I recently wrote an article for Asimov Press on The Origins of Aspirin. If you haven’t read that, it’d probably make more sense to read that before this. But I can’t stop you if you want contextless but interesting footnotes!
Writing the article was a great experience: I have mostly written academic journal articles, rapid evidence reviews for the Government, and blog posts. It was wonderful writing something that more than 10 people might actually want to read.
Having an editor was invaluable: thank you, Xander.
In particular, thanks for wading through the huge amount of content written in my own idiosyncratic writing style to produce something that, I think, is probably one of the most best and most interesting things I’ve ever written.
Most of what was left out (and wasn’t poorly written or just stupid) was just way too tangential to be included.
Most of that was footnotes.
I like footnotes.
They may be utterly irrelevant and distract from the story, but that’s why I like them.
This is also why I use so many parentheses: I so many things interesting, want to share them all, but sadly only some of them help the argument I’m making.
Case in point, I put a footnote in a footnote.
So, without further ado, I’m pleased to present the footnotes and other trivia that didn’t make it into the final article: I hope some of you enjoy some of them as much as I did!
Other ancient evidence
Most of the ancient evidence I found comes from Europe. However, I found other, more infrequent references to ancient people using willow to reduce pain, inflammation, or fever, such as to China and the indigenous peoples of America and South Africa. I decided to focus on the more common references, rather than try to go through every reference to willow that I could find.
This was for many reasons. First and foremost, it was in interests of time: I had already spent a frankly enormous amount of time trying to source the “30 million people take NSAIDs every day” claim (see my earlier blog post).
Secondly, however many claims there were for ancient willow bark aspirin, my main argument that Reverend Edward Stone was not influenced by history, and the origins of aspirin started with him, so it was fairly irrelevant whether ancient peoples used willow bark at all. It was sufficient to go through the most referenced examples as a broader point about how references need to both exist, and be correct.
Thirdly, I couldn’t find the evidence for other places, at least, not easily. Hippocrates, Pliny the Elder, Dioscorides, the Eber’s papyrus – these works are, relatively speaking, popular. Certainly in Europe. I could find translations easily. It felt like it would be a lot of work to source evidence that I didn’t really feel that I needed, and any effort may have been wasted if the evidence didn’t even exist.
Nonetheless, it is claimed that an Ancient Assyrian clay tablet (3,500 to 2,000 BC) described the use of willow leaves for pain and inflammation. I very much wanted to look at this tablet, and see a translation, so put a little effort into tracking it down. But I found nothing. I don’t even know where the tablet is now, let alone what it says.
There was still plenty to work with from the other ancient evidence, however.
The Eber’s papyrus
While some of the remedies in the Eber’s papyrus are still used today – at least, the guinea worm treatment it, some of the remedies are not.
One of my favourite treatments was for blindness. One needed to gather “the two eyes of a pig (remove the water therefrom), true collyrium, red-lead, and wild honey, then crush, powder, make into one, and inject into the ear of the patient. Thereby he will at once recover. When thou hast seen properly to this mixing, repeat this Magic Formula: ‘I HAVE BROUGHT THIS THING AND PUT IT IN ITS PLACE. THE CROCODILE IS WEAK AND POWERLESS.’ (Twice)”.
While I suspect this remedy would not work, next time I need medicine, I would love it if the pharmacist were to shout the Magic Formula at me. I’ve made myself laugh so much imagining a pharmacist bringing me some cream, looking me dead in the eyes, and shouting this:
I HAVE BROUGHT THIS THING AND PUT IT IN ITS PLACE. THE CROCODILE IS WEAK AND POWERLESS.
I would stare at them for a moment, unblinking, and they would have to shout it again:
I HAVE BROUGHT THIS THING AND PUT IT IN ITS PLACE. THE CROCODILE IS WEAK AND POWERLESS.
I would be so happy.
Hippocrates
You know the Hippocratic oath?
“First do no harm“?
That one?
Yeah, that’s not what it says.
One translation from the earliest surviving copy of the Hippocratic oath from AD 1595 (a couple of thousand years after Hippocrates – this would be another reason to maybe doubt the veracity of some of the ancient evidence…) starts with swearing to:
- Apollo Healer – Apollo, but with “Acestor”, or “healer”, added to describe his role as, presumably, a healer
- Asclepius – him of the rod
- Hygieia – his daughter, and the etymology of “hygiene”
- Panacea – another of his daughters, and the etymology of the cure-all drug of the same name
Then the oath makes the trainee healer make their teacher their partner in their livelihood, give money to them as they need it, teach their children for free, and not teach anyone else medicine.
