Popular Science Monthly/Volume 84/June 1914/Claude Bernard
ONE hundred years ago, in a little village in eastern France, there was born of humble parentage a man who was to become one of the greatest physiologists of France and of the world. Though a pioneer in a field despised and looked down upon at the time, he was to make discoveries which were of fundamental importance to physiology and medicine and were to influence the whole general aspect of biology toward certain questions.
Claude Bernard was born in the little village of Saint Julien, department of Rhone, July 12, 1813. His father was a small land owner of the district and earned a comfortable living from the fruit of his vineyard. Bernard later came into possession of the estate and spent his vacations there, working out of doors among his trees and vines. He describes it thus:
Bernard and a sister were the only children. He was apparently a bright child, for the cure made him a choir boy and taught him Latin. Later, he went to the small Jesuit college at Villefranche and from there went to Lyons, where he soon left school to enter a practical pharmacy. At first he received only board and lodging for his services, but soon his manual dexterity won for him a small salary. He remained here two years, but his employers mode of business made him sceptical of medical and pharmaceutical practise of the day as shown by the following story related by Sir Michael Foster.
Bernard had literary aspirations, being especially attracted toward the drama, and spent much of his time at the Théâtre des Célestines. He wrote a vaudeville comedy entitled "La Rose du Rhône" which was accepted and attained a fair degree of success. Thus encouraged, he started in earnest to write a five-act historical drama in prose and determined to seek his fortune in Paris. On reaching the city, in 1834 when
he was twenty-one years old, he presented his manuscript of "Arthur de Bretagne" with a letter of introduction to the great critic, Saint-Marc Girardin, who received him kindly and saw that the work possessed merit, but, knowing the uncertainties of a writer's life, suggested that Bernard take up some work whereby he could make a living. Hearing of his former pharmaceutical training, Girardin suggested that he study medicine. Bernard followed the suggestion and, for five years, applied himself to the work. He was especially interested in anatomy and physiology. Anatomy, at this time, was well advanced and scientifically presented but physiology consisted of a mass of uncorrelated and inexact data.
His father died during this period, having lost most of his fortune before his death, and left Claude to depend on his own resources. He lived frugally and payed his fees with money earned by giving lessons. He was retiring, thoughtful, awkward in manner and impressed neither his fellow students nor his professors as being brilliant or liable to a great career. Only in the dissecting room did he attract attention by his careful and beautiful dissections.
In 1839, after serving as "externe" at the hospitals, he was made "interne" and appointed to work under Magendie, who was one of the physicians at the Hotel Dieu and professor of medicine at the Collége de France. The professor was allotted a small, dark room at the college for conducting research and was allowed a "préparateur" to assist in research and in experiments conducted to illustrate the lectures. He soon noticed Bernard's skill in dissection and appointed him his "préparateur." With this appointment, Bernard's career as experimental physiologist began. A glance at the state of physiology at this time will show the great odds against which he was about to work.
The spirit of present-day research was only beginning to be allowed full play. Harvey, early in the seventeenth century, opened the way for the application of experimental methods to physiological inquiry by his observations leading to the discovery of the circulation of the blood; but the vitalistic theory had impeded, at every step, the attempts to study living organisms. Slowly, this theory was losing ground and physico-chemical explanations substituted.
The spirit of progress was most apparent in Germany. Liebig had recently opened at Giessen the first public laboratory for chemical research. Wohler had made urea from ammonium cyanate, thus destroying the old vitalistic argument that life was necessary to form organic from inorganic substances. Johannes Müller was the foremost physiologist. He was a vitalist, but only in a modified degree much more acceptable than Haller and his pupils. He believed in the necessity of recognizing a vital force, but maintained it was not independent of certain conditions. He did not depreciate the value of the experimental method in discovering physiological truths, as is shown by his own work and that of his pupils, among whom Ludwig, DuBois Raymond and Helmholtz, soon to be the foremost physiologists in Germany, were just beginning their careers.
In England, Hall, Reid, Sharpey and Bowman were advancing the science by experimental methods.
France had looked too much to her own scientists for the words of progress and was far behind her neighbors. Cuvier and Bichat were especially popular. Cuvier, a morphologist and an ardent vitalist, was supreme and depreciated any attempt to explain or solve physiological problems by physico-chemical means. Bichat, though long dead, was very powerful and his explanations which were finally to overthrow the vitalistic conception had been misunderstood and misapplied to overemphasize it. Many scientists of the time asserted that living organisms could not be subject to exact experimentation.
