the blood in this case was 0.922 of a part per thousand, a little above the largest proportion we had found in health.

Like the examinations of the blood in the three cases of paralysis, these pathological observations are not sufficient, in themselves, to establish the function of cholesterine; but taken in connection with our other experiments, they fully confirm our views with regard to the excretory function of the liver. It is pretty certain that organic disease of the liver, accompanied with grave symptoms generally affecting the nervous system, does not differ in its pathology from cases of simple jaundice in the fact of retention of the bili ary salts in the blood; but these grave symptoms, it is more than probable, are due to a deficiency in the elimination of cholesterine the true excrementitious principle of the bile -and its consequent accumulation in the system. Like the accumulation of urea in structural disease of the kidney, this produces blood-poisoning; and we have characterized this condition by the name of Cholesteræmia, a name expressing a pathological condition, but at the same time indicating the physiological relations of cholesterine.

CHAPTER X.

PRODUCTION OF SUGAR IN THE LIVER.

Evidences of a glycogenic function in the liver-Processes for the determination of sugar-Fehling's test for sugar-Examination of the blood of the portal system for sugar-Inosite-Examination of the blood of the hepatic veins for sugar-Does the liver contain sugar during life?-Characteristics of liver-sugar-Mechanism of the production of sugar in the liver-Glycogenic matter-Process for the extraction of glycogenic matter-Variations in the glycogenic function-Production of sugar in fœtal life-Influence of digestion and of different kinds of food on glycogenesis-Influence of the nervous system, etc., on glycogenesis-Artificial diabetes-Influence of the inhalation of anæsthetics and irritating vapors on glycogenesis-Destination of sugar-Alleged production of fat by the liver-Changes in the albuminoid and the corpuscular elements of the blood in their passage through the liver.

Ir was formerly supposed that the chief and the only important office of the liver was to produce bile, and all physiological researches into the functions of this organ were then directed to the question of the uses of the biliary secretion; but in 1848, it was announced by Bernard that he had discovered in the liver a new and important function, and he proceeded to show, by an ingeniously conceived series of experiments, that the liver is constantly producing sugar of the variety that had long been recognized in the urine of persons suffering from diabetes mellitus. The great physiological and pathological importance of the discovery, attested, as it was, by experiments which seemed to be positively conclusive in their results, excited the most profound scientific interest. During the present century, indeed, there

have been few physiological questions that have attracted so much attention; and the observations of Bernard were soon repeated, modified, and extended by experimentalists in different parts of the world. In 1857, Bernard discovered a sugar-forming material in the liver, analogous in its composition and properties to starch; and this seemed to complete the history of glycogenesis.

Shortly after the publication of the glycogenic theory, it was found that other changes were effected in the blood in its passage through the liver, and physiologists then understood, for the first time, how glandular organs might produce secretions, and yet not discharge them into excretory ducts; and this, indeed, pointed the way to the explanation of the function of the ductless glands. It is perfectly correct to say that the liver secretes sugar; but the secretion, in this instance, is carried away by the blood; and from this point of view, the liver is a ductless gland. It is evident, therefore, that even after having studied fully the secretion and the physiological relations of the bile, we have to consider other glandular functions of the liver, hardly less important.

Evidences of a Glycogenic Function in the Liver.-The proof of the glycogenic function of the liver rests upon the fact, experimentally demonstrated by Bernard, that in all animals, the blood coming from the liver by the hepatic veins contains sugar; and that the presence of this principle here is not dependent upon the starch or sugar of the food. Bernard assumes to have proven that, in carnivorous animals, never having taken starch or sugar into the alimentary canal, except in the milk, there is no sugar in the blood of the portal vein as it passes into the liver; but, under normal conditions, the blood of the hepatic veins always contains sugar. Having examined the blood from various parts of the body, and made extracts of all the other tissues and organs, Bernard was unable to find sugar in any other situations

than the liver and the blood coming from the liver. As the blood from the liver is mixed in the vena cava with the blood from the lower extremities, and in the right side of the heart, with the blood from the descending cava, the amount of sugar is proportionately diminished in passing from the liver to the heart. It was found that the sugar generally disappeared in the lungs, and did not exist in the blood of the arterial system. Assuming that these statements have been sustained by experimental facts, there can be no doubt that the liver produces or secretes sugar; that this secretion is taken up by the blood; and that the sugar is destroyed in its passage through the lungs.

The question of the production of sugar in the economy has given rise to a great deal of discussion, and the experiments of Bernard have been repeated very extensively. Many physiologists of high authority have been able to verify these observations in every particular; but others have published accounts of experiments which seem to disprove the whole theory.

There can be no doubt of the fact that sugar may, under certain conditions, be produced de novo in the organism. Cases of diabetes, in which the discharge of sugar by the urine continues, to a certain extent, when no starch or sugar is taken as food, are conclusive evidence of this proposition. It is a fact equally well established, that the sugar taken as food and resulting from the digestion of starch is consumed in the organism, and is never discharged. The fact with regard to diabetes shows, then, that it is not impossible, when no sugar or starch is taken as food, that sugar should be produced in the body; and the failure to find the sugar of the food in the blood or excreta shows that this principle is normally destroyed or consumed in the organism. It only remains, therefore, to determine whether the production of sugar in diabetes be a new pathological process, or merely the exaggeration of a physiological function.

We have so often repeated and verified the observations

of Bernard, both in experiments made for purposes of investigation and in public demonstrations, that we can entertain no doubt with regard to the glycogenic function of the liver. We have, however, made some late observations, which have modified our views concerning the mechanism of glycogenesis; but the fact of the production of sugar in the healthy organism is not affected. Notwithstanding that it seems so easy to verify these experiments, there is, particularly in Great Britain, a pretty wide-spread conviction, that the liver does not produce sugar during life, and that the sugar found by Bernard and others is due to post-mortem action. This view is based chiefly on the observations of Dr. Pavy, of Guy's Hospital; but it has been adopted by some authorities in Germany and in France. In this state of the question, it will not be sufficient to detail merely the experiments that seem to demonstrate the glycogenic function, but it will be necessary to examine these observations critically, and compare them with experiments which lead, apparently, to opposite conclusions; for it is but fair to admit that the observations of Pavy seem to be as accurate, and, at the first blush, as conclusive as those of Bernard.

The experiments of Bernard were published for the first time in 1848,' but were afterward much extended, and published as a thesis, in 1853. The most accessible account of the original experiments is in the first volume of his published lectures, delivered at the College of France, in 1854-55. In addition, many of the volumes of lectures published from time to time by Bernard contain new obser

1 BERNARD, De l'origine du sucre dans l'économie animale.—Archives générales de médecine, Paris, 1848, 4me série, tome xviii., p. 303, et seq.

2 BERNARD, Recherches sur une nouvelle fonction du foie, consideré comme organe producteur de matière sucrée chez l'homme et les animaux. Thèse présentée d la Faculté des Sciences de Paris pour obtenir le grade de Docteur ès Sciences Natu relles, Paris, 1853.

3 BERNARD, Leçons de physiologie expérimentale. Cours du semestre d'hiver, 1854-55, Paris, 1855.