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Tetrodotoxin, a Special Once Upon a Word Time Selection!

A powerful poison that is found in two different kinds of animals: puffer fish and newts

Tetrodotoxin is being investigated as a tool in nerve physiology and may be used as an anesthetic





Most of the common local anesthetics block conduction by mechanisms that are less specific than tetrodotoxin

On september 8, 1774, His Majesty's Sloop Resolution, commanded by Captain James Cook, lay at anchor off the South pacific island of New Caledonia, discovered by Cook a few days earlier.

That afternoon the ship's clerk traded with a native for a fish. Captain Cook asked to have the fish prepared for a supper he was to share with the expedition's two naturalists, J.R. Forster and his son Georg.

Later, Cook recorded in his journal: "The operation of describing and drawing took up so much time till it was too late so that only the Liver and Roe was dressed of which the two Mr. Forsters and myself did but just taste. About 3 or 4 o'clock in the Morning we were seized with an extraordinary weakness in all our limbs attended with a numbness or Sensation like to that caused by exposing ones hands or feet to a fire after having been pinched by frost, I had almost lost the sense of feeling nor could I distinguish between light and heavy bodies, a quart pot full of Water and a feather was the same in my hand. . . . In [the morning] one of the Pigs which had eaten the fish intestines was found dead."

Captain Cook's account and the Forsters' description of the fish leave no doubt that the three men had been served a puffer fish. It was fortunate that they ate sparingly, because many puffer fish contain a powerful toxin that can kill a man.

Curiously this toxin, which is now called tetrodotoxin, has also been found in an almost totally unrelated animal, the newt. Recently a number of investigators have become interested in tetrodotoxin's chemical nature and mode of action.

Characteristics and locations of puffer fish

The word tetrodotoxin is derived from the order of fish, tetraodontidae, which means "four-toothed". The fish got this name because they have four strong teeth which almost fuse together to form a beak-like structure. They use this "beak" to crack shells so they can get food, as well as to chew.

At least 40 species of puffer fish are known to be poisonous. Most of them belong to the family Tetraodontidae, but some species in at least three other closely related families are toxic when they are eaten. In puffer fish, tetrodotoxin is most highly concentrated in the ovaries and the liver; smaller amounts are found in the intestines and skin. In some species the muscle tissue is also toxic.

Many different kinds of fish and shellfish are known to be poisonous, and frequently it is difficult to identify the toxin that is responsible. Sometimes poisoning is caused by bacteria in spoiled fish; sometimes it results from one-celled organisms the fish have ingested.

In the latter case, a species may be safe to eat in one season of the year and poisonous in another. Mussels, for example, can be poisonous in the summer because in those months they sometimes ingest and concentrate one-celled dinoflagellates.

Some of these organisms contain saxitoxin, the potent toxin that is responsible for "paralytic shellfish poisoning". By the same token, a species of fish may be safe to eat if it is caught in some places and poisonous if it is caught in others.

In most waters, the red snapper is safe, but around certain islands in the South Pacific, it can cause a form of poisoning called ciguatera.

Puffer fish, on the other hand, are poisonous throughout the year (although the amount of tetrodotoxin in their viscera may vary with the season) and where ever they are caught.

Poisonous puffer fish are found in all the warm seas of the world. Their common names usually refer to their ability to inflate themselves when they are disturbed: puffer fish, swellfish, blowfish, toado, globefish, porcupine fish, and balloonfish.

The functioning of tetrodotoxin and experiments with its potential use as an anesthetic

It has been discovered that the toxin blocks the conduction of nerve signals, and in a highly specific manner. This action has already proven useful in the study of nerve-signal transmissions; it also suggests that tetrodotoxin possibly could serve as a model for valuable new local anesthetics.

The effect of the tetrodotoxin on the functioning of nerve and muscle has been particularly useful in unraveling its mode of action. The technique with which this effect has been explored is essentially a modern version of one used in 1856 by the French physiologist, Claude Bernard, to study the Indian arrow poison curare.


When conduction in a nerve axon is blocked, signals to and from the central nervous system are not transmitted.
—Frederick Fuhrman
 

After a poison is injected into an animal electrical stimulation is applied to a motor-nerve axon, the long fiber that extends from the bodies of nerve cells in the spinal cord to the muscle cells. When an axon associated with the muscle of a limb is stimulated in this way, it causes the muscle to contract just as a normal nerve impulse does.

After the injection of a toxin, however, the muscle may fail to respond to its nerve. In this event, electrical stimulation is applied directly to the muscle. If the muscle then contracts, the site of action of the toxin must be either the axon or the jucntion between nerve and muscle.

After much experimentation, tetrodotoxin is not considered to be a good local anesthetic. One reason is that when tetrodotoxin is injected in the vicinity of a nerve, it does not remain in contact with the nerve tissue but diffuses away.

In addition, it is carried by the blood to other tissues; there it can be toxic and may even cause death.

Workers in several laboratories have undertaken to learn what group of atoms in the tetrodotoxin molecule is responsible for its specific effect on nerve conduction.

If this active group can be identified, it should be possible to synthesize new compounds that have the favorable characteristics of other local anesthetics and that contain the active group of tetrodotoxin.

A special warning about avoiding tetrodotoxin illness and fatalities from the U.S. Centers for Disease Control and Prevention

According to information from the Centers for Disease Control and Prevention in Atlanta, Georgia, U.S.A.:

Although personal importation of fugu into the United States is prohibited, the FDA (Food and Drug Administration) has permitted fugu to be imported and served in Japanese restaurants by certified fugu chefs on special occasions.

A cooperative agreement with the Japanese Ministry of Health and Welfare ensures fugu is properly processed and certified safe for consumption before export by the government of Japan.

If cleaned and dressed properly, the fugu flesh or musculature is edible and considered a delicacy by some people in Japan, who may pay the equivalent of $400 U.S. for one meal.

Despite careful preparation, fugu remains a common cause of fatal food poisoning in Japan, accounting for approximately 50 deaths annually.

Although arriving travelers to the U.S. are required to declare all food products brought into the United States, control measures rely primarily on the traveler. Other food-borne outbreaks in the United States have occurred after consumption of illegally imported food products.

People who travel to countries where fugu is served should be aware of the potential risk to health and/or death resulting from eating this fish.


—Most of the information for this page came from
"Tetrodotoxin" by Frederick A. Fuhrman
Scientific American; August, 1967; pages 61-71.

 
 

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