The Fungus Among Us: Historically Bad Fungal Infections

Killer Fungi

• Cordyceps itself–I encourage everyone to go watch the BBC video (BBC article link in the show notes) David Attenborough is a treasure, and it’s scored like a horror movie.  Once an insect is infected, the fungus grows tendrils through the whole body of the insect, and they all work together; in an ant, they surround the brain but don’t take it over, and invade muscles to control actions, but the way they do that isn’t clear.
  • challenging to treat because they are similar to humans genetically?  (WaPo) but our immune system is good at resisting them (temp is a key component)
• ER specific fungi–mucormycosis, Amanita phalloides.  Who doesn’t love a penis mushroom.  Half a mushroom can kill a person, toxins are heat stable, implicated in the deaths of Roman Emperor Claudius, and Holy Roman Emperor Charles the IV.  Even God can’t save you.  Similar to many edible types.  Related mushroom species are called ‘destroying angels’.  Sidebar, mycologists are really dramatic.  Any favorites gents?
  • Amanitia–amatoxins halt protein synthesis 
  • False Morels–genus gyrometra, which contains gyrometrin, interferes with GABA, can cause methemoglobinemia, can cause liver necrosis
  • LBMs–quite a few, some that cause limited GI illness, some that have the same toxicity profile as amanita species

Transition–what about fungus in medical history?  We are a historical podcast after all

Historical Fungus Story–even one damn fungus caused a bunch of trouble (claviceps purpura), or does it?

Ergot and Salem

• Witch Trials were frighteningly common in Europe for about 300 years–thousands of people were executed, mostly women, because Christianity taught that the Devil would give people powers in exchange for allegiance
• Salem Witch Trials–a series of trials in colonial Massachusetts from 1692 until 1693, 200 total trials for suspected witchcraft, leading to 19 hangings (14 women, 5 men).
  • Fun fact: the only incidence in American history of execution by ‘pressing’--applying more and more weight until someone dies.  It used to be a method of punishment/torture for people that refused to say either guilty or not guilty, because, if you refused to enter a plea, you couldn’t go to trial, so your family got to keep their stuff
• One theory of a possible culprit is the fungus Claviceps purpura, which grows on spoiled rye, and contains ergot alkaloid toxins that activate the nervous system and constrict blood vessels
• ergotism: two main forms, one convulsive, one gangrenous; serotonergic, so it causes hallucinations, tremors, fever–serotonin syndrome–and maybe when people were acting this way it tricked people into saying they were witches.  Circumstantial weather data and symptom analysis from one 1976 paper; 1691 was a wet winter in New England
  • Symptoms started in the preacher’s family, and he was likely to be paid in grain at the time
  • LSD was originally synthesized from ergot
• Theory regarded as ‘fringe’--what about all the other witch trials?  More likely medical cause is what used to be called mass hysteria, now ‘mass psychogenic illness’, where a distinct group of people has either symptoms of anxiety or abnormal motor movements that have no discernible cause (which in the seventeenth century would be any illness lol)
  • may be related to a specific set of neurons called the mirror neuron, which activate when you see someone else do an activity
• Fun non-medical fact: there was a baseball team called the Salem Witches in the 1920’s for about four years.  Further details were not immediately available from the Internet.

Transition: ergotism does cause a long-standing medieval affliction called St. Anthony’s Fire, which spawned a whole hospital system run by monks 

• Causes St. Anthony’s Fire, convulsions and dry gangrene from the ergot; around 1095 when the son of Gaston of Valloire survived ergot poisoning after being exposed to the relics of St. Anthony, and ran medieval hospitals for hundreds of years.  One article mentions that the word ‘hospitaller’ at the time referred to a member of a religious order of monks, and this article notes that’s where the word ‘hospital’ came from this word, but there are a lot of latin roots relating to caring for someone blah blah blah (OED discussion?) Anyway a pope eventually made this order more powerful.  But where did this even come from???
• Let’s go all the way back to 251 CE; a guy named Anthony apparently gave away all his earthly possessions and lived in the desert.  He performed faith healings, is said to have lived to be 105, and his bones later became relics, one of the early Christian saints.  At least three groupings of human remains are thought to represent St. Anthony in Europe.  
  
