How Aspirin Changed Medicine Forever

How Aspirin Changed Medicine Forever


♪ Aspirin might seem like the most generic,
boring pill ever. I mean, the patent for it expired literally
a hundred years ago. And we have all kinds of better over-the-counter
painkillers these days. But behind those tiny, cheap, plain-looking
pills is a story that changed medicine forever. Because aspirin isn’t just an old pill. It was the one of the first pills — or at
least, one of the first medicines we learned how to make ourselves. And we’re still discovering new uses for it
today. So, the active ingredient in aspirin is a
compound called acetylsalicylic acid. But more than 3,000 years before we learned how to make it, doctors were using its original natural source, willow bark, as a medicine. Ancient Egyptians used willow and myrtle to treat fever and pain, some of the same symptoms we use modern-day aspirin for. And old school medical superstars like Hippocrates, Celsus, and Galen had come across the soothing effects of willow bark for treating inflammation. But it wasn’t until the 1700s that a British
reverend named Edward Stone made a crucial observation. During a particularly nasty outbreak of ague, a fever thought to be caused by malaria, Stone noticed that willow bark tasted an awful lot like Peruvian bark, the more common ague treatment of the time. Peruvian bark was good at relieving ague symptoms, but really expensive, and he thought willow might work as a cheaper alternative. So he spent the next few years collecting,
drying and powdering willow into a form that could be used to treat ague, eventually settling on a dosage of two scruples — which is a real unit of measure! It was about 2.5 grams of bark. His concoction wasn’t as powerful as Peruvian bark, which was a source of quinine a compound that actually kills the malaria parasite. But he did publish the first report of willow’s effects in a scientific journal, Philosophical Transactions. 35 years later, in 1826, a French researcher
isolated the active ingredient in willow bark: a yellowish crystal that was named salicin
a couple of years later. Around the same time, a much larger shift
was happening among scientists. For a long time, a lot of chemists thought
substances from living beings had some kind of vital force that made them different than non-living things an idea known as vitalism. A drop of human sweat would just be different than anything we could make in the lab. How? It just is! But in 1828, a German chemist named Friedrich Wohler showed otherwise when he synthesized urea, a substance found in both sweat and
urine — hence the name. This was the first time that someone made
an organic compound from inorganic materials in the lab. Wohler didn’t set out to disprove vitalism
— he was originally trying to make a totally different compound. But when he accidentally made urea instead, scientists began to think maybe living things weren’t so chemically different from non-living things. This event swung the doors wide open for experimentation into organic chemistry — the study of compounds usually found in living things. So for drugs like aspirin, the next few years
were one big progress party. In 1838, an Italian scientist named Raffaele
Piria synthesized a stronger form of the active ingredient in willow bark for the first time:
salicylic acid. This might not seem like that big of a deal,
especially compared to the neat and tidy synthesis in modern labs, but it marked an enormous
shift in our approach to drug development. Researchers weren’t just purifying what
they found in nature anymore they were actively working to change the chemical structure of compounds to develop more effective treatments. It’s one of the biggest differences between
old school and modern medicine. Salicylic acid might sound familiar if you’ve
used topical acne treatments, but it wasn’t quite modern-day aspirin yet. By 1876, a Scottish doctor had published a
positive review of salicylic acid’s effects on rheumatism in The Lancet, in a paper titled “Rheumatic Fever Treated by Salicylic Acid” It was no controlled, double blinded study
by any means, but the word was getting out that this stuff might turn into something
big. Except, there was a problem. Because that was only the first half of the
paper’s title. The second half was “Symptoms of Poisoning Produced by the Acid”. People weren’t actually being poisoned,
but it’s not hard to see why it looked like they were: salicylic acid worked for fever,
pain, and inflammation, but it also often caused gastritis, where the stomach lining becomes inflamed. Maybe a little bit ironic, considering the
medicine usually reduced inflammation, but it turns out the stomach lining doesn’t
really like being eroded, and that’s what the salicylic acid was doing. As you can probably imagine, this is not pleasant. It tends to lead to, like, nausea and vomiting. Meanwhile, something else was changing in the medical world. Researchers were starting to realize that
a lot of the chemical byproducts of dye manufacturing could be used in medicine. This is actually how some of the first pharmaceutical companies were born — they started out as dye manufacturers. The Bayer group in Germany was one of those dye companies that started branching out into medicine. And around the end of the nineteenth century, a couple of scientists at the Bayer group in Germany came up with a protocol to modify salicylic acid and make it less toxic. This is where the history of aspirin starts
to get a little controversial, because at least three different scientists all claimed
credit for the discovery. But either way, the process they came up with involved a reaction known as acetylation. It replaced one of salicylic acid’s hydroxyl
group — that’s an oxygen and hydrogen bonded to a carbon — with an acetyl group,
which is two carbons, one double-bonded to an oxygen and the other bonded to three hydrogens. The result was acetylsalicylic acid, the modern active ingredient in aspirin. The compound had technically been synthesized by a French chemist about 50 years earlier, but his version was impure and unstable. The reaction used by the chemists at Bayer
didn’t have those problems, and they ended up with a drug that reduced a lot of that
