"The true experimental study of digestion is of comparatively recent date; the ancients were content to find comparisons, more or less happy, with commonfacts. Thus, for Hippocrates, digestion was a 'coction': for Galen, a 'fermentation,' as of wine in a vat. In later times, van Helmont started this comparison again: for him, digestion was a fermentation like that of bread: as the baker, having kneaded the bread, keeps a little of the dough to leaven the next lot kneaded, so, said van Helmont, the intestinal canal never completely empties itself, and the residue that it keeps after each digestion becomes the leaven that shall serve for the next digestion."The first experimental studies on the digestion date from the end of the seventeenth century, when the Academy of Florence was the scene of a famous and long controversy between Borelli and Valisnieri. The former saw nothing more in digestion than a purely mechanical act, a work of attrition whereby the ingesta were finely divided and as it were pulverised: and in support of this opinion Borelli invoked the facts that he had observed relating to the gizzard of birds. We know that this sac, with its very thick muscular walls, can exercise on its contents pressure enough to break the hardest bodies. Identifying the human stomach with the bird's gizzard, Borelli was led to attribute to the walls of the stomach an enormous force, estimated at more than a thousand pounds; whose action, he said, was the very essence of digestion. Valisnieri, on the contrary, having had occasion to open the stomach of an ostrich, had found there a fluid which seemed to act on bodies immersed in it; this fluid, he said, was the active agent of digestion, a kind ofaqua fortisthat dissolved food."These two opposed views, resulting rather from observations than from regularly instituted experiments, were the starting-point of the experimental researches undertaken by Réaumur in 1752. To resolve the problem set by Borelli and Valisnieri, Réaumur made birds swallow food enclosed in fenestrated tubes, so that the food, protected from the mechanical action of the walls of the stomach, was yet exposed tothe action of the gastric fluid. The first tubes used (glass, tin, etc.) were crushed, bent, or flattened by the action of the walls of the gizzard; and Réaumur failed to oppose to this force a sufficient resistance, till he employed leaden tubes thick enough not to be flattened by a pressure of 484 pounds: which was, in fact, the force exercised by the contractile walls of the gizzard in turkeys, ducks, and fowls under observation. These leaden tubes—filled with ordinary grain, and closed only by a netting that let pass the gastric juices—these tubes, after a long stay in the stomach, still enclosed grain wholly intact, unless it had been crushed before the experiment. When they were filled with meat, it was found changed, but not digested. Réaumur was thus led at first to consider digestion, in the gallinaceæ, as pure and simple trituration. But, repeating these experiments on birds of prey, he observed that digestion in them consists essentially in dissolution, without any especial mechanical action, and that it is the same with the digestion of meat in all animals with membranous stomachs. To procure this dissolving fluid, Réaumur made the birds swallow sponges with threads attached: withdrawing these sponges after a definite period, he squeezed the fluid into a glass, and tested its action on meat. That was the first attempt at artificial digestionin vitro. He did not carry these last investigations very far, and did not obtain very decisive results; nevertheless he must be considered as the discoverer of artificial digestion."
"The true experimental study of digestion is of comparatively recent date; the ancients were content to find comparisons, more or less happy, with commonfacts. Thus, for Hippocrates, digestion was a 'coction': for Galen, a 'fermentation,' as of wine in a vat. In later times, van Helmont started this comparison again: for him, digestion was a fermentation like that of bread: as the baker, having kneaded the bread, keeps a little of the dough to leaven the next lot kneaded, so, said van Helmont, the intestinal canal never completely empties itself, and the residue that it keeps after each digestion becomes the leaven that shall serve for the next digestion.
"The first experimental studies on the digestion date from the end of the seventeenth century, when the Academy of Florence was the scene of a famous and long controversy between Borelli and Valisnieri. The former saw nothing more in digestion than a purely mechanical act, a work of attrition whereby the ingesta were finely divided and as it were pulverised: and in support of this opinion Borelli invoked the facts that he had observed relating to the gizzard of birds. We know that this sac, with its very thick muscular walls, can exercise on its contents pressure enough to break the hardest bodies. Identifying the human stomach with the bird's gizzard, Borelli was led to attribute to the walls of the stomach an enormous force, estimated at more than a thousand pounds; whose action, he said, was the very essence of digestion. Valisnieri, on the contrary, having had occasion to open the stomach of an ostrich, had found there a fluid which seemed to act on bodies immersed in it; this fluid, he said, was the active agent of digestion, a kind ofaqua fortisthat dissolved food.
"These two opposed views, resulting rather from observations than from regularly instituted experiments, were the starting-point of the experimental researches undertaken by Réaumur in 1752. To resolve the problem set by Borelli and Valisnieri, Réaumur made birds swallow food enclosed in fenestrated tubes, so that the food, protected from the mechanical action of the walls of the stomach, was yet exposed tothe action of the gastric fluid. The first tubes used (glass, tin, etc.) were crushed, bent, or flattened by the action of the walls of the gizzard; and Réaumur failed to oppose to this force a sufficient resistance, till he employed leaden tubes thick enough not to be flattened by a pressure of 484 pounds: which was, in fact, the force exercised by the contractile walls of the gizzard in turkeys, ducks, and fowls under observation. These leaden tubes—filled with ordinary grain, and closed only by a netting that let pass the gastric juices—these tubes, after a long stay in the stomach, still enclosed grain wholly intact, unless it had been crushed before the experiment. When they were filled with meat, it was found changed, but not digested. Réaumur was thus led at first to consider digestion, in the gallinaceæ, as pure and simple trituration. But, repeating these experiments on birds of prey, he observed that digestion in them consists essentially in dissolution, without any especial mechanical action, and that it is the same with the digestion of meat in all animals with membranous stomachs. To procure this dissolving fluid, Réaumur made the birds swallow sponges with threads attached: withdrawing these sponges after a definite period, he squeezed the fluid into a glass, and tested its action on meat. That was the first attempt at artificial digestionin vitro. He did not carry these last investigations very far, and did not obtain very decisive results; nevertheless he must be considered as the discoverer of artificial digestion."
