Before its development as a surgical anesthetic, ether was used throughout the history of medicine, including as a treatment for ailments such as scurvy or pulmonary inflammation. A pleasant-smelling, colorless and highly flammable liquid, ether can be vaporized into a gas that numbs pain but leaves patients conscious. In 1846, Georgia physician Crawford Williamson Long became the first doctor to use ether as a general anesthetic during surgery, when he used it to remove a tumor from the neck of his patient James M. Venable.

Long did not publish the results of his experiments until 1848, and by that time Boston dentist William T.G. Morton had already gained fame with the first publicly demonstrated use of ether as an effective surgical anesthetic. After watching his colleague Horace Wells unsuccessfully promote nitrous oxide as an anesthetic, Morton concentrated on the possibility of ether. On March 30, 1842, he administered it to a patient at Massachusetts General Hospital, before a surgeon removed a tumor from the patient’s jaw.

Also called trichloromethane, chloroform is prepared through the chlorination of methane gas. It was first prepared in 1831 by the American chemist Dr. Samuel Guthrie, who combined whiskey with chlorinated lime in an attempt to produce a cheap pesticide. In 1847, the Scottish physician Sir James Young Simpson first used the sweet-smelling, colorless, non-flammable liquid as an anesthetic. When administered by dripping the liquid onto a sponge or cloth held so that the patient inhaled the vapors, chloroform was seen to have narcotic effects on the central nervous system and produced these effects relatively quickly.

On the other hand, there were higher risks associated with chloroform than with ether, and its administration required greater physician skill. There were early reports of fatalities due to chloroform, beginning with a 15-year-old girl in 1848. Skill and care were required to differentiate between an effective dose (enough to make the patient insensible during surgery) and one that paralyzed the lungs, causing death. Fatalities were widely publicized, and the risks involved led some patients facing surgery to decline anesthesia and brave the pain. Still, the use of chloroform spread quickly, and in 1853 it was famously administered to Britain’s Queen Victoria during the birth of her eighth child, Prince Leopold.

American military doctors began using ether as an anesthetic on the battlefield during the Mexican-American War (1846-1848), and by 1849 it was officially issued by the U.S. Army. Though many army doctors and nurses had experience with using ether by the time of the Civil War, chloroform became more popular during that conflict, due to its faster-acting nature and a large number of positive reports of its usage during the Crimean War in the 1850s. During the Civil War, chloroform was used whenever it was available to reduce the pain and trauma of amputation or other procedures.

Usage of ether and chloroform later declined after the development of safer, more effective inhalation anesthetics, and they are no longer used in surgery today. Chloroform, in particular, came under attack in the 20th century and was shown to be carcinogenic by ingestion in laboratory mice and rats. It is now used mainly in the preparation of fluorocarbons, used in aerosol propellants and refrigerants; it is also found in some cough and cold medicines, dental products (including toothpaste and mouthwashes), topical liniments and other products.