The ancestors of Asperin

For millennia, pain, fever and inflammation were commonly treated with plants that contained salicylic acid glycosides: leaves of myrtle (Myrtus spp), bark of willow (Salix spp.), bark of poplar (Populus spp.), meadowsweet (Spirea spp. - recently reclassified as Filipendula spp.).

Even about 3500 years ago, an Egyptian papyrus recommended the application of a decoction of the dried leaves of Myrtle to the abdomen and back to expel rheumatic pains from the womb. A thousand years later, Hippocrates advised the juices of the poplar tree for treating eye diseases and those of willow bark for pain in childbirth and for fever.
Through the Middle Ages the medical use of salicylates continued. However, willows were increasingly used for basket-making and therefore the women grew meadowsweet (Spirea ulmaria, now Filipendula ulmaria) in their gardens and made decoctions from the flowers[1].

The first 'clinical trial' of willow bark was published by English country parson Reverend Edward Stone (1702-1768). He had accidentally tasted willow bark and was surprised by its bitterness, which reminded him of chinchona bark, which contains quinine, which was at that time already in use to treat malaria. He was a believer in the 'doctrine of signature' which dictated that the cures for the diseases would be found in the same location where malady occurs.

Since the ‘Willow delights in a moist and wet soil, where agues chiefly abound’, he gathered a pound of willow bark, dried it in a baker’s oven for three months, pulverized and administered it to 50 patients with safety and success. He reported his observations to the Royal Society[2].

In 1859 Friedrich Kolbe identified the structure of salicylic acid, managed to obtain it synthetically and introduced it to therapy. However, the extremely bitter taste of the substance and the side-effects of gastric irritation caused by the acid, made it a problem if you wanted to prescribe it a prolonged periods of time.
Then, in 1897, Felix Hoffman at Bayer’s Laboratory synthesized acetylsalicylic acid, shortly thereafter named 'aspirin' (it contained the root of spiric acid from Spirea Ulmaria - which is chemically identical to salicylic acid – and added the letter 'A' as an abbreviation for 'acetyl' because the orignal German name was once acetylierte spirsäure). Hoffman had personal reasons for wanting a more acceptable salicylic acid derivative, since his father who had been taking salicylic acid for many years to treat his painful arthritis had recently discovered that he could no longer take the bitter drug without vomiting.

More than a hundred years after its introduction to therapy, aspirin remains the most popular drug in the world. It now covers far more than inflammation and pain. It is nowadays prescribed for its anti-thrombotic effects, its prevention of strokes[3] and – most recently – its anti-cancer activities[4].

[1] Vane et al (eds): Aspirin and other salicylates – 1002
[2] Stone: An account of the success of the bark of the willow in the cure of agues in Philosophical Transactions of the Royal Society – 1763
[3] Isabel et al: Stroke Prevention in Presse Medicale – 2016
[4] Patrignani et al: Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: implications for the chemoprevention of colorectal cancer in Clinical Pharmacological Therapies - 2017

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