After Réaumur, the Abbé Spallanzani (1783) made similar observations on many other animals, including carnivora. He showed that even in the gallinaceæ there was dissolution of food, not mere trituration: and observed how after death the gastric fluid may under certain conditions act on the walls of the stomach itself.
"Henceforth the experimental method had cut the knot of the question raised by the theories of Borelli and Valisnieri: digestion could no longer be accounted anything but a dissolution of food by the fluid of the stomach, the gastric juice. But men had still to understand this gastric juice, and to determine its nature and mode of action. Nothing could be more contradictory than the views on this matter. Chaussier and Dumas, of Montpellier, regarded the gastric juice as of very variable composition, one time alkaline, another acid, according to the food ingested. Side by side with these wholly theoretical opinions, certain results of experiments had led to ideas just as erroneous, for want of rigorous criticism of methods; it was thus that Montègre denied the existence of the gastric juice as a special fluid; what men took for gastric juice, he said, was nothing but the saliva turned acid in the stomach. To prove his point, he made the following experiment:—He masticated a bit of bread, then put it out on a plate; it was at first alkaline, then at the end of some time it became acid. In those days (1813) this experiment was a real embarrassment to the men who believed in the existence of a special gastric juice: we have now no need to refute it."These few instances suffice to show how the physiologists were unsettled as to the nature and properties of the gastric juice. Then (1823) the Academy had the happy idea of proposing digestion as a subject for a prize. Tiedemann and Gmelin in Germany, Leuret and Lassaigne in France, submitted works of equal merit, and the Academy divided the prize between them. The work of Tiedemann and Gmelin is of especial interest to us on account of the great number of their experiments, from which came not only the absolute proof of the existence of the gastric juice, but also the study of the transformation of starch into glucose. Thus the theory of digestion entered a new phase: it was finally recognised, at least for certain substances, that digestion is not simply dissolution, but a true chemical transformation." (Cl. Bernard,loc. cit.)
"Henceforth the experimental method had cut the knot of the question raised by the theories of Borelli and Valisnieri: digestion could no longer be accounted anything but a dissolution of food by the fluid of the stomach, the gastric juice. But men had still to understand this gastric juice, and to determine its nature and mode of action. Nothing could be more contradictory than the views on this matter. Chaussier and Dumas, of Montpellier, regarded the gastric juice as of very variable composition, one time alkaline, another acid, according to the food ingested. Side by side with these wholly theoretical opinions, certain results of experiments had led to ideas just as erroneous, for want of rigorous criticism of methods; it was thus that Montègre denied the existence of the gastric juice as a special fluid; what men took for gastric juice, he said, was nothing but the saliva turned acid in the stomach. To prove his point, he made the following experiment:—He masticated a bit of bread, then put it out on a plate; it was at first alkaline, then at the end of some time it became acid. In those days (1813) this experiment was a real embarrassment to the men who believed in the existence of a special gastric juice: we have now no need to refute it.
"These few instances suffice to show how the physiologists were unsettled as to the nature and properties of the gastric juice. Then (1823) the Academy had the happy idea of proposing digestion as a subject for a prize. Tiedemann and Gmelin in Germany, Leuret and Lassaigne in France, submitted works of equal merit, and the Academy divided the prize between them. The work of Tiedemann and Gmelin is of especial interest to us on account of the great number of their experiments, from which came not only the absolute proof of the existence of the gastric juice, but also the study of the transformation of starch into glucose. Thus the theory of digestion entered a new phase: it was finally recognised, at least for certain substances, that digestion is not simply dissolution, but a true chemical transformation." (Cl. Bernard,loc. cit.)
In 1825 Dr. William Beaumont, a surgeon in the United States Army, began his famous experiments on Alexis St. Martin, a young Canadian travelling for the American Fur Company, who was shot in the abdomen on 6th June 1822, and recovered, but was left with a permanent opening in his stomach. Since the surgery of those days did not favour an operation to close this fistula, Dr. Beaumont took St. Martin into his service, and between 1825 and 1833 made a vast number of experiments on him. These he published,[2]and they were of great value. But it is to be noted that the ground had been cleared already, fifty years before, by Réaumur and Spallanzani:—
"I make no claim to originality in my opinions, as it respects the existence and operation of the gastric juice. My experiments confirm the doctrines (with some modifications) taught by Spallanzani, and many of the most enlightened physiological writers." (Preface to Dr. Beaumont's book.)
Further, it is to be noted that Alexis St. Martin's case proves that a gastric fistula is not painful. Scores of experiments were made on him, off and on, for nine years:—
"During the whole of these periods, from the spring of 1824 to the present time (1833), he has enjoyed general good health, and perhaps suffered much less predisposition to disease than is common to men of his age and circumstances in life. He has been active, athletic, and vigorous; exercising, eating, and drinking like other healthy and active people. For the last four months he has been unusually plethoric and robust, though constantly subjectedto a continuous series of experiments on the interior of the stomach; allowing to be introduced or taken out at the aperture different kinds of food, drinks, elastic catheters, thermometer tubes, gastric juice, chyme, etc., almost daily, and sometimes hourly."Such have been this man's condition and circumstances for several years past; and he now enjoys the most perfect health and constitutional soundness, with every function of the system in full force and vigour." (Dr. Beaumont,loc. cit. p. 20.)
