James Watt, of Steam Engine Fame, Offered Inhaled Carbon Monoxide for Putative Therapeutic Action.

James Watt (1736-1819) is remembered as a steam engine innovator and industrial magnate. A polymath, he was also a hands-on contributor to the Medical Pneumatic Institution of Thomas Beddoes. Watt recruited Humphry Davy, who there discovered analgesic action of inhaled nitrous oxide in 1799. Watt also built pneumatic equipment, and he introduced a gas mixture, dubbed hydro-carbonate, as a medical tonic. The bioactive component was carbon monoxide, a readily-lethal inhibitor of the transport and utilization of respiratory oxygen. Despite appreciable toxicity, carbon monoxide is an endogenous product of heme catabolism, and low doses of the gas are under laboratory investigation for therapeutic purposes. However, Watt's hydro-carbonate constituted a setback in the development of pharmacologically useful gases.

Burnett's "Cocaine" for dandruff.

Joseph Burnett manufactured the diethyl ether used for William T.G. Morton's public demonstration of inhaled surgical anesthesia on October 16, 1846 (Ether Day). A later Burnett product was a hairdressing oil claimed to prevent baldness and dandruff. It contained cocoa-nut oil and was called Cocoaine. In 1902 and 1903, it was sometimes advertised as Burnett's Cocaine (rather than Cocoaine), possibly to emulate the economic success of coca-based beverages such as Vin Mariani and Coca-Cola. Coca leaves are now decocainized before use in preparation of Coca-Cola, and the recovered cocaine is used for scientific and dwindling medical purposes.

Henry Jacob Bigelow Inhaled Nitrous Oxide While an Undergraduate at Harvard College.

When teenaged Henry Jacob Bigelow was an undergraduate at Harvard College in 1833-1837, he prepared nitrous oxide gas for demonstrations to other students. Bigelow's son, William Sturgis Bigelow, related the claim, and there is an eyewitness account from Augustus Goddard Peabody, a fellow Harvard undergraduate with Bigelow. Peabody wrote to Henry David Thoreau about a nitrous frolic. College chemistry primed Bigelow to support the concept of inhaled surgical anesthesia when the idea came to Boston in 1845-1846. Bigelow's chemistry professor was John White Webster. According to Harvard alumnus Edward Everett Hale, in addition to demonstrating effects of nitrous oxide, Webster presciently treated two cases of carbon monoxide poisoning with copious volumes of synthetic oxygen gas. The career of Webster was inhibited by financial difficulties that were suspected to be contributory when he was convicted of the 1849 murder of physician George Parkman at the Harvard Medical School, then adjacent to Massachusetts General Hospital and its Ether Dome. Webster suffered the death penalty in 1850.

Anesthesia-related Ramifications of Benjamin Franklin's Ether-based Refrigeration.

In 1758, Benjamin Franklin froze water by means of the evaporation of diethyl ether. Diethyl ether became the coolant in early mechanical refrigerators and ice makers. Refrigeration advances by Carl von Linde and others provide medical oxygen from the air, liquid nitrogen for cryopreservation and cryoablation, xenon for inhaled anesthesia, and liquid helium for supercooling of magnetic resonance image scanners.

Oxygen Was Almost Named Nitrogen.

In his Tractatus Quinque Medico-Physici of 1674, John Mayow wrote that a fifth of atmospheric air is comprised of nitro-aerial spirit. That so-called spirit participates in both respiration and combustion. The etymology of "nitro-aerial spirit" stems from a mineral long called niter and now specified as potassium nitrate. Niter mixed with sulfur and carbon is gunpowder, developed in the ninth century in China. Mayow appreciated that niter was the oxidant in the energy-yielding reaction of gunpowder. The word "oxygen," eventually prompting the word oxidant, was coined a century later by Antoine Lavoisier.

Kety-Schmidt Application of Nitrous Oxide to Determine Cerebral Blood Flow.

In the 1940s, Seymour S. Kety and Carl F. Schmidt measured cerebral blood flow in awake humans by means of subanesthetic doses of inhaled nitrous oxide. The inhalation route obviated the need for an arterial injection of the indicator, and nitrous oxide had virtues of metabolic inertness, rapid diffusion through the blood-brain barrier, comparable blood and brain solubility, and ease of analytical detection. The technique was also applied to the heart. Follow-up work by Kety contributed to the development of brain scanning methods.

Eponymous plot of Richard J. Kitz and Irwin B. Wilson in biochemistry.

Irwin B. Wilson and anesthesiologist Richard J. Kitz found the enzyme acetylcholinesterase to be inactivated in two steps by covalently acting molecules resembling acetylcholine in structure. Such molecules rapidly and reversibly bind to the active site of the enzyme. Next, the reversible complex undergoes covalent fixation at a characteristic rate. The Kitz-Wilson phenomenon applies to many cases of time-dependent enzyme inhibition. Experimental data are commonly graphed in linear fashion on "Kitz-Wilson plots". Kitz also contributed to a gas chromatography-mass spectrometry assay for acetylcholine that was suitable for the nonbiological detection of that neurotransmitter in mammalian brain.

