Ergotism – Man… why are they called “fingers”? I’ve never seen them fing. Oh, there they go.

1951, France: A Frenchman living amidst financial strife is fantastically excited when he gets his hands on flour that he can use to make some bread and feed his family with. The blackened rye flour is a disgusting grey colour but the bread tastes good and that’s all that matters. Over the next few weeks he and his family are struck down with disabling pain in the arms and legs. The father’s pain eventually recedes, but his finger turns black and falls off.

1024, England: A woman is giving birth. Midwives gather around. It looks to be going too slowly for their liking. They give the sweaty, agonised woman a preparation. Contractions are faster now. Grunting, groaning, calls to push. A stillbirth. It is a sad day.

1983, California: Kary Mullis is a biochemist. He is also stoned out of his mind on LSD. Inspiration hits amidst the Egyptians building pyramids and the butterflies of cassette tape ribbons. He has solved it. He has invented and developed polymerase chain reaction, or PCR. This technique will change the world: it will win him the 1993 Nobel Prize for Medicine, it will allow scientists to see unculturable bacteria and viruses for the first time, it will prosecute criminals through DNA fingerprinting… Sitting back and enjoying the ride, Dr. Kary Mullis remains unaware of the implications until on more solid ground.

PCR is now done in these babies (Pictured: Mr. Temperature Gradient and Mrs. Occasional Screwy Temperature Sensor, picture taken by Thomas Tu)

What connects these three stories?

Ergotism

Ergotism is caused by eating a fungus (called Claviceps purpurea) or drugs made from it. C. purpurea grows preferentially on rye, but is also known to grow on wheat. It surreptitiously replaces a seed of the plant (what we call the grain) with a germinating body. This body is black and has been described as looking like a cock-spur, also known as an ergot, thus the name. Usually that germinating body falls to the ground, then produces spores that are blown into the wind. Once it infects a new crop plant, it is excreted out of flowers in a milky “honeydew”. This honeydew blackens and hardens to produce another germinating body. Ergotism occurs when people eat this body.

Epidemic ergotism occurs where rye forms a staple diet, particularly uncooked or uncleaned. During the Middle Ages, this was Germany, France, Russia, and other places around the Rhine. Nowadays, ergotism is a rare disease, but still Russia and Somalia both had outbreaks in 1926 and 1977 respectively. More common now is ergotism due to taking drugs extracted from ergot.

How did they know that they had ergotism though? Upon eating contaminated rye (usually in the form of flour or rye bread), you would feel vaguely ill, maybe a bit nauseated or with some diarrhoea. Suddenly, your legs and arms would feel like ants were crawling over them and they would begin to ache or burn. From there, there were two different outcomes: convulsive ergotism or gangrenous ergotism.

Convulsive ergotism had the patient experience mainly neurological symptoms: you’d be ridiculously happy or sad, become drowsy, have leg or arm twitching, sweat profusely, experience hallucinations and so forth. Your muscles could cramp up so badly that you’d be forced into a ball from minutes to hours at a time. These attacks would recur over weeks or months and you’d feel inexplicably hungry between attacks.

More worrying was gangrenous ergotism: severe debilitating pains would crush your hands and/or legs for days to months. You would cease to feel a pulse in your limbs and they’d be a pasty white. Finally the pain would let up, but the limb would be numb. Slowly your fingers and toes turn black and fall off without pain or bleeding. There have also been reports of these effects in the face and legs as well.

On drugs and toxins

Ergot has carries toxins and these are what produce these horrific symptoms (I’ll explain how further below), but, in spite of this, has been used to produce drugs. To see why, we have to look at the body and its communication system. Many chemicals (e.g. hormones, neurotransmitters, carbon dioxide) in the body bind to receptors. Receptors are the radio receivers of a cell: they are the way that organs and cells in your body listen to other organs, cells or the external environment. Hormones and neurotransmitters are the radio system of the body; you send one signal so that the cells that are tuned right frequency (i.e. have the right receptor) can carry out orders based on that information. Drugs mimic those radio messages so that the body does what we want it to do. Toxins are the same radio messages but the changes they produce are things that we don’t want happening.

