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