History of aspirin
In 1897, scientists at the drug and dye firm Bayer began investigating acetylated organic compounds as possible new medicines, following the success of acetanilide ten years earlier.
[3]: 247–257 Aspirin sales revived considerably in the last decades of the twentieth century, and remain strong in the twenty-first with widespread use as a preventive treatment for heart attacks and strokes.
[8] Gerard[9] quotes Dioscorides, 'that [the bark] being burnt to ashes, and steeped in vinegar, takes away corns and other like risings in the feet and toes,' which is similar to modern uses of salicylic acid.
Nicholas Culpeper, in The Complete Herbal,[11] gave many uses for willow, including to staunch wounds, to 'stay the heat of lust' in man or woman, and to provoke urine ('if stopped') but, like Celsus, made no mention of any analgesic properties.
[16][18] In 1834, Swiss pharmacist Johann Pagenstecher extracted a substance from meadowsweet which, he suggested, might reveal an "excellent therapeutic aspect", although he was uninterested in increasing the number of chemicals available to pharmaceutical science.
[20][21] The German chemist who had been working to identify the Spiraea extract, Karl Jacob Löwig, soon realized that it was in fact the same salicylic acid that Piria had found.
[22][23][3]: 38–40 The first evidence that salicylates might have medical uses came in 1876, when the Scottish physician Thomas MacLagan experimented with salicin as a treatment for acute rheumatism, with considerable success, as he reported in The Lancet.
[27] By the 1880s, the German chemical industry, jump-started by the lucrative development of dyes from coal tar, was branching out to investigate the potential of new tar-derived medicines.
[3]: 40–46 The turning point was the advent of Kalle & Company's Antifebrine, the branded version of acetanilide —the fever-reducing properties of which were discovered by accident in 1886.
[28] Antifebrine's success inspired Carl Duisberg, the head of research at the small dye firm Friedrich Bayer & Company, to start a systematic search for other useful drugs by acetylation of various alkaloids and aromatic compounds.
Dreser, Eichengrün and Hoffmann would be the key figures in the development of acetylsalicylic acid as the drug Aspirin (though their respective roles have been the subject of some contention).
The next step would normally have been clinical trials, but Dreser opposed further investigation of ASA because of salicylic acid's reputation for weakening the heart—possibly a side effect of the high doses often used to treat rheumatism.
[25] Dreser's group was soon busy testing Felix Hoffmann's next chemical success: diacetylmorphine (which the Bayer team soon branded as heroin because of the heroic feeling it gave them).
Eichengrün, frustrated by Dreser's rejection of ASA, went directly to Bayer's Berlin representative Felix Goldmann to arrange low-profile trials with doctors.
[31] Axel Helmstaedter, General Secretary of the International Society for the History of Pharmacy, subsequently questioned the novelty of Sneader's research, noting that several earlier articles discussed the Hoffmann–Eichengrün controversy in detail.
Advertising drugs directly to consumers was considered unethical and strongly opposed by many medical organizations; that was the domain of patent medicines.
The company's attempts to hold onto its Aspirin sales incited criticism from muckraking journalists and the American Medical Association, especially after the 1906 Pure Food and Drug Act that prevented trademarked drugs from being listed in the United States Pharmacopeia; Bayer listed ASA with an intentionally convoluted generic name (monoacetic acid ester of salicylic acid) to discourage doctors referring to anything but Aspirin.
[3]: 88–96 [1]: 28–31 By the outbreak of World War I in 1914, Bayer was facing competition in all its major markets from local ASA producers as well as other German drug firms (particularly Heyden and Hoechst).
[1]: 38–39 Schweitzer set up a contract for a front company called the Chemical Exchange Association to buy all of Edison's excess phenol.
After the U.S. declared war on Germany in April 1917, alien property custodian A. Mitchell Palmer began investigating German-owned businesses, and soon turned his attention to Bayer.
Despite this, some people believed that Germans put the Spanish flu bug in Bayer aspirin, causing the pandemic as a war tactic.
[3]: 151–152 Sterling Products, equipped with all of Bayer's U.S. intellectual property, tried to take advantage of its new brand as quickly as possible, before generic ASAs took over.
After several moderately successful compound drugs that mainly utilized aspirin (Anadin and Excedrin), Bayer Ltd's manager Laurie Spalton ordered an investigation of a substance that scientists at Yale had, in 1946, found to be the metabolically active derivative of acetanilide: acetaminophen.
[3]: 212–217 Also in the early 1980s, several studies suggested a link between children's consumption of aspirin and Reye's syndrome, a potentially fatal disease.
In 1958 Harry Collier, a biochemist in the London laboratory of pharmaceutical company Parke-Davis, began investigating the relationship between kinins and the effects of aspirin.
He found that cutting the guinea pigs' vagus nerve did not affect the action of bradykinin or the inhibitory effect of aspirin—evidence that aspirin worked locally to combat pain and inflammation, rather than on the central nervous system.
In 1963, Collier began working with University of London pharmacology graduate student Priscilla Piper to determine the precise mechanism of aspirin's effects.
Vane and Piper tested the biochemical cascade associated with anaphylactic shock (in extracts from guinea pig lungs, applied to tissue from rabbit aortas).
Later research showed that NSAIDs such as aspirin worked by inhibiting cyclooxygenase, the enzyme responsible for converting arachidonic acid into a prostaglandin.
Medical Research Council haematologist John O'Brien picked up on Weiss's finding and, in 1963, began working with epidemiologist Peter Elwood on aspirin's anti-thrombosis drug potential.
