases the membrane's change in the nerve axon are selective permeability for sodium. The contrast­ and different from the channels for ing action of these two ancient Peruvian potassium. poisons has led to extremely important discoveries concerning the · molecular Poisonous fish physiology of nerves and muscles. Poison from a frog From the earliest days of their explo­ Another small frog which also seems rations in Peru, as comments in contem­ lt has been claimed that the ancient to have been familiar to the N azcas, porary chronicles show, the Spaniards Peruvians so often depicted batrachians Dendrobates histrionicus, also pro­ knew of the existence of an extremely on their finest pottery because, -accord­ duces highly taxie poison used on poisonous fish which, on account of its ing to their primitive polytheism, they arrows by the Amazonian Indians : ability to inflate itself rapidly to a much looked upon the toad as the rain-god. histrionicotoxin. larger size, became known as the "puf­ There is room for speculation here, but lt would be asking too much to take fer fish". Various eighteenth-century the truth is that little or no evidence of the reader into the arid wastes of mol­ sources tell us that people in Japan and this was uncovered by the early Spanish ecular biochemistry, and to describe all European sailors exploring the South missionaries bent on destroying pagan · the neurophysiological conclusions to Pacifie suffered from the highly taxie forms of worship. On the other hand, a which we are being led by the experi­ effects of this fish. The species most number of records mention that the mental use of these poisons as we study common in Peru, Spheroides spengleri, magicians and medicine men of the the generation and transmission of is found in the mangrove swamps of the subjugated culture used frogs and toads nerve impulses. To the alkaloids of cu­ Tumbes area. They are fish of the family for preparing various hallucinogenic or rare, tetr-0dotoxin, batracotoxin and his­ Tetraodontidae, so called because they poisonous potions. trionicotoxin, we can add other natural have four teeth. The family has given A frog painted in different colours poisons from elsewhere in the world its name to the toxin which is the ac­ appears very frequently on Nazca pot­ such as bungarotoxin ( derived from the tive principle for its lethal action: tery. A study of the poisonous frogs still krait snake), saxitoxin (from mussels), tetrodotoxin. valued by Peruvian and Colombian In­ and holothurin (from sea cucumber). As long ago as 1883, Yoshizumi , dians in modern times has led to the Perhaps the most appropriate place for Tahara in Tokyo attempted to isolate identification of two genera of small the motta displayed by the great the pure toxin from this fish, but it was brightly-coloured frogs, which are used Rudolf Virchow at the entrance to his not until 1950 that Akira Y okoo and for preparing very powerful hunting dissecting room would be the neuro­ Kyosuke Tsuda, working independently poisons by various tribal groups, par­ physiology laboratory: Hic mors gaudet of each other, managed to obtain it in ticularly in Colombia and the northern succurrere vitae-" Here death is pleased pure crystal form.
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