gastrointestinal irritation, at least compared to regular salicylic acid. Gastritis was still a side effect, but it
didn’t happen as often or as badly. And as far as industry was concerned, companies now had a reliable way to make a highly useful pill. It quickly became the world’s best selling
drug, in part because people were already used to taking salicylic compounds. This was just a safer and less toxic version. More positive medical reports kept coming
in, so aspirin continued to grow in popularity. And in 1915, it became available without a
prescription which made it the first synthetic, over the counter drug. This was about two years after Bayer stopped producing over-the-counter heroin, by the way, so for a while you could stroll into
any pharmacy and buy heroin but needed to get a prescription for aspirin. The times, they have changed. After aspirin became available over-the-counter, not much happened for a while. There were some legal changes when Bayer lost their trademark, which was part of Germany’s deal with the Allied powers after World War
I. But on the scientific side of things, there
wasn’t much progress for a few decades. Keep in mind that all this time, we really
had no idea how aspirin worked. We knew what it did, but not how. It took until around 1970 for British pharmacologist
Sir John Vane and his research team to figure that out. Their experiments involved inducing severe
allergic reactions in rabbit and guinea pig lungs, then studying both the chemicals produced during the allergic reaction and the effects of aspirin on those compounds. The team found that the allergic reactions
caused cells to produce more prostaglandins, a type of hormone. And aspirin seemed to inhibit that production. They were able to tie prostaglandins to fever, inflammation, and headaches, so this went a long way toward explaining how aspirin worked. A few years later, other scientists came across prostaglandins again. In 1976, researchers discovered cyclooxygenase, or the COX enzyme, which makes a few different biomarkers, including prostaglandins. And once you introduce it to aspirin, the
drug irreversibly binds to it. More COX binding, less prostaglandin, so less pain. The problem, though, is that there are multiple kinds of these enzymes, and they all do slightly different things. While COX-2 produces prostaglandins during inflammation, a COX-1 enzyme has the added duty of making prostaglandins to protect the lining of your stomach. And aspirin affects both COX-1 and COX- 2,
which is why it can act as a pain reliever, but also messes with the whole stomach lining thing. So doctors needed to find drugs that could
do the heavy lifting of aspirin, but without causing upset stomach. That’s where other NSAIDs, or non-steroidal anti-inflammatories, came in. As you might have guessed, their name comes from the fact that they reduce inflammation without being steroids. Pharmaceutical companies were after any drugs that would selectively inhibit COX-2 without touching COX-1. Acetaminophen seemed like a good alternative. We’d known about its pain-relief effects
for about a hundred years. But it’s not a proper NSAID. It reduces pain like one, but doesn’t do
anything for inflammation. Today, we have other actual NSAIDs, like ibuprofen, which can still irritate your stomach but seem to do it less than aspirin. Aspirin, though, is still extremely popular. That’s because, in addition to its pain
and fever reduction powers, it has benefits in preventing heart disease. It was a surgeon named Lawrence Craven — primarily an oral surgeon, oddly enough, not a cardiologist — who stumbled upon this idea in the early
1950s. Craven performed a lot of surgeries on tonsils and the adenoid glands, a pretty routine procedure by his standards. He’d usually do the surgery in the morning
and send the patient home in the afternoon, often prescribing aspirin chewing gum for
the pain. But he noticed that as the use of aspirin
gum increased, so did more oral bleeding. Craven was convinced that aspirin was preventing prothrombin, one of the factors in blood clotting. He even went as far as taking 12 aspirin a
day to give himself a nosebleed and show the blood thinning effects of the drug. Over the next few years, he prescribed aspirin to all of his patients who were at risk for a heart attack – mostly older, overweight men. His rationale was that rapid blood clotting
could cause in heart attacks in the arteries around the heart that experienced plaque buildup, or atherosclerosis. Craven thought aspirin would reduce coagulation, allowing blood to pass through the arteries smoothly, and reduce heart attacks. But really, all he had was anecdotal evidence and observations. Over the next few decades, multiple doctors and scientists would learn more about aspirin’s use as a blood thinner with much more rigorous science. And then, in the 1960s, researchers made a
game-changing discovery: aspirin had anti-platelet effects. Platelets are tiny cells in the blood that
help clots form, and aspirin acts as a blood thinner by keeping them from clumping together. That’s why they won’t let you donate platelets if you’ve taken aspirin in the last two days. So Craven’s speculation was actually pretty
close. Platelets bunch up around those atherosclerotic sites in blood vessels, causing heart attacks. Today, doctors will recommend low dose, daily aspirin for certain patients — it can reduce the chances of heart attacks in people who’ve already had a heart attack or stroke. And more recent research has shown that low doses of aspirin might help prevent other diseases, too — especially colorectal cancer. None of this means you, generic person, should start popping an extra pill with breakfast, unless your doctor tells you to. The risk of side effects isn’t generally
worth it, and we’re still learning more about which doses work and for whom. But one thing’s for sure: that old, boring,
little pill has come a long way since the early days of grinding up willow bark. Thanks for watching this episode of SciShow, which was brought to you by our patrons on Patreon! If you want to help us keep making episodes like this, just check out patreon.com/scishow. And if you’re as fascinated as I am by the
stories behind the science we have today, we have a whole, new History of Science series over at youtube.com/crashcourse. ♪

