Bernard, Claude

Bernard, Claude

(b. St.-Julien, near Villefranche, Beaujolais, France, 12 July 1813; d. Paris, France, 10 February 1878)

physiology.

Bernard’s parents, Pierre François Bernard and Jeanne Saulnier, who were vineyard workers, lived in very modest circumstances. His father seems to have exerted so little influence that several biographers have erroneously asserted that he died when Bernard was an infant. On the other hand. Bernard always remained close to his mother, a gentle and pious woman. All his life he remained attached to the place of his birth, the hamlet of Chatenay at the outskirts of the village of St.-Julien. Every fall here turned home to relax and to help with the grape harvest. His entire life revolved about two poles of attraction: the laboratories of Paris and the vineyards of Beaujolais. As a child Bernard lived close to nature and maintained his deep love of it through out his life. His education, first from the parish priest and then in religious schools in Villefranche and Thoissey, was humanistic rather than scientific. At the age of nineteen, he was apprenticed to an apothecary named Millet in Vaise, a suburb of Lyons. Thus he had occasion to observe the rude empiricism of the pharmaco therapy of that period. The apprentice pharmacist turned, however, not toward the sciences but toward the theater and belles-lettres. One of his comedies brought him some-local success, which induced him to write a heroic drama, entitled Arthur de Bretagne. (A first, posthumous edition of 1887 was suppressed by court decision upon the request of Bernard’s widow; the work was republished in 1943.)

In 1834 Bernard went to Paris, where he planned to seek a career in literature. The illustrious critic Saint-Marc Girardin discouraged him, however, and urged him first to acquire a profession in order to earn a living. In the same year, with great difficulty, Bernard passed the baccalaureate and entered the Faculty of Medicine in Paris. Thus, as Renan remarked in his Éloge, by turning his back on literature, Bernard took the road that nevertheless led him to the Académic Française.

Bernard was an average student. Conscientious but not really brilliant. In 1839 he passed the examinations for internship in the Paris municipal hospitals. A protégé of Pierre Rayer, he worked at the Charité and, as intern on the staff of François Magendie, at the Hôtel Dieu. What he admired in Magendie, however, was less the clinician than the physiologist, the bold experimenter, and the aggressive skeptic. It was in Magendie’s laboratory at the Collège de France that Bernard, even before the end of his clinical studies, discovered his real vocation: physiological experimentation.

From 1841 to December 1844, Bernard worked as préparateur to Magendie at the Collège de France, assisting him in experiments concerning the physiology of nerves (especially the problem of “recurrent sensitivity” of the spinal nerve roots), the cerebro spinal fluid, the question of the seat of oxidation in the body of horses (by important experiments with cardiac catheterization), and the physiology of digestion. In order to carry out his own research, Bernard installed a very modest private laboratory in the Courdu Commerce de Saint-André-des-Axts. He also made suse of the adjoining laboratory of Jules Pelouze, where he enjoyed the intelligent help of his friend Charles-Louis Barreswil. It was Magendie who taught Bernard to use animal vivisection as the principal means of medical research and to be suspicious of generally accepted theories and doctrines. But Bernard knew how to go beyond the empiricism and skepticism of his master and to create an especially productive method of research on living creatures.

Although he had graduated M.D. at Paris on 7 December 1843, Bernard never practiced medicine and always entertained ambivalent feelings about physicians. Nevertheless, his work was such that it laid new foundations for the profession. His doctoral thesis, Du suc gastrique et de son rôle dans la nutrition (1843), was a work both useful to medicine and dedicated to pure science, since it furnished new facts on gastric digestion and the transformations of carbohydrates in the animal organism.

In 1844 Bernard failed to pass the examinations for a teaching post with the Faculty of Medicine. Nevertheless, he resigned his position with Magendie. After having tried vainly to organize a free course in experimental physiology (in collaboration with his friend Charles Lasègue), Bernard resigned himself to giving up scientific research and to setting up as a country doctor in his native village. Rather than resolve his economic embarrassments in this way, however, Bernard decided to take the advice of Pelouze, and in July 1845 he married Fanny Martin, daughter of a Paris physician (they were to have three children: a boy who died in infancy and two daughters, Jeanne-Henriette and Marie-Claude). This match was to become a source of unhappiness, but for the moment his wife’s dowry enabled Bernard to continue his physiological research. He now entered the most fruitful and certainly the most hectic period of his scientific career.

In December 1847 Bernard was made suppléant to Magendie at the Collège de France. At first he gave the course ill the winter term, while Magendie continued to teach experimental medicine during the summer semester. In 1852 Magendie retired completely and turned over his chair and his laboratory to Bernard. In 1848 the Société de Biologie was founded, and Bernard became its first vice-president. Nameda chevalier of the Légion d’Honneur in 1849, he applied (unsuccessfully) for membership in the Académie des Sciences in 1850 and started to work on his thesis for the doctorate in science. On 17 March 1853 he received the doctorate in zoology at the Sorbonne after a brilliant presentation of his thesis, Recherches sur une nouvelle fonction du foie.

