Around 400 BCE, Hippocrates wrote that women in labor could chew the bark of the white willow tree to ease their pain, and that bark tea reduced fever. Native American medicine cabinets included willow bark for the same reasons. Egyptians had been using it since at least 1500 BCE. Across continents and millennia, willow bark was the world's most reliable painkiller.

Nobody knew why it worked.

In 1828, a German chemist named Johann Buchner extracted the active ingredient from willow bark. He called the bitter yellow crystals salicin, after Salix — the Latin name for willow. Twenty years later, salicin was refined into salicylic acid. It worked. It also wrecked stomachs and tasted vile. Patients vomited. Bleeding ulcers were common.

In 1897, a chemist at the Bayer dye company in Germany — Felix Hoffmann, possibly assisted by Arthur Eichengrün — modified salicylic acid by attaching an acetyl group. The result was acetylsalicylic acid: gentler on the stomach, easier to dose, equally effective. Bayer trademarked it Aspirin.

For the next 70 years, no one understood the mechanism. People took aspirin because it worked. Then in 1971, a British pharmacologist named John Vane showed that aspirin inhibits an enzyme called cyclooxygenase, which produces prostaglandins. Prostaglandins are the body's pain and fever messengers. Block them, and pain and fever fade. Vane won the Nobel Prize for it.

Aspirin is still one of the most widely used drugs on the planet. About 100 billion tablets are consumed every year. Researchers are still finding new uses — heart attack prevention, possibly some cancers.

A 2,400-year-old painkiller that humanity is still figuring out.