"During the whole of these periods, from the spring of 1824 to the present time (1833), he has enjoyed general good health, and perhaps suffered much less predisposition to disease than is common to men of his age and circumstances in life. He has been active, athletic, and vigorous; exercising, eating, and drinking like other healthy and active people. For the last four months he has been unusually plethoric and robust, though constantly subjectedto a continuous series of experiments on the interior of the stomach; allowing to be introduced or taken out at the aperture different kinds of food, drinks, elastic catheters, thermometer tubes, gastric juice, chyme, etc., almost daily, and sometimes hourly.
"Such have been this man's condition and circumstances for several years past; and he now enjoys the most perfect health and constitutional soundness, with every function of the system in full force and vigour." (Dr. Beaumont,loc. cit. p. 20.)
In 1834 Eberlé published a series of observations on the extraction of gastric juice from the mucous membrane of the stomach after death; in 1842 Blondlot of Nancy studied the gastric juice of animals by the method of a fistula, such as Alexis St. Martin had offered for Dr. Beaumont's observation. After Blondlot, came experiments on the movements of the stomach, and on the manifold influences of the nervous system on digestion.
It has been said, times past number, that an animal with a fistula is in pain. It is not true. The case of St. Martin is but one out of a multitude of these cases: an artificial orifice of this kind is not painful.
Claude Bernard's discovery of glycogen in the liver had a profound influence both on physiology and on pathology. Take first its influence on pathology. Diabetes was known to Celsus, Aretæus, and Galen; Willis, in 1674, and Morton, in 1675, noted the distinctive sweetness of the urine; and their successors proved the presence of sugar in it. Rollo, in 1787, observed that vegetable food was bad for diabetic patients, and introduced the strict use of a meat diet. But Galen had believed that diabetes was a disease of the kidneys, and most men still followed him: nor did Rollo greatly advance pathology by following not Galen, but Aretæus. Later, with the development of organic chemistry, came the work of Chevreuil (1815), Tiedemann and Gmelin (1823), and other illustrious chemists: and the pathology of diabetes grew more and more difficult:—
"These observations gave rise to two theories: the one, that sugar is formed with abnormal rapidity in the intestine, absorbed into the blood, and excreted in the urine; the other, that diabetes is due to imperfect destruction of the sugar, either in the intestine or in the blood. Some held that it underwent conversion into lactic acid as it was passing through the intestinal walls, while others believed it to be destroyed in the blood by means of the alkali therein contained."[3]
Thus, before Claude Bernard (1813-1878), the pathology of diabetes was almost worthless. And, in physiology, his work was hardly less important than the work of Harvey. A full account of it, in all its bearings, is given in Sir Michael Foster'sLife of Claude Bernard(Fisher Unwin, 1899).
In Bernard'sLeçons sur le Diabète et la Glycogenèse Animale(Paris, 1877), there is a sentence that has been misquoted many times:—
Sans doute, nos mains sont vides aujourd'hui, mais notre bouche peut être pleine de légitimes promesses pour l'avenir.
This sentence has been worked so hard that some of the words have got rubbed off it: and the statement generally made is of this kind:—
Claude Bernard himself confessed that his hands were empty, but his mouth was full of promises.
Of course, he did not mean that he was wrong in his facts. But, in this particular lecture, he is speaking of the want of more science in practice, looking forward to a time when treatment should be based on science, not on tradition. Medicine, he says, is neither science nor art. Not science—Trouverait-on aujourd'hui un seul médecin raisonnable et instruit osant dire qu'il prévoit d'une manière certaine la marche et l'issue d'une maladie ou l'effet d'une remède?Not art, because art has always something to show for its trouble: a statue, a picture, a poem—Le médecin artiste ne crée rien, et ne laisse aucune œuvre d'art, à moins d'appliquer ce titre à la guérison du malade. Mais quand le malade meurt, est-ce également son œuvre? Et quand il guérit, peut-il distinguer sa part de celle de la nature?
To Claude Bernard, experiments on animals for thedirect advancement of medicine seemed a new thing: new, at all events, in comparison with the methods of some men of his time. He was only saying what Sir John Burdon Sanderson said in 1875 to the Royal Commission:—
It is my profound conviction that a future will come, it may be a somewhat distant future, in which the treatment of disease will be really guided by science. Just as completely as mechanical science has come to be the guide of the mechanical arts, do I believe, and I feel confident, that physiological science will eventually come to be the guide of medicine and surgery.
Anyhow, lecturing a quarter of a century ago on diabetes, his special subject, Claude Bernard spoke out his longing to compel men into the ways of science, to give them some immediate sign which they could not refuse to see:—
"At this present time, medicine is passing from one period to another. The old traditions are losing ground, and scientific medicine (la médecine expérimentale) has got hold of all our younger men: every day it gains ground, and will establish itself against all its critics, and in spite of the excesses of those who are over-zealous for its honour.... And when men ask us what are the results of scientific medicine, we are driven to answer that it is scarcely born, that it is still in the making. Those who care for nothing but an immediate practical application must remember Franklin's words,What is the use of a new-born child, but to become a man?If you deliberately reject scientific medicine, you fail to see the natural development of man's mind in all the sciences. Without doubt, our hands are empty to-day, but our mouth may well be filled with legitimate promises for the future."
He died in 1878. The following account of the discovery of glycogen is taken from hisNouvelle Fonction du Foie(Paris, 1853):—
"My first researches into the assimilation and destruction of sugar in the living organism were made in 1843: and in my inaugural thesis (Dec. 1843) I published my first experiments on the subject. I succeeded in demonstrating a fact hitherto unknown, that cane-sugar cannot be directly destroyed in the blood. If you inject even a very small quantity of cane-sugar, dissolved in water, into the blood or under the skin of a rabbit, you find it again in the urine unchanged, with all its chemical properties the same.... I had soon to give up my first point of view, because this question of the existence of a sugar-producing organ, that I had thought such a hard problem of physiology, was really the first thing revealed to me, as it were of itself, at once."