Bernard made his principal discoveries early in his scientific career, in the period between his first publication “Recherches anatomiques et physiology quessur la corde du tympan” (1843), and his thesis for the doctorate in science (1853). The discoveries on the chemistry and nerve control of gastric digestion (1843–1845) were followed by the first experiments with curare, the discovery of the role of bile in the digestion of proteins, and research on the innervation of the vocal cords and the functions of the cranial nerves (1844–1845). In 1846 he made his first observations on the mechanism of carbon monoxide intoxication, discovered the difference between the urine of herbivores and that of carnivores, began studies on absorption of fats and the functions of the pancreas, and observed the inhibitory action of the vagus nerveon the heart. He solved the problem of “recurrent sensitivity” in 1847. In August 1848 Bernard discovered the presence of sugar in the blood under fasting conditions (non food-connected glycemia) and the physiological presence of sugar in the liver—which led rapidly to the revolutionary theory attributing a glycogenic function to the liver (October 1848). In February 1849, he published an important paper on the role of the pancreas in digestion and, in the same month, observed for the first time the presence of sugar in the urine after artificial traumatization of some particular cerebral structures. The following year Bernard made other discoveries concerning the metabolism of carbohydrates and resumed fruitful experiments with curare. In 1852 came the discovery of the vasoconstrict or nerves and the description of the syndrome now called the Horner-Bernard syndrome. This period concluded with a critical examination of Lavoisier’s theory on the seat of the production of heat in the animal and with the systematic presentation of discoveries concerning animal glycogenesis.

Bernard’s reputation was further enhanced by these works, and soon extended beyond the borders of France. Honor followed honor in quick succession. The government created a chair of general physiology for him at the Faculty of Sciences in Paris, and on 1 May 1854 he delivered his inaugural lecture at the Sorbonne. On 26 June of the same year he was elected to the Académie des Sciences, and in 1855, following the death of Magendie, he became professor of medicine at the Collège de France. He became a member of the Académic de Médecine in March 1861.

Bernard consolidated and completed his physiological discoveries between 1854 and 1860: in 1855 he made the experiment of the perfused liver and discovered glycogen; in 1857 he isolated glycogen; in 1858 he discovered the vasodilating nerves; and in 1859 he made experiments on the glycogenic functions of the placenta and of fetal tissues. This period of Bernard’s work is further marked by the creation of new concepts that were to facilitate the generalization of the results of his experimentation: the concepts of “experimental determinism:’ and “internal secretion” (1855; it must be stated that for Bernard this term did not have its precise present meaning), the “milieu intérieur” (1857), “local circulation,” “reciprocal innervation,” “paralyzing reflex actions:” and so on.

The transition from laboratory work to dogmatic synthesis was mirrored in Bernard’s teaching and in his Cahier de notes, 1850–1860 (also called the Cahierrouge), The Cahier clearly demonstrates a change of emphasis from the tenacious pursuit of concrete facts to a concentration on research methods and principles of biological science, and may be said to mark the junction between Bernard’s analytical and philosophical work; his teaching led him to the formulation of a comprehensive and didactic theoretical elaboration of his laboratory experience. As early as 1858, Bernard conceived a “plan for a dogmatic work on experimental medicine” in consideration of the new direction indicated by his teaching.

From 1860 on, Bernard spent all his vacations at St.-Julien, where he had bought the manor house of the landlord on whose farm he had been born. In March 1860 he came here to recover from the first of a series of illnesses that were to mark his last years, and here, during the leisure enforced by a period of convalescence in 1862–1863, he drafted his principal theoretical work, Introduction ô l’étude de la médecineexpérifmentale. This work was conceived of as the preface of a great treatise, Principes de médecine expérimentale, for which Bernard wrote the rough drafts of several chapters. The Introduction itself was rewritten in the course of the following two years, and was given its definitive form in the version published in August 1865. A grave illness in October 1865, from which he recovered after eighteen months, led Bernard to abandon the Principes. (In 1947 L. Delhoume published, under the same title, a reconstruction of the work based on the rough drafts and augmented by the unpublished text of Bernard’slecture course of 1865.)

During his convalescence of 1865–1867, Bernard turned his attention to philosophy, and read and annotated the philosophical works of Tenneman and of Comte; these notes revealed a subtle and critical attitude toward positivism. In 1866, at the request of the minister of public education, he prepared his Rapport sur les progrès et la marche de la physiologiegénérale en France. The Rapport, which was published on the occasion of the World Exposition of 1867 was to have been an objective, historico-encyclopedic treatment of physiology in France. Bernard used the opportunity, however, to issue a passionate statement of his personal opinions and presented a unified synthetic physiology, founded on the notion of the “milieu intérieur” and on the regulatory functions that, under the control of the nervous system, maintain the stability of the fluids and the living tissues.

On 12 December 1868 the chair of general physiology was transferred from the Sorbonne to the Muséum d’Histoire Naturelle; as the titular holder of the chair, Bernard succeeded Flourens (who had held the chair as professor of comparative physiology) on the council of professors of the museum. Flourens’s chair was transferred to the Sorbonne, and was awarded to Paul Bert, one of Bernard’s most faithful pupils.

In January 1869, after a hiatus of three years, Bernard resumed his courses in experimental medicine at the Collège de France. Although he was only a mediocre lecturer, he was able to hold the attention of his audience by the novelty and vividness of his arguments and by the experiments that he improvised in the amphitheater to support his statements. (At the beginning of his career, Bernard’s audiences had been composed almost exclusively of physicians and physiologists, especially foreigners; gradually, however, they became larger, more varied, and more fashionable.)

Bernard’s teaching at the College was analytical and dedicated to his own research—demonstrating, as he was wont to say. Science in the making rather than science already made. His methods attracted such listeners and collaborators as d’Arsonval, Bert, Dastre, Gréhant, Jousset de Bellesme, Moreau, Pasteur (whose notes made from Bernard’s lectures remain unpublished), Ranvier, and Tripier; the Germans Kühne and Rosenthal; the Russians E. de Cyon, Setchenov, and Tarkhanov; the Italians Mossoand Vella; the Dane Panum; the Englishmen Ball and Pavy; such Americans as J. C. Dalton, Austin Flint, W. E. Horner, and S. W. Mitchell; and Emperor Pedro II of Brazil. Even those physiologists and physicians who did not actually attend Bernard’s lectures knew his ideas from the ten volumes of Leçons delivered at the Collège de France, publications that ranged from the Leçons de physiologie expérimentale appliquée à lamédecine (1855) to the Leçons de physiologie opératoire (published posthumously, 1879.).

