Voit, Carl von
VOIT, CARL VON
(b. Amberg, Bavaria, 31 October 1831; d. Munich, Germany, 31 January 1908), Physiology.
Voit was the son of August Voit, a well-known architect, He entered medical school in Munich, in 1848, and completed his training there in 1854, after spending the year 1851 at Würzburg. In 1855 he studied chemistry in Göttingen with Wöhler, and the following year became an assistant to Theodor Bischoff at the Physiological Institute in Munich. In 1859 he became a lecturer at the University of Munich, and in 1863 he was named professor of physiology, a position he held for the rest of his career. During the next three decades Voit became the leader of the dominant school investigating metabolism. He acquired an authoritative position through the technical mastery with which he refined previously developed procedures, and by means of which he was able to resolve fundamental problems into which his predecessors had fallen.
When Voit returned to Munich in 1852, he attended Liebig’s chemistry course, and was inspired by Liebig’s writings on “animal chemistry” to investigate the “laws” of animal nutrition. For many years Voit was guided by Liebig’s theory that the organized parts of the body are formed exclusively by nitrogenous “albuminoid” nutrient substances (plastic aliments), and that non-nitrogenous nutrients (respiratory aliments) are oxidized in the blood to produce animal heat. He also adhered to Libig’s belief that all mechanical work is produced by the “metamorphosis” of the nitrogenous tissue constitutents. Liebig’s contention that one could measure the amount of tissue metamorphosis by formation of urea provided the research program to which Voit devoted much of his career. At the time Voit entered this field, Jean-Baptiste Boussingault, Friedrich Bidder and Carl Schmidt, and Bischoff had already carried out extensive comparative measurements of the intake and output of the elements (carbon, hydrogen, oxygen, and nitrogen) constituting the bulk of the food excretions, and respiratory gases of animals. Their results had created several theoretical and practical dilemmas. They realized that one should ideally measure the composition of the food and excrements simultaneously with the gaseous exchanges, but the different experimental conditions appropriate respectively to the collection of the excrements and to that of the respiratory gases had prevented this. In 1852 Bischooff encountered another serious setback. Using a simple and reliable new method developed by Liebig for measuring urea, Bischoff found that large portions of the dietary nitorgen were unaccounted for in the urine; this unexplained nitrogen “deficit” seemed to preclude direct measurements of the turnover of nitrogenous tissue constituents.
When he became Bischooff’s assistant, Voit continued Bischoff’s feeding experiments on dogs. Taking care to assure that the nitrogen content of the meat that was fed to the dogs was uniform, and to collect the feces and urine without losses, Voit found that the nitrogen absorbed in the meat was always nearly equal to that in the urea. or could be accounted for by the weight changes in the animal. This outcome reassured Voit that under rigorously controlled conditions one could rely on the quantity of urea excreted as a measure of nitrogenous metabolism.
Encouraged by this success. Voit carried out extensive further investigations with Bischoff, determining the quantities of urea formed by a dog under various dietary conditions. Between 1857 and 1860 they tried pure meat diets, in which they systematically increased and decreased the daily quantities, and combinations of meat with varying quantities of sugar, starch, fat, and gelatin. The changes in the urea production under these conditions led them to conclude that the rate of decomposition of nitrogenous matter in an animal does not depend directly upon the quantity of nitrogenous nutrient but upon the nutritive condition of the animal. As the nitrogenous mass of the body increases or decreases, so does the rate of metamorphosis of these constituents. The same diet might at one time supply enough nitrogen and at another time not, because the requirement itself varies with the changing condition of the animal. Additions of sugar, starch, or fat decrease the output of urea by a relatively small amount. In 1860 they published their results in a lengthy treatise entitled The Laws of the Nutrition of Carnivorous Animals .Practically, they believed they had established methods that could be used for determining the most economical quantitative combination the most economical quantitative combination of nitrogenous and non-nitrogenous foods, which would maintain a given animal. Theoretically, they thought they had confirmed Liebig’s distinction between plastic and respiratory nutrients.
