Long, who was born in Danielsville, Georgia, received his MD from the University of Pennsylvania in 1839. He then practiced in the small Georgian village of Jefferson where he became probably the first physician to perform surgery using ether as an anesthetic. (There is one earlier record of the administration of ether, for a tooth extraction: in January 1842, William Clark gave ether to a patient whose tooth was then removed by Elijah Pope.)

The idea of using ether came to Long after he had engaged in ‘ether frolics’ – wild parties at which ether was inhaled for exhilarative effect. Long noticed that he developed many bruises during such parties but had no recollection of sustaining any injuries. This suggested to him the possibility of using it more constructively to provide surgical anesthesia. Consequently on 30 March 1842, Long removed a small tumor from the neck of an etherized patient who assured him, when he regained consciousness, that he had not experienced any pain. Long followed this up in July by painlessly amputating the toe of a young etherized boy. However, Long had little chance to use his dramatic discovery in major operations and did not publish details until 1849. By this time William Morton had already (1846) given a public demonstration of the use of ether as an anesthetic and Long thus received little credit for his discovery.