Magendie was the foremost physiologist in France and believed in a modified vitalism. While he paid his respects to vitalism by admitting that some of the phenomena of life were beyond the scope of experimental investigation, he realized that physico-chemical explanations could solve many problems of physiology. Disgusted with the empty discussions of the vitalists, he went to the other extreme and threw his energies entirely into experimental study without thought or plan, and though his accomplishments were many, they fell far short, considering the time spent and energy consumed.
Bernard saw the fallacies of each line of endeavor and, at the outset strove to use all his powers of theoretical and practical reasoning, together with careful manipulation and observation. Besides his work at the college, he gave a course of private lectures and spent the remainder of his time at research, usually in some temporarily improvised private laboratory or in the chemical laboratory of some one of his friends. There was no room for his private research at the Collège de France.
In May, 1843, he published his first communication: "Recherches anatomiques et physiologiques sur la corde du tympan, pour servir à l'histoire de l'hemiplégie faciale," followed in the same year by his doctor's thesis—" Du suc gastrique et du son rôle dans la nutrition." The work on the chorda tympani nerve, suggested by Magendie's work on nerves, started a long series of similar studies. This was typical of his analytical and logical reasoning. He proceeded, step by step, in his experiments to their logical conclusion or until an observation suggested a separate line of inquiry which seemed to be more fruitful. His thesis on the gastric juice was also the first of a series which led to his great discovery of glycogen and the glycogenic function of the liver. The main result of this thesis was that cane sugar, injected into the blood, was excreted unchanged; but sugar which had previously been acted upon by gastric juice was not excreted when injected, but was retained and used by the tissues. These two pieces of work illustrate Bernard's line of thought. He was always interested in the action of the nervous system on the chemical changes involved in nutrition and worked from both the physiological and chemical aspect of the problem whenever possible.
In studying the difference in the digestion and nutrition between carnivora and herbivora, he noticed that fat fed to rabbits was digested and absorbed much lower down than was the case when it was fed to dogs, and soon found that the variation was due to the different points of entrance of the pancreatic duct into the intestine in the two animals. This led to a long series of experiments on the function and properties of the pancreas. He showed for the first time that the pancreas and not the stomach was the chief organ of digestion and that the gastric juice merely started the digestion which was completed by the more powerful pancreatic juice. Its three-fold function for digesting proteins, fats and carbohydrates was also demonstrated. For this work, which was reported in 1848-9 and published complete in 1856, Bernard was awarded the prize of experimental physiology by the Académie des Sciences and was introduced to the scientific world as a physiologist of remarkable ability and great promise.
The story of the discovery of glycogen, which revolutionized prevalent biological theories concerning functions of the organs and differences between plant and animal metabolism, is interesting in showing how a quick, alert mind can "grasp the hints that Nature gives" and advance, step by step, to a final realization of the complete truth.
The prevalent view concerning the differences between plant and animal metabolism had been proposed by Dumas, the chemist, and Boussingault, the agronomist. They showed that plants build up complex organic compounds from inorganic substances and animals, by feeding, take the complex compounds already formed and break them down to simpler ones. Animals might modify them, but never make them more complex. There was a complete cycle in which compounds were built up by plants and broken down by animals. While this was the prevalent view, there were some strong minds who opposed it. Liebig confirmed Huber's old observation that bees, fed on sugar alone, produce wax and showed that fattening geese accumulate fat in excess of the fat fed.
Bernard proposed to trace the successive steps by which the various food-stuffs are transformed in the body and chose sugar as the subject for his first investigation because it seemed liable to the simplest explanation. The other foodstuffs were never investigated. He was early interested in diabetes and wished to find the cause for the excess of sugar in the blood and thereby assist in working out a remedy. His plan was as follows:
He had shown that cane sugar must be changed before it can be retained by the blood. Tiedemann and Gmelin had proved that starch is changed to sugar before it is absorbed from the alimentary tract. This indicated to him that all carbohydrates enter the blood as simple sugars. Where was this sugar destroyed? If he could find the tissues that caused the destruction and by some means decrease their activity, the blood would become overloaded with sugar and experimental diabetes would be produced. Thus, the discovery which he made was not the result of a "haphazard dive in Nature's full pocket" but came from a carefully planned experiment. As was often the case, the investigation did not yield the expected results, but something equally valuable.
