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The discovery of aspirin

This month in 1897: aspirin, one of the world's best-known drugs, was synthesised
1897

Ask most people if they recognise the names of some of the most commonly used drugs launched in the past few decades, and chances are – unless they themselves take the medicines - they'll be caught in a confusion of Zs and Xs jumbled in a way that's impossible to pronounce.

By contrast, one drug that everyone in the world is aware of – and not just for its simple to pronounce name – is aspirin, which can add diversity, efficacy and longevity to the list of reasons why almost every household has a box or two and everyone knows what the pharmacist is on about when he recommends it.

And the painkiller has longevity indeed, celebrating its 116th birthday this year and still being among the most commonly used medicines in the world.

To be specific, aspirin's anniversary occurs on August 10, for it was on that date in 1897 that Felix Hoffmann, a chemist at German life science firm Bayer, first synthesised the active ingredient of aspirin – acetylsalicylic acid – in a form that was pure and stable.

Mostly by chance
According to Bayer's biography of Hoffman, it was 'mostly by chance' that the chemist succeeded in mixing salicylic acid with acetic acid to create what is now widely recognised as a breakthrough treatment in the history of medicine.

A common story to explain Hoffman's research is that he was encouraged by his father, who had arthritis, to develop an alternative treatment to sodium salicylate – juice from the willow tree bark that had been used for centuries as a painkiller and treatment for fever, but carried several unpleasant side effects, including nausea, gastro-intestinal irritation, tinnitus and liver damage.

The solution was promising enough to catch the attention of the head of Bayer's pharmaceutical laboratory, Heinrich Dreser, who alongside Hoffman tested acetylsalicylic acid on animals and then humans, where its effect was notable enough to encourage them to apply for a patent.

However, Walter Sneader offers an alternative account in his article 'The discovery of aspirin: a reappraisal' for the British Medical Journal (BMJ), in which he explains that this explanation first appeared in 1934 as part of an unreliable footnote in a history of chemical engineering written by Albrecht Schmidt.

Instead, Sneader explains that Hoffman's research into synthesising acetylsalicylic acid was actually done under the instruction of his colleague Arthur Eichengrün.

Although disputed by Bayer, Sneader's piece suggests that Eichengrün had wanted to develop an alternative to sodium salicylate, and was present when several derivatives of salicylic acid were tested by Dreser.

Sneader cites Eichengrün's 1949 paper, published in the journal Pharmazie, in which Eichengrün claims that Dreser actually vetoed further study of acetylsalicylic acid, wrongly believing it to be harmful to the heart.

Despite these concerns from his boss, Eichengrün tested acetylsalicylic acid on himself to confirm its safety, before supplying the compound to fellow Bayer scientist Felix Goldmann, who then recruited physicians to evaluate the drug.

Reports from these effects were encouraging, according to Sneader, with the drug able to provide antirheumatic effects without side effects, such as tinnitus.

Eichengrün even quotes a patient with toothache who exclaimed “My toothache's gone!” almost immediately after receiving treatment with acetylsalicylic acid.

As part of Sneader's paper, he goes on to explain that Dreser still doubted the benefits of acetylsalicylic acid, and it was only on the intervention of Bayer's head of research, Carl Duisberg, that further research of the compound was undertaken, including Dreser's own reinvestigation in September 1898.

Those who doubt Sneader's paper have noted that Eichengrün waited 15 years to refute the claims about Hoffman and his father published in 1934.

However, Sneader's riposte is that Eichengrün had a very valid reason – he was a Jew living in Nazi Germany.

This circumstance made it impossible to write a high profile rebuttal, although he did write a letter in 1944 during a period in the Theresienstadt concentration camp, in which he described how his name was not positioned alongside his invention of acetylcellulose in the German Museum in Munich, whereas both Dreser and Hoffmann were credited beside the exhibition for aspirin.

“To what influences this omission is to be attributed, can be only assumed,” he muses.

Sneader offers his own guess in his paper: “There can be little doubt that he felt that he had been written out of history because he was a Jew.” 

In any case, Hoffman did synthesise a pure and stable form of acetylsalicylic acid on August 10, 1897, and just two years later, Bayer was producing the drug under the name Aspirin as a powder supplied in glass bottles.

Since then, the drug has gone on to achieve unimaginable success, making Bayer's name in the medicines world.

Of those who contributed to its creation (depending on what story you trust) Hoffmann, who also synthesised a stable version of heroine, went on to become head of the pharmaceutical marketing department at Bayer, before retiring in 1928 then dying in 1946.

Eichengrün was released from Theresienstadt after the war ended in 1945, but would only live for four more years before dying in 1949 at the age of 82.

Article by
Tom Meek

web editor at PMLiVE

9th August 2013

From: Research, Healthcare

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