The mid- to late 19th century saw the science of chemistry declare war on pain and physical suffering. Some of the new developments had their roots in traditional medicines, others were the result of years devoted to trial and error, and a few were simply pure luck.
The first wholly synthetic drugs were gases. In 1799, English chemist Humphry Davy (1778-1829) discovered the painkilling properties of nitrous oxide, also known as laughing gas. In 1815, similar properties were noted for ether vapor. Both proved to be popular social novelties due to their intoxicating side effects.
But, amazingly, it was another 30 years before medical practitioners were to take advantage of their painkilling properties to perform surgery. In 1847, a stronger anesthetic gas, chloroform vapor, was developed by Scottish obstetrician James Simpson (1811-70), and used to help women during childbirth. None of the gases was free from side effects, notably that they made the patient unconscious, or at least insensible, and they were poisonous in large doses.
The use of certain plants to treat pain and fever has an extremely long history. Ancient Egyptians used myrtle, ancient Greeks and medieval Europeans used willow and meadowsweet, and Native Americans used birch. It turns out that all of these plants contain the same active ingredient, called salicin after the scientific name for willow, Salix.
The medicinal use of willow was rediscovered by English clergyman Edward Stone (d. 1768). In 1763, he reported that he had successfully used willow bark to reduce fever in 50 of his patients. German pharmacist Johann Buchner (1783-1852) first isolated salicin from willow in 1828. Ten years later, Italian chemist Raffaelle Pira (1814-65) extracted the active ingredient, salicylic acid, which took the form of colorless crystals. In 1853, French chemist Charles Gerhardt (1816-56) modified the structure of salicylic acid and created acetylsalicylic acid. But the crucial breakthrough in the evolution of the drug came in 1859, when another German chemist, Hermann Kolbe (1818-84), figured out the chemical structure of salicylic acid, and came up with a means of synthesizing it on a large scale—not from plants but from coal tar. Using the Kolbe reaction, the new drug went into mass production.