#061: Ergot of Rye, Claviceps purpurea

Imagine for a moment that it is the late 17^th century and you live in rural America.  Your day starts off like any other day: you wake up, have breakfast, and begin working on your farm.  However, before too long your daughter starts behaving oddly.  At first she just seems agitated, but her symptoms quickly escalate.  She convulses, hides under the table, yells unintelligibly, and complains of a prickly sensation in her arms and legs.  Terrified, you call for the town doctor.  The doctor has never seen a disease like this before and cannot find anything physically wrong with your daughter.  After a while, he comes up with the only possible cause: witchcraft.  Just then, one of your neighbors bursts in, looking for the doctor.  His daughter has been exhibiting the same symptoms!  You look at his frightened face and realize what you have to do: in order to protect the safety of the entire village, you must root out the evil witch at any cost!  Unbeknownst to you, you have just kicked off the most infamous witch hunt in history.

Similar situations surround witch hunts in medieval Europe, but these symptoms didn’t always lead to such a conclusion.  Around the tenth century, there were huge outbreaks of a similar disease, mostly in what is today France and parts of Germany.  Those inflicted suffered from a burning sensation in their extremities as well as from convulsions and hallucinations, though symptoms varied by person and area.  The burning sensation led to the name “Holy Fire” (“Holy” because it was thought to be a punishment from God for some wrongdoing).  In 1039, Gaston de la Valloire set up a hospital dedicated to St. Anthony (the patron saint of lost causes) in order to treat the victims of Holy Fire.  After this, hundreds of hospitals were set up in St. Anthony’s name to treat the disease, which came to be known as “St. Anthony’s Fire.”  Although people who went to the hospitals often recovered, the death rate from the mystery disease could be as high as 40%.  These deaths were caused by secondary infections from gangrene, so those that did survive often lost some of their extremities.

This disease has a very long history: the first record of the disease is possibly from ancient Greece and the most recent outbreak occurred in France in 1957.  Despite the fact that the cause of the disease was known by the twentieth century, the mystery disease baffled doctors and terrorized the town of Pont-St.-Esprit for weeks.  It turns out that unethical business practices obfuscated the disease’s origin.  But more on that later.  For the moment, we’ll go back to 1670 and the discovery of the cause of the disease.  At that time, a French doctor by the name of Thuillier put all the pieces together to figure out what was going on.  Thuillier noticed that the St. Anthony’s Fire did not obey the traditional rules of infectious diseases.  Outbreaks tended to occur in sparsely populated areas and occasionally to those with little contact with other people.  Those living in the cities seemed to be spared of the disease.  He also observed that rich people never contracted the disease.  To Thuillier, these factors indicated that the disease was found in the environment and was not spread from person to person.  After quickly ruling out air, sun, and water (not everyone who drank the same water got the disease), he figured it must be something in their diet.  By recording the food eaten by those affected, he noticed that everyone who contracted the disease had recently eaten rye bread.  Rye tended to be eaten in cool, wet years when wheat did poorly, especially by the poor who could not afford the high price for wheat flour.  This simple observation accounted for the unusual demographics of the disease.  Eventually, he decided that St. Anthony’s Fire must be caused by these funny little growths on some rye crops known to French farmers as “ergots” (named for their resemblance to “spurs” on chicken feet).  These ergots (pronounced “AIR – gots”) were so common on rye that they were included in early botanical drawings as a natural part of the rye plant.  Unfortunately for Thuillier, he could not conclusively prove that the ergots were causing St. Anthony’s Fire and the disease would continue to plague Europe for another two centuries.  The mystery was finally unraveled in 1853 by Louis Tulasne, a mycologist who figured out that the ergots were actually fungal parasites on rye flowers.

The fungus that causes these ergots is Claviceps purpurea (Ascomycota: Sordariomycetes: Hypocreales: Clavicipitaceae).  The fungus can infect cool-season grasses such as rye, fescue, and bluegrass.  When spores land on a flower of a susceptible grass, they germinate and infect the flower’s ovary.  Once the ovary has been colonized, the fungus starts producing asexual spores.  At this point the injured flower starts to exude honeydew, which carries the fungal spores along with it.  Once on the surface of the flower, the spores can be spread to other flowers in three ways: by pollinators who stop by for a taste of the sweet honeydew, by physical contact with a nearby flower, and by splashing raindrops.  In this way, C. purpurea continues to infect flowers as long as they remain open.  After the flowering season ends, the fungus stimulates the plant cells to divide.  This increased cell division results in the long, thin, curved, black structures known as ergots.  The ergots are actually the overwintering stage of the fungus’s life cycle.  They either drop from the plant or are harvested by humans with the rest of the seeds.  In the spring, they germinate and produce perithecia (small, lollipop-shaped structures), which produce and disperse the sexual spores.  The perithecia form during wet weather just before flowering season.  How successful the sexual spores are at infecting new flowers depends largely on how long flowering season lasts.  In years with cool, wet weather, the flowers stay open longer, allowing C. purpurea to infect more flowers.  Europe, especially France and parts of Germany, tends to have these conditions every five to ten years.  This resulted in cyclical outbreaks of St. Anthony’s Fire (now known as ergotism).  But why does eating the ergot cause such a bizarre disease? In order to reproduce, the ergot must be sitting on the surface of the ground in the spring.  The disease cycle ends if the ergot is eaten.  To discourage animals from eating it, C. prupurea produces a variety of mycotoxins.  These toxins have a long history of medicinal use.  Before the true nature of the ergot was understood, ergots were used to induce childbirth or abortions.  Modern science has studied ergots extensively and has found numerous uses for their mycotoxins, including: treatment of migraines, treatment of post-partum hemorrhaging, and treatment of psychological disorders.  The most well-known mycotoxin found in ergots is lysergic acid, which was developed into lysergic acid diethylamide (LSD).  That’s right, LSD is based on a mycotoxin designed to kill things that try to eat the fungus C. purpurea.

