Ergot sclerotia on wheat
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”.
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.
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.
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”.
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.
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.
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.
Pont-St.-Esprit
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.
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.
Chemistry of ergot
O
N
N
O
HN
O
O
CH3
OH
N
CH3
H
N
H
Ergotamine
O
N
CH3
H
N
H
D-lysergic acid
Chemistry of ergot
Hoffman prepared a series of lysergic acid
derivatives to evaluate their activity.
Lysergic acid diethylamide (Lyserg-SaureDiäthylamid 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.
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.
Chemistry of ergot
HN
O
OH
N
CH3
H
N
H
Ergonovine
NH2
O
N
N
CH3
H
N
H
LSA-11
O
N
CH3
H
N
H
LSD-25
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.
Ergot and headaches
HN
O
OH
HN
N
CH 3
H
N
H
O
OH
N
CH 3
H
N
CH3
Methergine
Methysergide
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.
Triptans
N
NH
O
H
N
N
O S
O
O
S
H2N
O
N
H
Sumatriptan (Imitrex)
N
H
Eletriptan (Relpax)
N
H
Frovatriptan (Frova)