Then Voit took up on his own the question of whether other factors can influence the rate of decomposition of organic substances. He began by examining the effects of coffee but concluded that it does not significantly affect the nitrogenous metabolism. During this series of experiments, Voit realized that he could distinguish effects of an added factor most clearly if the animal were in a condition of equilibrium between the intake and output of nitrogenous substances. He learned that if a dog is fed a steady nitrogenous daily diet, the nitrogen consumption gradually rises or falls until it balances the intake, and the nutritional condition of the animal thereafter remains constant.
From Liebig’s assertion that the metamorphosis of nitrogenous tissue substance is the sole source of motion and his claim that the urea formed is a measure of that metamorphosis, it followed that muscle activity ought to increase the amount of urea excreted. To test that inference, Voit trained a dog to run rapidly, for ten minutes at a time, on a large treadmill. He compared the urea output over three days on which the dog had run six times daily with the output over three days on rest. He found that the performance of a great amount of mechanical work produced only very small increments of urea excretion. These unexpected results seemed to him at first completely incompatible with his previous conceptions. In order to reconcile the results he assumed that the energy released by nitrogenous decomposition during rest is converted into an “electromotive force,” which can be transformed in turn into muscle motion. There is therefore a store of energy available, limited by the amount of nitrogenous matter that decomposes each day. This theory explained why an animal can do only a certain amount of work in a day. Thereafter Voit considered the urea production as a measure not of the muscle activity at any particular time, but of the capacity for such activity over a longer time period.
The rigor and comprehensiveness of Bischoff and Voit’s investigations quickly won them a leading position in the field of nutrition, and after 1860 their experimental results were featured in influential physiological textbooks. Their interpretations of their results, however, were not generally accepted. Carl Vogt published a sweeping polemic review in which he tried to show that their analytical foundations were not adequate to support their theories concerning internal processes. In a more penetrating critique, Moritz Traube argued in 1861 that Voit’s treadmill experiment repudiated the doctrine that organized muscle is decomposed by its work, and that urea gives a measure of the muscle force expended. Of all the objections that voit’s views encountered, that which caused him the most trouble was the repeated denial of his claim that all of the nitrogen of the substances decomposed in the body is excreted in the urine and feces. From 1860 to 1870 Voit devoted much of his effort to the defense of his methods and conclusions from such criticisms.
In their joint experiments Voit and Bischoff calculated indirectly the quantities of carbon, hydrogen, and oxygen exhaled, by subtracting the amounts of these elements excreted from the amounts ingested. From these differences and a rough estimate of the daily heat production, they judged whether the substances gained or lost, in addition to the nitrogenous constituents, were likely to be fat, water, or both. In order to obviate the uncertainties arising from such estimates, Voit afterward sought means to measure directly the respiratory products. His colleague and former teacher Pettenkofer constructed a respiration chamber large enough to accommodate either a man or an animal for a day. In 1861 they began combined feeding-respiration experiments. In the first group of experiments they measured the carbonic acid exhaled, but not the water, so that they could not calculate the oxygen consumption. The quantity of carbonic acid exhaled daily varied widely and, like urea production, seemed to depend on changes in the nutritional conditions. With a large pure meat diet, less carbon was exhaled than ingested, a result that led Pettenkofer and Voit to think that after the decomposition of the “flesh” in the body, a portion of the non-nitrogenous residue may be deposited as fat. This and similar subsequent results led Void to question the prevailing view that the fat formed in animals is derived from carbohydrate.