He kept two dogs on different diets, one with sugar, the other without it; then killed them during digestion, and tested the blood in the hepatic veins:—
"What was my surprise, when I found a considerable quantity of sugar in the hepatic veins of the dog that had been fed on meat only, and had been kept for eight days without sugar: just as I found it in the other dog that had been fed for the same time on food rich in sugar...."Finally, after many attempts—après beaucoup d'essais et plusieurs illusions que je fus obligé de rectifier par des tâtonnements—I succeeded in showing, that in dogs fed on meat the blood passing through the portal vein does not contain sugar before it reaches the liver; but when it leaves the liver, and comes by the hepatic veins into the inferior vena cava, this same blood contains a considerable quantity of a sugary substance (glucose)."
"What was my surprise, when I found a considerable quantity of sugar in the hepatic veins of the dog that had been fed on meat only, and had been kept for eight days without sugar: just as I found it in the other dog that had been fed for the same time on food rich in sugar....
"Finally, after many attempts—après beaucoup d'essais et plusieurs illusions que je fus obligé de rectifier par des tâtonnements—I succeeded in showing, that in dogs fed on meat the blood passing through the portal vein does not contain sugar before it reaches the liver; but when it leaves the liver, and comes by the hepatic veins into the inferior vena cava, this same blood contains a considerable quantity of a sugary substance (glucose)."
His further discovery, that this formation of sugar is increased by puncture of the floor of the fourth ventricle,was published in 1849. It is impossible to exaggerate the importance of Claude Bernard's single-handed work in this field of physiology and pathology:—
"As a mere contribution to the history of sugar within the animal body, as a link in the chain of special problems connected with digestion and nutrition, its value was very great. Even greater, perhaps, was its effect as a contribution to general views. The view that the animal body, in contrast to the plant, could not construct, could only destroy, was, as we have seen, already being shaken. But evidence, however strong, offered in the form of numerical comparisons between income and output, failed to produce anything like the conviction which was brought home to every one by the demonstration that a substance was actually formed within the animal body, and by the exhibition of the substance so formed."No less revolutionary was the demonstration that the liver had other things to do in the animal economy besides secreting bile. This, at one blow, destroyed the then dominant conception that the animal body was to be regarded as a bundle of organs, each with its appropriate function, a conception which did much to narrow inquiry, since when a suitable function had once been assigned to an organ there seemed no need for further investigations...."No less pregnant of future discoveries was the idea suggested by this newly-found-out action of the hepatic tissue, the idea happily formulated by Bernard as 'internal secretion.' No part of physiology is at the present day being more fruitfully studied than that which deals with the changes which the blood undergoes as it sweeps through the several tissues, changes by the careful adaptation of which what we call the health of the body is secured, changes the failure or discordance of which entails disease. The study of these internal secretions constitutes a path of inquiry which has already been trod with conspicuous success, and which promises to lead tountold discoveries of the greatest moment; the gate to this path was opened by Bernard's work." (Sir M. Foster,loc. cit.)
"As a mere contribution to the history of sugar within the animal body, as a link in the chain of special problems connected with digestion and nutrition, its value was very great. Even greater, perhaps, was its effect as a contribution to general views. The view that the animal body, in contrast to the plant, could not construct, could only destroy, was, as we have seen, already being shaken. But evidence, however strong, offered in the form of numerical comparisons between income and output, failed to produce anything like the conviction which was brought home to every one by the demonstration that a substance was actually formed within the animal body, and by the exhibition of the substance so formed.
"No less revolutionary was the demonstration that the liver had other things to do in the animal economy besides secreting bile. This, at one blow, destroyed the then dominant conception that the animal body was to be regarded as a bundle of organs, each with its appropriate function, a conception which did much to narrow inquiry, since when a suitable function had once been assigned to an organ there seemed no need for further investigations....
"No less pregnant of future discoveries was the idea suggested by this newly-found-out action of the hepatic tissue, the idea happily formulated by Bernard as 'internal secretion.' No part of physiology is at the present day being more fruitfully studied than that which deals with the changes which the blood undergoes as it sweeps through the several tissues, changes by the careful adaptation of which what we call the health of the body is secured, changes the failure or discordance of which entails disease. The study of these internal secretions constitutes a path of inquiry which has already been trod with conspicuous success, and which promises to lead tountold discoveries of the greatest moment; the gate to this path was opened by Bernard's work." (Sir M. Foster,loc. cit.)
But the work to be done, before all the clinical facts of the disease can be stated in terms of physiology, is not yet finished. In England, especial honour is due to Dr. Pavy for his life-long study of this most complex problem.
Here again Claude Bernard's name must be put first. Before him, the diverse actions of the pancreatic juice had hardly been studied. Vesalius, greatest of all anatomists, makes no mention of the duct of the pancreas, and speaks of the gland itself as though its purpose were just to support the parts in its neighbourhood—ut ventriculo instar substerniculi ac pulvinaris subjiciatur. The duct was discovered by Wirsung, in 1642: but anatomy could not see the things that belong to physiology. Lindanus (1653) said,I cannot doubt that the pancreas expurgates, in the ordinary course of Nature, those impurities of the blood that are too crass and inept to be tamed by the spleen: and, in the extraordinary course, all black bile, begotten of disease or intemperate living. Wharton (1656) said,It ministers to the nerves, taking up certain of their superfluities, and remitting them through its duct into the intestines. And Tommaso Bartholini (1666) called it thebiliary vesicle of the spleen.
