Neither rye nor reason

Steve Ainsworth explores the origins of the compound ergot, which in modern times became a source for pharmaceutical drugs.

According to the Book of Exodus ‘Thou shalt not suffer a witch to live’. Yet it’s always been a little tricky trying to distinguish between witches and warlocks from bona fide dispensers of pills, potions, amulets and incantations. Only a little more than a decade ago an Egyptian pharmacist working in Saudi Arabia found himself languishing in jail charged with sorcery.

Mustafa Ibrahim was accused of practicing magic. Evidence of witchcraft was allegedly found at his home, including books on magic, a candle with an incantation on it used ‘to summon devils’, and ‘foul-smelling herbs’.

Being a pharmacist was ever a risky profession. The original Greek form of the word, ‘pharmakeutes’, signified the vendor of any kind of drug, potion or spell, and hence also implied poison and witchcraft.

But how might one tell if an apothecary, herbalist or druggist is a witch? Easy. Throw him or her into a river, and if they don’t sink then their guilt is self-evident.

Helpfully, for folk worried about witchcraft, one of the first books ever printed using the newly invented printing press was a handbook on how to identify and torture confessions of witchcraft.

Hammer of Witches

Malleus Maleficarum (The Hammer of the Witches) was written by two German monks, Jacobus Sprenger and Heinrich Kramer, in 1486. Over the next 300 years its advice would help the authorities identify and condemn to death thousands of men and women in both Europe and America.

Infamously in Salem, Massachusetts in January 1692 three girls began blaspheming, having convulsions and falling into trances. A doctor who examined them easily diagnosed such an obvious case of witchcraft. Best practice suggested that a witch-cake should be baked using the girls’ urine as part of the recipe. Eating the cake would enable the girls to identify who had bewitched them. And so they did.

They named Tituba, an Indian slave and two of their neighbours, Sarah Good and Sarah Osborne. Tituba quickly confessed to practising witchcraft. And there was more: she admitted that there was a whole coven of witches in the town.

The two Sarahs, however, maintained their innocence, not that it did either of them any good: Sarah Good was hanged and Sarah Osborne died in prison. Yet the witchcraft didn’t stop. More people came forward to claim they were bewitched. It had to be stamped out. By the year’s end some 20 ‘witches’ had been executed.

But what was really going on? A plausible explanation is that the witch-induced ‘demonic possession’ was simply a result of eating rye bread infected with the fungus claviceps purpurea, better known as ergot. The fungus is a storehouse of compounds that in modern times became useful as a source of pharmaceutical drugs. The species was the original source of the chemical precursor to the hallucinogenic drug LSD.

The symptoms of convulsive ergotism are nervous dysfunction, trembling and shaking, convulsions and fits. Muscle spasms, confusion, delusions and hallucinations may also be experienced. Gangrenous ergotism may lead to the loss of the extremities. In very severe cases entire limbs may be lost.

‘Holy Fire’

The first description of an outbreak of gangrenous ergotism was in the Rhine Valley in 857 A.D. The disease was given the name ‘Holy Fire’ because of the burning sensations felt in the extremities, and Holy because of a belief that it was a punishment from God. A later outbreak of Holy Fire occurred in France in 1039. During that outbreak, a hospital dedicated to St. Anthony was built to care for the victims. ‘Holy Fire’ was now renamed ‘St. Anthony’s Fire’.

Six hundred years later a French physician named Thuillier theorised that St Anthony’s Fire might be due to eating rye infected with ergot.

Noting that small amounts of ergot of rye were used by midwives and wise women to hasten childbirth, Thuiller theorised that it might be toxic if swallowed in larger quantities. Unhappily no one took much notice of Thuiller’s speculations.

There were still outbreaks of ergotism in the 20th century: 10,000 cases occurred in Russia in 1926-27, and 200 in England that same year.

At the start of the 20th century ergot was still little used clinically, except to promote postpartum involution of the uterus. In 1906 and 1918, however, two active alkaloids of ergot, ergotoxine and ergotamine, were isolated.

In 1935 J Chassar Moir, Professor of Obstetrics at the University of Oxford, succeeded in synthesising ergometrine. Ergometrine contracted the uterus and blood vessels, and significantly reduced haemorrhages. Moir later wrote that his synthesised drug ‘surpassed by great measure the activity of any drug which I had previously used in the same manner...In one case only four minutes elapsed between the swallowing of the extract and the onset of powerful uterine contractions’.

Numerous ergot-based drugs were subsequently developed. Yet ergot has since begun to fall out of favour. In 2013, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended restricting the use of medicines containing ergot derivatives since the risks were deemed greater than the benefits.

Witchcraft too has long since fallen out of favour, mostly. Mutafa Ibrahim, the Egyptian pharmacist accused of sorcery, was found guilty and executed in November 2007.

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