From its natural base substance, salicin, to the invention of its synthetic derivative form that we still use, the story of aspirin has its own controversy and conflict, including whether the proper chemist has been given credit for its invention. .
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Mr history class, the production of I hurried used how stuff works hello and welcome to the broadcast, I'm how we try and I've tracing move, then
for all of recorded history, Tracy and certainly before, history is being recorded. Humans have been experiencing pain of one form or another gap that might see
like were leading into a very dark place. Early. We're talking about ways that we have managed in alleviated, pain and today, of course, or also time out fairly minor ones. In this case, the it's just a simple as like running to your local, drugstore, supermarket or even big box store to pick up nonprescription painterly,
easy pc and we're gonna talk today about specifically one of the possible pain relievers that you might reach for in such a circumstance, which is aspirin from its natural base. Substance Alison to the invention of its synthetic derivative form that we still use the story of aspirin is longer than people might expect, and it also has its own controversy.
Conflict. For example, there is one man whose name always comes up and is credited with inventing aspirin and we're gonna get to him and whether he should get credit card urban. Some challenges to that. But first we need to talk about the ancient history of the medicinal base of this, as well as some of the other people who figure into the development of our knowledge about the workings of salary, select, acid and its medicinal possibilities, and just to be super clear, were not suggesting that, like eh
we pay that a person could have can be solved with a quickie little trip to the store to have enough. Now I got a headache: I'm gonna run across the street and get some
today, minor pains, minor behaviour at a minor aches them pains, not the more serious steps, so thousand is found in the bark of the White Willow tree and in winter. Green leaves as well as a number of other plant life in various concentration
and they can be converted pretty easily in a lab or in the human body, into salus, hillock acid, and then those can get a little bit confusing because sometimes the to seem to be used almost interchangeably
yeah, even in in my research, there were moments where people were talking about the history of this and they were pretty
casually tossing them back and forth. But that's not exactly
he correct, I will talk about how even in the medical community that's been a problem at various points in time. Salazar, like acid, is, what's called a beta,
Roxy acid, and you have probably heard of it before, because it is used to tell various
in cares all the time, and that's because beta
Proxy acids are excellent excellence and, unlike alpha hydroxide acids, which are also very good experience. Beta hydroxide acids are also really good,
reducing wrinkles in improving overall skin texture, and they don't have the
tendency to cause irritation that their alpha hydroxide counterparts do. It is also anti fungal aunt. I, in fact,
and it can be used to remove and he'll epidermal problems like palaces and works in a day
You all of that. Sell us, like acid, can also help with pain and that something that humans have known about for a very long time, although they didn't have that name for it and didn't understand how this pain relief was relating to south and the first record that we have of Willow bark being used as a pain. Remedy comes from scenario four thousand years ago and in addition to really
pain. It was also used to treat inflammation and fever, and this knowledge of the extract, a willow bark is a medicinal compound, did not stay in Mesopotamia travelled the globe in China
going back at least two thousand years Willow was being used to treat everything from the common cold to haemorrhages. Hypocrisy, tease documented the idea of a t made from Willow bark to tame pain during childbirth, right around the transition from the fifth to the fourth century Bc E. Several hundred years later, another greek physician discourteous routinely took advantage of the entire region.
Tori properties of Willow Bark, when treating as patients plenty, the elder and Galen, also wrote about their uses of the extract of willow, bark and then in the seventeen sick,
these Reverend Edmonstone, who was a member of the royal society, in addition to being an Oxfordshire vicar conducted his own steam.
