SPECIAL FEATURE – HISTORY OF NEUROLOGY Claude Bernard JMS Pearce MD, FRCP Emeritus Consultant Neurologist, Department of Neurology, Hull Royal Infirmary, UK. “Mais la méthode expérimentale a pour objet de transformer Correspondence to: cette conception a priori fondée sur une intuition..., en une J.M.S. Pearce, 304 Beverley Road Anlaby, East Yorks, HU10 7BG, UK. Email: [email protected] interprétation a posteriori établie sur l’étude expérimentale des phénomènes...” Claude Bernard: Introduction à l’étude de la Conflict of Interest statement: None declared. médecine expérimentale. Date first submitted: 10/7/17 [“But the experimental method aims at transforming this Acceptance date: 11/07/17 a priori conception based on a vague intuition...into an a To cite: Pearce JMS, ACNR 2017;17(2);14-15 posteriori interpretation established on the experimental study of phenomena...”] he name Claude Bernard (1813-1878) lodgings with Charles Lasègue. He studied ings of the liver and showed that not only did it is known across the world to medical under François Magendie (1783-1855) in the secrete bile but was, like the pancreas, an ‘organ T students for the Claude Bernard-Horner’s Hotel Dieu. Magendie, impressed by Bernard’s of internal secretions’ (enzymes) that converted syndrome; but more important are his ground- dissecting skills appointed him in 1841 as labora- glycogen into glucose (glycogenolysis), and breaking works in physiology, particularly tory assistant. could store glucose in the form of glycogen homeostasis. Peter Wise provides an excellent, An ‘arranged marriage’ with the prosperous (glycogenesis).5 detailed account of his life and bibliography.1 Marie Françoise Martin was engineered in 1845 To see whether the release of glucose from Claude Bernard was one of the epoch- by his mentors, Pierre Rayer and Théophile- liver glycogen depended on a neural stimulus making giants of experimental medicine, Jules Pelouze to allow their protégé to develop via the vagus, in a classical experiment in who dominated the nineteenth century. His his research potential under Magendie. Marie 1849 Bernard used a needle to stimulate the ideas, researches and scientific principles are Françoise, an ardent anti-vivisectionist, chas- vagus in the floor of the fourth ventricle, and enshrined in his Cahier Rouge2 (compiled, 1850 tised him for his animal experiments; their long noted that the urinary and blood glucose -1860), his Pensées – Notes Détachées, and marriage was unhappy and ended in separation increased. Bernard called this piqûre [puncture] the now-famous Introduction to the Study of in 1870. They had two daughters, and a son who diabetes. He later cut the spinal cord above the Experimental Medicine3 that remain undimin- died in infancy. After separation he formed a splanchnic sympathetic nerves; this blocked ished by time as inspiring works of reference for close friendship with Marie Raffalovich, a Jewish the piqûre phenomenon. He concluded that students of physiology and the natural sciences. intellectual from Odessa, who later nursed him the sympathetic nerves directly released liver Claude Bernard (Figure 1) was born in 1813 in his final illness. glucose. Subsequently, it was shown it was in the village of Saint-Julien-en-Beaujolais. He Before receiving a galaxy of awards and adrenaline released from sympathetic nerve attended the Jesuit school, and then the college distinctions,1 in 1847 he was elected Magendie’s endings that was the main cause of glucose at Lyon, which he soon left to become assistant deputy at the Collège de France, and in 1855, discharge from the liver. at the Millet pharmacy in Lyon-Vaise. With when Magendie died, Bernard was appointed a flare for the theatrical he wrote a comedy, to his Chair of Medicine at the Collège and Sympathetic paralysis and a play titled: ‘Arthur de Bretagne’ which succeeded to his Chair of Physiology at Assisting Magendie he began his neurological in 1834 he presented to Saint-Marc Girardin a Sorbonne University. His crucial scientific prin- researches.6 His first in 1843, concerned the famous Parisian drama critic, who unimpressed, ciples flourished: an idea or observation led chorda tympani which when cut in the dog, discouraged him from a career in theatre but to a hypothesis, and then to either support or was followed by a slow continuous secretion of urged him to study Medicine. He soon enrolled disprove it, he embarked on systematic experi- saliva from the sub-maxillary gland. This secre- at the Faculty of Medicine of Paris, sharing mentation making many scientific contribu- tion was called the ‘paralytic’ secretion.7 From tions, sketched below. His reputation spread several experiments he established the exist- and at Louis Napoleon’s instigation he moved ence both of vasodilator