The courses that Bernard taught at the Sorbonne were, from their inception, of a more general character. His Leçons sur les propriétesdés tissues vivant, delivered in 1864 and published in 1866, illustrate these tendencies. In this course, it was Bernard’s aim to “determine the elementary conditions of the phenomena of life:” that is, “to return to the elementary condition of the vital phenomenon, a condition that is identical in all animals.” In contrast to comparative physiology, general physiology “does not seek to grasp the differences that separate beings, but the common points that unite them and which constitute the essence of the vital phenomena.” It is obvious why, when Bernard went to the Muséum d’Histoire Naturelle in 1868, the name of the chair that he was to occupy was changed.

In all the courses that he taught at the Muséum, Bernard sought to demonstrate the vital unity of all organisms. In contrast to the naturalists, Bernard was interested only in vital manifestations that did not differ from species to species. Encouraged by the general development of cellular theory and by his own research on the non specificity of the nutritive processes, he extended his work into plant physiology. In the first volume of his Leçons phénomenesde la vie communs aux animaux et aux végétaux. (1878;Bernard corrected the proofs on his deathbed), he went beyond the framework of traditional physiology to treat problems of general biology. His last experimental researches dealt with anesthesia of animals, influence of the ether application on plants, embryonic development, and fermentation.

Bernard was showered with honors in the final years of his life: he was commander of the Légion d’Honneur (1867), president of the Société de Biologie(1867), senator of the Empire (6 May 1869), member of the Académie Françise (27 May 1869) and its president (1869). His legal separation from his wife and the Franco-Prussian War affected him profoundly, but he took pleasure in long stays at St.-Julien and in a tender friendship with Marie Raffalovich, to whom his letters reveal a glimpse of his poetic sensibility.

Bernard died of what was probably a kidney disease. He received a national funeral, an honor reserved until then for France’s military and political leaders.

Scientific Works. As much through concrete discoveries as through the creation of new concepts, the work of Claude Bernard constitutes the founding of modern experimental physiology. His scientific career started with two series of precise and well delimited researches: on the one hand, the chemical and physiological Study of gastric digestion, and on the other, experimental section of nerves. In both cases, the responsibility for the choice of method and subject rested less with Bernard than with his teacher Magendie. But once the initial impetus had been given, the disciple quickly gave his work a completely new orientation—one that had not been fore seen at the start.

Despite some errors (for example, Bernard believed that the acidity of the gastric juice was caused by the presence of lactic acid), his experiments on the digestive action of saliva, gastric juice, and bile resulted in discoveries of undeniable value: the presence of an organic enzymatic factor in the gastric juice (1843), the nervous control of gastric secretion, the decomposition of all carbohydrates into monosaccharides prior to their absorption the special defense mechanism of the gastric wall against the digestive activity of the gastric juice, the proteolytic properties of bile(1844), the exact localization of gastric secretion; and so on.

Bernard’s most impressive discoveries in the field of digestion proper concern the functions of the pancreas, especially the importance of pancreatic juice in the digestion and absorption of fats, Two observations showed him the road to follow, First, he had noted that the urine of herbivores is alkaline, while that of carnivores is acid. Bernard showed that fasting brought about acidity of the urine in herbivores (they lived off their body fat) and that man and carnivorous animals put on a vegetarian dietexcreted alkaline urine (1846). Bernard then applied himself to the comparative study of the phenomena of digestion in both carnivores and herbivores. He initiated experiments by which to follow the changes in the chyle in the various parts of the intestinal tract of a dog and a rabbit. Thereby he noted that the absorption of fat by the chyliferous vessels occurred at a rather considerable distance from the pylorus in the rabbit and immediately at the beginning of the duodenum in the dog. Bernard discovered that this difference coincided with an anatomical difference at the point of discharge of the pancreatic juice into the intestine. Thus the role of the pancreas in the first phase of fat metabolism was demonstrated (“Du sucpancreéatique et de son rôle dans les phénomènes dela digestion,” 1849). In order to collect pancreatic juice in its pure state and to study the regulation of its secretion, Bernard conceived and made the ternporary pancreatic fistula, later improved by Pavlov. Bernard found that pancreatic juice acted on fats by a saponification process.

In studying the digestive properties of the gastric and pancreatic Juices. Bernard did not intend to restrict himself to a narrow view of the problem of local digestion alone, or of the decomposition of food in the gastrointestinal tract. Although he studied intensively the chemical changes in food exposed, both in vivo and in vitro, to saliva, gastric Juice, or pancreatic juice, this was to him only one, fragmentary aspect of a vast research subject. What interested him above all was what happened to the food in the animal organism, from its entry until its total assimilation or excretion. Thus the horizon of Bernard’s research kept widening and, by going beyond the limits of simple “digestion,” it made its true object “nutrition” (or, in modern terminology, “metabolism”).

Never wavering, Bernard was to advance beyond the then prevailing notions of “animal statics” and to set up the first milestones on the road to the understanding of intermediate metabolism. To begin with, Bernard accepted the theory of his teachers that animals are incapable of synthesizing sugar, fat, and albumin. These three substances would always originate in plants, and their percentage in the blood would vary and would depend essentially on the food consumed. Nutrition would consist of three stages: digestion, transport of digested substances, and chemical in corporation or combustion.

Then he discovered that the alleged transport of absorbed substances is an extremely complicated process, more chemical than physical, more a series of transformations than a series of displacements. He also understood that nutrition is a phenomenon of synthesis as much as it is an analytical process. If food intake is an intermittent process, “nutrition” (in the sense of metabolism) is continuous and is stopped only by death. “Nutrition” is also indirect: prior to being integrated into the tissues, the organic alimentary substances must be broken down to a certain degree and then recombined. In formulating and demonstrating these ideas, Bernard was able to talk with pride of his work on nutrition: “I am the first one to have studied the intermediary stage. The two extremes were known and the rest was accomplished by means of the physiology of probability.”

