Self experimentation anaesthesia

Chief editor note: As in previous issues, and already as a tradition, we are publishing some scientific reports coming from the last annual Euroanaesthesia (Vienna 2019) and from the incoming Focus Meeting (Rome, October 2019)

Fernando Gilsanz
Fernando.gilsanz@salud.madrid.org

In the history of anaesthesia there are reports of at least 108 self-experiments, where the primary or lead investigator used themselves as research subject. Inhalation agents, muscle relaxants, local anaesthetics, regional anaesthesia, have all been a matter of investigation. This paper briefly cites some examples.

Some reasons of conducting self-experimentation are:

• Notify effects with more flexibility in the early stage of an investigation;
• Confirm the research performed in animals,
• Avoid the considerable amount of time, expense, bureaucracy;
• Pilot on one person an experimental procedure that would be impractical;to test in larger groups
• Report that the drug is safe when there are discussions.

Self-experiments with anaesthetic drugs can be dangerous (risk addiction) and sometimes lethal as;

• Robert Mortimer Glover (1815-1859), “Lecturer in Materia Medica” in Newcastle upon Tyne. He died at the early age of 43 due to addiction to chloroform.
• Joseph Toynbee (1815-1866), otologist, experimenting on tinnitus, with chloroform combined with hydrocyanic acid, was found dead with cotton over his face and a strong smell of chloroform in 1866.
• William Stewart Halsted (1852-1922), and Richard John Hall (1857-1897), prominent surgeons in John Hopkins, Baltimore, became addicted to cocaine and morphine, due to self-experiments on regional blocks.

Self-experimentation with inhalation agents.

Sir Humphry Davy (1778-1829) the first scientific anaesthesiologist, working in the “Pneumatic Institution” in Bristol, with Thomas Beddoes (1760-1808), published in 1800, his famous book: “Researches, Chemical and Philosophical, chiefly concerning Nitrous Oxide, or dephlosgisticatedNitrous Air and its respiration”. Davy inhaled pure carbon dioxide and describes laryngospasm and carbon monoxide poisoning. He measured lung volumes (tidal volume, residual volume, and vital capacity), oxygen consumption, solubility and uptake of gases. He describes euphoric and heightened imagination when he inhales nitrous oxide (laughing gas). But the most important discovery of his self-experimentation was: “In cutting one of the unlucky teeth called dentes sapientiae, I experienced and extensive inflammation of the gum, accompanied with great pain, which equally destroyed the power of repose and consistent action. On the day when the inflammation was most troublesome, I breathed three large doses of nitrous oxide. The pain always diminished after the first four or five respirations: the thrilling came on as usual, and uneasiness was for a few minutes swallowed in pleasure. As the former state of mind returned, the state of organ returned with it; and I once imagined that the pain was more severe after the experiment than before” , ….. “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”.

Davy also contributed with six elements to the periodic table, he introduced electrolysis, Davy miner’s safety lamp, and was mentor of Michael Faraday (1791-1867).

Other self-experiments with nitrous oxide were performed by William Paul Crillon Barton (1786-1856) in 1807. He wrote in his MD thesis: “A dissertation on the chemical properties and exhilarating effects of nitrous oxide gas and its application to pneumatic medicine” where he wrote: “From the results of this experiment , I am decidedly of the opinion with Mr. Davy, that this gas has the power of removing intense physical pain”.

William Denis Ashley Smith is also a notable self-experimenter (1918-2002). Senior Lecturer at Leeds University, author of “Under the influence. A history of Nitrous Oxide and Oxygen Anaesthesia”,published in 1982. He performed self-experiments, in 1964, 1967, 1974 to re-examine the research of pioneers, but with modern techniques for measuring uptake, concentration effect, EEG, pharmacokinetics, etc. of nitrous oxide. He included breathing and non-rebreathing circuits, a neumotachograph, a body plethysmograph, which he made himself, and a hyperbaric chamber. He employed his bio-engineering skills and familiarity with the latest technology in his self-experiments in dental and out-patient anaesthesia. He was assisted by William Wellesley Mapleson (1926-2018) in the mathematical formulas of the pharmacokinetics.

Self-experiments with ether were performed by: Crawford Williamson Long (1815-1878) in 1841; Charles Thomas Jackson (1805-1880) in 1841; Horace Wells (1815-1848) in 1844; William Thomas Green Morton (1819-1868) in 1846; William Squire (1825-1899) ; Nicolai Ivanovich Pirogoff (1810-1881) in 1846; David John Thomas (1813-1871) in 1847; Robert Ritter Welz (1814-1878) in 1847; Joseph Vulfranc Gerdy (1809-1873) in 1847; Jean-Joseph Sauvet (1817-1904) in 1847.

Sir James Young Simpson (1811-1870), Professor of Midwifery in Edinburgh, and his assistants Mathews Duncan (1826-1890) and George Keith inhaled chloroform on the evening of 4 of November 1847, in the dining room of Simpson’s home in the 44 Queen Street in Edinburgh.“Having inhaled several substances, but without much effect, it occurred to Dr Simpson to try the ponderous material which he had set aside on a lumbar table……. That happened to be a small bottle of chloroform. …Immediately an unwanted hilarity seized the party; they became bright-eyed, very happy and very loquacious-expatiating on the delicious aroma of the new fluid … a moment more and them all was quiet – and then crash”.