Of the potential medicinal properties of Willow bark based entirely on a hunch, as an
You will also see him mentioned
as the Reverend Edward Stone both show up, don't beacon
these images own writing, though he uses Edmund, but he wrote out his.
findings in a letter to the royal society titled an account of the success of the bark of the willow and the cure of egg use, which he wrote
to the right. Honourable George, Earl of Macclesfield, who was the societies president at the time so in this account stone made it clear that he believed he
and then a find something really important and he wrote in the opening quote among the many useful discoveries which this age hath made. There are very few which better deserve the attention of the public than what I am going to lay before your lordship
stone goes on to describe in this letter how he accidentally tasted the willow bark of a tree, and it was
blown over by how bitter it was any notice that way
those grew in the same places that egg use were common ailments, so egg use are intense episodes of fever or shivering. They have often been associate
with malaria and stone believe that
many natural maladies carry their cures along with them, or that
remedies lie not far from their cures. So he made.
Of other bitter plants that had healing properties, including the peruvian
can shown a tree which also contains Alison in its bark, so he's
the bitter willow growing so near to where egg use were common might similarly offer a solution to the fevers that he saw his community. So stone said that he looked for informed
on the willow being used before he did not have access to the various accounts and records that we mentioned, because all he could find was the name of the tree and bought me books that he consulted. He found nothing about its pharmaceutical possibilities. This is a hey where we are very spoiled by the internet and search engines. Yes, yes, I often language we're talking about
historic. All scientists, mathematicians philosophers Et Cetera, like what would they do at the command of information that we have at our fingertips in our pockets, but so stone? Not
finding anything himself on willow ever being used in this way, set out to do some experimenting and reverence
gathered, a pound of willow bark over the course of a summer? And then he put it in a bag? And he hung this.
Outside of a bakers oven for three months and while it sat there, it was exposed not to direct heat but from the indirect heed of the stove. For this prolonged,
period of time and over that time, the contents of the bag dried out and just crumbled. The powder whence he had this powder stone started, giving it the people in very tiny amounts at first, just twenty grains of the powder as a dose. So if there is anything toxic and the substance, the negative impact to his patients would hopefully be pretty minimal, as the people he was treating for ague appeared to tolerate this blue dried powder. He started giving them additional doses, still pretty small every four hours and then he carefully observe the results.
and his patience had some improvement, but none of them were cured of their problems, but as they still seem to have no negative reactions to this experimental treatment, stone increase the dose, noting quote, I grew bolder with it and in a few days, increase the dose too to screw
rules and the egg you was soon removed, so a screw
oh, is that initial doses, twenty greens, so stone was basically doubling the dosage stone continued on with his study for five years, noting that over and over and fifty cases has patients egg use were either cured or at a few very severe cases. They were made much better
stones letter goes on to talk about the trees themselves and how abundant they are and how easy to access it he concluded. With quote. I have no other motives for publishing this valuable specific, then that it may have a fair and full trial in all its variety of circumstances and situations, and that the world may reap the benefits
going from it. So coming up we're going to talk about some of the advances in chemistry that enables scientists to more fully understand why Willow bark helps with pain and fever. But first we are going to pause and have a little sponsor break
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while Reverend Stones work am his success with patients came from using.
Hello, bark, he didn't really understand the chemistry
all. He knew that it was the bark or something in it, but that was it and it wasn't until the eighteen hundreds that signal
against strides were made in isolating and identifying the naturally occurring agent that had these beneficial properties and the eighteen? Twenty?
Some thirty years there were a number of advancement in the scientific communities, understanding of what it was about Willow Tree bark and other plants that offered pain, relief and anti inflammatory properties to patients, and every step was building on the work of one that came before it.
Eighteen twenty eight, a professor of Pharmacology and Munich named Johan Bueller, made a big breakthrough. He was able to extract and purify the compound,
That was doing all of that good, and he named it solace in that has been
on the latin word for willows Alex.
The following year, french pharmacist all three Larue built on buglers work. He was able.
Isolate a pure crystalline form of salasin in eighteen, twenty nine and one thousand eight hundred and thirty eight Raphael. He was a chemist from ITALY was able to produce salicylic acid in a lab. He did this by resolving the chemical structure of Salicin into a sugar and spousal alcohol and then oxidize the south. Will alcohol
Sal acidic acid. The precise chemical structure of celestial alcohol was identified by two german chemists at Mark Burg University Herman
Albert and allowed to man, but the end of the eighteen fifties and
the next fifteen years. That teams were continued until they were able to develop a process for industrial production of Salus hillock acid.