In his thesis on gastric juice (1843), Bernard published, marginally to the principal subject, the first results of his experiments on the ingestion of food substances by other than natural means. His thesis relates two important discoveries: (1) if so-called “type I” sugar (sucrose) is injected directly into the blood, it is eliminated by the kidneys, while the so-called “type 2” sugar (glucose) is retained in the organism; (2) gastric juice transforms sucrose into assimilable sugar, that is, sucrose exposed to the action of gastric juice and then injected into the blood no longer appears in the urine. “Type 2” sugars (in modern terminology, sugars of the monosaccharide group) represent the only “physiological” form of carbohydrates in the animal organism. Gastric juice changes all other forms of carbohydrates into assimilable physiological sugar.

Blinded by prevalent theories, Bernard searched in vain for the site and the manner of breakdown of sugar in the animal organism. He wished especially to give experimental proof to Lavoisier’s ideas, according to which sugar is burned in the lungs. After four years of experimentation an apparently contradictory observation, a new experimental fact upset the entire theoretical structure. In August 1848, Bernard noted the presence of sugar in the blood of an animal from which all solid food had been withheld for several days. Greatly surprised, he turned his research in anew direction. Thus he was soon able to discover (1) that glycemia is a normal and constant phenomenon, independent of food intake and (2), that the liver produces sugar and empties it into the blood. Published in October of the same year in “De I’originedu Sucre dans I’économic animale,” the discovery of the glycogenetic function of the liver compelled physiologists to revise certain fundamental notions and threw new light on the understanding of diabetes. Bernard was sometimes contradicted. If the criticisms by Louis Figuier, Pavy, and several other adversaries today appear justified with respect to certain details. Bernard was nevertheless on the right track.

In 1849 Bernard believed he bad found a method of causing “artificial diabetes” by means of a locallesion of the nervous system. There followed the discoveries of the presence of sugar in the allantoic and the amniotic fluids (1850) and in the cerebrospinalfluid (1855), the proposition to utilize the quantitative determination of sugar in the liver of afresh corpse in order to establish whether death had been sudden (January 1855), and the astonishing observation that the liver manufactures sugar even after the death of an animal (September 1855). By forcing a stream of water through the hepatic vessels into the still-warm liver as soon as possible after the death of the animal, the hepatic tissue is completely freed of its sugar content. But if the liver is kept at moderate temperature, several hours afterward, or even the next day, the tissue will once more contain a quantity of sugar, produced since the irrigation. From this experiment Bernard derived proof of the existence of a special “glycogenetic substance.” This was, strictly speaking, the first artificial perfusion of an organ separated from the body.

His handwritten notes reveal that Bernard had perfectly understood the general implication of this process and that he wanted to study the artificial survival of certain organs by means of continuous perfusion with blood. The discovery of glycogen, a kind of “animal starch” that could be converted into sugar and was barely soluble in water, was communicated to the Académie des Sciences on 24 September 1855, but this substance was not extracted in a relatively pure state until February 1851, Almost simultaneously. V. Hensen, a young German physiologist, isolated glycogen by a process different from Bernard’s.

In the glycogenetic function of the liver Bernard distinguished henceforth two types of phenomena: the creation (or synthesis) of glycogen in the liver and the transformation of this substance into sugar. According to Bernard, the first phenomenon was a “vital function whose true beginning is still unknown,” while the second phenomenon is “purely chemical” and consequently can also be produced after the death of the individual. Thus, a fundamental distinction is established between the “plastic or organically created” phenomena and the “phenomena of attrition,“or vital destruction.

The true culmination of Bernard’s work in the field of carbohydrate metabolism was shown in the chapter on extrahepatic glycogenesis: the role of the placenta (1859), the ontogenetic and phylogenetic aspects of glycogenesis, production of sugar in animals without a liver, carbohydrate metabolism in muscle (for example, lactic fermentation of muscle glycogen), the breakdown of sugar in the tissues and its relation to the release of heat, the role of glycogenetic ferments, and, above all, the explanation of glycogenesis as a cellular process.

Since the discovery of the formation of sugar in the liver, Bernard had been convinced that the latter was subject to control by the nervous system, This hypothesis found strong support in the discovery of the so-called piqûre sucrée, In February 1849, Bernard experimented with severing the cerebellar peduncle in rabbits, in order to determine the accuracy of certain observations on the behavior of animals thus traumatized—observations that had been reported by Magendie and contradicted by François Longet. To his great surprise, Bernard found that this type of trauma caused glycosuria. He then showed that the lesion of a specific spot in the brain (the floor of the fourth ventricle) was regularly accompanied by increased glycemia. Experiments involving section of the vagus nerve also showed the influence of the nervous system on the intensity of glycogenesis.

In order to study the functions of nerves Bernard often resorted to severing them and to local galvanic stimulation. If the first research experiments on the chorda tympani (1843) today appear to have been a step in the wrong direction, his other work in this field represents a series of extraordinary successes: the “destruction” experiments on the spinal and vagus nerves and the innervation of the vocal cords (1844), the observation of the change in the sense of tastein paralysis of the facial nerves (1845), his research on the pneumonia that occurred in animals whose vagus nerves had been severed (1853), the fine experiments on the influence of the different nerves on saliva secretion (1857), and, above all, the discovery of the vasomotor nerves. Bernard had clarified the functions of the accessory nerve, particularly its connection with the vagus nerve in the innervation of the larynx.

