1798–1800: Humphry Davy and Nitrous Oxide

• 1798: Thomas Beddoes establishes the Pneumatic Institution in Bristol, England, to explore the use of various gases in treating pulmonary tuberculosis. A young chemist, Humphry Davy (aged 20), is appointed to superintend the laboratory.
• 1798–1800: Davy engages in extensive self-experimentation with nitrous oxide, observing its capacity to diminish or abolish pain. He proposes its potential application in surgical procedures but does not pursue the idea further.
• 1800: Davy publishes a comprehensive 580-page book on nitrous oxide experiments. Within it, he includes the now-famous statement: “As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place.”Despite the significance of this suggestion, it goes largely unnoticed at the time.

References:

• Keys TE. The History of Surgical Anesthesia. New York: Schuman’s; 1945.
• Mitchill SL. Remarks on the Gaseous Oxyd of Azote or Nitrous Oxide. New York: T. & J. Swords; 1795.
• Davy H. Researches, Chemical and Philosophical: Chiefly Concerning Nitrous Oxide, or Dephlogisticated Nitrous Air, and Its Respiration. London: J. Johnson; 1800.
• Fujinaga M, Maze M. Neurobiology of nitrous oxide-induced antinociceptive effects. Mol Neurobiol. 2002;25(2):167–89.
• Ramsay DS, Watson CH, Leroux BG, Prall CW, Kaiyala KJ. Conditioned place aversion and self-administration of nitrous oxide in rats. Pharmacol Biochem Behav. 2003;74(2):263–74.

Early 1800s: The Emergence of Morphine

• 1800: The United States has only four medical schools. At the University of Pennsylvania, Benjamin Rushattempts to relieve labor pain through bloodletting, reflecting the limitations of contemporary practice.
• 1803: German pharmacist Friedrich Sertürner isolates morphine from opium. This represents a landmark in pain management, being the first purified alkaloid used for analgesia.
• 1809: Accounts describe extreme bloodletting, including the case of Captain James Niblett in the United States, who was bled of approximately 600 ounces of blood over a two-month period.

References:

• Stanley P. For Fear of Pain: British Surgery, 1790–1850. Amsterdam: Rodopi; 2003.

1810–1820: Surgical Agony and Psychological Trauma

• 1811: The novelist Fanny Burney undergoes a mastectomy without anesthesia. She later documents her experience, describing profound suffering and persistent psychological distress—an early account consistent with what is now recognized as post-traumatic stress disorder (PTSD).
• 1818: Michael Faraday observes that ether vapor produces effects similar to nitrous oxide. He cautions, however, about possible dangers, including prolonged lethargy.
• 1819: Sir Walter Scott undergoes repeated bloodletting and blistering for severe stomach cramps, illustrating the acceptance of pain and invasive therapies as a routine part of medical care.

References:

• Stanley P. For Fear of Pain: British Surgery, 1790–1850. Amsterdam: Rodopi; 2003.
• Brooks D. The agony of surgery before anesthesia. The New York Times. 2011 Oct 10.
• Simpson J. Personal communication cited in: Eger EI II, Westhorpe RN, Saidman LJ, editors. The Wondrous Story of Anesthesia. New York: Springer; 2014.
• Faraday M. On the effects of inhaling the vapour of sulphuric ether. Q J Sci Arts. 1818;4:158–61.
• Faraday M. Additional observations on the effects of inhaling the vapour of ether. Q J Sci Arts. 1818;5:423–4.

The 1820s: The Hickman Era

• 1822: Surgeon Robert Liston performs a complex tumor excision under rudimentary and painful conditions, demonstrating the severe physical toll on patients prior to anesthesia.
• 1823: The Lancet is first published, marking a major step in the dissemination of medical knowledge. In 1828, the Boston Medical and Surgical Journal (later the New England Journal of Medicine) begins publication, further broadening medical communication.
• 1823–1824: Physician Henry Hickman experiments with animals, inducing “suspended animation” using carbon dioxide, which allows painless surgery. He reports these findings to the Royal Society and to King Charles X of France, but his work is disregarded.
• 1829: Benjamin Babbington pioneers indirect laryngoscopy, using mirrors to visualize the glottis. This represents an important step toward modern airway management.

References:

• Stanley P. For Fear of Pain: British Surgery, 1790–1850. Amsterdam: Rodopi; 2003.
• Wolfe RJ. Robert C. Hinckman and Inhalation Anesthesia. Boston: Boston Medical Library; 2001.

The 1830s: The Rise of Chloroform

• 1830: Surgeon James Syme performs ninety-five major operations in a single year—including amputations, tumor excisions, and hernia repairs—all without anesthesia.
• 1831: Chloroform is independently discovered by Justus von Liebig, Eugène Soubeiran, and Samuel Guthrie.
• 1832–1837: In Australia, William Bland attempts subclavian aneurysm ligations. These operations are prolonged and often fatal, reflecting the severe limitations of surgery before anesthesia.
• 1839: French surgeon Alfred Velpeau famously declares that pain in surgery is inevitable and dismisses the possibility of anesthesia as a “chimera.”
• 1840: The United States now has thirty medical schools. Curricula remain limited, and women are excluded from admission. Surgical practice expands internationally into Latin America and the Nordic countries, but still without anesthetic techniques.

References:

• Stanley P. For Fear of Pain: British Surgery, 1790–1850. Amsterdam: Rodopi; 2003.
• Fergusson W. A System of Practical Surgery. London: John Churchill; 1842.

The 1840s: Ether’s Lost Moment

• 1842: Dentist William Clarke administers ether to anesthetize Miss Hobbie for a tooth extraction. Although the procedure is successful, Clarke does not recognize its broader significance and does not promote the discovery.
• 1842: Physician Crawford Long in Georgia uses ether to anesthetize James M. Venable during removal of a neck tumor. Long subsequently performs several ether-based surgeries with success, but delays publication until 1849, losing the chance to be credited as the first discoverer.
• 1846: Elton Romeo Smilie administers an ether-opium mixture to a patient with tuberculosis. The patient becomes anesthetized, but Smilie attributes the effect to opium, overlooking the true role of ether.

References:

• Keys TE. The History of Surgical Anesthesia. New York: Schuman’s; 1945.
• Long CW. An account of the first use of sulphuric ether by inhalation as an anaesthetic in surgical operations. South Med Surg J. 1849;5:705–13.
• Wolfe RJ. Robert C. Hinckman and Inhalation Anesthesia. Boston: Boston Medical Library; 2001.
• Smilie ER. Inhalation of ethereal tincture of opium in a case of phthisis. Boston Med Surg J. 1846;35:153–4.
• Wolfe RJ. Tarnished Idol: William Thomas Green Morton and the Introduction of Surgical Anesthesia. San Anselmo: Norman Publishing; 2001.