Beginning in 1862 Pettenkofer and Voit measured the water vapor as well as the carbonic acid exhaled. They were then able to calculate the absorbed oxygen from the difference between the initial weight of the dog—together with the food and water it ingested—and its final weight plus the excretions and the expired carbonic acid and water. Their first experiments produced anomalous ratios between the oxygen absorbed and that contained in the exhaled carbonic acid. In February 1863, after making various refinements, they succeeded in attaining a complete balance of the incoming and outgoing elements for their dog at equilibrium on a pure meat diet. The difference between the total measured daily input of carbon, hydrogen nitrogen, and oxygen, and the totals contained in the excretions and exhaled gases, was less than one precent of the total mass of material exchanged. As Pettenkofer and Voit pointed out, this was the first measurement of the intake and output of an animal for which every single value was ascertained by experiment. They had reached a goal that numerous investigators had pursued for nearly twenty-five years. To do so they had had to combine two types of experiment—nutritional and respirational measurements—which had previously been carried out separately because the conditions required for accurate measurements of one type of experiment seemed incompatible with those required for the other. It had been difficult to extend respirational experiments beyond a few hours, whereas nutritional experiments had appeared reliable only if they lasted several days. Pettenkofer’s large, accurate respiration apparatus, in addition to the precise control Voit had attained over the diets and analysis of excretions, enabled the two collaborators to make both sets of measurements on one animal over the same time period.
Throughout the 1860’s Voit kept up the same kind of measurements of the nitrogenous Stoffwechsel of dogs that he had been making since 1857. In the later experiments he elucidated in closer detail the variables affecting the consumption of nitrogenous substances in particular nutritional states, and he further refined his control over the analytical factors. By 1866 he could show that the excretion of urea by a dog on a uniform diet is so regular that the daily quantities deviate from the mean by less than three grams. Voit increasingly stressed the primacy of method over theories concerning the internal nature of nutritional phenomena.Gradually he lost his commitment to the central theoretical ideas for the support of which he had originally devised his methods. Yet he never gave up the goal of understanding the intermediate steps in the metamorphosis of nutrient materials within animals.
In 1866 Voit showed that the daily urea production of a dog in periods of hunger declined in diminishing decrements until after the sixth day, when the rate remained nearly steady. The initial decrease was largest when the animal had been best nourished just before the period of abstinence. When he subtracted the nearly constant amount secreted after fifth day from the amount excreted during the first day of hunger, the remainder was proportional to the quantity of “flesh” stored up in the animal during its preceding period of nourishment. These patterns led Voit to propose that there are two types of protein in the body—a large proportion derived directly from the nourishment, of which about 70 percent undergoes decomposition daily, and a much smaller amount, of which only about 1 percent can decompose during one day. He called the two types storage protein and organ protein, and in his later investigations he sought to determine the effects of various kinds of nourishment on their proportions.
Using the respiration chamber, Voit also continued his collaborative work with Pettenkofer. In August 1865 they applied their methods to a diabetic patient in order to see how the rates of the nutritional decomposition processes are changed by this disease. In 1866 they carried out similar investigations on a leukemia patient. They then realized that they needed bases of comparison with the rates of decomposition in normal humans. Therefore, over the next twelve months they carried out investigations on two healthy men. The papers that resulted from these and their subsequent experiments provided the foundation for the many studies on metabolism in health and disease that were carried out over the rest of the century.
During the 1860’s a number of events, including especially the experiements of Fick and Wislicenus, undermined Liebig’s theory that the decomposition of nitrogenous substances is the sole source of muscle work. With Pettenkofer, Voit confirmed his own earlier treadmill experiments showing that exercise produces no increase in the formation of urea. With the respiration chamber they also observed the large augmentation in the expiration of CO2 and water, which they and others linked with the increased consumption of fat or carbohydrate. Voit continued to resist the conclusion that the combustion of non-nitrogenous substances provided mechanical work, for that view ignored the obvious influence of the protein content of the nourishment and of the body on the sustained capacity of the organism for work. Nevertheless, his own belief that there are two sources of urea—organ and storage protein—had rendered nearly meaningless Liebig’s definition of nitrogenous nutrients as “plastic” aliments. By 1867 Voit acknowledged that there was no evidence for Liebig’s idea that proteins are decomposed only during the activity of the organs, or that nitrogenous nutrients must become part of organized tissue before they are decomposed. The old concept of the Stoffwechsel which represented this view had, he said, lost its meaning. At the same time Voit was developing further support for his theory that animal fat was produced from the decomposition products of nitrogenous substances rather than from carbohydrate. Liebig strongly disagreed with Viot’s view. By 1869, when Voit presented all of the accumulated evidence for his own position, he had dissociated himself from most of Liebig’s theories concerning nutrition. In that year Liebig wrote a defense of his concepts of the source of muscle motion and of the conversion of carbohydrate to fat. In his article he referred to Voit’s demonstration of the formation of fat from protein as worthless. Deeply offended, Voit wrote in 1870 a long reply in which he relentlessly exposed the inadequacies of Liebig’s theories on nutrition.