Bernard put an end to a long dispute between Magendie and Longet on the significance of “recurrent sensitivity,” that is that stimulation of the anterior root of a spinal nerve (motor root) can in certain cases, produce sensibility phenomena. In explaining the apparent contradictions between Magendie’s experiments and those of Longet, Bernard drew a general conclusion: contradictions in experimental results always stem from a difference in the conditions under which such conflicting experiments are performed.

At the beginning of his important discovery of the vasomotor nerves, Bernard presented a brief communication (“Influence du grand sympathique sur lasensibilité et sur la calorification”) in 1851 to theSociété de Biologie relating the observations of phenomena that occurred after section of the cervical sympathetic nerve in rabbits. He had expected acooling of the animal’s face, since the experiment had been based on the hypothesis that the sympathetic system exerts a direct influence on the nutritive and calorific processes of the tissues. To his surprise, he found a very sharp increase in the temperature of the entire region innervated by the severed nerve. Although he noted and described the increased blood circulation in the parts affected, Bernard did notrealize at the time—not even in his notes on this subject that were dated March and October 1852—the relation between these phenomena and vascular paralysis.

In November 1852 Bernard informed the Sociétéde Biologie that the galvanization of the peripheralend of the sympathetic nerve produced effects that are the exact opposite of those obtained by severing this nerve. At that time Bernard did not know that he had been anticipated by Brown-Séquard. In fact, the latter had published in the United States—in August 1852—the results of experiments with the Galvanization of the sympathetic nerve that preceded those performed by Bernard but were certainly inspired by Bernard’s observations made in 1851, of which Brown-Séquard learned just before his departure for America.

Through the work of Brown-Séquard, Schiff, and Bernard, the knowledge of the vasoconstrictor nerves was incorporated into science. But we are indebted to Bernard alone for the second stage in the explanation of vasomotor function: the discovery of the vasodilator nerves and the establishment of the concept of the physiological equilibrium of the two antagonistic innervations. In analyzing the causes of changes in the color of venous blood in the salivary glands, Bernard discovered the active vasodilator reflex (“De l’influence de deux ordres de nerfs quidéterminent les variations de couleur du sang veineuxdans les organes glandulaires,” 1858). Research on vasomotor nerves was very closely connected with (1) the description of the so-called Horner-Bernard ocularsyndrome (paralysis of the sympathetic nerve provokesmiosis, narrowing of the palpebral fissure, and enophthalmos on the side of the lesion; see “Expériences sur les fonctions de la portion céphaliquedu grand sympathique,” 1852); (2) the elaboration of the concept of “local circulation” subject to variations occurring in the various organs, depending on whether they are functioning or in a state of rest (“Surla circulation générale et sur les circulations locales,” 1859); and (3) the idea of double and reciprocal innervation that enables the organ to function not only as a result of stimulation but also as a result of an inhibitive mechanism (for example, according to Bernard, the chorda tympani determines salivary secretion by a “paralyzing action” on the tonus of the sympathetic nerve; see “Du rôle des actions paralysantes dans Ie phénoméne des sécretions,“1864).

Bernard was deeply involved in the problems of animal heat production and its regulation. While he accepted Lavoisier’s theory, which attributed the origin of animal heat to a combustion process (i.e., oxidation), Bernard insisted on two fundamental modifications: (1) this vital combustion could not be direct oxidation, an immediate union of oxygen with tissue carbon; it had to be a particular organic process, an indirect combustion taking place with the aid of special ferments; (2) organic combustion could not occur in the lungs exclusively, as Lavoisier had taught, but in all tissues. In order to demonstrate the latter statement, Bernard used (particularly in June 1853) cardiac catheterization: comparison of blood temperature in the left and right ventricles furnished results that disproved Lavoisier’s original theory of pulmonary combustion. Research concerning the site of sugar decomposition furnished additional proof for “respiration of the tissues.” Bernard also conducted experiments on the lowering of body temperature either by severing the spinal cord and certain nervesor by prolonged exposure to cold. He connected the sephenomena with those observed during the hibernation of certain animals, involving artificial transformation mation of a homoiothermic animal into a Poikilothermic one.

Several other subjects of Bernard’s research in this field deserve mention: the mechanism of death caused by exposure to high temperature, the slowing down of the vital processes in a cold environment, and the pathogenesis of fever. Bernard’s experiments on rigor mortis and on the acidity and alkalinity of muscles after death represent an anticipation of twentieth century discoveries.

Bernard was a true innovator in the study of the effects of toxic and medicinal substances. No one before him had understood so well the role of drug metabolization. He regarded poisoning as a local phenomenon, and advocated the use of certain poisons in physiological research. Curare and carbon monoxide had served him, he said, as “chemical bistoury,” making it possible to destroy specific structures selectively.

As early as his first experiments with curare in 1844, Bernard had noted that this substance somehow isolated the contractile property of the muscle from the motor property of the nerve (observation published in 1850). But only ten years later he thought— practically at the same time as Albert von Kölliker—of an experiment that would prove that curare acted only upon the peripheral ends of the motor nerves. Contrary to what is generally believed, Bernard never wanted to accept the correct explanation of curare’s action, that is, that it paralyzes the motor end plates described by his pupil Kühne.

In studying the mechanism of carbon monoxideintoxication, Bernard Found that animals died of asphyxiation because this gas replaces oxygen in thered blood cells(1855–1856). At last Bernard’s theoryon organic combustion in the tissues was confirmed. In toxicology, we must not forget, moreover, Bernard’s work on opium, on strychnine, and on anesthetics. According to him, anesthesia was a biological phenomenon common to all living things and caused by a reversible coagulation of protoplasm (1875). Etherization can eliminate the sensitivity reactions, temporarily arrest germination in grain, and suspend fermentation (1876).