100 thoughts on “How Aspirin Changed Medicine Forever

  1. I'm alergic to asprin, I have athsma and it basiclly stops me being able to breathe! Salbutamol, the most common treatment for an athsma attak, is a relative of asprin!

  2. @ Marcus Taber I am a retired physician (Psychiatry is my specialty). I really like organic chemistry and pharmacology. I enjoyed some of your comments. It was nice to learn acetaminophen changes and then comes in affecting the cannabinoid pain system.
    An old herb I ran across (reading Native American Information) is Wild Lettuce. This is a pain medication working on the dopamine receptors. I suspect by feedback with Serotonin it balances Substance P. The main cause of fibromyalgia is an imbalance of Substance P with Serotonin. This Wild Lettuce has been helpful with my fibromyalgia.
    Another cause of imbalance of Substance P and Serotonin is not enough magnesium. Far too many USA people are magnesium and iodine deficient. If these two minerals were corrected in many people, they would have much less trouble with their body/less pain.
    Nutrition is a much neglected subject in an AMA school (3 hours is all there is ; I did NOT SAY 3 credit hours, I literally mean 3 hours on one day! Disgustingly in my 3 hours I taught my dietician bc I was more updated than she! ) My educated advice is if you want a really good diet? Ask a chef or a body builder; they get better educated in diets than an AMA physician or a dietitian. This is the problem with government being involved (The government regulates real education out of education! Anything the government has to do with—> it begins to fail). Yes, I worked really hard getting around of the crap the government roadblocks just to get a good education all my educational life. It really was much extra work.

