In literature and alchemy the salamander is a fabled creature. Salamanders have long been known to be toxic animals, the poisons they produce usually being associated with secretions of specialized glands or of the skin itself. An extraordinarily powerful neurotoxin, called tarichatoxin, has recently been isolated in crystalline form from the eggs of various species of western American newts of the genus Taricha. This toxin, present in adult newts as well as in newt eggs and embryos, is very different chemically and pharmacologically from other known salamander toxins. This makes all the more remarkable the finding, in recent work, that tarichatoxin is identical to a toxin known as tetrodotoxin which occurs in the Japanese Fugu or puffer fish. The substance appears to occur only in one family of Amphibia (the Salamandridae) and one suborder of fishes (the Tetraodontoidae). This extremely limited distribution is a remarkable biogenetic finding.Here we discuss the course of the investigations which led to the isolation of the toxin from the California newt, the history of tetrodotoxin, the evidence, both physical and physiological, which points to the conclusion that tarichatoxin and tetrodotoxin are one and the same substance, and the deductions which can be made concerning the chemical structure of the toxin. Tarichatoxin Discovery and history. In the early 1930's Victor C. Twitty, an experimental embryologist, came to Stanford University from Yale. At New Haven he had worked with the eastern salamander, Ambystoma punctatum, and at 1100 Dr. Mosher is professor of chemistry, Dr. Fuhrman is professor of experimental medicine, and Drs. Buchwald and Fischer are research associates in chemistry at

A~STRACT Tarichatoxin, isolated from California newt eggs, has been found to selectively block the increase of sodium conductance associated with excitation in lobster giant axons at nanomolar concentrations. This resulted from a reduction in the amplitude of the conductance increase rather than a change in its temporal characteristics. The normal potassium conductance increase with depolarization is not altered. A high concentration of calcium applied concomitantly with the toxin significantly improves the reversibility of the sodium blocking. This toxin has recently been identified as chemically identical with tetrodotoxin from the puffer fish. Toxins from the two sources are equally effective and are shown to have an action which is distinctly different from that of procaine.