This chaos of ideas was brought into some sort of order by Regnier de Graaf, pupil of François de Bois (Sylvius). De Bois had guessed that the pancreas must be considered not according to its position in the body, but according to its structure: that it was analogous to the salivary glands. He urged his pupil to make experiments on it: and de Graaf says:—
"I put my hand to the work: and though many times I despaired of success, yet at last, by the blessing of God on my work and prayers, in the year 1660 I discovered a way of collecting the pancreatic juice."
And, by further experiment, he refuted Bartholini's theory that the pancreas was dependent on the spleen.
Sylvius had supposed that the pancreatic juice was slightly acid, and de Graaf failed to note this mistake; but it was corrected by Bohn's experiments in 1710.
Nearly two hundred years come between Regnier de Graaf and Claude Bernard: it is no wonder that Sir Michael Foster says that de Graaf's work was "very imperfect and fruitless." So late as 1840, there was yet no clear understanding of the action of the pancreas. Physiology could not advance without organic chemistry; de Graaf could no more discover the amylolytic action of the pancreatic juice than Galvani could invent wireless telegraphy. The physiologists had to wait till chemistry was ready to help them:—
"Of course, while physical and chemical laws were still lost in a chaos of undetermined facts, it was impossible that men should analyse the phenomena of life: first, because these phenomena go back to the laws of chemistry and physics; and next, because they cannot be studied without the apparatus, instruments, and all other methods of analysis that we owe to the laboratories of the chemists and the physicists." (Cl. Bernard,Phys. Opér., p. 61.)
Therefore de Graaf failed, because he got no help from other sciences. But it cannot be called failure;he must be contrasted with the men of his time, Lindanus and Bartholini, facts against theories, not with men of this century. And Claude Bernard went back to de Graaf's method of the fistula, having to guide him the facts of chemistry observed by Valentin, Tiedemann and Gmelin, and Eberlé. His work began in 1846, and the Académie des Sciences awarded a prize to it in 1850:—
"Let this vague conception (the account of the pancreas given in Johannes Müller's Text-book of Physiology) be compared with the knowledge which we at present have of the several distinct actions of the pancreatic juice, and of the predominant importance of this fluid not only in intestinal digestion but in digestion as a whole, and it will be at once seen what a great advance has taken place in this matter since the early forties. That advance we owe in the main to Bernard. Valentin, it is true, had in 1844 not only inferred that the pancreatic juice had an action on starch, but confirmed his view by actual experiment with the juice expressed from the gland; and Eberlé had suggested that the juice had some action on fat; but Bernard at one stroke made clear its threefold action. He showed that it on the one hand emulsified, and on the other hand split up, into fatty acids and glycerine, the neutral fats; he clearly proved that it had a powerful action on starch, converting it into sugar; and lastly, he laid bare its remarkable action on proteid matters." (Sir Michael Foster,loc. cit.)
Finally came the discovery that the pancreas—apart from its influences on digestion—contributes its share, like the ductless glands, to the general chemistry of the body:—
"It was discovered, a few years ago, by von Mering and Minkowski, that if, instead of merely diverting itssecretion, the pancreas is bodily removed, the metabolic processes of the organism, and especially the metabolism of carbo-hydrates, are entirely deranged, the result being the production of permanent diabetes. But if even a very small part of the gland is left within the body, the carbo-hydrate metabolism remains unaltered, and there is no diabetes. The small portion of the organ which has been allowed to remain (and which need not even be left in its proper place, but may be transplanted under the skin or elsewhere) is sufficient, by the exchanges which go on between it and the blood generally, to prevent those serious consequences to the composition of the blood, and the general constitution of the body, which result from the complete removal of this organ." (Prof. Schäfer, 1894.)
Here, in this present study of "pancreatic diabetes," by Dr. Vaughan Harley and others, are facts as important as any that Bernard made out: in no way contradicting his work, but adding to it. The pancreas is no longer taken to be only a sort of salivary gland out of place: over and above the secretion that it pours into the intestines, it has an "internal secretion," a constituent of the blood: it belongs not only to the digestive system, but also, like the thyroid gland and the suprarenal capsules, to the whole chemistry of the blood and the tissues. So far has physiology come, unaided by anatomy, from the fantastic notions of Lindanus and the men of his time: and has come every inch of the way by the help of experiments on animals. Professor Starling's observations, on the chemical influence of the duodenal mucous membrane on the flow of pancreatic fluid, have advanced the subject still further.
The work of du Hamel proved that the periosteum is one chief agent in the growth of bone. Before him, this great fact of physiology was unknown; for the experiments made by Anthony de Heide (1684), who studied the production of callus in the bones of frogs, were wholly useless, and serve only to show that men in his time had no clear understanding of the natural growth of bone. De Heide says of his experiments:—
"From these experiments it appears—forsan probatur—that callus is generated by extravasated blood, whose fluid particles being slowly exhaled, the residue takes the form of the bone: which process may be further advanced by deciduous halitus from the ends of the broken bone."
And Clopton Havers, in hisOsteologia Nova(London, 1691), goes so far the wrong way that he attributes to the periosteum not the production of bone, but the prevention of over-production; the periosteum, he says, is put round the shaft of a bone to compress it, lest it grow too large.