thermal and secretory, to the Muséum National d’Histoire Naturelle in and the sympathetic vasoconstrictor nervous 1868. He was later elected to the Academy of mechanisms.8 He differentiated their functions: Sciences, the Academy of Medicine, and to the ‘The sympathetic nerve is the constrictor Imperial Senate — at the behest of the Emperor. of the blood vessels; the tympanicolingual A memorial plaque in Paris (Figure 2) nerve [chorda tympani] is their dilator’3 displays the site of Claude Bernard’s laboratory (p.158) from 1847 until his death in 1878. The Claude In his several experiments he also established Bernard Lyon University commemorates his the concept of the physiological equilibrium name. When he died he was accorded a public of these two components of the autonomic funeral – an honour never before bestowed by nerves.9 France on a man of science. He was interred in Le Père Lachaise Cemetery in Paris. A stone statue (Figure 3) graces the entrance to the Collège de France, replacing the original bronze Figure 1 barbarically destroyed by the Nazis. Figure 3 Some scientific contributions Glycogenesis He began by studying pancreatic juices which he was able to show were vital in the process of digestion.4 For this he was awarded the prize for experimental physiology from the French Figure 2 Academy of Sciences. He next studied the work- 14 > ACNR > VOLUME 17 NUMBER 2 > NOVEMBER-JANUARY 2018 SPECIAL FEATURE – HISTORY OF NEUROLOGY Claude Bernard-Horner syndrome This was the first demonstration of the selective method was of scrupulous observation and In 1727, Pourfour de Petit (1664-1741) had action of curare on nerves. If the animal logical deduction. Amongst many memorable described dilatation of the pupil (mydriasis) survived, the paralysing effects of curare would quotations his writings disclose: owing to stimulation of sympathetic nerves fully recover. This led to its use as a muscle • What makes a scientist important, he states, in a man whose neck had been injured by a relaxant. However, he failed to implicate the is how well he or she has penetrated into gunshot wound. When he cut the sympathetic neuromuscular junction; Alfred Vulpian (1826- the unknown. nerve on one side of the neck Petit showed 1887) showed that curare acted on the motor • Observable reality is our only authority. the opposite phenomenon (miosis). In 1851 endplate that had been described by Kühne. • Experimental science is a constant inter- Claude Bernard repeated Petit’s experiment; These studies led Bernard to study asphyxia change between theory and fact, induction and gave a more precise description: and anaesthetics. He also showed that spinal and deduction. Induction, reasoning from “After the section of the cephalic branch reflexes were initiated by excitation of sensory the particular to the general, and deduc- of the great sympathetic, it is possible nerves without involving consciousness, but tion, or reasoning from the general to the to observe a contraction of the pupil of acted on motor nerves through the spinal cord. particular, are never truly separate. the corresponding eye, accompanied by Vulpian confirmed this in experiments on • The “philosophic spirit” is always active in a narrowing of the palpebral opening, decapitated salamanders and frogs.13 its desire for truth. It stimulates a “kind of a retraction of the ocular globe, and thirst for the unknown” which ennobles an increase of the circulation, as well Milieu intérieur and enlivens science. as of the temperature, in all parts of Bernard’s numerous experiments caused him the corresponding face. If the upper to recognise a Milieu intérieur, a phrase that extremity of the sectioned sympathetic is he coined to refer to the extra-cellular fluid galvanized, all the phenomena observed environment, and its physiological capacity to after the removal of the influence of buffer changes, to ensure protective stability the great sympathetic changes at once, for the tissues and organs of living organisms. REFERENCES appearing an opposite presentation. The He wrote: 1. Wise P. A Matter of Doubt – the novel of Claude pupil enlarges, the palpebral opening ...The blood constitutes an actual organic Bernard. CreateSpace Independent Publishing Platform augments, the eye protrude out the orbit. environment, an intermediary between (December 28, 2011). see also: Claude Bernard. http:// The former active circulation becomes the external environment and the www.claude-bernard.co.uk/page2.htm weak, the conjunctiva, the nose, the (internal) living molecules, which cannot 2. The ‘Cahier Rouge’. English translation of the Cahier des Notes by Hoff HH, Guillemin L, and Guillemin R. ears previously red become pale. If the safely be brought into contact with their Schenkman, Cambridge, Massachusetts