Then something about dietary regimens, and then “I will do no harm or injustice to them [their patients]”.
The oath also restricts the trainee healer from poisoning people, stops them from giving women a pessary to cause abortion (though other methods may be acceptable, as may women applying the pessary themselves, it isn’t clear), stops them from cutting people open (looks like this is reserved for another profession?), makes them help the sick in any house they enter (this is a good one), and stops them from “abusing the bodies of man or woman, bond or free”.
So, you know, good and all that (though it’s always questionable when you need to swear an oath to not poison or abuse anyone). But it’s not “first do no harm”.
It’s more:
First, swear to these Gods. Second, set your teacher up for life. Third, diet diet diet! Fourth, do no harm. And don’t abuse anyone. Or poison them. Yes, even if they’re women. Or slaves. Why do we need to keep going over this? STOP IT.
Edward Stone
This is for anyone in Devon.
In his report about willow bark and agues, Reverend Stone also noted that:
“the beft Cyder-apples grow in Herefordfhire, Devonfhire and the adjacent counties”.
A claim that I’m sure the residents of those counties would agree with.
Why did he feel the need to state this in a report about willow bark and agues?
Who knows…
William Withering
Foxgloves and digoxin are such a good parallel with willow bark and aspirin: I also learned at medical school about the old lady who gave out foxglove tea, but that’s also apocryphal. “Mother Hutton” was a marketing gimmick.
But one interestingly part of this story was that Withering gave a second opinion on a patient of Erasmus Darwin (grandfather of Charles Darwin), suggesting foxgloves as a treatment. Darwin evidently ran with this, and in 1785 submitted a paper called “An Account of the Successful Use of Foxglove in Some Dropsies and in Pulmonary Consumption” to the College of Physicians in London, referencing Withering.
Later Withering and Darwin had a falling out, because Darwin’s son, Robert Darwin (Charles Darwin’s father) accused Withering of poaching patients. Not literally, one would assume.
Withering was also once chased by pirates while returning for Portugal, hoping the better winter climate would help his self-diagnosed TB (it didn’t).
There are a few other well-known historical figures that pop up as asides, but this is the first one, I think. It’s like that Kevin Bacon “five degrees of separation” game, but for people from history.
“What connects Hippocrates, several Darwins, Mother Hutton, Napoleon, and Edison? Why, the origins of aspirin, of course.”
Napoleon
Between 1806 and 1814, Napoleon set up the Continental Blockade, which blocked British imports to much of continental Europe, in response to a blockade by the British of the French coasts.
This may have affected supplies of Cinchona tree bark, widely used to treat malaria, including (earlier) by Stone. This may have led to the search for alternative remedies, resulting in much of the timeline in the article.
The increasing rarity, price, and necessity of Cinchona tree bark as European powers colonised areas with endemic malaria likely also contributed.
But still, arguably Napoleon is part of the origin story of aspirin.
Neat.
Fever trees
By the mid-19th century, the British had created “fever tree” plantations in Southern India, comprised of Cinchona trees. This provided them with a ready source of quinine to combat malaria in their soldiers and civil servants.
Because quinine was very bitter, it was regularly put into “tonics” containing bubbly water and sugar, as well as some alcohol to mask the taste. Often, this was gin (hence, gin and tonic, particularly “fever-tree” tonics – tonic contained more quinine then than now, but still contains some), but other alcohols were used as well, including whisky and wine.
Tasty bitter tonicy wine. Lovely.
XKCD – the difference between a normal person and a scientist
In 1855, Cesare Bertagnini, a student of Pirìa (who was also cut), described tinnitus caused by ototoxicity from taking massive doses of salicylic acid (about 6g) derived from wintergreen oil over 2 days:
“On the first day no symptoms appeared, but on the second a continuous noise in the ears and a kind of dizziness appeared, after which the ingestion was suspended”
He subsequently gave a “healthy and robust man” 7.5g of salicylic acid, and the man also experienced a ringing in the ears.
This immediately made me think of this XKCD comic.
Bertagnini also stated that Laveran, Millon, and Rauke (not elsewhere mentioned) had experimented on the urine of “patients who have taken salicin”, implying salicin was being used as a treatment at this time.
Heroin
What did Hoffman do after creating aspirin?
Heroin.