Haydn Chemical company in Germany started producing synthetic salus, hillock acid for pain and fever in eighteen. Seventy, four
making them the first commercial producer in the eighteen. Seven, these Thomas MC leg in the medical superintendent at Dundee Royal, infirmary and Scotland had a lot of patience with rheumatism, and he noticed that there were similarities between the symptoms of those patients and patients with fevers that weren't related to rheumatism. That patients with general fevers had often been successfully treated with China, bark wit
as we mentioned in the section on Reverend Edmonstone contains salesman and so Maclean decided to test the bark extracts Alison out for himself just a stone had, although obviously through
no more knowledge about it. At this point, and in this case the doktor first tested the substance on himself and he approached this is a progressive test. So first he took five greens and had no negative reaction
Then he took ten greens, which was similarly benign, and then he took thirty with no quote inconvenience or discomfort, and at that point he was convinced this Alison was safe. So he next used it to address a rheumatic patient with a fever high heart rate and swollen and eighty joints. This patient was given twelve grains of sand and, at a time repeating the day, was every three hours after seven doses over the course of a twenty four hour period. The patient's condition had improved the feed
and heart rate, we're both reduced significantly, although they were still slightly above normal to more days of treatment, reduced swelling in alleviated. The patient's pain after two more years of trials with his patience, Maleagans published his results in the lancet and this article features eight case. Studies of patients with varying degrees of rheumatism- and he wrote, quote the sudden arrest of the painful symptoms
and the coincidence rapid fall of pulse and temperature, followed so immediately on the administration of the solace, in that it is in
possible, not to a tribute them to its use, cases of acute rheumatism do some
I'm, improve in the most unexpected manner, but I never saw it
Please get well so quickly, as those of which I have given details above Mc Leg and went on to say that
Alison, was the most effective treatment for rheumatism and also that its use, dosage and effects should be carefully documented. Interestingly, he believed that fallacy folic acid, which had been isolated and was favoured by some medical practitioners, was not as effective or palatable a treatment as thousand even during this time. There was some confusion about whether the terms thousands and thousands of asked
were to separate things among some members of the medical community. We, I did see a note in one article about backlog in that there was a doctor
wrote him an apology note, because he got really mad, that this guy kept of using a do terms. But this is what brings us
You are familiar name, bear the firm
fabric and warm Friedrich Bare and company started as a die company, but in the eighteen
going to use. The decision was made that the company would turn its efforts to pharmaceuticals, and this might seem like a weird gear shift to go from pigments to pharmaceuticals, but both of them
chemistry- and this was a new and growing field and additionally,
the company at a really good name among consumers, and so it was able to leverage that brand trust into these new ventures. So we ve been talking about how practitioners, like the Reverend Stone, were very careful in dosage of solace in and how and stones cases in Britain,
where he recorded no negative side effects. But that is really not an accurate picture of the use of oral sounds like acid treatment over time. It can cause significant issues with digestive health, including nausea, ulcers vomiting. These are all things that can come from using sounds like ass,
as a medicine overtime. Yes, Alison is more easily tolerated. We're gonna get into why in a minute but Salah silly gas at once. Its isolated is alot rougher on the gastro intestinal tract, and this is what we
thus to the name that is most commonly associated with aspirants origins, and that is Felix, Hoffman and Hoffman
who was born in eighteen. Sixty eight initially pursued a career as a pharmacist when he finished his education, but
He realised that he actually
and to do some more in depth science and become a chemist, and so he went back to school in eighteen. Ninety three, he finished his.
