Hoffmann acetylated salicylic acid to make it tolerable

Salicylic acid, extracted from willow and other plants, had long been used to relieve pain and fever. But it had a serious drawback: taken in the doses needed, it badly irritated the stomach, and it could only be used in a limited way. In the 1890s chemists at Bayer, the German company founded in 1863, were looking for a better-tolerated version.

In the summer of 1897 Felix Hoffmann, a young Bayer chemist in Wuppertal-Elberfeld, took up the problem. Legend has it his own father was being treated with salicylic acid for arthritis and was suffering severe side effects, so Hoffmann had a personal stake in finding a form his father could take. He tried many different synthesis processes until, on August 10, 1897, he produced the first chemically pure and stable form of acetylsalicylic acid, as noted in his lab journal.

The chemical change he made is the whole idea. He added an acetyl group to the salicylic acid molecule. That masked the free acid that was doing the damage to the stomach, so the new compound was much less directly irritating, and it acted as a prodrug: once in the body it is broken back down into the active salicylate that relieves pain and fever. So he kept the therapeutic benefit and removed the worst of the side effect, and the acetylation also made the compound pure and stable enough to be made as a consistent pill.

Bayer registered the trademark Aspirin in Berlin in 1899 and patented the process in the United States the following year. It became the most widely used medicine of the twentieth century, an essential medicine on the World Health Organization's list, and was even taken to the moon on Apollo 11 in 1969.