Voit,1 in his necrology of Pettenkofer, writes: "Imagine our sensations as the picture of the remarkable processes of the metabolism unrolled before our eyes, and a mass of new facts became known to us! We found that in starvation protein and fat alone were burned, that during work more fat was burned, and that less fat was consumed during rest, especially during sleep; that the carnivorous dog could maintain himself on an exclusive protein diet, and if to such a protein diet fat were added, the fat was almost entirely deposited in the body; that carbohydrates, on the contrary, were burned no matter how much was given, and that they, like the fat of the food, protected the body from fat loss, although more carbohydrates than fat had to be given to effect this purpose; that the metab - olism in the body was not proportional to the combustibility of the substances outside the body, but that protein, which burns with difficulty outside, metabolizes with the greatest ease, then carbohydrates, while fat, which readily burns outside, is the most difficultly combustible in the organism".

1 Voit: "Zeitschrift fur Biologie," 1901, xli, 1.

Since the days of these researches repeated experiments have established the verity of the conclusions drawn. It is interesting to note that among the earliest experiments made were some upon patients in pathologic conditions, one suffering from leukemia, another from diabetes.

Besides the influence of foods upon metabolism, the changes brought about by exercise, temperature, and drugs were investigated not only by the Munich school, but by many other workers. Similar investigations are actively progressing today.

Among the important conclusions reached by Voit was that concerning the manner of the metabolism. It has been stated that Liebig believed that fat and carbohydrates were destroyed by oxygen, while protein metabolism took place on account of muscle work.

Voit1 showed that muscle work, did not increase protein metabolism and that the metabolism was not proportional to the oxygen supply. The oxygen absorption apparently depended upon, what metabolized in the cells. Voit believed that the cause of metabolism was unknown, that the process was one of cleavage of the food molecules into simpler products, which could then unite with oxygen. Yeast cells, for example, convert sugar into carbonic acid and alcohol without the intervention of oxygen. In like manner the first products of the decomposition of fat, sugar, and protein are formed in metabolism through unknown causes. Some of these preliminary decomposition substances may unite with oxygen to form carbon dioxid and water, others may be converted into urea, while others under given circumstances may be synthesized to higher compounds. In any case the absorption of oxygen does not cause metabolism, hit rather the amount of the metabolism determines the amount of oxygen to be absorbed (see P. 32).

1 Voit: "Zeitschrift fur Biologie," 1866, ii, 535.

The statement is frequently met with in the literature of the subject that such and such a disease is the consequence of deficient oxidative power in the tissues. For example, it has been stated that alcohol decreases the oxidative power of the liver for uric acid.1 Such apparent decrease in oxidative power may, however, be due to the fact that the normal oxidizable cleavage products are not formed and, therefore, no oxidation can take place. It is not due to lack of oxygen that sugar is not oxidized in diabetes, or cystin in cystinuria.

There is the normal supply of oxygen present, but the cleavage of these substances into bodies which can unite with oxygen cannot be effected, and hence they cannot be metabolized.

Voit's pupil, Lossen,2 showed that the carbon dioxid elimination in respiration was independent of the ventilation of the lungs except in so far as forced breathing increased the muscular work and the consequent output of carbon dioxid.

When the depth of respiration was voluntary the results were as follows:

1 Beebe, S. P.: "American Journal of Physiology," 1904, xii, 36. 2 Lossen: "Zeitschrift fur Biologie," 1866, ii, 244; 1870, vi, 298.

Pfluger,1 who through different reasoning came to the same conclusion as Voit, devised an experiment in which a rabbit breathed quietly through a cannula, and the oxygen absorption was compared with that of the same animal when rapid artificial ventilation of the lungs with air took place, producing apnea or hyperarterialization of the blood. There was no difference, as is seen from the following table:

From these experiments it is made sure that the respiration does not cause or regulate metabolism. On the contrary, the metabolism regulates the respiration. The metabolism of the tissues, through its oxygen requirement and its carbon dioxid production, changes the condition of the blood and thereby regulates the respiration. These distinctions are of fundamental importance.

Thus far the history of the principles which underlie the exact measurement of the metabolism has been briefly given.

By metabolism is meant the chemical changes of materials under the influence of living cells. The first cause of these chemical changes, it has been seen, is unknown, but their results lead to motions of the smallest component parts of protoplasm, motions whose totality we call life. Phenomena of life are phenomena of motion due to liberation of energy in the breaking down of molecules. The motions are principally manifested as heat, mechanical energy, and electric currents. In the organism mechanical energy may be converted into heat, as appears when work of the heart is converted into heat by the friction of the blood upon the capillaries. Also the current of electricity developed at each systole of the heart, or in any other active tissue, is resolved into heat. Thus heat may become a measure of the total activity of the body. It is derived from the total metabolism and must be dependent on it and be a measure of it. Hence the physical activities noted in life are the results of chemical decompositions. Metabolism vivifies the energy potential in chemical compounds.

1 Pfluger: "Archiv fur die ges. Physiologie," 1877, xiv, 1.