  
• St. Anthony was said to use pork fat to cure skin ailments, thus the association with skin diseases.  Some desert weirdo rubbed fat on people and was therefore a saint.  I am skeptical.
• St. Anthony’s Fire was linked to erysipelas, ergotism, and shingles because they affected the skin
• Ergot poisoning from claviceps came with the spread of Rye to Europe around 857; it caused many outbreaks, the most serious of which killed more than 8000 people in Southern France in the 1700s, with the culprit not identified until 1596 when the German physician Wendelin Thelius.
• Mixed adrenergic and serotonergic effects.  Discuss?
• The Order of St. Anthony grew to encompass about 370 hospitals across central Europe at their height.

Second Story–ringworm, social status, and irradiating children

• Second major story is a different kind of outbreak–ringworm among English school children in the middle of the 19th century (Yes! Victorian England)
• Ringworm is a fungal infection of the skin caused by a group of fungi called dermatophytes; Microsporum and Trychophyton are common species that do this
• Spread by contact with other infected individuals, animals, bedding, clothes
• when it gets on the scalp it causes hair loss and can be very uncomfortable; we have multiple treatments now and it’s usually recognized pretty quickly
• in Victorian England, it was more feared than TB.  There were, of course, hundreds of curative creams and lotions on the market already at the time, and medical treatment was usually some form of acid–carbolic acid, sulphuric acid, and mercuric chloride, but these caused severe burns and side effects.  Part of the problem is that the scalp is just hard to treat–the fungus uses the hair and the follicle as a refuge, and some forms are inside the hair shaft itself.  On the skin, the students could just pour their school ink on the skin, which was very effective because ink at the time contained all sorts of chemicals.
• Socially, it was attributed to poverty and poor hygiene, and was therefore a social catastrophe; children were kept out of school sometimes for years (one report notes a child missed four years of school).
• In the middle of the nineteenth century, as Victorians worked to improve society, England passed the 1870 Education Act, which ‘promoted’ free schooling when not available, and worked to ‘reduce’ child labor (lol).  Mass public schooling led to outbreaks of tinea capitus (scalp ringworm)--along with scabies, scarlet fever, and all sorts of other maladies–and the more severe tinea favus, which caused yellow crusting and huge areas of swollen skin, OR, also possible, as people saw the state of children, they realized how common it was.  Ringworm had previously been quite common in private schools, workhouses, and so on, but wasn’t addressed.
• There were very public disagreements between experts.  The leading experts in the 1830s and on were Robert Willans, who saw hundreds of outbreaks, and his successor Robert Plumbe, who felt that the trigger of the disease was related to diet–even a single sweet cake could cause acidity that led to the disease–after which it was contagious.  He advised isolation and washing the bedding, but not much more.  There was a whole discussion of the ‘seed and soil’ metaphor of disease.
• Others pushed back against the lack of cleanliness aspect–Robert Lieveing, a noted dermatologist, noted that ‘gutter children’ were exempt because they didn’t go to school or comb their hair.
• Generally, though, students who were infected were excluded from school altogether, and since they had no treatment options that worked back then, these exclusions were disastrous.
• Let’s just go through some brief highlights involved in trying to solve this problem.
  • Malcolm Morris, a leading dermatologist and syphlologist (lol!) was the one who advocated for segregation of ringworm sufferers from the schools
  • The London Asylums Board (call-back) got involved and included treatment schools specifically for ringworm along with ‘contagious diseases of the eye’, ‘mental defectives’, ‘physically disabled’, and ‘young offenders’
  • the French did something similar and one of their schools was nicknamed ‘the school for scabby children’
• Germ theory was just starting, but there was still a lot of confusion.  It was understood that there was an organism causing this, because you can see the fungus forms–however, there are different forms of fungus at different life stages, and there was still enough confusion that bacteria was initially categorized as a fungus as well.
• Enter a solution: x-rays
  • In the 1900s, a doctor named Raymound Sabaroud achieved fame by pioneering x-ray treatment for ringworm.  Essentially, he’d treat patients’ scalps with enough x-ray radiation to make their hair fall out, and then the infection would be cleared, because, no hair, no hair fungus.
  • During this era, x-ray exposure was all the rage, given that it showed the body’s internal structure, but not a lot else was known.  The hair loss was a noted side-effect of significant exposure, as were burns–so they figured out too high a dose was bad.  X-rays aren’t great at killing bacteria and fungus directly, unfortunately.  The Lancet even suggested that x-ray exposure might replace shaving as a way of removing hair.
  • Leopold Freund in 1897 reported all sorts of cosmetic uses of x-rays for hair removal, like from hairy moles and such.
  • Keep in mind that the depilation methods at the time included mercuric chloride or thallium, both of which caused chemical burns, so this seemed–and probably was–safer.
  • Sabouraud invented a way to modulate the x-rays so the burns were fixed; the treatment protocols usually involved sitting in an x-ray bath for about forty minutes at a time, each time for a separate part of the head, making sure there was no overlap.  Then, when the hair fell out, you could apply antifungals on the skin like anywhere else.
  • The London Asylum Board started to use regular x-ray treatments at their ringworm asylums in the early 1900s, and had good successful ‘cures’ around 50% of the time.  Because these were children, and because they were in an asylum, there was no discussion of informed consent, and no chance for wards to refuse the procedures, mainly because they were pauper children, so had been essentially remanded to the state.  They did perform a ‘trial’, like a study, but there was no control group.
  • After these ‘successes’, school children who were identified as having ringworm were compelled to accept treatment as well, even if they were not in an asylum situation.  There were the expected parental refusals at this point–in the records of these trials, one family says that the child’s mother is a nurse, so they’ll do it themselves, and another says that their children are already using sassafras oil, which sounds like the vitamin C for COVID of the early 1900s.
  • At the peak of recorded numbers, in the early 1900s, ringworm affected about 1% of the English school population, but the exclusions were lasting.  It meant a rolling average of around 3,000 absences per day, with exclusions lasting a mean of nine weeks.  Over the next few years, it slowly abated, and died out, although the cause of the reduction is still not well known.  Possible causes include the x-ray treatments, improving hygeine, or even the use of BrylCream, which was said to have mild anti-fungal properties.

