He was educated at Phillips Academy in Andover, Massachusetts, and at Harvard College. In 1833 Holmes attended the famed École de Médecine in Paris. He pursued his medical studies in the Parisian hospital system, popularly viewed as the birthplace of modern medicine and the modern style of medical education, at institutions such as La Charité and La Pitié Salpêtrière. Holmes was a student of Dr. Pierre Charles Alexandre Louis, who demonstrated the ineffectiveness of bloodletting as a treatment for fevers and other disorders, which method had been a mainstay of medical practice since antiquity. Dr. Louis was one of the fathers of the méthode expectante, the therapeutic doctrine claiming that the physician's role was only to assist nature as it healed. Upon his return to Boston, Oliver Wendell Holmes Sr. became one of leading proponents of the méthode expectante in America.. Holmes' M.D. was ultimately granted from Harvard, where he would later become Parkman Professor of Anatomy and Physiology. He also served on the faculty of Dartmouth Medical School from 1838 to 1840.
He first attained national prominence with his poem Old Ironsides about the 18th century frigate USS Constitution, which was to be broken up for scrap; the poem generated public sentiment that resulted in the historic ship being preserved as a monument. One of his most popular works was The Autocrat of the Breakfast Table. He was one of the five members of the group known as the Fireside Poets. He contributed poems and essays to the Atlantic Monthly from its inception, and also published novels. Holmes is also known for his writing of several religious-themed hymns.
In 1843, Holmes published The Contagiousness of Puerperal Fever which argued that puerperal fever, a deadly disease of women giving birth, was frequently carried from patient to patient by physicians and nurses. A few years later, Ignaz Semmelweis would reach similar conclusions in Vienna, where his introduction of prophylaxis (handwashing in chlorine solution before assisting at delivery) would lower the puerperal mortality rate considerably. Holmes, seeing more clearly than Semmelweis that something like microbial action must be involved -- his famous essay was an uncanny anticipation of Pasteur's discovery of the germ theory of disease later in the century -- was altogether more radical. A physician in whose practice even one case of puerperal fever had occurred, wrote Holmes, had a moral obligation to purify his instruments, burn the clothing he had worn while assisting in the fatal delivery, and cease obstetric practice for a period of at least six months.
Holmes was a vocal critic of homeopathy, while his major argument centered on the failure to use the scientific method. In 1842 he published an essay Homeopathy and Its Kindred Delusions in which he denounced the practice.
Holmes's essay had a major impact. Though it largely escaped notice when published as an article in a Boston medical journal, it commanded a great deal of attention it reappeared as a book several years later, on the occasion of an attack on Holmes by two famous professors of obstetrics who denied his theory of contagion. Republished with a new and powerfully written introduction by Holmes, "The Contagiousness of Puerperal Fever" then became a center of controversy on both sides of the Atlantic. By the 1860s, as Holmes himself would remark in "The Professor at the Breakfast Table," both American and British physicians had come to understand that a physican or midwife who assisted at puerperal fever case must cease obstetric practice until the threat of contagion was past. In New England, where Holmes's arguments had their earliest and most pronounced influence, the death rate from puerperal fever dropped dramatically.
In 1846, in a letter to William T. G. Morton, the dentist who was the first practitioner to publicly demonstrate the use of ether during surgery, Holmes coined the word anesthesia. Dr. Holmes developed the popular model of the stereoscope, a 19th century entertainment in which pictures were viewed in 3-D. He was widely known and admired during his life. The noted Sherlockian Michael Harrison conjectured that the British author Arthur Conan Doyle drew one inspiration for his famous fictional detective Sherlock Holmes from a real-life self-described "consulting detective" named Wendel Scherer changing "Scherer" to "Sherlock" and "Wendel" to "Holmes" by association with Oliver Wendell Holmes. For many years, Mary Eleanor Wilkins Freeman was his private secretary.
There is a frequently repeated story about Dr. Holmes, but not always mentioning him by name. While awakening from ether induced unconsciousness, he strongly believed he had discovered the key to all the mysteries of the universe. He wrote down the secret, but when his head had cleared he found he'd written "A strong smell of turpentine prevails throughout.
Holmes died quietly after falling asleep in the afternoon of Sunday, October 7, 1894. He is buried in Mount Auburn Cemetery in Cambridge, Massachusetts.