Du Hamel's discovery (1739-1743) came out of a chance observation, made by John Belchier,[4]that thebones of animals fed near dye-works were stained with the dye. Belchier therefore put a bird on food mixed with madder, and found that its bones had taken up the stain. Then du Hamel studied the whole subject by a series of experiments. To estimate the advance that he gave to physiology, contrast de Heide's fanciful language with the title of one of du Hamel's papers—Quatrième Mémoire sur les Os, dans lequel on se propose de rapporter de nouvelles preuves qui établissent que les os croissent en grosseur par l'addition de couches osseuses qui tirent leur origine du périoste, comme le corps ligneux des Arbres augmente en grosseur par l'addition de couches ligneuses qui se forment dans l'écorce.Or take an example of du Hamel's method:—
"Three pigs were destined to clear up my doubts. The first, six weeks old, was fed for a month on ordinary food, with an ounce daily of madder-juice—garance grappe—put in it. At the end of the month, we stopped the juice, and fed the pig in the ordinary way for six weeks, and then killed it. The marrow of the bones was surrounded by a fairly thick layer of white bone: this was the formation of bone during the first six weeks of life, without madder. This ring of white bone was surrounded by another zone of red bone: this was the formation of bone during the administration of the madder. Finally, this red zone was covered with a fairly thick layer ofwhite bone: this was the layer formed after the madder had been left off.... We shall have no further difficulty in understanding whence transudes the osseous juice that was thought necessary for the formation of callus and the filling-up of the wounds of the bones, now we see that it is the periosteum that fills up the wounds, or is made thick round the fractures, and afterward becomes of the consistence of cartilage, and at last acquires the hardness of bones."
These results, confirmed by Bazan (1746) and Boehmer (1751), were far beyond anything that had yet been known about the periosteum. But the growth of bone is a very complex process: the naked eye sees only the grosser changes that come with it; and du Hamel's ingenious comparison between the periosteum and the bark of trees was too simple to be exact. Therefore his work was opposed by Haller, and by Dethleef, Haller's pupil: and the great authority of Haller's name, and the difficulties lying beyond du Hamel's plain facts, brought about a long period of uncertainty. Bordenave (1756) found reasons for supporting Haller; and Fougeroux (1760) supported du Hamel. Thus men came to study the whole subject with more accuracy—the growth in length, as well as the growth in thickness; the medullary cavity, the development of bone, the nutrition and absorption of bone. Among those who took up the work were Bichat, Hunter, Troja, and Cruveilhier; and they recognised the surgical aspect of these researches in physiology. After them, the periosteal growth of bone became, as it were, a part of the principles of surgery. From this point of view of practice, issued the experiments made by Syme (1837) and Stanley (1849): which proved the importance of the epiphysial cartilages for the growth of thebones in length, and the risk of interfering with these cartilages in operations on the joints of children. Finally, with the rise of anæsthetics and of the antiseptic method, came the work of Ollier, of Lyon, whose good influence on the treatment of these cases can hardly be over-estimated.
As with the circulatory system, so with the nervous system, the work of Galen was centuries ahead of its time. Before him, Aristotle, who twice refers to experiments on animals, had observed the brain during life: for he says, "In no animal has the blood any feeling when it is touched, any more than the excretions; nor has the brain, or the marrow, any feeling, when it is touched": but there is reason for believing that he neither recognised the purpose of the brain, nor understood the distribution of the nerves. Galen, by the help of the experimental method, founded the physiology of the nervous system:—
"Galen's method of procedure was totally different to that of an anatomist alone. He first reviewed the anatomical position, and by dissection showed the continuity of the nervous system, both central and peripheral, and also that some bundles of nerve fibres were distributed to the skin, others to the muscles. Later, by process of the physiological experiment of dividing such bundles of fibres, he showed that the former were sensory fibres and the latter motor fibres. He further traced the nerves to their origins in the spinal cord, and their terminations as aforesaid. From these observations and experiments he was able to deduce the all-important fact that different nerve-roots supplied different groups of muscles and different areas of the skin.... An excellent illustration of his method, and of the fact that we ought not to treat symptoms, but the causes of symptoms, is shown veryclearly in one of the cases which Galen records as having come under his care. He tells us that he was consulted by a certain sophist called Pausanias, who had a severe degree of anæsthesia of the little and ring fingers. For this loss of sensation, etc., the medical men who attended him applied ointments of various kinds to the affected fingers; but Galen, considering that that was a wrong principle, inquired into the history, and found that while the patient was driving in his chariot he had accidentally fallen out and struck his spine at the junction of the cervical and dorsal regions. Galen recognised that he had to do with a traumatism affecting the eighth cervical and first dorsal nerve; therefore, he says, he ordered that the ointments should be taken off the hand and placed over the spinal column, so as to treat the really affected part, and not apply remedies to merely the referred seat of pain."[5]
Galen, by this sort of work, laid the foundations of physiology; but the men who came after him let his facts be overwhelmed by fantastic doctrines: all through the ages, from Galen to the Renaissance, no great advance was made toward the interpretation of the nervous system. Long after the Renaissance, his authority still held good; his ghost was not laid even by Paracelsus and Vesalius, it haunted the medical profession so late as the middle of the seventeenth century; but the men who worshipped his name missed the whole meaning of his work. This long neglect of the experimental method left such a gap in the history of physiology, that Sir Charles Bell seems to take up the experimental study of the nervous system at the point where Galen had stopped short; we go from thetime of Commodus to the time of George the Third, and there is Bell, as it were, putting the finishing touch to Galen's facts. It is true that experiments had been made on the nervous system by many men; but a dead weight of theories kept down the whole subject. For a good instance, how imagination hindered science, there is the following list, made by Dr. Risien Russell, of theories about the cerebellum:—
"Galen was of opinion that the cerebellum must be the originator of a large amount of vital force. After him, and up to the time of Willis, the prevalent idea seems to have been that it was the seat of memory; while Bourillon considered it the seat of instinct and intelligence. Willis supposed that it presided over involuntary movements and organic functions; and this view, though refuted by Haller, continued in the ascendency for some time. Some believed strongly in its influence on the functions of organic life; and according to some, diseases of the cerebellum appeared to tell on the movements of the heart.... Haller believed it to be the seat of sensations, as well as the source of voluntary power; and there were many supporters of the theory that the cerebellum was the seat of the sensory centres. Renzi considered this organ the nervous centre by which we perceive the reality of the external world, and direct and fix our senses on the things round us. Gall, and later Broussais, and others, held that this organ presided over the instinct of reproduction, or the propensity to love; while Carus regarded it as the seat of the will also. Rolando looked on it as the source of origin of all movements. Jessen adduced arguments in favour of its being the central organ of feeling, or of the soul, and the principal seat of the sensations."