Thunberg's Barospirator, a Fully Encasing Predecessor of the Iron Lung.

Used as a ventilator for assisting victims of polio, the barospirator was described by Swedish physician-scientist Torsten Thunberg in 1924. An immediate predecessor of the iron lung of Philip Drinker, the barospirator fully encased the entire body. Cyclic air-pressure changes within the chamber achieved ventilation during equilibrations of intrapulmonary and ambient pressures. Pulmonary medicine innovator Alvan Leroy Barach used a modified barospirator for lung rest as a treatment of tuberculosis in the 1940s. Adverse effects included damage to patients' tympanic membranes. Despite its limited clinical success, the barospirator was successfully used by one of Drinker's competitors, John H. Emerson, to invalidate Drinker's US patent filings.

Divine's CO2 Absorber of 1867.

Chemist and inventor Silas R. Divine (1838-1912) sold ammonium nitrate and other anesthesia supplies in New York City. He offered a carbon dioxide absorber for the purpose of rebreathing nitrous oxide. Like his colleague Gardner Q. Colton, he denied the need for nitrous oxide to be supplemented with O2 gas.

George Washington Frost Mellen and Resuscitation with Nitrous Oxide in 1847.

In The Boston Medical and Surgical Journal of 1847 (later to be called The New England Journal of Medicine), Boston chemist George Washington Frost Mellen claimed that inhaled nitrous oxide gas supports human life in the manner of oxygen gas, and he proposed the use of nitrous oxide in resuscitation from drowning and from carbon monoxide poisoning. The claim was reprinted in at least one dental journal and was long cited as justification for the use of 100% nitrous oxide for inhaled anesthesia. Advocates included anesthesia pioneer and painless dentist Gardner Quincy Colton. Though misguided as to nitrous oxide, Mellen was a prominent member of the Boston community for the abolition of slavery.

Phineas T. Barnum, Gardner Q. Colton, and Painless Parker Were Kindred Princes of Humbug.

Phineas T. Barnum (1810-1891) and Gardner Q. Colton (1814-1898) both entered the laughing gas show business in Manhattan in 1844. With Horace Wells (1815-1848), Colton introduced inhaled nitrous oxide for dental anesthesia in December 1844. The Barnumesque nature of laughing gas exhibitions may have contributed to the initially negative reception of nitrous anesthesia as humbug. Colton continued laughing gas shows after 1844, and he performed in a Barnum forum in Boston in 1862. In 1863, Barnum encouraged Colton to establish a flourishing painless dentistry practice in Manhattan. Barnum designated himself to be the Prince of Humbug. He embraced humbug for entertainment purposes but decried medical humbug. Notwithstanding, Barnum explicitly evinced awareness of the power of the placebo response. Accordingly, the proneness of individuals to deem impersonal all-purpose assessments to be personally applicable is dubbed the Barnum effect. Barnum was indirectly connected to Painless Parker (1872-1952), a dentist who exploited sensational advertising and humbug and ran a circus.

The Perfect and Famous Anesthetic Known as Methyl in Boston in 1895.

Extravagant claims were made for proprietary dental anesthetics in Boston, MA, in the late 1800s. For instance, in 1883, Urial K. Mayo introduced an inhaled Vegetable Anaesthetic comprised of nitrous oxide that had been uselessly pretreated with botanical material. This misguided concept may have been inspired by homeopathy, but it was also in line with the earlier false belief of Elton R. Smilie, Charles T. Jackson, and William T.G. Morton that sulfuric ether could volatilize opium at room temperature. In 1895, the Dental Methyl Company advertised an agent they called Methyl, a supposedly perfect topical anesthetic for painless dental extraction. The active ingredient was probably chloroform. Anesthetic humbug did not cease in Boston on Ether Day of October 16, 1846.

Charles T. Jackson and William T.G. Morton Patented the "Ethereal Solution of Opium" of Elton Romeo Smilie.

The Jackson-Morton 1846 patent for surgical insensibility by means of sulphuric ether states that opiates can be added to the ether and co-administered by inhalation. The erroneous concept that ether could carry opiates in its vapor phase at room temperature was proposed in Boston in 1846 by Elton Romeo Smilie (1819-1889), who believed that the opiates were more important than the ether vehicle.

John Snow and the First Second-Gas Effect.

In 1847, British anesthesia pioneer John Snow (1813-1858) observed that patients did not manifest cyanosis during induction with hypoxic mixtures of ether vapor in air. He hypothesized a molecular mechanism that would be understood over a century later as the second gas effect.