He fed a diet rich in sugar to a dog, killed it at the height of digestion and examined the blood leaving the liver by way of the hepatic vein to see if the liver caused a destruction. An abundance of sugar was found here. To see if this was the sugar which had been fed, the experiment was repeated, giving the dog only meat. To his great surprise, an abundance of sugar was again found in the hepatic vein and very little in the blood from the other organs. He immediately divined the truth that the liver makes the sugar which was found in such large amounts. Repetition of the experiments with many modifications always produced the same results. The sugar was shown to be dextrose. Different animals showed the same phenomenon. These results were published in 1849-50, when he described the sugar production by the liver as similar to a secretion and not influenced by the kind of food eaten.
These observations, confirmed by others, established the glycogenic function of the liver; that is, they proved that the liver produces sugar by a mechanism similar to secretion. Going further, he showed that the sugar is not made from substances in the blood flowing through the liver, but from a substance present in the liver tissue. This was demonstrated by washing out all the blood and sugar from an isolated liver. After letting it stand for some time in a warm place, more sugar could be washed out with water. Boiled liver tissue did not react in this way, but if a small amount of fresh liver decoction was added to the boiled tissue, sugar was produced as before. This experiment showed that the sugar was formed by enzyme action from something present in the liver tissue. He isolated this substance and showed it did not give the tests for dextrose, but was easily changed into it by fermentation. These results were announced to the Académie des Sciences on September 24, 1855. Two years later, he obtained the substance in a pure state and gave it the name "glycogen." Analysis showed it to be a carbohydrate.
Bernard believed the formation of glycogen in the liver to be a vital process, but the formation of dextrose from glycogen to be a simple enzyme action independent of life. This was contrary to the teaching of the time, for all enzyme actions were considered to be inseparable from the living cell. He showed that the blood contains an enzyme capable of forming dextrose from glycogen and suggested that a nervous control of the circulation governs the sugar formation. Comparisons were drawn between the formation of glycogen and sugar in the animal body and starch and sugar in plants.
While work was continued along this line, the fundamentally important results have been mentioned above. Other experiments and writings confirmed, extended and defended his views. Bernard had made a great discovery and pushed it to the end and did not have to suffer the humiliation so often falling to the lot of a pioneer who pronounces a great fundamental truth and is outstripped by his contemporaries in producing proofs and developing details. Though it took several years to work out all the details, he always kept the lead.
This discovery supplied much that had been obscure concerning the sugar metabolism in the body and the functions of the liver, and greatly influenced general biological thought. It overthrew the idea that animals can not construct but only destroy products built up by plants. It broke down the prevailing theory that each organ has only one function. Previous work had shown that the liver produces bile and the pancreas and stomach furnish digestive juices. Nothing more seemed left to be learned except the function of the spleen. The discovery of the second function of the liver destroyed the bonds which the theory of functions had thrown around the biological thought of the time and encouraged more work in this field. The introduction of the idea of an internal secretion which was poured into the blood to assist in the normal nutrition of the body has been very productive and still fills the minds of physiologists and bids fair to produce some of the most valuable contributions to modern physiology.
Glycogen was soon found in all the tissues and quantitative relations were investigated. Others have contributed but little new to the subject and Bernard's ideas stand to-day as he expressed them then.
During this work, Bernard discovered the remarkable fact that a puncture of the fourth ventricle of the brain causes temporary diabetes. This, like other of his discoveries, was not happened upon accidentally, but was the result of logical reasoning concerning the nervous control of the sugar production by the liver, which he assumed to be a typical internal secretion. He found that cutting the vagus nerve stopped the sugar production and reasoned that stimulation of the nerve should lead to increased production. Being unsuccessful when all the ordinary means of nerve stimulation were used, he resorted to an expedient which he had noted previously, that a marked stimulation occurred when the point of origin of the nerve in the brain was punctured. In this case, an over-production and excretion of sugar was obtained. Here, as in a number of instances, a wrong view led him to an important discovery for he soon showed that the vagus is not a true secretory nerve governing the hepatic sugar secretion.
This illustrates one of Bernard's important characteristics. He developed a line of theoretical reasoning to its fullest and, by watching his experimental evidence, could grasp whatever facts showed themselves unbiased by the reasoning which had suggested the experiment. He emphasized imagination and preconceived theory when used in their proper places and used to say:
Put off your imagination as you take off your overcoat when you enter the laboratory; but put it on again, as you do the overcoat, when you leave the laboratory. Before the experiment and between whiles let your imagination wrap you round; put it right away from yourself during the experiment itself, lest it hinder your observing power.