It is plain, from this list, that physiology had become obscured by fanciful notions of no practical value. If a better understanding of the nervous system could havebeen got without experiments on animals, why had men to wait so long for it? The Italian anatomists had long ago given them all the anatomy that was needed to make a beginning; the hospitals, and practice, had given them many hundred years of clinical facts; nervous diseases and head injuries were common enough in the Middle Ages; and by the time of Ambroise Paré, if not before,post-mortemexaminations were allowed. The one thing wanted was the experimental method; and, for want of it, the science of the nervous system stood still. Experiments had been made; but the steady, general, unbiassed use of this method had been lost sight of, and men were more occupied with logic and with philosophy.
Then, in 1811, came Sir Charles Bell's work. If any one would see how great was the need of experiments on animals for the interpretation of the nervous system, let him contrast the physiology of the eighteenth century with that one experiment by Bell which enabled him to say, "I now saw the meaning of the double connection of the nerves with the spinal marrow." It is true that this method is but a part of the science of medicine; that experiment and experience ought to go together like the convexity and the concavity of a curve. But it is true also that men owe their deliverance from ignorance about the nervous system more to experiments on animals than to any other method of observing facts.
The great authority of Sir Charles Bell has been quoted a thousand times against all experiments on animals:—
"Experiments have never been the means of discovery; and a survey of what has been attempted of late years in physiology, will prove that the opening of living animals has done more to perpetuate error than to confirm the just views taken from the study of anatomy and natural motions."
He wrote, of course, in the days before bacteriology, before anæsthetics; he had in his mind neither inoculations, nor any observations made under chloroform or ether, but just "the opening of living animals." He had also in his mind, and always in it, a great dislike against the school of Magendie. Let all that pass; our only concern here is to know whether these words are true of his own work.
They occur in a paper,On the Motions of the Eye, in Illustration of the Uses of the Muscles and Nerves of the Orbit; communicated by Sir Humphry Davy to the Royal Society, and read March 20, 1823.[6]This essay was one of a series of papers on the nervous system, presented to the Royal Society during the years 1821-1829. In 1830, having already published four of these papers under the title,The Exposition of the Nervous System, Bell published all six of them, under the title,The Nervous System of the Human Body.
In his Preface to this book (1830) he quotes the earliest of all his printed writings on the nervous system, a pamphlet, printed in 1811, under the title,An Idea of a New Anatomy of the Brain, Submitted for the Observation of the Authors Friends. We have therefore two statements of his work, one in 1811, the other in 1823 and 1830. The first of them was written when his work was still new before his eyes.
Those who say that experiments did not help Bell in his great discovery—the difference between the anterior and the posterior nerve-roots—appeal to certain passages in the 1830 volume:—
"In a foreign review of my former papers, the results have been considered as a further proof in favour of experiments. They are, on the contrary, deductions from anatomy; and I have had recourse to experiments, not to form my own opinions, but to impress them upon others. It must be my apology that my utmost efforts of persuasion were lost, while I urged my statements on the grounds of anatomy alone. I have made few experiments; they have been simple and easily performed, and I hope are decisive...."My conceptions of this matter arose by inference from the anatomical structure; so that the few experiments which have been made were directed only to the verification of the fundamental principles on which the system is established."
"In a foreign review of my former papers, the results have been considered as a further proof in favour of experiments. They are, on the contrary, deductions from anatomy; and I have had recourse to experiments, not to form my own opinions, but to impress them upon others. It must be my apology that my utmost efforts of persuasion were lost, while I urged my statements on the grounds of anatomy alone. I have made few experiments; they have been simple and easily performed, and I hope are decisive....
"My conceptions of this matter arose by inference from the anatomical structure; so that the few experiments which have been made were directed only to the verification of the fundamental principles on which the system is established."
If it were not for the 1811 pamphlet, the opponents of all experiments on animals might claim Sir Charles Bell on their side. But while his work was still a new thing, he spoke in another way of it:—
"I found that injury done to the anterior portion of the spinal marrow convulsed the animal more certainly than injury to the posterior portion; but I found it difficult to make the experiment without injuring both portions."Next, considering that the spinal nerves have a double root, and being of opinion that the properties of the nerves are derived from their connections with the parts of the brain,I thought that I had an opportunity of putting my opinion to the test of experiment, and of proving at the same timethat nerves of different endowments were in the same cord (nerve-trunk) and held together by the same sheath."On laying bare the roots of the spinal nerves, I found that I could cut across the posterior fasciculus of nerves, which took its origin from the posterior portion of the spinal marrow, without convulsing the muscles of the back; but that on touching the anterior fasciculus with the point of the knife, the muscles of the back were immediately convulsed."Such were my reasons for concludingthat the cerebrum and cerebellum were parts distinct in function, and that every nerve possessing a double function obtained that by having a double root.I now saw the meaningof the double connection of the nerves with the spinal marrow; and also the cause of that seeming intricacy in the connections of nerves throughout their course, which were not double at their origins."
"I found that injury done to the anterior portion of the spinal marrow convulsed the animal more certainly than injury to the posterior portion; but I found it difficult to make the experiment without injuring both portions.
"Next, considering that the spinal nerves have a double root, and being of opinion that the properties of the nerves are derived from their connections with the parts of the brain,I thought that I had an opportunity of putting my opinion to the test of experiment, and of proving at the same timethat nerves of different endowments were in the same cord (nerve-trunk) and held together by the same sheath.