A lot of drugs are synthesised from fungus and plants. There’s only so many ways you can assemble small molecules with a limited Lego set (carbon, nitrogen, hydrogen, oxygen, the blocks of life), so somewhere along the line, there’s going to be some chemicals in plants or fungi that are only slightly different from the chemicals in your body.

The similarities means that it can bind to receptors in the body and alter the normal functioning of it. The slight differences means different things depending on the change: it could inactivate the receptor, it could activate the receptor for much longer than the natural chemical, it could be a lot harder to get rid of in the body and stick around for a long long time, it could activate some only a subset of receptors that recognise the natural chemical… Small differences make big impacts in a complex system such as the body.

We haven't had a picture of Indy in a while, so here's one for no reason at all. (Picture taken by Lael Woodham, I hope she doesn't mind)

Medical uses

One of the effects that ergot was known to have was it could speed up childbirth. Some chemicals extracted from ergot look like the body’s hormones that make your uterus contract. And so ergot extracts were given to women in labour during the Middle Ages to induce contractions and were used as standard medical practice in the early 19th century. They were eventually abandoned because they discovered that the strong uterine contractions would increase the risk of stillbirth.

Later on in 1918, a chemical named “ergotamine” was discovered and extracted from ergot. This was a known vasoconstrictor, a chemical that closes off blood vessels. Now, I’ve talked about blood vessels before and described them as sort of a plumbing system. Well, turns out instead of valves and shunts to alter the flow of blood, the pipes themselves shrink or open up. There are muscles around some blood vessels that tighten to slow down blood flow or relax to speed it up. If you’re cold, your body reacts by closing the vessels that lead to your skin, meaning less blood is exchanging heat with the outside, thus you stay warmer. Ergotamine does the same thing, but you don’t have to be cold. It just mimics the signal for the vessels leading to your head, arms and legs to close. People ended up taking this medication for migraines. It stopped excessive blood from rushing to the head, and relieved the symptoms of migraines.

What people may not have realised is that this is one of the compounds that caused gangrenous ergotism. People in the past had eaten so much rotten rye and ergot that they were filled to the brim with ergotamine. This closed down the blood vessels leading to the arms and legs, so much that the muscles would not get enough nutrients and just started dying, eventually falling off altogether. Indeed, people have overdosed on ergotamine and found themselves with arms and legs that have started to fall off. They usually caught these cases before any permanent harm was done.

Another famous drug extracted from ergot is lysergic acid diethylamide, otherwise known as LSD. Its famous hallucinatory effects were first discovered by Albert Hofmann (whose story I won’t get into, but is amazing, you should look it up) and indeed was named by Kary Mullis to be his inspiration for inventing PCR. LSD is probably one of the compounds that contribute to convulsive ergotism. It does this by mimicking several types of neurotransmitters in the brain. But, despite ergot producing all these frightful effects, LSD is one of the most non-toxic drugs known to man. 25-75 nanograms of LSD has an effect in most people, but people have taken 1000000 times that dose and have still lived. Indeed not a single case of death has been reported from LSD overdose alone, although permanent psychosis has been reported.

So, medical drugs and toxins, while they invoke different images of Good and Bad in our minds, are really very similar and can even be the same physical thing. In nature, there is nothing that is intrinsically good or bad for us. We just have to look at what happens to us when we take them and see if it benefits us in our own personal contexts.

TT

Sources

http://cardiovascres.oxfordjournals.org/content/33/1/23.full

http://ang.sagepub.com/cgi/reprint/52/5/349

http://www.ncbi.nlm.nih.gov/pubmed/12849122

1951, France: A Frenchman living amidst financial strife is fantastically excited when he gets his hands on flour that he can use to make some bread and feed his family with. The blackened rye flour is a disgusting grey colour but the bread tastes good and that’s all that matters. Over the next few weeks he and his family are struck down with disabling pain in the arms and legs. The father’s pain eventually recedes, but his finger turns black and falls off.

1024, England: A woman is giving birth. Midwives gather around. It looks to be going too slowly for their liking. They give the sweaty, agonised woman a preparation. Contractions are faster now. Grunting, groaning, calls to push. A stillbirth. It is a sad day.