In the 20^th century self-experimentation with inhalation agents were published by:

• Arno Benedict Luckhardt (1885-1957) and Jay Bailey Carter (1898-1957) in 1927 with ethylene in the University of Chicago.
• Harold Randall Griffith (1894-1985), Head of the Department of Anaesthesia at McGill University in Montreal, published in 1934, self-experiments with cyclopropane: “In the low concentration used cyclopropane has a pleasant odour, is not at all irritating and induces unconsciousness about as rapidly as nitrous oxide or ethylene. I have put myself to sleep with it several times, and found it very pleasant. The quietness of induction and quiet breathing remind me of chloroform anaesthesia”.
• Max Samuel Sadove (1914-1997) at Illinois University in 1952 self-experimentation with fluroxene.
• Newton DEF in 1990 with sub-MAC concentrations of isoflurane in anaesthesiologist volunteers.
• Professor Burnell R Brown (1933-1995) in Tucson, Arizona, with sevoflurane; “His confidence in the drug was complete but he had a tough time convincing his colleagues that he would make a suitable substitute for a paid volunteer”.
• Professor Robert Morley Jones in Guys Hospital, London, did self-experiments with desflurane.
• Jeremy N Cashman, Reader of the Department of Anaesthesia was the first subject to inhale desflurane in the world.

Self-experimentation with cocaine.

Carl Koller (1857-1944) and Sigmund Freud (1856-1939) tested de anaesthetic effects of cocaine in themselves in 1874. William Halsted and Richard John Hall injected themselves with cocaine to develop regional anaesthesia.  Vasily Konstantinovich von Anrep, Russia,  (1852-1927), in 1884, wrote: “Application of cocaine solution of different strength to the tongue always produces weakening or complete loss of gustation for sweet and sour, pinprink on the mucosa feels only like a light touch . Subcutaneous injection of such minuscule amounts of cocaine as 1-5 mg results in complete sensory loss in the skin around the injection: puncturing the skin with a pin is not felt and burn with a match does not produce pain. Lubrication of mucous membranes with cocaine as well as its internal use causes dryness of the membranes, diminishing distinctly their secretion”.

Self-experimentation with muscle relaxants.

Frederick Prescott, Clinical Research Director, Wellcome Institution, did self-experiments with “Tubarine”, (curare), in 1946. They injected 10 mg, 20 mg and 30 mg and registered the symptoms and signs of muscular paralysis. Sir Geoffrey Stephan William Organe (1908-1985) and Edgar Stanley Rowbothan (1890-1979) of Westminster Hospital were the anaesthetists responsible.  A similar self-experiment was completed in Salk Lake City, University of Utah School of Medicine, in 1947, by Scott Smith and the pharmacologist Professor Louis Goodman. Prescott and Smith research gives a minute-by-minute subjective account of the events.

Research with Dimethyl-D-Tubocurarine, self-experiments were done in Illinois, in 1949 -1950 by Professor Max Samuel Sadove (1914-1997). Professor Richard Bodman, in 1952, did self-experiments with compound C15 (not commercialised), compound C20 (laudexium BP), and Dimethyl-D-Tubocurarine, in St Thomas, London, and Bristol. William Mushin (1910-1993) and William Wellesley Mapleson (1926-2018) of the Welsh National School of Medicine did self-experiments with M&B 9105A, in 1964.

Professor Otto K Mayrhofer, Viena, published six self-experiments with succinylcholine in 1952, when he was 30 years old.

Miscellaneousself-experimentation.

Edgar Alexander Pask (1912-1966), Professor of Anaesthesia in Newcastle upon Tyne was involved with self-experimentation during the Second World War. Working in the “Physiological Laboratory, RAF Research Station” at Farnborough, with Professor Sir Robert Macintosh (1897-1989) he was involved as a guinea-pig in several self-experiments:

• Related to RAF problems, particularly in connection with high-flying. One aim was to establish the maximum height at which an airman could safely bale-out and survive without oxygen-breathing apparatus. These anoxia experiments produced alveolar tensions equivalent to those obtaining at variant altitudes (40 000 feet was established as the ceiling for bale-outs without breathing equipment).
• Test for the effectiveness of different methods of artificial respiration in drowned airmen fished out at the sea. He used a spirometer for recording tidal volumes in Eve Rocking, Schuler, Sylvester, and mouth-to-mouth methods of resuscitation. He self-experimented with curare in this setting.
• Test de effectiveness of a wide variety of lifejackets, to prevent airman drowning because their faces were underwater even though their lifejackets kept them afloat. Seventeen lifejackets were tested in four lengthy sessions in the pools.

Edgar Alexander Pask was awarded the OBE in 1944 as result of these self-experiments. In 1947 he presented at Cambridge University his MD thesis “Anaesthetic Techniques in Research”. Sir Robert Macintosh commented “Pask must have been the only person to gather material for an M.D. thesis while deeply anaesthetised with ether”.

References.

• Gilsanz F. Auto-experimentación en Anestesia, Analgesia y Reanimación. Canal Estrategia Editorial S.L. Madrid. 2019.

Chief editor comment:

This excellent paper describes the long route of self-experimentation in anesthesia, as reflected in the relevant literature all over the time.

It would be interesting to get from our readers some data on more trials like those mentioned in the review, mostly personal experiences or data form other trials, not yet published. The Newsletter is open to comments and supplementary details.