Eating Ergot of Rye can cause two types of ergotism: convulsive and gangrenous.  Convulsive ergotism causes the victim to twist and contort their body in pain and is often accompanied by trembling, muscle spasms, confusion, and hallucinations (the last of these is most certainly due to the presence of lysergic acid).  Gangrenous ergotism decreases the blood flow to the victim’s extremities by constricting the blood vessels.  This causes a crawling or burning sensation in the skin and promotes other infections in the extremities.  As with other forms of gangrene, the end result is often the loss of fingers, toes, ear lobes, and/or limbs.  Symptoms vary based on the types and levels of toxins present in each individual ergot as well as each person’s tolerance to those toxins.  Because of this, people with one type of ergotism often have at least some of the symptoms of the other.

C. purpurea does not have much of an impact on the grasses which it infects. The ergot only replaces one grain, but it decreases the host plant’s yield even further because it takes extra resources from the plant. The most significant impact of C. purpurea, however, is through ergotism.  Today, humans rarely get ergotism because of increased safety standards and better cultivation practices.  Crop rotation, plowing (to at least 4cm), and mowing or grazing nearby wild grasses are effective ways of keeping the fungus under control.  When these are not an option, fungicides can be used, although this is often not economical.  The last resort is to drop the grains into a solution of 30% KCl.  The ergots float in this solution and thus can be easily removed from the denser grass seeds.  The development of these practices has prevented any major outbreaks since the 1920’s.  Ergotism is still problematic for livestock, which may unwittingly graze on heavily infected grass.  The notable exception to this rule is the 1951 outbreak of ergotism in Pont-St.-Esprit, France.  In an attempt to cut costs, the village baker, a miller, and a farmer had conspired together to sell bread made from wheat flour mixed with cheap rye.  The strange behavior of the villagers in August was not immediately linked to ergotism because the bread was supposedly wheat.  Since then, the fungus’s main impact on society has been through the various drugs it has given us.  However, it still continues to capture the human imagination.  C. purpurea has been featured in episodes from the TV shows “Quincy, M.E.” and “The X-Files,” has inspired Robin Cook’s novel, Acceptable Risk, and has provided a name for a 90’s Australian rock band (“The Ergot Derivative”).

So how do we know that C. purpurea is responsible for various witch hunts?  A lot of the evidence is circumstantial but compelling.  Those investigating the link must rely heavily on local records of diseases and witch trials, which are often biased and inaccurate.  To complicate matters, the symptoms of ergotism vary and could also be explained by other diseases or mental illnesses.  However, there are other lines of evidence that can help clear up the matter.   C. purpurea does particularly well in years that are cold and wet.  Wheat does poorly in those conditions, so the price of rye goes up because wheat is scarce and rye has a higher demand.  Local records show that the price of rye often increases during years characterized by St. Anthony’s Fire or witch hunts.  Additional evidence for cool, wet weather can be found in tree rings.  From this analysis, it becomes clear that some witch hunts had nothing to do with C. purpurea.  These were likely driven by individuals who wanted to get revenge on a neighbor.  Although this evidence is by no means conclusive, it does provide a compelling argument for the events surrounding Salem in 1691-92.  Linda R. Caporael (1976) and Mary K. Matossian (1989) have argued that the weather during the period of the Salem Witch Trials and crops grown in Pennsylvania at that time would have encouraged the formation of ergots.  Of course, it is impossible to know exactly what happened in 1961.  I think the most likely explanation is that convulsive ergotism was responsible for the initial cases, but a culture of anger and suspicion perpetuated the symptoms.

This type of analysis has also indicated that C. purpurea had a role in a number of other historical events.  For one, the disease may have had a role in the downfall of the Holy Roman Empire and the creation of France and Germany.  A group of Scandinavians (Northmen/Vikings) had the good fortune of attacking the Holy Roman Empire shortly after it had suffered an epidemic of Holy Fire.  They managed to settle in Normandy and continued to harass the Holy Roman Empire.  Because of recurring epidemics of Holy Fire (the Northmen were “immune” as they did not eat rye) and dwindling resources, the Holy Roman Empire was forced to break apart around 887 CE.  Another possible impact of ergotism relates to the curious aftermath of the Bubonic Plague.  After the height of the plague had passed (around 1350), the population of Europe did not return to pre-plague levels.  One explanation for this puzzling phenomenon is the cool, wet weather that followed.  This could have increased C. purpurea infections on rye, which in turn would increase cases of ergotism.  Ergotism can cause abortions in pregnant women, which could account for the mysteriously depressed population numbers.  Ergotism is also apparently responsible for Peter the Great’s failure to conquer Constantinople in 1722.  His troops were stopped at the Volga River – long before he reached Constantinople – by ergot poisoning that sickened both his men and his horses.  Of course, we can’t forget that C. purpurea gave us LSD, a drug which had a significant impact on Western culture in the 1960’s and 70’s (especially among the hippie circles).  This small, unassuming fungus probably ranks second only to Baker’s Yeast in terms of its impact on human history.

See Further:

http://botit.botany.wisc.edu/toms_fungi/oct99.html

http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM

http://www.apsnet.org/edcenter/intropp/lessons/fungi/ascomycetes/Pages/Ergot.aspx

http://www.agriculture.gov.sk.ca/ergot-of-cereal-grasses

http://www.botgard.ucla.edu/html/botanytextbooks/economicbotany/Claviceps/

http://www.chm.bris.ac.uk/motm/lsd/lsd1_text.htm