ERGOTISM In 1976 psychologist Linda Caporael proposed a novel explanation for the peculiar behavior that led to charges of witchcraft in 17th Century Salem Village. She suggested that those who displayed symptoms of "bewitchment" in 1692 were actually suffering from the disease known as ergotism. The source of the problem, ergot, comes from the fungus Claviceps purpurea which usually grows on rye. Caporael's proposal met with criticism by Spanos and Gottlieb in 1976 and support from Matossian in 1982, and it also prompted a renewed interest in ergotism. Claviceps purpurea is an ascomycete whose mycelium invades and destroys the ovaries of the rye plant and other grasses, causing disease in the host plant and in so doing producing alkaloids that are deadly to humans and livestock if consumed. The fungus also provides useful chemicals. Ergotism probably represents the first human mycotoxicosis to be recognized. Poisoning through the ingestion of infected grains was observed by the ancient Greeks and Romans, but epidemics of major proportions with thousands of deaths are associated with Europe of the Middle Ages, particularly France. It was not until the mid-sixteenth century that the etiology of ergotism was established and the disease associated with the fungus on the grain. In spring, about the time that certain susceptible grasses such as rye are in bloom, threadlike ascospores are forcibly discharged from the perithecium of the fungus. If the ascospores, which are disseminated by the wind, reach the flower of a rye plant or other suitable host, they germinate sending tubes into the flower's ovary. As the mycelium develops, it destroys the ovary tissues and replaces them in the flower with a soft, cottony mass that soon becomes covered by layers of short conidiophores bearing minute, oval conidia on their tips. These conidia are mixed with a sticky, sweet, nectar-like secretion. Attracted by this nectar, insects visit the infected ovary and distribute the conidia to uninfected plants thus spreading the fungus. In the meantime, the mycelial mass which produced the conidiophores continues to develop, begins to harden, and is eventually transformed into a hard, pink or purple sclerotium which surrounds the grain and exceeds it in length. The grains appear as though they were baked and darkened by the sun. This sclerotium is the ergot. Substances in the sclerotium responsible for ergot poisoning were isolated and chemically identified in the 1930s. The pharmacologically active substances were shown to be alkaloids which are acid amide derivatives of D-lysergic acid. The toxicological and physiological effects of ergot are due to ergotamine and alkaloids of the ergot-oxine group (ergocornine, ergocryptine and ergocristine). These drugs are so useful that rye and wheat fields are artificially inoculated in Europe and elsewhere to increase sclerotial production. This is particularly true in Portugal where ergot production is a valuable source of income. Ergot alkaloids are smooth muscle stimulants and cause vasoconstriction. The also cause uterine contractions in late pregnancy (oxytocic effect). Ergot alkaloids have also been shown to produce neurohormonal effects such as serotonin antagonism and the reversal of both the stimulatory and inhibitory actions of epinephrine (adrenergic blockage). Additionally, these compounds promote central nervous system effects by interacting with the medulla oblongata and the brainstem to produce symptoms such as bradycardia (abnormal slowness of the pulse), vomiting, inhibition of the vasomotor activities, hyperthermia, hyperglycemia, and hyperreflexia. Wild rye occurred naturally as a weed in fields of wheat, and as the wheat was harvesting soErgotism - Page 2 also was the rye. The rye was discovered to be a more reliable crop under cool, moist conditions, and it tended to supplant wheat where such conditions prevailed. The cultivation of rye also allowed the increasing human population to utilize wet areas that had previously been unproductive. Needless to say, the intensified use of rye led to a simultaneous increase in ergotism. It became customary during the Middle Ages for millers to clean the grain and separate it into two piles, one good and one ergoty. The ergot-free grain was used for bread for the nobility and clergy and the rest was left for the peasants. The result was described in 857: "A great plague of swollen blisters consumed the people by a loathsome rot." The condition came to be known as "Saint Anthony's fire" or "holy fire." Depending upon the concentration of the ergot consumed, even relatively small doses over a period of weeks can result in a variety of miseries. In some of the epidemics that occurred in France and Germany hundreds of years ago, bread was found to contain by actual measure 2-15% ergot. The Canadian Department of Agriculture, by comparison, has established a maximum limit (tolerance) of 0.1% in animal feed sold in Canada. Some feel that even this limit may be too high for safety. Ergotism comes in two forms, gangrenous and convulsive. Livestock may develop gangrenous ergotism by grazing on infected grasses or in fields where sclerotia have fallen off during harvesting. Their legs, hooves, and tails become gangrenous, and cows may abort their calves. [This property of aborting fetuses appears to have been part of the knowledge of midwifery and folk-medicine generally since ancient times.] It develops with an onset of lassitude, muscular pains, and prickly sensations in the limbs. The affected limbs become swollen, inflamed, and subject to sensations of intense heat and cold (postischemic inflammation), which is followed by necrosis, gangrene, and sloughing off of limbs without bleeding. This form of the disease predominated in central Europe from the 9th to the 14th century and in France and Germany during the 1770s. Gangrenous ergotism in humans may include violent pains for twenty-four hours or more. The gangrene itself may set in suddenly with spontaneous separation at a joint without pain or loss of blood. One account describes a woman riding to a hospital on an ass when she was pushed against a shrub. Her leg became detached at the knee without any bleeding, and she carried it to the hospital in her arms. The convulsive form of ergotism is characterized by involvement of the central nervous system. The symptoms of early and mild convulsive ergotism