Voit’s own nutritional theories remained controlversial. Pflüger and others opposed his distinction between organ and storage, or “circulating,” protein and his arguments for the conversion of protein into fat. Voit’s laboratory nevertheless became increasingly the center of activity in the field. Because the methods he had developed were crucial to his success, those hoping to enter the field found it important to work under his direction. A large proportion of the leaders of the era in which metabolic balance investigations reached their high point came out of Voit’s laboratory. They included Max Rubner, Joseph Bauer, Friedrich von Müller, Alexander Ellinger, Edward Cathcart, Max Cremer, Graham Lusk, and Voit’s successor, Otto Frank.
The work in the Munich laboratory continued along the lines Voit had established during the 1860’s. In later investigations purified protein preparations replaced the trimmed whole meat, which Voit had earlier used. Attention focused on defining an adequate nourishment and on determining whether substances such as asparagine and peptones have nutritive value—that is, whether their addition to a non-nitrogenous diet can substitute for protein, and whether their addition to a diet including protein can “spare” protein. Beginning in the 1880’s some of the experiments were done on white rats, the small size and omnivorous habits of which made them particularly convenient for such investigations.
In later years Voit spent much of his time on official university duties, and served as secretary for the mathematics and physical sciences section of the Bavarian Academy of Sciences. Voit continued to deliver memorable course lectures up until the last year of his life, when ill health finally forced him to forgo his “greatest pleasure,”
BIBLIOGRAPHY
I. Original Works. Major articles or monographs by Voit include Physiologisch-chemische Untersuchungen, I (Augusburg, 1857); Untersuchungen über den Einfluss des Kochsalzes, des Kaffee’s und her Muskelbewegungen auf den Stoffwechsel (Munich, 1860); “Physiologiec des Allgemeinen Stoffwechsels and der Ernährung,” in Handbuch der Physiologic. L. Hermann, ed., VI. pt. I (Leipzig, 1881), and Die Gesetze der Ernährung des Fleischfressers durch neue Untersuchungen festgestellt (Leipzig. 1860), written with T. L. W. Bischoff.
The germinal articles by Pettenkofer and Voit using the respiratory chamber are “Untersuchungen über die Respiration,” in Annalen der Chemie und Pharmacie, supp. 2 (1863), 52–70; and “Ueber die Producte der Respiration des Hundes bei Fleischnährung und über die Gleichung der Einnahmen und Ausgaben des Körpers dabei,” ibid., 361–377. For a detailed description of a later, smaller version of the Pettenkofer respiration apparatus, including detailed drawings, see “Beschreibung eines Apparates zur Untersuchung der gasförmigen Ausschiedugen des Thierkörpers,” in Abhandlungen der Bayerischen Akademie der Wissenschaften, 12 (1876). 219–271.
Beginning in 1865, articles by Voit and his students reporting the research carried out in the Munich Institute of Physiology appeared regularly in the Zeitschrift für Biologie, of which he was a founding editor. Preliminary communications were often published in the Sitzungsberichte der Bayerischen Akademie der Wissenschaften zu München.
II. Secondary Literature. Otto Frank, Carl von Voit, Gedächtnisrede (Munich, 1910), a eulogy by Voit’s successor, contains a long, but not exhaustive bibliography of Voit’s publications. Graham Lusk, Nutrition (New York, 1969), contains a lengthy summary of Voit’s contributions, and “Carl von Voit, Master and Friend,” in Annals of Medical History, 3 (1931), 583–594, is a very informal reminiscence, with four photographs of Voit, two photographs of the Physiological Institute, and transcriptions of letters from Voit to Lusk.
Frederic L. Holmes