Ergot sclerotia on wheat

1. Ergot sclerotia on wheat

2. History of ergotism • Rye was not cultivated until the 5th century AD. • Ergot prefers to infect rye flowers. • Ergotism was widespread during the Middle Ages, since rye grows easily even in poor soils. • The first historically documented outbreak of ergotism was in 857 AD in the Rhine valley. • Ergot grows best in a damp climate like that in Germany or Northern France. • Ergot was so common that it was called “Holy Fire”.

3. History of ergotism • An order of monks was founded just to take care of ergotism sufferers, the Order of St. Anthony's. • Ergotism became known at “St. Anthony's Fire”. • Dr. Thuiller in 1670 was the first to recognize that the disease was caused by ergot. • Dr. Louis Tulasne showed in 1853 that ergot was a fungus that infected rye and caused the disease.

4. The symptoms of ergotism • Convulsive ergotism results in severe twisting of the body and neck in pain, together with shaking and trembling. • Gangrenous ergotism causes constriction of the blood flow in the extremities, which results in burning pain. • Fingers and toes die and they can even break off or drop off. • Both convulsive and gangrenous ergotism can be associated with vivid hallucinations, physical and mental excitement, and disorientation. • All forms of ergotism have a relatively high mortality rate.

5. The life cycle of ergot • After the winter, the sclerotia sprout to produce mushroom-shaped stroma, which release spores, in the spring. • These spores infect rye flowers to form asexual spore-forming spacelia, which in turn release spores. • Bees then transfer the spores to other rye flowers, and these spores grow eventually to reform the sclerotia. • This is an example of “alternation of generations”.

6. Ergotism and the Salem Witch Trials • Ergotism may have caused the Salem Witch Trials—Linda Caporeal. • In December 1691, a number of girls in Salem, including the daughter of the minister, Samuel Parris, developed unusual behaviors, including convulsions, odd postures and strange gestures. • They accused several women of being witches. • The girls did not improve, and eventually more than 100 people were accused and imprisoned. • Twenty people were executed as witches. • The remainder were eventually released.

7. Ergotism and the Salem Witch Trials • The summer of 1691 was especially wet. • Most people in Salem grew rye as a staple crop. • The symptoms developed as soon as the rye crop was used. • The affected girls were from families who had the wettest fields. • As soon as a new rye crop was used, the symptoms disappeared.

8. The last outbreak of ergotism • The most recent outbreak of ergotism may have occurred at Pont-St.-Esprit, France in 1951. • Hundreds of townspeople suddenly developed strange symptoms, including intense pain, complaints of feeling cold, and dementia, accompanied by vivid hallucinations. • The doctors found that wheat bread was the common food item. • It may have been mixed with contaminated rye flour. • It has been recently suggested that the CIA poisoned the townspeople with LSD.

9. Pont-St.-Esprit

10. Animals also get ergotism • Tall fescue, a pasture grass for grazing cattle, can be infested with a fungal endophyte. • Animals that eat infected grass can develop vasoconstriction and gangrene in ears and hooves. • Afflicted animals do not eat and gain weight, causing economic loss to farmers.

11. Chemistry of ergot • Chemists were very interested in the components of ergot. • Ergotamine was isolated in 1918 by Arthur Stoll. • Ergotamine was found to be a derivative of lysergic acid (lysis ergot ic acid) by Jacobs and Craig at Rockefeller. • Albert Hoffman started working on lysergic acid derivatives at Sandoz in the 1930's. • He prepared ergonovine as a hemostatic drug for obstetrics.

12. O N N O O C H H N O H 3 C H C H 3 3 O N O N H H N N H H Ergotamine D-lysergic acid Chemistry of ergot

13. Chemistry of ergot • Hoffman prepared a series of lysergic acid derivatives to evaluate their activity. • Lysergic acid diethylamide (Lyserg-Saure-Diäthylamid in German, or LSD) was the 25th derivative. • In 1943, after handling LSD-25, Hoffman noticed he felt odd for several hours. • The next day, he purposefully ingested 250 μg of LSD to determine if the compound caused the effects.

14. Chemistry of ergot • Hoffman felt very strong effects and decided to ride his bicycle home. • He called the doctor, thinking he was dying. • The doctor found only that his pupils were dilated but he was otherwise normal. • After a few hours, the effects subsided. • Sandoz began to market LSD as an aid for psychotherapy. • In 1965, they took it off the market due to negative publicity.

15. O H H N N H N 2 C H C H C H 3 3 3 O N O N O N H H H N N N H H H Ergonovine LSA-11 LSD-25 Chemistry of ergot

16. Ergot and headaches • Hoffman prepared other lysergic acid derivatives with activity against migraine headaches. • Methysergide is a serotonin antagonist which is prophylactic for migraines. • Dihydroergotamine can be taken after a migraine has started. • LSD has also been reported by users to relieve migraine and cluster headaches, and is under investigation now.

17. O H O H H N H N C H C H 3 O N 3 O N H H N N H C H 3 Methergine Methysergide Ergot and headaches

18. Triptans for headache treatment • Serotonin antagonists are useful to treat migraine headaches. • A class of serotonin antagonists has been designed to treat migraines—triptans. • Sumatriptan (Imitrex) was the first triptan to be developed.

19. H N N N O N H S O O O S H N O 2 N N N H H H Eletriptan (Relpax) Sumatriptan (Imitrex) Frovatriptan (Frova) Triptans