  3. I watched this the day it came out while taking aspirin for my headaches… Three days latter a lot of painin my abdomen, and a doctor visit telling me to take pepcid because I got stomach ulcers.

    I'm not fan of salicylic acid. Not anymore

  4. Aspirin is still my go to for migraines/headaches and joint pain.
    Ibuprofen and Acetaminophen both do nothing and cause digestive problems when taken in quantity.
    Aspirin is my friend.

  5. Hey, we’re learning about aspirin and clinical trials in school right now! Of course, our curriculum succeeded in making something that is genuinely interesting boring.

  6. "ague" is pronounced "AYg" with a hard g and silent ue much like "tongue". it means an unspecified or non-locus pain as opposed to an Ache which afflicts a specific locus in the body. it's frequently misspelled as 'egg' in the misphrasing "to egg someone on" ("to ague someone on" is correct) which means to harass someone into impulsive action.

  7. Hey! Who are you calling generic person!! You Mountain science hippy!…. Yeah… Take that.. also, i love that you guys do a green screen, and replace the background. With a green, screen..

  8. Just a quick Erratum: The guy's name was Wöhler, not Wohler (and yes, o and ö are pronounced differently). And Bayer isn't pronounced "Bear", but almost exactly like the English word "Buyer". Other than that, thumbs up, as always.

  9. the victorians weren't stupid. heroin is without doubt far more effective at relieving pain than asprin.
    thank you for the video, hank.

  10. No kidding about (uncoated) aspirin hurting your stomach. My mother's job had her sitting in a very uncomfortable position all day, so she took aspirin (the regular dose, spaced the right number of hours apart) regularly for back and neck pain. For years.

    …unTIL one day she found out she had a MAJOR ulcer, had lost a lot of her blood to internal bleeding, and nearly freaking DIED. (The exact same thing happened to Nash of "WTFIWWY?" a few years back, too.) Don't mess with aspirin lightly, people.

    (There is a lighter side to this story–she was in the hospital on/near Halloween, so me, my dad, and some friends who lived nearby all came to visit her in costume. The nurses were apparently talking about it for months afterwards. :P)

  11. Children from 4 to 14 years old should never take aspirin. They are at risk of Reye's syndrome, a sometimes fatal reaction to salicylates. I take an 81 milligram low dosage aspirin daily to reduce my risk of heart disease. When that first became popular the doctor would usually tell you to chew a Flintstones baby aspirin every morning. Although chewable aspirin is no longer marketed as "baby aspirin," Flintstones multivitamins are still a tempting danger lurking in many homes.

  12. @4:15 — iirc there's a claim that many 1918 flu pandemic deaths especially in younger healthy (army) patients were really results of huge doses of Aspirin administration

  13. @6:30 — I heard that Bayer's invention of Heroin was basically just apply the acetalation technique that worked with their invention of Aspirin except they apply it to an opiate instead of salacin

  14. Hey, you didn't address Reye's syndrome! That was why i clicked to watch this! I'm a geek, so I knew most of what this video covered already, but I'm not really familiar with the history of aspirin in connection with syndrome and viruses! Please do a video on that!

  15. Great video! You did talk about pharmaceuticals trying to find a cox-2 inhibitor but didn’t mention that they did. It’s called celecoxib.

  16. In some cases scientists were right, some molecules have 'handedness' or chirality, living organisms make some compounds with only one of the two possible mirror images of such molecules. Sometimes the unnatural handedness is toxic.

  17. This has never happened while watching SchShow, but I am mildly insulted by being called "generic person". I know in a sort of objective, statistical sense that I am but thats not supposed to get said. WTH Hank?

  18. Laudanum, opium tincture, was available over the counter in the 19th and part of the 20th century. It was used as a sleep medicine and mothers used to put some on their baby’s pacifier in order to make them sleep. They must have had nice dreams and a full out addiction from childhood on… indeed times have changed.

