Summary
In 1957, Professor Daniel Bovet received the Nobel Prize in Physiology or Medicine for his studies on various compounds including the muscle relaxants gallamine and succinylcholine that became very useful in anaesthesia. Textbooks credit Professor Bovet for the discovery of these drugs. However, although he indeed did discover their pharmacological character, the actual syntheses were made by Ernest Fourneau and Reid Hunt, respectively; sadly, these two scientists have largely been ignored. In this paper, a brief biography of Bovet is presented along with some of his more notable accomplishments. Particular emphasis has been placed on gallamine and succinylcholine along with their history. In an attempt to undo the “injustice” dealt to both Fourneau and Hunt, brief accounts of their history, story and character are provided.
Zusammenfassung
Professor Daniel Bovet erhielt 1957 den Nobelpreis für Physiologie oder Medizin für seine Studien zu verschiedenen Wirkstoffmischungen einschließlich der Muskelentspannungsmittel Gallamin und Succinylcholin, welche in der Anästhesie äußerst hilfreich sind. Fachbücher ehren Professor Bovet für die Entdeckung dieser Arzneimittel. Allerdings muss bemerkt werden, dass trotz der Tatsache, dass Professor Bovet ihren pharmakologischen Charakter entdeckt hat, die eigentlichen Zusammensetzungen von Ernest Fourneau bzw. Reid Hunt entwickelt wurden. Diese beiden Wissenschaftler wurden bisher leider größtenteils ignoriert. In diesem Dokument wird eine kurze Biographie Bovets zusammen mit seinen wichtigsten Errungenschaften aufgezeichnet. Besondere Schwerpunkte bilden Gallamin und Succinylcholin und ihre Geschichte. In einem Versuch, die „Ungerechtigkeit“, die sowohl Fourneau als auch Hunt angetan wurde, aufzuheben, wird ihnen ein kurzer Abriss ihrer Geschichte und ihres Charakters gewidmet.
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Notes
The need for such drugs would become critical, especially for the Allied military forces when the Japanese conquered the Philippines and Java, the main sources of the bark of Cinchona sp.
Berger describes a singular use of curare on patients with parkinsonism—for their spasticity, they received curare, 50 mg intramuscularly, either by the physician or themselves. An ampoule of edrophonium was kept on hand [12].
George B Koelle, Distinguished Professor of Pharmacology, University of Pennsylvania
Willstätter was a Jew who, in spite of his scientific achievements, was not spared Hitler’s persecution and so with heaviness of heart, left his native land in 1939, for a village close to Locarno in Switzerland.
A pleasing revelation concerning Stovaine surfaced in Stedman’s Medical Dictionary (18th ed.) where Stovainization is defined as: “The induction of spinal anaesthesia by subarachnoid injections of Stovaine”.
Polypterus bichir was mistakenly believed to be a lungfish and a link between fishes and amphibians. Coloured greenish-yellow-brown, it has 13–18 dorsal finlets. The lower jaw is longer than the upper jaw. It is covered by scales of enamel, crawls with its fins and swims like an eel. Basking in the mud, it jumps from the water to gasp air into its air sacs. The adult male is some 75 cm long and weighs about 2.5 kg
References
Bovet D. Le idee di mio padre e le mie. Interview by Mariano Dolci. Zerosei. April 1980. 7–9.
Fourneau E, Tréfouël J, Tréfouël T, Bovet D, Benoit G. Contribution à la chimiothérapie du paludisme. Essais sur les calfats. Ann Inst Pasteur. 1931;46:514–41.
Silvestrini B. Il Maestro. Ann Ist Super Sanita. 1993;(Suppl 1):41–4.
Bignami G. Testimonianza di un alliervo. Ann Ist Super Sanita. 1993;(Suppl. 1):51–66.
Fourneau E, Bovet D. Récherches sur l’action sympathicolytique d’un nouveau dérivé du dioxane. Arch Int Pharmacodyn Ther. 1933;46:178–91.
Bovet D, Staub AM. Action protectrice des éthers phénoliques au cours de l’ intoxication histaminique. C R Seances Soc Biol. 1937;124:547–9.
Halpern BN. Les antihistaminiques de synthèse. Essais de chimiothérapie des états allergiques. Arch Int Pharmacodyn Ther. 1942;68:339–408.
Tréfouël T, Tréfouël F, Nitti F, Bovet D. Activitè du p‑aminophénylsulfamide sur les infections streptococciques expérimentales de la souris et du lapin. C R Seances Soc Biol. 1935;120:756–8.
Fourneau E, Tréfouël T, Tréfouël F, Nitti F, Bovet D. Chimiothérapie des infections streptococciques par les dérivés du p‑aminophénylsulfamide. C R Seances Soc Biol.1936;122:258-9.
Bovet D, Simon A. Action hypnotique des acides éthobutyl, alcoylbarbituriques et éthobutylalcoyl-N-méthylbarbituriques. Contribution à l’étude de la narcose par voie intraveineuse. Anesth Et Anal. 1936;2:41–51.
Clark RW. The life of Ernst Chain. New York: St. Martin’s Press; 1985.
Bovet D, Bovet-Nitti F, Marini-Bettòlo GB. Curare and curare-like agents. Amsterdam: Elsevier; 1959.
Sigward J, Bovet D, Dumont G. Le traitement de la malade de Parkinson par le chlorhydrate de diéthylaminoéthyl-N-thiodiphénylamine (2987 RP). Premier resultants. Rev Neurol. 1946;78:581–4.
Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Eng J Med. 1967;276:374–9.