Bernard’s last works concentrated on the nature of alcoholic fermentation. In them he distinguished two types of fermentation, one produced by intervention of a “figurative” ferment, the other produced by soluble ferments. Nevertheless, he hoped to reduce the activities of the former (Pasteur’s ferments) to the soluble chemical principles of the latter (Berthelot’s ferments). After Bernard’s death, a series of his noteson alcoholic fermentation were made public by Berthelot (see “La fermentation alcoolique. Dernières experiences de Claude Bernard, 1878). Pasteur, surprised and embittered, published a rather angry reply. There was truth and error on both sides. Today we know that Berthelot and Bernard were wrong in accepting spontaneous generation of yeast in afemmentable medium and that they were right, in contrast with Pasteur, in claiming the existence of asoluble ferment, not living but nevertheless capable of causing alcoholic fermentation.

Philosophical Opinions. Although Bernard stated that he had “no philosophical pretensions,” hisworks—particularly the Introduction a l’etude de la m—decine experimentale (1865)—are of such general scope that they enter the domain of philosophy. In the lycees France, the Introduction is one of the official philosophy textbooks. Almost paradoxically, the “philosophical” aspects of Bernard’s work resulted in a bibliography much larger than that of hisstrictly scientific work.

Bernard’s views on philosophy and religion are imbued with the idea that the essence of things inevitably escapes us. Phenomena have two kinds of causes: Immediate, or secondary, and primary causes. Only secondary causes are accessible to scientific investigation. The others remain beyond all possibility of proof and scientific control. It is the duty of the scholar to determine, by observation and experimentation the immediate conditions of the phenomena. Investigation of primary causes lies beyond Science, and the scholar—insofar as he is a scientist—must abandon it.

Such an attitude readily reflects the influence of positivism. Yet although he was in debted to this philosophical trend, Bernard deviated from it on several points and did not refrain from criticizing Comte with pronounced rudeness. Reaching beyond narrow positivism, Bernard rediscovered certain topics of Kantian thought and accorded extrascientific legitimacy to metaphysical deliberations.

What interested Bernard first of all, however, was not so much the general theory of knowledge as the psychology and logic of scientific research. Primarily a man of the laboratory, he was interested in philosophical questions principally as a theoretician of the experimental method.

Bernard’s “experimental rationalism” is opposed both to Descartes’s rationalism and to Magendie’s empiricism while some how embracing both and synthesizing them in a wider doctrine. For Bernard, the experimental method proceeds by three stages: observation, hypothesis, and experimentation. Observation and experiment, he wrote, are two extreme terms of “experimental reasoning:” They furnish the knowledge of “facts,” but between them there extends like a bridge the “experimental idea” (also called the “idea a priori” or simply hypothesis”). The hypothesis is the primum moves of all scientific reasoning and the essential part of every discovery, but it is worthless if it is not followed and confirmed by experimental verification. Experiment is precisely an observation elicited under certain conditions for the verification of a hypothesis. Bernard’s rationalismimplies constant recourse to a test of the experimentalfacts:’ If he can change the conditions of an event, “man can become its master. This is the difference between the sciences of observation—essentially passive—and those of experimentation:

With the aid of these active experimental sciences man becomes an inventor of phenomena, a real foreman of creation: and in this respect no limits could be set to the power man can acquire over nature through future progress of the experimental sciences [Introduction, I, eh. 1, § V].

The conscious aim of all of Bernard’s work was to give medicine the decisive push along the road of its transformation into an “experimental” and “conquering” science.

Bernard confirmed the primordial role of “feeling” or “intuition” as the point of departure for “creative” experimental research. Convinced that “method by itself produces nothing,” he did not insist on positive practical precepts. Nevertheless, he carefully set forth a series of precautions for the experimental biologist. His principal advice concerned the “experimental doubt” and the necessity to avoid fixed ideas and to keep one’s mind free of doctrinal preconceptions. A good experimenter must—as he was himself—be simultaneously theoretician and practitioner: “A skilled hand without the head to direct it is a blind instrument: the head without the hand to carry out an idea remains impotent.”

The success of the Introduction is due, at least in part, to the glimpse that it affords of the personal adventures of a great biologist and its claims to the revelation of the secrets of his scientific success. Infact, almost all the examples cited by Bernard in support of his general concepts stem from his own work. A careful analysis of his original laboratory notes shows, however, that at times there were some rearrangements in the chronology of Bernard’s discoveries. The decisive turning point was almost always his extraordinary capacity for noting, in the course of an experiment, a fact that was some what marginal and did not accord with the prevailing theory.

Against a strong vitalist current—harking back to Bichat and the school of Montpellier—Bernard stressed the necessity of assuming that vital phenomena are subject to a determinism of the same kind as that which governs inert matter. This amounted to saying that “a vital phenomenon has—like any other phenomenon—a rigorous determinism, and [that] such determinism could only be a physico-chemical detenninism.” Application of the experimental method in physiology would not be justified without acceptance of this principle. To proclaim this kind of determinism in biology signified rejection of vitalism in its classic form. Furthermore, Bernard was convinced that determinism renders the use of statistics in physiological research illusory. This cricticism was nevertheless meant only for the method of the arithmetic mean.

Bernard’s position between the vitalism and the materialism of his contemporaries was complex. He opposed the former by virtue of the principle of physicochemical determinism, but by the same token he did not rally to the cause of the latter, since he attributed a “directive and creative idea” to life. According to Bernard, life phenomena fall into two groups: the phenomena of organization, of creation, or of organic synthesis, on the one hand; and the phenomena of organic destruction, on the other. If the latter can be explained only by the laws of physics and chemistry, the phenomena of the first group (that is, embryonic development, the anabolic processes of nutrition, psychic life, and regeneration) defy physico-chemical explanations, although they obey all the laws governing inert matter. “Life is creation”; it has a sense, a direction.