  19. I never expected to be in my mid 30’s, sitting up at 4:30am watching a video about Aspirin- and totally ok with it.. Lol

  20. Is it weird I use aspirin for period blocks and menstrual pain?? Often my period blood is way too thick and blobby so it hurts me a lot while it just sits there, trying to force itself out. It helps SO much! For any of you ladies out there who have trouble passing thick period blood, a 200-300 mg dosage at the beginning of my periods, makes SO much difference. Mine is very severe, so you might not need as high of a dosage as I do. If you have blood clotting or over-bleeding issues, this might be more dangerous for you than helpful. But if you know you're medically okay, but viscous periods make you suffer, give it a try. It has actually changed that part of my life completely!

  21. I've used aspirin for over 50yrs. The only time I didn't use it was when I was going through chemo, and my Doctors suggested not using it so they could get good blood samples. They always suggest Tylenol. Really, Tylenol, that shit's poison!

  22. The whole therapeutic relationship between aspirin and cardiovascular health is now under fire due to bleeding and strokes. UPDATE THIS VIDEO!!!

  23. I could add so much to this video!!!! i have studied aspirin for years. Since i worked on the Spanish flu. people didn't die of the flu but asprin overdose, Reyes syndrome.

  24. I was taking it and other NSAIDs for nearly 50 years and it has never worked unless throwing up was the intended outcome. I did a dna test a couple of years ago and found out my body can not metabolize NSAIDs. I think the bad gene was r191 .

  25. Damn, crazy times indeed. I mean yeah, back then, you could buy heroin over the counter and they had actual cocaine in the coca cola. That's freaking insane. Thanks for making this video and sharing this information with us. It was pretty interesting and really crazy to learn about this stuff, so again, thank you. But then again, I always learn something new from watching your videos and I love that about your videos. I always walk away with new information that I never knew before and you guys do it in such an interesting way that keeps me coming back and wanting to learn more, so thank you for teaching me about these topics.

  26. Hi @SciShow! This was a great segment. If you have the chance, I'd love to know more about other blood thinning agents. The manufactured ones, but also the plant Tulsi or "Holy Basil" taken as a tea. Thanks!

  27. They used to use heroin in baby's cough medicine as it was safer than codeine. It's actually a very effective and relatively safe pain killer. The problem came with patients being given it and then having it stopped cold turkey instead of weaning them off it, which would leave people with an addiction problem.

    It's quite disgusting when you look at the problem with oxycodone and how that came about that many in the medical profession (who are more educated on addiction now) are often even more irresponsible today, considering the greater knowledge they have, regarding prescribing addictive medications to patients and then just leaving them hanging with a raging addiction.

  28. I'm the age where I thought it was a good idea to have aspirin for the heart. However, "Over all, the benefits of aspirin were partially counterbalanced by the risks. For every 1,000 people taking aspirin, 11 avoided a serious vascular event (heart attack, stroke, ministroke, or cardiovascular-related death). But nine experienced bleeding that was serious enough to result in hospitalization or death, which means the risks and benefits were about the same. The study appeared in the August 26 New England Journal of Medicine." With every medicine there are risks. So, I stopped the aspirin and decide to eat garlic more often because it's a natural way to thin your blood. Also, adding apple cider vinegar in your diet will help. These are both acids which help the blood flow better. And the benefit is they have no side effects when used. Yes, the stink– so there's that.

  29. my grandmother has an old newspaper advertising Bayer Cocaine, Heroin, and Aspirin. It says "When you have pain reach for Bayer Cocaine, Heroin, and Aspirin".

  30. There isn't anything wrong with Cocaine or heroin. Cocaine is a needed pain killer. I am allergic to things like novacane the only thing that can be used on me is Cocaine. The reason they were banned was because of the drug addicts.

  31. We need to think long and hard before pulling a medicine from the market. My step mother's mom had heart surgery and the only medicine that will control her blood pressure is Xanax. I hurt a disk in my back a couple of years ago. The only medications that stopped the spasms was Ativan and Aspirin.

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