Saturday, October 31, 2009

The Biochemistry of Halloween: Installment II

Mothers and fathers watched the shriveled toes of a poor beggar swing from the gallows. They placed their faith in God that the death of this unfortunate person might take away the torment, fits, and visions  that plagued their children. That somehow through supernatural forces the sensations of ants crawling underneath skin, delusions of bursting into flames, and frenzied shrieks of terror in the night would cease. As the the seasons brought new harvests the number of swinging bodies dwindled. But bouts of bewitchment would visit the same locales for centuries.

This was a typical scene in the medieval villages that lined the dank Rhône and Rhine River valleys following the seam of modern-day Germany and France south through Switzerland to the Italian boarder. Here and in other curiously coincidental micro-climates all over Europe something dark and treacherous lurked in the fields.

During the cold, wet growing seasons a deep maroon colored fungus Claviceps purpurea reared its ugly sclerotium amongst the ears of rye. Looking much like the rooster's spur the killer was given the french name - erogot. When rye was milled the flour could contain up to 30% ergot by dry weight. And so it goes that the biochemistry of bewitchment had its origins under the millstones of fifteenth century Europe.
During this age the peasantry ate an enormous proportion of the darker cheaper rye bread; upwards of three pounds a day. As the alkaloids synthesized by the ergot made their way into the blood and brains of those apparently seized by demons, the unaffected were left to assume they had been bewitched. The linguistic fossil preserved in the very word - seizure - describes the uncontrolled fits the affected displayed. A condition known at the time as "St Anthony's fire"  (aka Ignis Sacer) did not become known as ergotism until 1853 when the clinical connection to the mycotoxins was finally made.

Mycotoxins contained in ergot infested rye caused two distinct varieties of ergotism. These toxins are known as the ergot alkaloids and the two classes each have separate physiological effects - gangrenous or convulsive ergotism. Ergotamine, a powerful vaso-constrictor preventing blood flow to the extremities, is the main culprit in gangrenous ergotism.  Whereas ergine and lysergic acid hydroxyethylamide cause convulsive ergotism. These lysergic acid compounds have 10% the activity of the infamous psychoactive drug -LSD.  Both LSD and the ergot alkaloids induce hallucinations by a similar and yet poorly understood mechanism.  Structurally similar to serotonin these compounds bind serotonin receptors in the brain. It is not known how this induces hallucinations but it is thought that agonist activity to serotonin releases higher concentrations of the neurotransmitter glutamate in the brain's cortex exciting neurons in random ways.  This would explain the varied psychological effects reported by individuals under the influence of this class of drugs.

By their activity these compounds were known long before their chemical makeup was uncovered. Ergotamine had been used for nearly two centuries in midwifery to stop hemorrhaging after birth and also to induce abortion. In the first half of the 20th century the other ergot alkaloids were probed for other uses such as blood pressure and migraine treatments.  A young chemist named Albert Hofmann working for Sandoz pharmacueitcal company in Basel, Switzerland literally stumbled across LSD while performing organic synthesis of ergot alkaloids.  His wild bicycle ride is a story of scientific lore worthy of its own post.

But here we are focused on the science behind medieval bewitching. The connection between ergotism and witch trials was first proposed by Linda Caporael in 1976 where she hypothesized in the Journal Science that Ergot could have been the real world cause of the supposedly supernatural events that transpired in the village of Salem, Massachusetts in 1692.  
In her paper  Caporael outlines the evidence for convulsive ergotism being the scourge that set off the string of hangings accompanying the infamous witch trials.  Mainly she points out that the symptoms of ergotism, -spasms, the sensation of ants crawling under skin, and the feeling of being disemboweled - were all recorded by the court clerk when taking the testimony of the affected teenage accusers.  Indeed the very fact that the accusers were female and in their teens also implicates ergotism as these are the most susceptible individuals in any community where there is an outbreak.  Lastly, she turns to the geographic distribution of the bewitchment. Here she reconstructs a map of Salem village where she hypothesizes that a contamination of grain grown on the eastern bank of the Wolleston river could have been the only source of ergot and still affected all the families involved.
Less than a year after her paper was published skeptical scientists came in to refute her claims.  Spanos and Gottlieb assert that Caporael is incorrect in her hypothesis and they give several reasons. They  report that more towns people should have shown signs of convulsive  ergotism, that the afflicted girls did not testify to to having exactly the same kind of symptoms expected form classic ergotism, and that the town most likely did not have a vitamin A deficiency that normally accompanies convulsive over gangrenous ergotism.  Reading these rebuttals there is no hard evidence in either direction.

Despite this  disagreement Caporael's work inspired Mary Matossian to conduct further investigations into the possible connection between witch trials and ergotism outbreaks throughout the middle ages up until the 19th century.  In her book Poisons of the Past Matossian lays out an incredibly convincing argument that outbreaks of ergotism indeed correlate to increased incidence of witch trials.  She explains how tree ring data taken by x-ray measurements of tree ring density compiled for every year from 1269 - 1977 C.E. can be compared to an annual index of number of witch trials with statistical correlation in southwestern Germany and the Swiss alps. 
Years where the growing season was cool and wet correspond to thicker tree rings and therefore seasons in which the amount of fungus growing amongst the rye was high.  These long wet seasons directly preceded autumns with more witch trials. Like the medieval trials the Salem affair was also preceded by two years of unusually cold spring weather. Though there is evidence for a connection between ergot and witch trials in both Salem and the multitude of trials that took place in Europe throughout the middle ages, evidence is stronger for the later. In 2000 Alan Wolf writing from the Harvard Medical School further put the cabash on the Salem ergotism hypothesis.  But if Carporeal had never posed the question the work of Matossian may never have been conducted.

Further evidence for medieval outbreaks of both gangrenous and convulsive ergotism in Europe during the 16th century can be taken from a contemporary reporter.  Transcending language and centuries the oil paintings of Pieter Bruegel the Elder give us an unusually clear window into recent human history.  In the ergot alkaloid figure above a painting titled "the beggars" depicts peasants in what is now Belgium in the mid 1500's begging for food with stubs for limbs.  Considering the geography and timing of these depictions it is not difficult to imagine that these poor souls are suffering from gangrenous ergotism.  Following his brush further we see in the 1562 painting below the story of Dull Gret or "Mad Meg" as she is known in English.  Leading a band of paranoid peasant women she storms the gates of hell, armed with cooking utensils, fearful that Spanish soldiers will pillage her village.   "Mad Meg" of Flemish folklore may be under the influence of lysergic acid compounds found in Ergot!

When the imagery of Bruegel is conjured into mind one can't help but wonder if generations of creative medieval  minds weren't  unwittingly dosed with background levels of the psycoactive components of Ergot.

As samhain approaches it would do us good to contemplate the possibility that some of the most infamous characters of all hallows eve my indeed have had very real biochemical origins.

I would like to thank Nick Clark for our many discussions and collaboration on this topic and George Hudler for his kind advice and additional references.

Caporael, L. (1976). Ergotism: the satan loosed in Salem? Science, 192 (4234), 21-26 DOI: 10.1126/science.769159  

Schweingruber, Fritz H., BrÄker, Otto U. & SchÄr, Ernst (1979). Dendroclimatic studies on conifers from central Europe and Great Britain Boreas, 8, 427-452  

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