Bernard did not seek to reconcile opposing theories but, in going beyond them, to bring them into accord by means of an antisystematic attitude. In Bernard’s mind, once research into determinism of the phenomenon is accepted as the only aim of the experimental method, there is no longer materialism, nor spiritualism, nor inanimate-matter, nor living matter: there are only natural phenomena, the conditions of which should be determined.

The notion of “milieu intèrieur” occupies a central place in Bernard’s thought. It took form gradually: beginning in 1851 the formed a group of ideas on an intermediate animal milieu that nourished and protected. The term itself was coined in 1857 and, little by little, it was enriched with new meanings. The concept arose from the generalization of Schwann’s theory of blastemas, and of the collision between Schwann’s theory and the new forms of the cellular theory (Virchow, Brücke). It was strengthened by his research on how to overcome the conflict between Bichat’s vitalism and the epistemological necessity of absolute determinism. Onto all this were grafted reflections on the “aquatic” character of life’s elementary form and the idea of regulatory mechanisms that watch over the stability of the internal conditions of an organism. Life is a phenomenon of relationship—or, still better—a permanent conflict between the living particles and the outer world. The stabilityof the “milieu intérieur.” Bernard declared, is the precondition of a free, independent life. The notion of homeostasis(Cannon) and even the beginnings of cybernetics relate to Bernard’s ideas on the “milieuintérieur” and the way in which the equilibrium between this milieu, the tissues, and the outside world is maintained.

Although Bernard contributed to the spread of the cellular theory in France, he remained, attached for a long time to the ideas of Schwann and never completely accepted Virchow’s reform. For him, life was a protoplasmic, and not really a cellular, phenomenon. He thought life was tied more closely to chemical compounds than to histological structures. His astonishing criticism of Pasteur’s experiments on spontaneous generation appears to us today as an extra ordinary anticipation of molecular biology.

For Bernard, physiology had to be the basis of “experimental medicine.” There is no qualitative difference between normal and pathological functions. Diseases have no ontological existence; in disease one always deals merely with exaggerated, weakened, or abolished physiological functions. If this is not the view of the majority of modern pathologists, it must be recognized that Bernard must be considered the pioneer of the “positive” concept of health (the state of health is not only the absence of illness) that characterizes modem hygiene.

BIBLIOGRAPHY

I. Original Works Bernard’s books published during his lifetime are Du suc gastrique et de son rõle dans lanutrition (Paris, 1343), his thesis for the M.D.; Des matierescolorantes chez l’homme (Paris, 1844), his thesis for the aggrégation; Recherches expérimentales sur les fonctions dunerf spinal ou accessoire de Willis (Paris, 1851); Recherches sur une nouvelle fonction du foie considéré comme organe producteur de mati‘re sucr‘e chez l’homme et les animaux (Paris, 1853), thesis presented to the Faculty of Sciences; Notes of M. Bernard’s Lectures on the Blood on the Blood, W. F. Atlee, ed. (Philadelphia, 1854); Précis iconographique de médecineopératoire et d’alomie chirurgicale (Paris, 1984), written with C. Huette; Recherches experimèntales sur le grand sympathique et spècialement sur lnfluence qlle la section de ce nerf exerce sur la chaleur animale (Paris, 1854); Illustrated Manual of Operative Surgery and Surgical Anatomy trans. with notes and addition by W. H. Van Buren and C. E. Isaacs (New York, 1855): Leçons de physiologie experimentale appliquee a la medecinen vots, (Paris, 1855–1856); Mémoires sur’ le pancréas et sur le rôle du suc pancréatique dans les phénomènes digestifs parlitculirèment dans la digestion des matières grasses neutres (Paris, 1856); Leçons sur les effets des substances toxiques et méicarnemeusts (Paris, 1857); Leçons sur la physiologie et la pathologie du système nerveux (Paris, 1858); Leçons sur les proprietes physiologiques et les altèrations pathologiquesdes liquides de l’orgcmisme (Paris, 1859): Introduction à l’etude de la médecine expérimentale (Paris, 1865, and many later eds., including that of F. Dagognct, Paris, 1966), trans, into English by H. C. Greene (New York, 1927, 1957); Leçons sur les propriétés des tissus vivants (Paris, 1866) Lectures on the Physiology of the Heart and Its Connections with the Brain, J. S. Morel, trans. (Savannah, Ga., 1867); Rapports sur les progres et la marche de la physiologie généraleen France (Paris, 1867); repub. as De la physiologie générale (Paris, 1872); Éloge de Flourens (Paris, 1869), delivered before the Académie Française; Leçons de pathologie expérimentale (Paris, 1872); Leçons sur la anesthesiqtues et sur l’asphyxie (Paris, 1875); lecons sur la chaleur animale, sur les effets de la chaleur et sur fièvre (Paris, 1876); and Lecons, sur les effects et la glycogenese animale (Puris, 1877).

Books published after Bernard’s death are Lecons sur les phenomeans de la vie communs aux animaux et aux veégéaux, A. Dastre, ed., 2 vols. (Paris, 1878–1879). Vol. Ireed, by G. Canguilhem (Paris, 1966). La Science expérimentale (Paris, 1878); Leçons de physiologie opératotire, M. Duval, ed. (Paris, 1879); Pensées. ’Notes détachées. L. Delhoume, ed. (Paris, 1937); Philosophie, J. Chevalier, ed. (Paris, 1937); Le cahier rouge (partial ed.), L. Delhourne, ed. (Paris, 1942): Priniciples de médecine experimentale. L. Delhoume, ed. (Paris, 1947); Leures beaujolaises. J. Godard, ed. (Villefranche, 1950); Esquissesde notes de travail inédites L. Binet, ed. (Paris, 1952); Cahier de notes (1850–1860 (complete ed.), M. D. Grmek, ed.(Paris, 1965); Notes mémoris et lecons sur la glycogence animate et le diabé selected by M. D. Grmek (Paris, 1965): and Notes inédites de Claude Bernard sur les proprietets physiologiques des poisons de flèches (curare, upas, strychinine et autres), M. D. Grmek, ed. (Paris, 1966).