"On laying bare the roots of the spinal nerves, I found that I could cut across the posterior fasciculus of nerves, which took its origin from the posterior portion of the spinal marrow, without convulsing the muscles of the back; but that on touching the anterior fasciculus with the point of the knife, the muscles of the back were immediately convulsed.
"Such were my reasons for concludingthat the cerebrum and cerebellum were parts distinct in function, and that every nerve possessing a double function obtained that by having a double root.I now saw the meaningof the double connection of the nerves with the spinal marrow; and also the cause of that seeming intricacy in the connections of nerves throughout their course, which were not double at their origins."
It is impossible to reconcile the 1830 sentences with this vivid personal account of himself;I had an opportunity of putting my opinion to the test of experiment ... an opportunity of proving ... Such were my reasons for concluding ... I now saw....It is just what all men of science say of their experiments: the very phrase of Archimedes, and Asellius, and de Graaf. If Sir Charles Bell had been working at the facts of chemistry or of botany, who would have doubted the meaning of these words?
This same inconsistency of sentences occurs elsewhere in hisNervous System of the Human Body. In one place he says that he has made few experiments:They have been simple, and easily performed, and I hope are decisive.In another he says: "After making several experiments on the cerebrum and cerebellum, I laid the question of their functions entirely aside, and confined myself to the investigation of the spinal marrow and the nerves;a subject which I found more within my power, and which forms the substance of the present volume."
Next, take his account of the cranial nerves:—
"It was necessary to know, in the first place, whether the phenomena exhibited on injuring the separate roots corresponded with what was suggested by their anatomy...."Here a difficulty arose. An opinion prevailed that ganglions were intended to cut off sensation; and every one of these nerves, which I supposed were the instruments of sensation, have ganglions on their roots. Some very decided experiment was necessary to overturn this dogma. (Account of the experiment.) By pursuing the inquiry, it was found that a ganglionic nerve is the sole organ of sensation in the head and face: ganglions were therefore no hindrance to sensation; and thus my opinion was confirmed....It now became obviouswhy the third, sixth, and ninth nerves of the encephalon were single nerves in their roots...."Observing that there was a portion of the fifth nerve which did not enter the ganglion of that nerve, and being assured of the fact by the concurring testimony of anatomists, I conceived that the fifth nerve was in fact the uppermost nerve of the spine.... This opinion was confirmed by experiment.... (Account of an experiment on the dead body.) On dividing the root of the nerve in a living animal, the jaw fell relaxed. Thus its functions are no longer matter of doubt: it is at once a muscular nerve and a nerve of sensibility. And thus the opinion is confirmed, that the fifth nerve is to the head what the spinal nerves are to the other parts of the body, in respect to sensation and volition."
"It was necessary to know, in the first place, whether the phenomena exhibited on injuring the separate roots corresponded with what was suggested by their anatomy....
"Here a difficulty arose. An opinion prevailed that ganglions were intended to cut off sensation; and every one of these nerves, which I supposed were the instruments of sensation, have ganglions on their roots. Some very decided experiment was necessary to overturn this dogma. (Account of the experiment.) By pursuing the inquiry, it was found that a ganglionic nerve is the sole organ of sensation in the head and face: ganglions were therefore no hindrance to sensation; and thus my opinion was confirmed....It now became obviouswhy the third, sixth, and ninth nerves of the encephalon were single nerves in their roots....
"Observing that there was a portion of the fifth nerve which did not enter the ganglion of that nerve, and being assured of the fact by the concurring testimony of anatomists, I conceived that the fifth nerve was in fact the uppermost nerve of the spine.... This opinion was confirmed by experiment.... (Account of an experiment on the dead body.) On dividing the root of the nerve in a living animal, the jaw fell relaxed. Thus its functions are no longer matter of doubt: it is at once a muscular nerve and a nerve of sensibility. And thus the opinion is confirmed, that the fifth nerve is to the head what the spinal nerves are to the other parts of the body, in respect to sensation and volition."
The value of the experimental method could hardly be stated in more emphatic words. He supposed something, conceived it, had an opinion about it. Anatomy had suggested something to him. He put his opinion to the test of phenomena, that is to say, to the test of visible facts; and then his opinion was confirmed. Aswith the spinal nerve-roots, so with the fifth cranial nerve—his work was successful, because he followed the way of experiment.
He was by nature of a most complex and sensitive temperament, full of contrary forces—one man in 1811, another in 1830. In 1811 he wrote,I now saw the meaning of the double connection of the nerves; in 1830 he had come to hate thestupid sterile materialismof the French school: he beheld anatomy falling behind physiology, and his Windmill Street school perishing to make way for the Hospital schools and for the University of London. He was before everything else a great anatomist: he stood up for the honour of anatomy against the new physiology, and for the honour of the Monroes and the Hunters against Magendie: he hated the notion that any man should proceed to experiments on function till the very last secrets had been got out of structure. He died a few years afterward. The 1830 writings are his last stand for the defence of his country, his school, and his beloved anatomy, against the methods of Magendie; who said of himself, "I am a mere street scavenger,chiffonier, of science. With my hook in my hand and my basket on my back, I go about the streets of science, collecting what I find."
This open conflict between Bell's first and last thoughts is a part of his character: he was brilliant, impulsive, changeable, inconsistent; and, what is more important, his honour kept him from trying to evade this trumpery charge of inconsistency; and he reprinted the 1811 Preface in the book that he published in 1830. Doubtless he would have picked his words more carefully if he had foreseen that one of the 1830 sentences would be wrested out of its place in his life'swork, and used as false evidence against the very method that he followed.
His observations on the cranial nerves brought about an immediate change in the practice of surgery:—