James Lind conducted the 1st randomized medical trial in 1747 when he gave sailors different remedies for scurvy.
In 1863, Austin Flint gave patients with rheumatism a "placebo," and it worked as well as medicines - possibly the first placebo-controlled trial. #histmed 1/7
"Placebo" was already a well-known term and concept. Initially defined as a common medication (seen here in a dictionary from 1785), it came to mean an inert substance that had no effect on a disease, but pleased the patient. 2/7
The history of medicine is full of placebos: commonly, impure placebos, meaning they did something (made you poop or vomit, got you drunk or sedated, or tasted spicy or bitter), but didn't do the thing they were supposed to do (fix your cold, or your cancer, or your tetany). 1/7
People knew that many treatments weren't helpful.
In 1364, Petrarch proposed an experiment to Bocaccio, assigning half of "1000 men, of the same age and character and [eating] the same diet, affected by the same disease" to either take medicine or not - and see what happens. 2/7
Placebos make people feel better because of two things: 1) a phenomenon called regression towards the mean. You take a medicine when you are sickest, and then you either die or get better; and 2) complex brain stuff (I’ll let #NeuroTwitter explain that one) 4/7
The "placebo effect" can be astonishing. When researchers were studying cannabidiol for seizures in 2017, 1 out of 4 parents giving their child placebo - inert oil - reported a 50% reduction in seizures during the study. 5/7
The parents in the CBD study weren't lying, and they weren't fools who were tricked by the placebo. This is just what our brains do - especially when there is strong hope for a better treatment. 6/7
It wasn't until the 1940s that two big clinical trials - one, testing streptomycin for tuberculosis, and the other testing immunization against pertussis - changed the way we design and perform clinical trials.
More on Bradford-Hill and clinical trial design tomorrow! 7/7
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Isabelle Rapin is the perfect Luminary to discuss today, because she was born December 4🎂and was a founding member of the @ChildNeuroSoc in 1973 in #Nashville (where everyone is going for #AES2022).
Peds neurologists know why she has a pinwheel on her card - do you? 2/🪑
Born in Lausanne, Switzerland - where Augusta Déjerine-Klumpke studied - Rapin went to medical school locally. Like ADK, she worked at the Salpétrière - and like ADK, she wrote a brief autobiography (please write one, send to @JChildNeurol) journals.sagepub.com/doi/10.1177/08… 3/🪑
Happy birthday (November 29) to the Father of Neurology, Jean-Martin Charcot (1825-1893)!
I wouldn't say we're best friends exactly, but yeah, we used to hang out in Paris together. 1/4
Charcot was a neurologist in Paris in the late 1800s, when neurology was developing as a field. He was the 1st chair of neurology, and was a celebrity doctor at the time (this is a poem written and published in the newspaper after his death in 1893). 2/8
He was so famous that charlatans used his name after his death to sell "Kola Nervine Tablets" made from the "wonder-working Kola nut." 3/8
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Luminary #4: Dorothy Russell (1895-1983)
1/🪑
Hands up if you used this textbook! The 7th edition of "R&R" was published in 2007.
You may have known that this was written by eminent neuropathologist Dorothy Russell, but did you know she had epilepsy? 2/🪑
Russell was born in Australia, but after both her parents died (her mother from measles), Dorothy and her sister Petronella went to live in England with an aunt. 3/🪑
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Luminary #1: Sarah McNutt (1839-1930)
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In 2002, Horn and Goetz published this excellent paper on McNutt - the 1st woman elected to the American Neurological Association (@TheNewANA1) - and her work with other early female physicians, including the Blackwells. n.neurology.org/content/59/1/1… 2/🪑
McNutt came from a long line of female midwives and healers, including Sarah Weir, who worked on Nantucket, and Rachel Hussey, who delivered 2992 children (both called physicians here, but neither MDs) 3/🪑
Edwin Smith, born in Connecticut, lived in Egypt in the late 1800s. An antiquities dealer, he bought a papyrus in 1862 that he was unable to translate.
Smith died in 1906, and his daughter donated the scroll to the New York Historical Society.
In 1920, Egyptologist Caroline Ransom Williams found it and recognized its worth. She wrote to her mentor James Henry Breasted and asked him to translate it. brewminate.com/the-contributi…
Ransom Williams felt she was too occupied with family to take it on.
“The papyrus is probably the most valuable one owned by the Society and I am ready to waive my interest in it, in the hope that it may be published sooner and better than I could do it.” [November 22, 1920]
Bradford-Hill's trial of streptomycin for TB (see my thread from earlier today) was the first randomized controlled trial - but not blinded, and not placebo controlled. There was another trial, around the same time, for a medication called patulin. 1/6
You've never heard of patulin? It's a mycotoxin (it grows on apples), once used as an antibiotic (but not any more, due to toxicity).
In the 1940s, it was billed as the cure for the common cold. 2/6
A study showed that if you spray patulin in someone's nose when they have a cold, they feel much better - within 48 hours - than people who didn't receive any treatment.
This was huge! Everyone wanted patulin to treat colds.
So what happened? 3/6