Bernard’s article include “Recherches anatomiques et physiologiques sur la corde du tympan,” in Annales medicophysiologiques, 1 (1843), 408–439; “De I’origine du sucredans l’économic animale:’ in Archives generales de médecine, 4th ser., 18 (1848), 303–319; “Du sue pancréatique et de son rôle dans les phénomènes de la digestion,” in Mémoires de la Société de biologie, 1 (1849), 99–113; “Recherches sur le curare,” in Comptes rendus hebdomadaires de l’Acadénié des sciences, 31 (1850), 533–537, written with J. Pelouze; “lnfluence du grand sympathique sur la sensibilité et sur la calorification,” in Comptes rendus de la Société de biologie, 3 (1851), 163–164; “Expériences sur les fonctions de la portion céphalique du grand sympathique:’ ibid., 4 (1852), 155; “De l’influence de deux ordres de nerfs qui déterminent les variations de de couleur du sang veineux dans les organes glandulaires,; in Comptes rendus hebdomodaires de l’Académie des sciences 47 (1858), 245–253; “ètudes Physiologiques sur quelques poisons américains. I . Curare,” in Revue des deuxmondes, 53 (1864), 164–190; “Du rôle des actions paralysantes dans le phénomène des sécrétions,” in Journal d’anotomie et de physiologie, 1 1864), 507–513; and “Lafermentation alcoolique. Dernières expériences de Claude Bernard,” M. Berthelot, ed., in Revue scientifique, 16 (1878), 49–56.

For a complete bibliography, see G. Malloizel, “Bibliographiedes travaux scientifiques,” in L ’oeuvre de Clausde Bernard (Paris, 1881); and M. D. Grmek, Catalogue des manuscrits de Claude Bernard, avec la bibliographie de sestravaux imprimés el des études sur son oeuvre (Paris, 1967).

II. Secondary Literatore. Works on Bernard are P. Bert, “Les travaux de Claude Bernard,” in Revue scientifique de la France, 2nd ser., 16 (1879), 741–755; G. Canguilhem, L’idée de médecine expérinrentale selon Claude Bernard (Paris, 1965); P. E. Chauffard, Claude Bernard, sa vie et ses oeuvres (Paris, 1878); L. Delhoume, De Claude Bernard a d’Arsonval (Paris, 1939); J. L Faure, Claude Bernard (Paris, 1925); M. Foster, Claude Bernard, in the series Masters of Medicine (London, 1899); M. D. Grmek, “La conception de la maladie et de la santé chezClaude Bernard,” in Mélanges Koyré, I. L’aventure de la science (Paris, 1964), pp. 208–227; “Les experiences de Claude Bernard sur l’anesthésie des plantes,” in Comptes rendus du 89° Congrès des sociétés savants (Lyons, 1964), pp. 65–80; “Examen critique de la genése d’une grande découverte: La piqūre diabétiquede Claude Bernard,” in Clio medica, 1 (1966), 341–350; “First Steps in Claude Bernard’s Discovery of the Glycogenic Function of the Liver,’ in Journal of the History of Biology, 1 (1968), 141–154; and La glycogenése et le diabéte dans l’oeuvre de Claude Bernard (Paris, 1968); B. Halpern, “Concepts philosophiques de Claude Bernard d’apres l’Introduction,“in Revue d’histoire des sciences, 19 (1966), 97–114; H. Hermann, “A propos d’un centenaire. Comment se fit la découvcrte des nerfs vaso-moteurs,” in Biologie medicale, 41 (1954), 201–230; G. L. Jousset de Bellesme. “Notes etsouvenirs sur Claude Bemard,” in Revue internationale des sciences biologiques, 10 (1882), 433–461; L. N. Karlik, Klod Bernar (Moscow, 1964), in Russian; P. Lamy, Claude Bernard et le matérialisme (Paris, 1939); N. Mani, Diehislarischen Grundlagen der Leberforschung, II (Basel, 1967), 339–369; P. Mauriac, Claude Bernard, 2nd ed., rev.(Paris, 1954); R. Millet, Claude Bernard ou l’aventure scientifique (Paris, 1945); G. Monod et Thyss-Monod, “Claude Bernard, l’homme, sa vie,” in Revue du mois, 17 (1917), 222–242; J. M. D. Olmsted, Claude Bernard, Physiologist (New York-London, 1938); J. M. D. Olmsted and E. Harris Olmsted, Claude Bernard and the Experimental Method in Medicine (New York, 1952); E. Renan, Éloge de Claude Bernard (Paris, 1879); W. Riese, “Claude, Bernard in the Light of Modem Science,” in Bulletin of the History of Medicine, 14 (1943), 281–294; J. Rostand, Hommes de vérité (Paris, 1943), pp. 53–123; P. Van Tieghem, Notice sur la vie et les travaux de Claude Bernard (Paris, 1910); P: Vendtyés, Les “conditions déterminées” de Claude Bernard (Paris, 1940); R. Virtanen, Claude Bernard and His Place in the History of Ideas (Lincoln, Neb., 1960).

Collections are L’oeuvre de Claude Bernard (Paris, 1881); Centenoirede de Claude Bernard (Paris, 1914); Claude Bernard and Experimental Medicine, F. Grande and M. B. Visscher, eds, (Cambridge, Mass., 1967); and Philosophie etméthodologie scientifique de Claude Bernard, B. Halpern, ed. (Paris, 1967.

M. D. Grmek