graduate work with honors and he joined bear as a chemist in their newly established pharmaceuticals division in eighteen. Ninety, seven Hoffman added the single group c h three c, o to sell slick acid. The result was a single salus, hillock acid, which would have
Finally come to be known as aspirin, and this sounds like a really insightful experiments and you could say that it is
but really Osman was a sea leaving a lot of different molecules to potentially create patentable. Medicines bears
really medicines. Venice, eaten and timing were also developed using the same process in projects that were run by other chemists. The origin for Hoffman experiment has a number of different stories to it. One version is that his boss, at Bayer, Arthur I can group, had passed him with figuring out away to make sound, select acid, more tolerable, and the other was that his father took sounds like asset for his rheumatism and was experiencing the negative side.
effects that come along with using it for a prolonged period. So Hoffman was driven by a desire to help him there's another man involved in this named. I'm Rick dresser and he ran the pharmaceutical lab at Bare and it was his responsibility to test Hartman's new substance and dresser
slow to work with a single cell acidic asset. He openly said that he thought it had no value and, moreover, that it could be damaging to the heart.
With another assimilated compound creative by Hoffman around the same time, which dresser thought would be a lot more lucrative and that was heroin. Hoffman had created it when he assimilated morphine, but that was not patentable because it had been discovered by another scientist twenty five years earlier Bay or sold heroin as a pain,
labour and a cough suppressant for years. Many other companies did too. We want to put that on bare. You have probably seen as a I'm presuming
listener that Euro history fan. You probably seem like the old, timely adverts.
we our heroine as like a magical cure all, but after
Than a year of this aspirin compound being developed
dresser. After getting pressure from Arthur. I can groom, who also kind of got some other people
air involved in the cause to kind of push for this thing to get tested, got back to Hoffman, Seagulls, Alice, hillock, acid and dresser first test
on himself, and then he ran and animal study and next bear ran tests in hospitals. I can ruin started this more widespread trial of the new compound offering it to doctors to use with their patience, and the results were as hoped. This new medication successfully treated patients, particularly as a pain reliever. The full clinical trials were published in early eighteen. Ninety nine bear was quick to recognise the financial potential of aspirin and we,
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The german patent application that bear file was actually rejected to other chemists in Europe. Had created the single salad cyrillic asset that before,
man, although those were in lab scenarios and even though they they submitted Patten's, neither of those parties had been able to create a stable version that can go to Mars,
but Bayer, went ahead and found a patent application in the? U S, and that was accepted. It was written by feel, is Hoffman and it begins
be it known that I Felix Hoffman Doktor of philosophy chemist assigned to the farmer for Beacon of Elbow field, company of New York residing at elbows,
Germany have invented a new and useful improvement in the manufacture or production of a single salus, Elect acid and often described his process in detail in that patent paper. Writing quote.
In producing my new compound, I can proceed as follows: without limiting myself to the particulars, given a mixture prepared from fifty parts of salmonella gases and seventy five,
art acidic am hydride is heated for about two hours at about one hundred fifty degrees centigrade in a vessel
provided with a reflex condenser, thus clearly,
web is obtained from which on cooling, a crystal and mass is separated, which is the essential salus hillock acid is freed from the acidic am hydride by pressing and then recrystallised from dry chloroform. The acid is thus obtained in the shape of glittering white needles melting at about one hundred.
five degrees centigrade which are easily soluble in benzene, alcohol, glacial acidic acid and chloroform, but difficultly soluble in cold water, unmarked, sixth, eighteen. Ninety nine aspirin was registered as a trademark name by the Bayer company. The name takes the aid from a single sb. I are from the genus of plants that are alternative sources of thousand, which is Spiraea. The inn suffix was a popular one at the time and drag names heroin being another example gather a number if you look at drugs being developed at the time the enemy,
I am the first aspirin that appeared in tablet form rather than a powder was in nineteen hundred. Although powder aspirin continued to be offered in these various options made,
incredibly easy for doctors to prescribe and aspirin can actually still only be acquired with a prescription up until one thousand nine hundred and fifteen, even in dosages that we today would easily be able to buy without one.