Sulser F, editor. Neuropharmacology. In: Ban TA, editor. An oral history of neuropsychopharmacology - the first fifty years: peer interviews. Vol. 3. Nashville: American College of Neuropsychopharmacology; 2011. pp. 297-328.
Bovet D. Une chimie qui guérit. Paris: Payot; 1989.
Birmingham AT. Waterton and Wouralia. Br J Pharmacol. 1999;126:1685–9.
Bernard Spilsbury: his life and cases. In: Browne DG, Tullett EV, editors. Wheeldon case 1951. pp. 96–8.
Bovet D, Depierre F, de Lestrange Y. Propriétés curarisantes des éthers phénoliques. C R Acad Sci. 1947;225:74–6.
Huguenard P, Boué A. Un nouvel curarisant français de synthèse – le RP3697. Communication faite à la Séance de la Société d’ Anesthésie du 17 juin 1948.
Bovet D. Some aspects of the relationship between the chemical constitution and curare-like activity. Ann N Y Acad Sci. 1951;54:407–37.
Hunt R, de Traveau RM. On the physiological action of certain cholin functions derivatives and new methods for detecting cholin. BMJ. 1906;:1788–91.
Hunt R, Traveau R de M. The effects of a number of derivatives of cholin and analogous compounds on blood pressure. Public Health and Marine Hospital Service of U.S. Public Health Hospital. U.S. Hygienic Laboratory Bull. No. 73; 1911.
Bovet D, Bovet-Nitti F, Guarino S, Longo VG, Marotta M. Proprietà farmacodinamiche di alcuni derivati della succinilcolina dotati di azione curarica. Rend Ist Super Sanita. 1949;12:106–37.
Glick D. Some additional observations on the specificity of cholinesterase. J Biol Chem. 1941;137:357–62.
MacIntosh FC. Third Sarrazin lecture. Quebec: Centre d’Arts d’Orford; 1979.
Barlow RB, Ing HR. Curare-like action of polymethylene bis-quaternary ammonium salts. Nature. 1948;161:718.
Organe GSW, Paton WDM, Zaimes EJ. Bistrimethylammonium decane and pentrane (C10 and C5) in man. Lancet. 1949;1:21–3.
Churchill DH. Suxamethonium (Succinylcholine) chloride and muscle pain. BMJ. 1954;1:74.
Foldes F. Prolonged respiratory paralysis after succinylcholine. BMJ. 1952;I:1352.
Forbat A, Lehmann H, Silk F. Prolonged apnoea following injection of succinyldicholine. Lancet. 1953;II:1067–8.
Dorkins HR. Suxamethonium – the development of a modern drug from 1906 to the present day. Med Hist. 1982;26:145–68.
Valdoni P. Osservazioni clinche sull’impiego del curarizzante 362. I S Rend Ist Supersanità. 1944;12:255–62.
Scurr CF. A relaxant of very short action. BMJ. 1951;2:831–2.
Tracing the intraceable. Time. 1967; 89:34
Rousseau P. Un bienfaiteur de l’humanité ignoré et vaincu: Ernest Fourneau. Notre Temps. 1968;4:35–8.
Fourneau J‑P. Ernest Fourneau, fondateur de la chimie thérapeutique française : feuillets d’album. Rev Hist Pharm (Paris). 1987;275:335–55.
Adams SH. The great American fraud. Collier’s. 1908;7(29):14–5.
Bernschneider-Reif S, Huber WT, Possehl I. Was der Mench thun kann… History of the pharmaceutical and chemical company Merck. Darmstadt: Merck KGaA; 2002.
Fourneau E. Un nouvel anesthésique: la stovaine. J Pharm Chim. 1904;20:108–9.
Reclus P. L’analgésie locale par la stovaine. Bull Acad Med. 1904;52:7–11.
Fourneau E, Janot M‑M. Les curares. II. – Aperçu sur la chimie des curares et de quelques substances curarisantes. Ann Pharm Fr. 1949;7:353–68.
Fougére P. Grands Pharmaciens. Paris: Buchet-Chastel; 1956.
Fourneau E. Organic medicaments and their preparation. Philadelphia: P. Blakiston’s Son; 1925.
Marshall EK Jr. Reid Hunt: 1870–1948. Nat Acad Sci Biogr Mem. 1951;26:25–41.
Harrington NR. dead: was the leader of Columbia University’s expedition to the Nile. The New York Times. 1899 Aug 12.
Starr I Jr, Elsom KA, Reisinger JA, Richards AN. Acetyl-ß-methylcholin. I. The action on normal persons. Am J Med Sci. 1933;186:313–23.
Acknowledgements
I am most grateful to the following: Professor Daniel Pierre Bovet for inviting me to his apartment in Rome and giving details of his father; Professor Marcel Bickel, Department of Medical History, University of Bern, for guidance during our many meetings in Zurich; Philippe Galanopoulos, Curator, BIU Santé, Paris, for the days spent with me in the literature search. I wish to thank the professors of anaesthesia: Richard SJ Clarke, Belfast, Gottfried Benad, Rostock and Klaus Olkkola, Helsinki, for reading the manuscript. The paper is in memory of those who taught me at the Faculty of Medicine, Alexandria University.
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D.A. Cozanitis declares that he has no competing interests.
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Cozanitis, D.A. Daniel Bovet, Nobelist: muscle relaxants in anaesthesia. Wien Med Wochenschr 166, 487–499 (2016). https://doi.org/10.1007/s10354-016-0481-y
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DOI: https://doi.org/10.1007/s10354-016-0481-y