His discovery of the vasomotor nerves was hardly less important than the discovery of glycogen. These nerves control the circulation of the blood by causing the muscles in the walls of the blood vessels to increase or diminish the bore thus allowing more or less blood to flow through at one time. The nerves belong to the sympathetic system, that is, they are not under the control of the will but stimulated by sensory impulses. The part played by him in this work was different, for he did not realize the importance of his discovery. As usual, he was looking for something else, and did not immediately turn aside to follow the new line of work.
The knowledge of the blood vessels at this time was very limited and inexact. Johannes Müller, the foremost physiologist in Germany, in his classical work on physiology in 1838, concluded that the arteries did not possess a muscular coat but only physical elasticity. He was entirely unprepared for the idea of vasomotor nerves. The sympathetic nerves had been traced to the blood vessels and some thought they should have something to do with the circulation. Stilling introduced the word "vasomotor" in arguing from theoretical grounds that the circulation must be governed by nerves not subject to the will, but influenced by sensory stimuli. In 1846, Kolliker discovered that plain muscle was made up of minute spindle-shaped cells either in clumps or scattered. This cleared up the doubts concerning the muscle coat of the blood vessels. The way was now open for the proof of the vasomotor nerves, but no one saw it.Bernard proposed to study the influence of the nerves on animal heat, and began by attempting to ascertain the effect of cutting a sympathetic nerve on the temperature of that part of the body affected by it. He conceived that the action of the nerve, if any, would be in governing the chemical changes involved in heat production, and expected to find a section of the nerve would cause a lowering of temperature. Working on the cervical sympathetic nerve in a rabbit, he was astonished to find an increase instead of a diminution in heat on the side of the head where the section was made. He reported:
He reserves for further consideration "whether the vascular changes are the cause or the effect of the rise of temperature." While the work was published as experiments on animal heat, it is the first clear and decided experimental proof for the vasomotor functions of nerves. The operation had been performed for one hundred and fifty years and the constriction of the pupil of the eye had been noticed, but the increased heat and the dilatation of the arteries had never before been observed. With this experiment, the true knowledge of vasomotor nerves begins.
This discovery caused a great stir in the scientific world and several investigators proceeded to work on the subject independently. Brown-Sequard proposed the correct interpretation of the phenomena that section of the nerve caused a dilatation of the blood vessels and the dilatation allowed increased blood flow which resulted in an increase in temperature and irritability. Bernard held continually that part of the heat effect might be due to the influence of the nerves on the chemical activities in the tissues.
Several years later, working on the submaxillary gland, Bernard observed that the blood coming from the gland was bright red, like arterial blood when the chorda tympani nerve was stimulated, and that it was dark, venous and small in quantity when the sympathetic nerve was stimulated. Thus, he showed that the chorda tympani is a vasodilator nerve causing dilatation and increased blood flow, while the sympathetic is a vasoconstrictor nerve. This effect was shown to be true for other glands. This was the first clear announcement of the presence of vasodilator and vasoconstrictor nerves.
Other lines of work occupied his attention, but the results do not possess such fundamental value as those described above. He worked on the physiological effects of curare, the arrow poison of the South American Indians. Carbon monoxide poisoning was explained as due to a stable combination of the gas with the red blood corpuscles. This explanation was made before respiration had been explained as due to an unstable combination of oxygen with the hemoglobin of the red blood corpuscles. He presented a proof against the spontaneous generation of life when that question was a vital issue in the scientific world. He carried out some work on fermentation opposing Pasteur's views that the living cell is necessary, thus anticipating Buchner's proof by twenty years.
Bernard began work when opportunities for research were scarce and his chosen field was looked down upon and scoffed at, but he persisted despite the obstacles in his way. In 1847, he was appointed a deputy at the Collège de France and a career seemed assured. He now could work in an official laboratory. He said at the beginning of his lectures:
Four years later, he was much disappointed in his career and thought of giving up scientific work and going into private practise. Unhappy domestic relations made matters worse, for his wife had no sympathy for his scientific endeavors. He was, however, beginning to be recognized as a coming man in science and was given the newly created chair of general physiology in the University of Paris at the Sorbonne. This was the first honorable position for him to occupy and his devotion to science was now assured. In the same year, he was elected to the Academy of Medicine and Surgery. In 1855, Magendie died and Bernard took his place as professor at the Collège de France.