In nineteen nineteen Bayer lost its exclusivity right to use the name aspirin through its. U S, patent as part of the preparations for world where one company had to sell its? U S! Factories sterling incorporated, bought the rights to olive, bears; U S, drug properties for three million dollars, the name didn't state trademarked under sterling, though, and it's been considered a generic term in the? U S for decades,
and dozens of other countries, though it still a trademarked name, bear, was able to get the international trade mark on the name back when it bought it from Smithkline Beecham for one billion dollars that large pray.
TAT was not only for the trademark on the name aspirin that acquisition was rolled into a larger deal, that included other points and other drugs as well
myth climb, Beecham had bought out sterling's worldwide right, so in countries where the trademark is still held, aspirin was once it
and under the Bayer Umbrella. Funny detail in all of this was that exactly how Hoffman work without slick acid actually made the substance more tolerable to people adjusting, it was still a little fuzzy. Essentially he transform it into a new molecule that one doesn't trigger issues amid Gee. I tracked and two is converted back to sell Zoellick acid by the bodies so that the pain and fever relief characteristics of it still apply, but that whole process was not really understood until the nineteen Seventys was only after work in the second half of the twentieth century,
that the potential benefits of aspirin related to heart disease and stroke came to be known now. How things actually played out at bear related to the discovery of aspirin have continued to be debated, and we mentioned when we
introduce that segment. The two different stories about how the experiments that led to the development of aspirin actually began, but that is not the end of it. In nineteen, forty four, forty seven years after Hoffman development of aspirin in the Bayer LAB Arthur, I can grinned while being held at tourism, start concentration camp because he was jewish, wrote his version of the story and this letter, which is in the Bayer archives. He said that he was the one who wanted to come up with a version of Salus Elect acid that would diminish these negative gastrointestinal side effects. According to his account, he wrote down all the instructions and Hoffman carried them out without really understanding.
you have it. I can group also published this account in nineteen forty nine three years after husband's death. He published that in the german periodical pharmacy in the ninety nine, these Walter Sneaker Pharmaceutical historian and deputy head of the Department of Pharmaceutical Sciences at the University of Strap Clyde Glasgow took up the cause of. I can groans credit and one of the key pieces of sneakers argument.
hinges on what he believed might have been a mistranslation of one of Hoffman's, one thousand eight hundred and ninety seven knows which may have confused verb tense a little bit while most translations
Kate. That Hoffman was saying the compound was about to be tested. Sneaker put four
the idea that actually should be translated to indicate that had already was being tested. I
The work that has been was doing was corroborative of an existing process, rather than developmental,
and ninety ninety nine, the one hundred years of our three of the patent and Felix Hopkins Name Bayer issued a press release addressing this ongoing debate about Hoffman and Arthur, I can groom narrowly states quote the claim that not half been, but his colleague doktor, Arthur, I can group is responsible for the development cannot be proven. The statement goes on to mention Walter's meter and his assertion that Hoffman
working off notes by I can ruin and that I can Grimsby be giving credit, but Bear stance was that I can group was never Hoffman superior, that they were equals, and so it would be
weird for him to have assigned him a task and that sneakers
contradicted, establish documentation. Some of the confusion.