As in, synthesize heroin, although given the propensity for self-testing…
From the Wikipedia page: “Hoffmann synthesized heroin on 21 August 1897, just eleven days after he had synthesized aspirin.”
Heroin was named as such due to its “heroic” nature (fairly certain Dreser did this naming, but can’t be sure): it could treat everything from a child’s cough to horrific injuries from war. Hoffman wasn’t the first person to synthesise diamorphine (heroin), that was likely Charles Romley Alder Wright, who wanted to create a non-addictive version of morphine (good work, buddy).
After Hoffman synthesised heroin, Bayer tested, manufactured and sold it over the counter (until 1913).
It stopped once people realised how addictive it was.
What a fortnight for Hoffman though.
The Great Phenol Plot
This is just bonkers.
Phenol was used to make aspirin. But it has many other uses.
From the Wikipedia page on the Great Phenol Plot (on which this is all based):
“The Great Phenol Plot was a clandestine effort by the German government during the early years of World War I to divert American-produced phenol from the manufacture of high explosives that supported the British war effort. Phenol was used by the German-owned Bayer company, which could no longer import the compound from Britain, to produce aspirin.”
So, Germany needed phenol to make aspirin (via salicylic acid), and Britain needed phenol to make high explosives (via picric acid).
Britain made phenol, Germany needed to import it, which was a problem when they were at war.
The US also needed phenol.
Why?
Because it was needed for Thomas Edison’s “Diamond Disc” phonograph records, which were partly made from an early plastic made from phenol.
By 1915, the British were barely exporting any phenol, since it was diverted to explosive making. Bayer was finding it hard to make aspirin (even at their US plant, which was apparently feeling a bit cut off from the German headquarters due to the war anyway), and counterfeiters were swooping in to hoover up aspirin sales.
The US was finding it hard to make phonographs.
So, Edison set up a plant in Pennsylvania to produce a tonne of phenol (well, 11 tonnes per day). Any excess production was likely to be sent to the British to support their explosives production.
In 1915, the US was officially neutral on The Great War, though it was a bit anti-German in their trading, especially after a German U-boat sank a British ship, the RMS Lusitania, carrying 128 US ctizens.
The German ambassador to the US, Johann Heinrich von Bernstorff, and an Interior Ministry official, Heinrich Albert, were tasked with undermining American industry and maintaining public support for Germany. They recruited a former Bayer employee, Hugo Schweitzer, to help them.
Schweitzer, using money funnelled from Germany by Albert, help set up a contract to buy all of Edison’s excess phenol, which was sent to a German-owned American subsidiary company to make salicylic acid for aspirin production. About 3 tonnes a day were sent by July 1915, which gave the US Bayer plant more than enough salicylic acid to make aspirin. Any leftovers were sold on to non-war-related industries for profit.
In July 1915, Albert was under investigation by the Secret Service. He left his briefcase, containing important papers about the phenol plot (among other incriminating papers) on a train, which the Secret Service picked up. Because clearly they knew they were in a spy film.
The papers, while note enough to take down Albert, were leaked to the New York World, an anti-German newspaper. The resulting public backlash forced Albert to stop funding phenol purchases and damaged Edison’s reputation. They managed to keep some payments going for a little while longer by funnelling money from elsewhere, but it didn’t last long. Edison switched to sending his excess phenol to the US military.
Apparently, this scheme diverted enough phenol to make 2,000 tonnes of explosives, and netted the plotters the equivalent of about $44 million.
Collier’s magazine
Sneader evidently wasn’t the first person to delve into the aspirin controversy.
Harry Henderson agreed with Sneader’s article, stating that he had also looked into the evidence back in 1953 for a magazine article (only 4 years after Eichengrün’s article).
The magazine article exists, but sadly I couldn’t find a copy online. I didn’t try nearly as hard to find the magazine as I did trying to find the Eichengrün article, though.
The number of cigarette adverts in other 1953 editions of Collier’s magazine that I found was a little jarring, however.
That’s all, folks
I didn’t keep careful track of all the footnotes and asides that I wrote and then discarded, but I think that’s pretty much everything.
So, I’ll end this with a hearty:
I HAVE BROUGHT THIS THING AND PUT IT IN ITS PLACE. THE CROCODILE IS WEAK AND POWERLESS.
I HAVE BROUGHT THIS THING AND PUT IT IN ITS PLACE. THE CROCODILE IS WEAK AND POWERLESS.
Sean Harrison: Blog 