1983, California: Kary Mullis is a biochemist. He is also stoned out of his mind on LSD. Inspiration hits amidst the Egyptians building pyramids and the butterflies of cassette tape ribbons. He has solved it. He has invented and developed polymerase chain reaction, or PCR. This technique will change the world: it will win him the 1993 Nobel Prize for Medicine, it will allow scientists to see unculturable bacteria and viruses for the first time, it will prosecute criminals through DNA fingerprinting… Sitting back and enjoying the ride, Dr. Kary Mullis remains unaware of the implications until on more solid ground.

What connects these three stories?

Ergotism

Ergotism is caused by eating a fungus (called Claviceps purpurea) or drugs made from it. C. purpurea grows preferentially on rye, but is also known to grow on wheat. It surreptitiously replaces a seed of the plant (what we call the grain) with a germinating body. This body is black and has been described as looking like a cock-spur, also known as an ergot, thus the name. Usually that germinating body falls to the ground, then produces spores that are blown into the wind. Once it infects a new crop plant, it is excreted out of flowers in a milky “honeydew”. This honeydew blackens and hardens to produce another germinating body. Ergotism occurs when people eat this body.

Epidemic ergotism occurs where rye forms a staple diet, particularly uncooked or uncleaned. During the Middle Ages, this was Germany, France, Russia, and other places around the Rhine. Nowadays, ergotism is a rare disease, but still Russia and Somalia both had outbreaks in 1926 and 1977 respectively. More common now is ergotism due to taking drugs extracted from ergot.

How did they know that they had ergotism though? Upon eating contaminated rye (usually in the form of flour or rye bread), you would feel vaguely ill, maybe a bit nauseated or with some diarrhoea. Suddenly, your legs and arms would feel like ants were crawling over them and they would begin to ache or burn. From there, there were two different outcomes: convulsive ergotism or gangrenous ergotism.

Convulsive ergotism had the patient experience mainly neurological symptoms: you’d be ridiculously happy or sad, become drowsy, have leg or arm twitching, sweat profusely, experience hallucinations and so forth. Your muscles could cramp up so badly that you’d be forced into a ball from minutes to hours at a time. These attacks would recur over weeks or months and you’d feel inexplicably hungry between attacks.

More worrying was gangrenous ergotism: severe debilitating pains would crush your hands and/or legs for days to months. You would cease to feel a pulse in your limbs and they’d be a pasty white. Finally the pain would let up, but the limb would be numb. Slowly your fingers and toes turn black and fall off without pain or bleeding. There have also been reports of these effects in the face and legs as well.

On drugs and toxins

Ergot has carries toxins and these are what produce these horrific symptoms (I’ll explain how further below), but, in spite of this, has been used to produce drugs. To see why, we have to look at the body and its communication system. Many chemicals (e.g. hormones, neurotransmitters, carbon dioxide) in the body bind to receptors. Receptors are the radio receivers of a cell: they are the way that organs and cells in your body listen to other organs, cells or the external environment. Hormones and neurotransmitters are the radio system of the body; you send one signal so that the cells that are tuned right frequency (i.e. have the right receptor) can carry out orders based on that information. Drugs mimic those radio messages so that the body does what we want it to do. Toxins are the same radio messages but the changes they produce are things that we don’t want happening.

A lot of drugs are synthesised from fungus and plants. There’s only so many ways you can assemble small molecules with a limited Lego set (carbon, nitrogen, hydrogen, oxygen, the blocks of life), so somewhere along the line, there’s going to be some chemicals in plants or fungi that are only slightly different from the chemicals in your body.

The similarities means that it can bind to receptors in the body and alter the normal functioning of it. The slight differences means different things depending on the change: it could inactivate the receptor, it could activate the receptor for much longer than the natural chemical, it could be a lot harder to get rid of in the body and stick around for a long long time, it could activate some only a subset of receptors that recognise the natural chemical… Small differences make big impacts in a complex system such as the body.

Medical uses

One of the effects that ergot was known to have was it could speed up childbirth. Some chemicals extracted from ergot look like the body’s hormones that make your uterus contract. And so ergot extracts were given to women in labour during the Middle Ages to induce contractions and were used as standard medical practice in the early 19th century. They were eventually abandoned because they discovered that the strong uterine contractions would increase the risk of stillbirth.

