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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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
Here’s a good story about the placebo effect – on physicians:
If you had a stroke in 1810, it would have been diagnosed clinically, without MRI. Your doctors knew that if you died, your brain held either fluid (edema, ischemic stroke) or blood (hemorrhagic stroke). 1/
So obviously the problem was that there was too much fluid in your body.
Solution? Reduce fluid, by blood-letting. This was the solution to a lot of things (one of these days I'll do a #histmed#tweetorial on Benjamin Rush).
And many people got better. 2/
People got better because when you have a small stroke, inflammation and edema make symptoms worse initially, and then, over time, symptoms improve.
If they didn't get better? Easy - you didn't bleed them enough. 3/
One of my favorite #histmed stories is the discovery of EEG by Hans Berger in the 1920s. #NeuroTwitter
At age 19, Berger (1873-1940) fell off a horse. On the same day, his sister, miles away, sent a telegraph to ask if he was doing ok. 1/10
He was fine, but he thought he had communicated his frightened thoughts about getting hurt to his sister by telepathy. He decided to study psychiatry, to learn more about inter-brain communication. 2/10
Berger wanted to measure the "psychic energy" that, he thought, tied us all together. He wrote about the "radioactivity of the brain," he studied circulation, he measured temperature of the brain during mental exertion (in a 23 yo patient with a gunshot wound to the head) 3/10