IV Glycogen
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’s Life of Claude Bernard (Fisher Unwin, 1899).
In Bernard’s Leçons 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 the direct 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 his Nouvelle 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).”
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 to untold 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.