Mystic Chemist: The Life of Albert Hofmann and His Discovery of LSD

In the Beginning was the Ergot

Ergot is the name given to the spore, the sclerotium, of the parasitic filamentous fungus Claviceps purpurea which attacks various cereal grains and wild grasses, especially rye. The sclerotium is a black-violet, slightly curved, conical body, a few millimeters to up to six centimeters in length that can develop in place of a pollen grain. The name ergot (Mutterkorn in German) derives from its earlier use as an abortifacient and a midwife’s aid, since the components trigger labor. The ergot of rye, Secale cornutum, is primarily used medically. Depending upon the habitat, host grass, and climate, the fungus contains different ergot alkaloids, for the most part lysergic acid derivatives. It was long used medicinally in many areas of the northern hemisphere.

Ergot first figured in the historical record during the early Middle Ages when it caused the mass poisoning of thousands. The poisoning was caused by consuming bread that, in extreme cases, contained up to twenty percent ergot. Most affected were the poorer classes who ate rye bread in quantity, whereas the wealthier had more wheat at their tables. Epidemics of ergot poisoning occurred in different regions of Europe and North America. St. Anthony was the patron of the sick and the Antonines the order which cared for the afflicted. Because of the terrible effects of ergot poisoning, known as St. Anthony’s Fire or Ergotism, it was deemed to be divine punishment until the true cause was discovered in the 17th century. This knowledge, along with improved planting methods, led to the decline of such epidemics.

The healing effect of ergot was discovered quite early. The first written record of its medical use is found in Herbal, published in 1582 by Frankfurt’s city physician, Adam Lonitzer. He recommends it for labor pains and mentions that ergot extracts have long been used by midwives to promote contraction of the uterus and to speed up birth. In 1907, the English chemists George Barker and Howard Carr isolated an ergot alkaloid mixture that affected the uterus. Because of its toxic side effects, it was named ergotoxine and was never used medically. After 1932, the English gynecologist Chassar Moir used aqueous ergot extracts which strongly affected the uterus.

Albert Hofmann’s superior, Arthur Stoll, began investigating ergot in 1917 and by the following year had succeeded in isolating pure alkaloids of ergotamine. The compound was brought to market in 1921 as Gynergen®. After that, Stoll ended his research in this area.

In 1935, Albert Hofmann was looking for a new project and suggested to Stoll that he resume investigation of ergot alkaloids. Based on what was known about them so far, Hofmann believed things looked promising. His objective was to continue Stoll’s work and develop new medicines out of ergot. Stoll approved, but warned about the difficulty of working with these unstable substances… It was 1938 before Hofmann applied the Curtius Synthesis, a method which enabled him to combine and stabilize lysergic acid with basic groups for further ergot research… Hofmann achieved the first synthesis of a natural ergot alkaloid by combining lysergic acid with propanolamine.

After Stoll’s isolation of ergotamine, this was a further step in ergot research and proved to be of practical as well as scientific importance. This partial synthesis made it possible to convert the other alkaloids in ergot into ergobasine, which was valuable in obstetrics. Hofmann’s method of synthesis became the generally recognized basis for producing a number of related structures from the original ergot alkaloid…

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