Later on in 1918, a chemical named “ergotamine” was discovered and extracted from ergot. This was a known vasoconstrictor, a chemical that closes off blood vessels. Now, I’ve talked about blood vessels before and described them as sort of a plumbing system. Well, turns out instead of valves and shunts to alter the flow of blood, the pipes themselves shrink or open up. There are muscles around some blood vessels that tighten to slow down blood flow or relax to speed it up. If you’re cold, your body reacts by closing the vessels that lead to your skin, meaning less blood is exchanging heat with the outside, thus you stay warmer. Ergotamine does the same thing, but you don’t have to be cold. It just mimics the signal for the vessels leading to your head, arms and legs to close. People ended up taking this medication for migraines. It stopped excessive blood from rushing to the head, and relieved the symptoms of migraines.

What people may not have realised is that this is one of the compounds that caused gangrenous ergotism. People in the past had eaten so much rotten rye and ergot that they were filled to the brim with ergotamine. This closed down the blood vessels leading to the arms and legs, so much that the muscles would not get enough nutrients and just started dying, eventually falling off altogether. Indeed, people have overdosed on ergotamine and found themselves with arms and legs that have started to fall off. They usually caught these cases before any permanent harm was done.

Another famous drug extracted from ergot is lysergic acid diethylamide, otherwise known as LSD. Its famous hallucinatory effects were first discovered by Albert Hoffman (whose story I won’t get into, but is amazing, you should look it up) and indeed was named by Kary Mullis to be his inspiration for inventing PCR. LSD is probably one of the compounds that contribute to convulsive ergotism. It does this by mimicking several types of neurotransmitters in the brain. But, despite ergot producing all these frightful effects, LSD is one of the most non-toxic drugs known to man. 25-75 nanograms of LSD has an effect in most people, but people have taken 1000000 times that dose and have still lived. Indeed not a single case of death has been reported from LSD overdose alone, although I’m not sure their mental status was in the greatest of shapes.

So, medical drugs and toxins, while they invoke different images of Good and Bad in our minds, are really very similar and can even be the same physical thing. In nature, there is nothing that is intrinsically good or bad for us. We just have to look at what happens to us when we take them and see if it benefits us in our own personal contexts.

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5 Comments

Filed under Thomas' Corner

5 responses to “Ergotism – Man… why are they called “fingers”? I’ve never seen them fing. Oh, there they go.

  1. murfomurf

    I’m glad you did a blog on ergotism- it’s interested me since I was a school kid. I thought the way ergotamine worked for migraines was in taking down the swelling in the blood vessel walls (I assume by making the little muscles there contract and thus lose their blood volume). Then I thought the lumen opened and the little muscles stopped pressing on the pain nerve-ends. Anyway- that’s what I imagined happening when I took it for migraines from about the age of 13 to 30- I could feel the congestion in the blood vessels of my face and sinuses subside and my cheeks and ears would cool down in parallel- and the gold-danged painnnnn would go away if I was lucky! It would also give me cramps in the large muscles furthest from my heart- forearms and calves, plus freezing cold hands and feet; also some weird visual effects and crazy dreams. Once I tried acid (LSD) at uni I could see the similarity and wasn’t all that thrilled. By the way, I used ergotism as an explanation for some of the phenomena in the Salem witch hunt story when we studied it at school and got some top marks out of it!

  2. Mim

    Pictures of Indy are probably the only reason I keep reading this blog.

  3. Uwe

    Cool article, I liked it. Certainly informative and interesting, I vaguely remember the story of the black rye nice to have the memory refreshed . BTW the disease was also known as Holy Fire, because of the feeling in the extremities of burning and Holy since it was thought to be a punishment from God.
    Only issue Albert Hoffman was Swiss therefore should be Albert Hoffmann. Two N’s pls.

    • thomastu

      Also called Saint Anthony’s fire, because the monks of Saint Anthony were credited with curing it.

      ACTUALLY, Uwe, it’s Hofmann (Mim pointed it out to me later). Crazy Swiss German spelling.

      TT

  4. That’s cool about the discovery of PCR, I didn’t know that! As for it being supremely nontoxic to humans, there was a famous case where it killed an elephant during an experiment… awkward…

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