References:

1. https://microbialcell.com/researcharticles/2020a-kainz-microbial-cell/ overview of Fungal infections, Kainz et. al., 2020 (linked in BBC article)
   
2. https://www.bbc.com/news/health-64402102 BBC Health article about The Last of Us
3. https://en.wikipedia.org/wiki/Salem_witch_trials Wikipedia page on Salem Witch Trials
4. https://arstechnica.com/science/2019/07/study-zombie-ant-death-grip-comes-from-muscle-contractions-not-the-brain/ Ars Technica blog post on Cordyceps
5. https://www.washingtonpost.com/climate-environment/2023/01/20/cordyceps-fungus-last-of-us-hbo/ WaPo article on climate change related to the show
6. https://www.smithsonianmag.com/history/a-brief-history-of-the-salem-witch-trials-175162489/#:~:text=The%20Salem%20witch%20trials%20occurred,accused%20and%20compensated%20their%20families Smithsonian Salem Witch Trials article
7. https://www.vox.com/2015/10/29/9620542/salem-witch-trials-ergotism Vox article on Ergotism in the trials
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898692/ mirror neuron review article
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975928/#:~:text=Herpes%20zoster%20(HZ)%2C%20a,%2C%20or%20varicella%2C%20in%20childhood St. Anthony’s Fire survey article
   
10. https://www.ncbi.nlm.nih.gov/books/NBK169210/ Ringworm Chapter, Fungal Diseases in the US and Britain 1850-2000
    

Aaron

Silver Fox Doc