The company claims comes from. The fact that I can group did have a subordinate named Hoffman, but that was Fritz Hoffman, not Felix. The Bayer account points out that Arthur, I can grew, never claimed credit for aspirin until he was in his eighties after instances over five decades when he attributed the work to Felix Hoffman. Of course, there's a case to be made that, because he was jewish, he might never have felt that he had the
currency in Germany to be able to do that, and one of the places, though, where sneakers case, for I can groom kind of falls apart, is
so noted in that press release, so any his paper on the subjects neater mentions that Hoffman was now
publicly, credited with the invention of aspirin until nineteen thirty, four
Certainly, it is that this was an attempt to write the jewish. I can grow out of the record during a period of intense Aunt
Semitism in Germany
The problem here is that half moon was credited on the patent application all the way back in eighteen. Ninety nine, as well as in other paperwork that dated back,
when he was doing the experiments in eighteen. Ninety seven Bayer statement concludes by noting that both Ike, angered and Hoffman were researchers working for Bayer in eighteen. Ninety seven
basically saying they were in a work for higher situation. This statement finished with quote: it would have made no difference to either the company or the success of the aspirin brand, whether one or the other is considered the first to succeed in the US assimilation of South Elect acid for the first time in a chemicals
you're and in stable form yet easy for a big company to go. It doesn't matter
credit. Neither of them was really get anything out of it, but, of course, the different people involved in this effort. It matters a great deal we
Talk Times time's up several times lately about how scientific discovery and credit is an issue of great debates and great passion zone,
but which of the bear scientists truly invented. Aspirin will likely never be conclusively settled is in
thing. Reading modern, more modern accounts of the whole thing that they do kind of mention that this this debate goes on. Although some
lately just go with the Felix Hoffman version and fascinating, but there is no mention of aspirin. Do you have some listener may also
I this is from our listener summer and she is writing
US about our recent episode, the Crampness Inference Holiday, special for and specifically the seven lucky gods, and she writes my name is summer, and I've been listening to your podcast for probably for years now. I started when I needed something to do also in costumes for the high school drama club
run my family, and I have lived in Japan for nine and a half years now my husband teaches that a high school on an american military base. I had to write
and after listening to the seven lucky. God segment, because I have a crazy story about them. My friend Amanda and I
I had to do a seven lucky gods, tour last January in Yokohama many
cities or areas have their own tours. They can either be walked or driven in one day I've been driving in Japan.
for many years now. So I felt confident and comfortable getting around
There are always surprises here. They are
roads that are technically to aim, but in reality only one car can fit down them. Also, something Google maps struggle
Where is knowing where the real entrance to a place? Is these two things conspired against us on our quest to get all seven of our lucky gods on our way to the?
stop. We were following our Google maps instructions that led us into a rest.
Until neighbourhood with those two lane roads that only fit my minivan. We went up
hill and Google instructed us to turn at the top, which made sense because directly in front of us was a set of stairs, though I started respect
It was not going to work as the road that I turned on
now gravel bordered on the left by a wall and on the right by a steep twenty four drop off with no guardrail. We drive
very slowly on this road for about twenty metres and turned again. Only to this,
for that we were now definitely on something that was more again to a sidewalk. It
it about twenty metres in front of us in stairs which we obviously we're not going to drive down
I now have the unenviable task of backing up around two corners on a not road about seven feet wide in a minivan. Also did I mentioned the cliff drop off on ones,
and my three year old in the back seat. Thank heavens for backup cameras in my four
Nanda who got out and help to guide me around the corners and the telephone poles, but we. Finally,
back on a real road. We part of the car at last from this year, terror of it all. We assume the stairs in front of us we're a back entrance to the shrine and we wandered on
sure enough. It was and we were able to get our very lucky God and continue on, though this time, with a little less reliance on Google. I look forward to doing another touring come a good eye in twenty twenty, although I will probably do it on foot. Thank you for creating such a fund, an informative podcast. I always recommend your episode on such a co and that one thousand cranes to any friends that visit her Ozma. That story is very close to my heart after directing show on it, and I wept like a child at the mention of the Hiroshima Peace Park. I we get weepy just thinking about it, see they give me my company, while I so hundreds of costumes that drive around on adventures in Japan summer. This is such a fund slightly. Terror,
story. I agree the backup cameras magic, I'm glad you're, saying that drop off sounds very scary to me, and I I I hope that your visit to
the lucky gods. Granted you luck for the rest of the year. Will you never found yourself in such a precarious position? Again,
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