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 behind those tiny cheap plain looking pills is a story that changed medicine forever because aspirin isn't just an old pill it was 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 acetyl salicylic acid but more than three thousand 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 an 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 aid you treatment of the time Peruvian bark was good at relieving au 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 egg you 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 willows effects in a scientific journal philosophical transaction thirty-five 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 from nonliving things an idea known as vitalism a drop of human sweat would just be different than anything we could make in a lab how it just is but in 1828 a German chemist named Friedrich volar showed otherwise when he synthesized urea a substance found in both sweat and urine hence the name this was the first time someone made an organic compound from inorganic materials in the lab volar 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 nonliving 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 the Raphael ipiria 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 the Scottish doctor had published a positive review of salicylic acids effect on rheumatism in the Lancet and a paper titled rheumatic fever treated by salicylic acid page-turner 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 papers 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 straightest 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 world's 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 19th century a couple scientists at the Bayer group 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 acids hydroxyl groups that's an oxygen and a hydrogen bonded to a carbon with an acetyl group which is two carbons one double bonded to an oxygen the other bonded to three hydrogen's the result was a siedel salicylic 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 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 a 19-15 it became available without a prescription which made it the first synthetic over-the-counter drug this was about two years after Bayer stops producing over-the-counter heroin by the way so for a while you could stroll into any pharmacy and buy heroin but needed up to get aspirin the times they have a 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 1 but on the scientific side of things there wasn't much progress for a few decades she's 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 1974 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 and then studying both the chemicals produced during the allergic reaction and the effects of aspirin on those compounds team found that the allergic reactions caused cells to produce more prostaglandins a type of hormone an aspirin seemed to inhibit that production they were able to tie prostaglandins to fever inflammation and headaches so this one 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 prostaglandins 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 one 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've 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 it seemed like a good alternative we'd known about its pain relief effects for about a hundred years it's not a proper NSAID it reduces pain like one but it 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 and 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 Kraven performed a lot of surgeries on tonsils and the adenoid glands a pretty routine procedure by his standards he 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 Kraven 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 showed 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 heart attacks in the arteries around the heart that experienced plaque buildup or atherosclerosis raven 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 aspirins use as a blood thinner with much more rigorous science and then in the 1960s researchers made a game-changing discovery aspirin had antiplatelet effect slave –let's are tiny cells in the blood that help clots form an aspirin acts as a blood thinner by keeping them from clumping together that's why they won't let you donate platelets if you take an aspirin in the last two days so Kraven speculation was actually pretty close platelets bunch up around those atherosclerosis and blood vessels causing heart attacks today doctors will recommend low-dose daily aspirin for certain patients it can reduce the chances of heart attacks and 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 that you generic person should start popping 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 working for whom but one thing's for sure that old boring little pill that's 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 slash crash course

48 comments

  1. 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!

  2. 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

  3. 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.

  4. 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?

  5. 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.

  6. 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.

  7. Have to watch this for science, currently in class I’m so cool yo sorry for my comment I’m bored 👌

  8. 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!

  9. @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

  10. @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

  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.

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