Hippocrates, a Greek physician, wrote in the 5th century BC about a bitter powder extracted from willow bark that could ease aches and pains and reduce fevers. This remedy is also mentioned in texts from ancient Sumer, Lebanon, and Assyria. The Cherokee and other Native Americans used an infusion of the bark for fever and other medicinal purposes for centuries. The medicinal part of the plant is the inner bark and was used as a pain reliever for a variety of ailments. The Reverend Edward Stone, a vicar from Chipping Norton, Oxfordshire, England, noted in 1763 that the bark of the willow was effective in reducing a fever.
The active extract of the bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated to its crystalline form in 1828 by Henri Leroux, a French pharmacist, and Raffaele Piria, an Italian chemist. Piria was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.
Salicylic acid was also isolated from the herb meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as gastric irritation and bleeding and diarrhea, and even death when consumed in high doses.
A French chemist Charles Frederic Gerhardt was first to prepare acetylsalicylic acid (future aspirin) in 1853. In the course of his work on the synthesis and properties of various acid anhydrides, he mixed acetyl chloride with a sodium salt of salicylic acid (sodium salicylate). A vigorous reaction ensued, and the resulting melt soon solidified. Since no structural theory existed at that time Gerhardt called the compound he obtained "salicylic-acetic anhydride" (wasserfreie Salicylsäure-Essigsäure). When Gerhardt tried to dissolve the solid in a diluted solution of sodium carbonate it immediately decomposed to sodium salts of salicylic and acetic acids. This preparation of aspirin ("salicylic-acetic anhydride") was one of the many reactions Gerhardt conducted for his paper on anhydrides, and he did not pursue it further.
Six years later in 1859 von Gilm obtained analytically pure acetylsalicylic acid (he called it "acetylirte Salicylsäure") by a reaction of salicylic acid and acetyl chloride. In 1869 Schröder, Prinzhorn and Kraut (Prinzhorn is credited in the paper with conducting the experiments) repeated both Gerhardt's (from sodium salicylate) and von Gilm's (from salicylic acid) syntheses and concluded that both reactions gave the same compound--acetylsalicylic acid. They were first to assign to it the correct structure with the acetyl group connected to the phenolic oxygen.
In 1897 Felix Hoffmann a chemist at Friedrich Bayer & Co. obtained acetylsalicylic acid by a reaction of salicylic acid and acetic anhydride, that is essentially repeating the Gilm/Kraut procedure but substituting acetic anhydride for acetyl chloride. This synthesis served as the basis for Bayer claims to discovery of aspirin. According to a legend publicized by Bayer, Hoffmann made some of the formula and gave it to his father, who was suffering from the pain of arthritis and could not stand the side-effects of salicylic acid. Much later in 1949 another Bayer researcher Arthur Eichengrün asserted his own priority as a discoverer of aspirin (see below for the details of Hoffmann-Eichengrün controversy). This argument did much to obscure the real history of aspirin, whose origins is not the pharmaceutical industry but an earlier academic research. Despite the fact that pure aspirin was synthesized by von Gilm and by Kraut's group many years before Hoffmann (see above), Bayer continues to insist that "The active ingredient in Aspirin®, acetylsalicylic acid, was synthesized for the first time in a chemically pure and thus stable form in 1897 by a young chemist working for Bayer, Dr. Felix Hoffmann."
However, German patent office refused to grant Bayer patent for acetylsalicylic acid on the grounds that neither the product nor the process of preparation were novel. In 1905 Bayer sued Chemische Fabrik von Heyden in Britain for infringing the British patent on aspirin granted to it in 1900. Hayden claimed that existing prior art, in particular Kraut's work invalidated Bayer's patent. Bayer advanced the argument that they were first to prepare pure form of aspirin. Judge agreed with Hayden and invalidated Bayer patent. Similar struggle took place in the Circuit court in Chicago; however, in the US the Bayer's patent was upheld in 1909. This created a situation when aspirin in the US was three times more expensive than in Canada and ten times more expensive than in Europe, and resulted in rampant smuggling of aspirin, which Bayer unsuccessfully tried to contain. 
Bayer began marketing aspirin in July 1899. It was marketed alongside another of Hoffmann's products, an acetylated derivative of morphine called 'Heroin' that he invented 11 days after aspirin. Heroin was initially the more successful of the two painkillers and it was common belief that it was healthier than aspirin. But, as heroin's shortcoming of addictiveness became more obvious, aspirin stepped to the forefront. Aspirin was originally sold as a powder (still the preferred form in many European countries) and was an instant success; in 1914, Bayer introduced aspirin tablets.
Several claims to invention of acetylsalicylic acid have arisen. Acetylsalicylic acid was already being manufactured by the Chemische Fabrik von Heyden Company in 1897, although without a brand name. A new pretender to the title of aspirin discoverer appeared in 1949. Arthur Eichengrün who was 81 "claimed that he had instructed Hoffmann to synthesise acetylsalicylic acid and that the latter had done so without knowing the purpose of the work". In 2000, Walter Sneader of University of Strathclyde in Glasgow reexamined the case and concluded that "Arthur Eichengrün was telling the truth when he wrote that acetylsalicylic acid was synthesised under his direction and that the drug would not have been introduced in 1899 without his intervention". Subsequently, in his polemic with Sneader, Axel Helmstaedter, General Secretary of International Society for the History of Pharmacy, noted that Sneader did not credit several earlier publications which discussed the Hoffmann-Eichengrün controversy in detail, with most historians doubting Eichengrün's account. Bayer countered to Sneader in a press-release that according to the records, Hoffmann and Eichengrün held equal positions, and Eichengrün was not Hoffmann's supervisor. Hoffmann was named on the US Patent as the inventor, which Sneader did not mention. Eichengrün who left Bayer in 1908 had multiple opportunities to claim the priority and had never before 1949 done it; neither he claimed or received any percentage of the profit from aspirin sales.
It was not until the 1970s that the mechanism of action of aspirin and similar drugs called NSAIDs was elucidated (see below).
The content of this section is licensed under the GNU Free Documentation License (local copy). It uses material from the Wikipedia article "Aspirin" modified June 3, 2007 with previous authors listed in its history.