The lectures were not specified at the college, so he usually chose some topic on which he was working and developed it, from lecture to lecture, illustrating with old and new experiments. He used his lectures to make known new facts and new or corrected and extended views. The reports which were made to the Académie des Sciences and the Société de Biologie were very brief and incomplete. Only in his published "Leçons" is a full account given of his experiments and results, many of which are found there alone. They were reported by one or another of Bernard's students, revised by him and published. These are his greatest written contributions. The series began with "Leçons de Physiologie expérimentale," published in 1855, dealing with the physiology of sugar and the glycogenic function of the liver. He published seventeen volumes in all.
In the winter of 1862-63, he was bothered with an abdominal trouble, probably appendicitis, from which he did not recover for five or six years. Part of the time he spent at his old home at St. Julien tending his gardens and living out of doors. Here he had an opportunity to broaden and generalize his ideas and write an "Introduction to the Study of Experimental Medicine." In his later years, his thinking became more general. He always tried to show the true spirit of physiological inquiry and to realize the general aspects of the whole field. This is well shown in his lectures on the phenomena of life common to plants and animals.
In 1864, he visited court and greatly interested Emperor Louis Napoleon, who entered into a lively discussion with him which lasted for two hours, and was so well pleased that he ordered his minister of public instruction to see that he had whatever he wanted. Bernard obtained in this way two well-furnished laboratories, one at the Sorbonne and the other at the Jardin des Plantes, where he held the chair of general physiology. Thenceforth, his life was full of distinction and honor. In 1868, he was elected to the Académie Française and became one of the "Immortals."
He was separated from his wife and children and lived by himself on the Rue des Écoles, opposite the chief entrance to the Collège de France. He was always retiring and shrank from social distinctions. Foster thus describes him:
He was a great friend of Berthelot, the chemist, and Renan, the philosopher, both of whom were his colleagues at the college. His pupils worshiped him.
Bernard was seized by a chill in the laboratory, developed an acute affection of the kidneys, and died, after a lingering illness, February 10, 1878. He was accorded a public funeral at the expense of the state, an honor previously bestowed upon none but statesmen, princes and soldiers. France paid her highest tribute to this quiet man of science who had contributed much, by fact and inspiration, to the advancement of the knowledge of physiological phenomena.
What were the attributes of mind and character which made Bernard a genius as an investigator?
His conscientious adherence to truth at all times need not be emphasized, as that is necessary for all true scientists, great or mediocre. His greatest attribute may have been his fruitful imagination, always under control, active before and after an experiment and asleep when observations were being made. Imagination is necessary to produce original hypotheses and it must be tempered with judgment to produce hypotheses capable of being put to experimental test. Bernard considered none but those of practical value, capable of being proved right or wrong. His readiness to turn aside from a line of research to take up a new inquiry suggested by some observed fact was remarkable for its frequent though opportune use. When to turn aside and when not to do so demands the mind of a genius for solution.
A thing of practical importance and of great value to him was his manual dexterity. In such experiments as some of his, a poor dissection or bunglesome manipulation might easily have complicated the experimental conditions so that the results would have been difficult of correct interpretation and a false step at any point might have led him astray.
It has been said that Bernard has not influenced scientific thought and stimulated investigation as others have, for he so nearly completed the work suggested by his great discoveries. However true that may be in a limited sense, the statement is unjust, for, as with all important scientific discoveries, the effect produced indirectly on scientific thought can not be estimated. He was the first to prove beyond a doubt that animals can build up as well as break down complicated products in the course of their normal nutrition. Few ideas have been more stimulating than this and it undoubtedly greatly influenced thought which subsequently led to the proof of the synthesis of fat and the discovery of the complicated process of protein metabolism whereby protein foods are broken down and built up in the body. Destruction of the theory of functions encouraged further work on the various organs of the body. Since then, many valuable facts have been produced showing the close interrelation of functions of the organs and their interdependence on each other for normal activity. The discovery of the vasomotor nerves opened up an entirely new conception of the regulation of circulation and temperature. It has been of untold value in explaining physiological and pathological phenomena concerning this, one of the most fundamentally important functions of the body. Medical science has applied it to practical problems and made the knowledge of vasomotor activity indispensable to the practising physician.
Taken altogether, his work produced results which greatly advanced knowledge of physiological phenomena, placed physiology among the great sciences, and opened new lines of inquiry which yet promise to bear fruit of which his fertile imagination could not conceive.