To Liebig (1842) the next great advance was due. This phenomenally clear-minded man, while recognizing at their full value the fundamental theories advanced by Lavoisier, saw and fully appreciated their incompleteness, and he likewise understood their failure to explain many of the phenomena of life more familiar to the physiological mind than to that of a simple chemist like Lavoisier. Liebig bad made a special study of the chemical composition of foodstuffs, and likewise of the tissues and organs of the body. He had, moreover, given great attention to the decomposition products formed in the body, especially the nitrogenous substances excreted through the kidneys, as well as the carbon dioxide and water passed out through the lungs and skin. It was not strange, therefore, that he should take exception to Lavoi-Bier's view that oxidation in the body consisted in the combustion of a fluid, rich in carbon and hydrogen, which was brought to the lungs. On the contrary, Liebig contended that it was the organic compounds, proteids, fats, and carbohydrates, that underwent oxidation, and not necessarily in the lungs, but all over the body, wherever organs and tissues were active. Especially noteworthy was the view advanced by Liebig, and upheld for many years, that of these three classes of compounds the proteids alone served for the construction of organized tissues, like muscle, and that in the activity of this tissue, as in muscle contraction or musck work, the energy for the work was derived solely from the breaking down or oxidation of this organized proteid. On this ground he termed the proteid foodstuffs "plastic," or tissue-building foods. Liebig further pointed out that the substances of the body have the power of combining with and holding on to the inspired oxygen, and that fats and carbohydrates, i.e, the non-nitrogenous compounds, easily undergo oxidation or combustion, and thereby furnish the heat of the body. For this reason he termed the corresponding foodstuffs "respiratory" foods. Proteids, on the other hand, according to Liebig's view, are capable of combustion only in slight degree. The cause of the decomposition of proteid substances in the body was to be traced solely to muscle work, i.e., the energy of muscle contraction, or muscle work, was derived from the breaking down of the proteids of the muscle tissue, and work was the stimulus which brought about proteid decomposition. Non-nitrogenous substances played no part in these reactions; muscle work was without influence on these compounds, oxygen being the sole stimulus which led to their combustion, and heat was the sole product of the combustion.

If Liebig's theory is correct, that the proteids of the body are decomposed only as the result or the accompaniment of muscle work, and the proteids of the food are used up only as they take the place of the organized proteid so metabolized, it follows that with a like degree of muscular activity a given body will always decompose the same amount of proteid. If excess of proteid food is taken, the surplus will be stored in the tissues, or, in other words, the excretion of nitrogen will not be influenced by the amount of proteid consumed in the food. This was the line of argument made use of by various physiologists1 who were disposed to criticise Liebig's view, and quite naturally the question was soon made the subject of many experiments. It will suffice here merely to say that many concordant results were obtained, showing that an abundance of proteid food leads to an increase in the excretion of nitrogen, muscle activity remaining at a constant level. Hence, as Voit states, some other ground than muscle work must be sought as the true cause of proteid katabolism. Consequently, we find this hypothesis of Liebig replaced by the theory of "luxus consumption," in which it is maintained that while whatever proteid is used up by the work of the muscle must be made good from the proteid of the food, any excess of proteid absorbed from the intestinal canal is to be considered as "luxus," and like the non-nitrogenous foods may be burned up in the blood, by the oxygen therein, without being previously organized. Hence, we see suggested two causes for the decomposition of proteid in the body, viz., the work of the muscle and the oxygen of the blood. Further, as stated by C. Voit,2 the nitrogen excretion of the hungry or fasting animal affords, according to these views, a measure of the extent to which tissue proteid must be broken down in the maintenance of life, and of the amount of proteid food necessary to be consumed in order to make good the loss; viz., the minimum proteid requirement. Again, since any excess of proteid food beyond this minimal requirement, according to the theory, is destined to be burned up in the blood, or elsewhere, to furnish heat the same as non-nitrogenous foods, it follows that the excess of proteid food can be replaced by non-nitrogenous aliment.

1 See C. Voit: Hermann's Handbuch der physiologie des Gesamtnt-StoffwechseU. Band 6, Theil 1, p. 269, 1881. 2 Loc. cit, p. 270.

Oxidation, however, is the keynote in any explanation of the processes of metabolism, whether nitrogenous or non-nitrogenous matter is involved. Both alike undergo oxidation, but it is not simple oxidation or combustion that we have to deal with. In the time of Lavoisier, as already stated, it was thought that oxygen alone was the cause of the decomposition going on in the body, but simply increasing the intake of air or oxygen, as in quickened breathing or deeper inspiration, does not increase correspondingly the rate of oxidation. In other words, it is not a direct combination of oxygen with the carbon and hydrogen of the foodstuffs, or tissue elements, that takes place in the body, but rather a gradual, progressive decomposition of complex organic compounds into simpler products; made possible, however, by the agency of the oxygen carried from the lungs by the circulating blond. It was demonstrated years ago that animals breathing pure oxygen do not consume any more of the gas than when breathing ordinary air, and likewise no more carbon dioxide is produced in the one case than in the other. Fifty years ago, Liebig and other physiologists showed that frogs' muscle placed in an atmosphere free of oxygen could be made to contract or do work for some considerable time, and with liberation of heat. This fact implies a breaking down of muscle substance into simpler bodies, but there is here no free oxygen to act as the inciting cause; indeed, what actually occurs is a cleavage or splitting up of substances in the muscle tissue, but at the expense of oxygen in some form of combination in the muscle. This oxygen must have been taken from the blood at some previous time and stored in the tissue for future use. Again, as C. Voit has expressed it, if oxygen were really the immediate cause of the decompositions taking place in the organism, we should expect combustion to occur in harmony with the well-known relationship of the three classes of organic foodstuffs to oxygen. In other words, fats would undergo combustion most readily, carbohydrates next, and lastly the nitrogenous or albuminous compounds. In reality, however, proteid matter is decomposed in largest quantity; a generous addition of proteid food is always accompanied by an increased consumption of oxygen. Yet oxygen is not the inciting cause of the proteid decomposition, as is seen from the fact that in muscle work, where the intake of oxygen is greatly increased, there is no noticeable change in the amount of proteid material broken down. Plainly, in the body we have to deal not with a direct oxidation of the complex compounds of the tissues or of the food, but rather with a gradual cleavage of these higher compounds into simpler substances, these hitter undergoing progressively a still further breaking down with intake of oxygen. To repeat, oxygen is not the cause of the decompositions within the body, but the extent of the breaking down of the tissue or food material is the determining factor in the amount of oxygen taken on and used up. The products of decomposition contain more oxygen than the original substances undergoing the breaking down process, which means that oxygen is taken from the blood and used in the physiological combustion that is going on. It is not, however, strictly a combustion process; it is more complicated and more gradual than ordinary combustion, involving first of ail a series of what may be termed oxidative cleavages, in which large molecules are gradually, step by step, broken down into simpler molecules, and these latter then oxidized to still simpler forms. Hence, we find the oxidative changes preceded by a variety of alterations in which oxygen may take no part whatever; such as hydrolytic cleavage, where the elements of water are taken on as a necessary step in the cleavage process; dissociation of a simple sort, as when a large molecule breaks up directly into smaller molecules, etc. These statements by no means detract from the importance of oxygen in the katabolic processes of the body, but it is physiological oxidation that we have to do with, and not simple combustion. Oxygen is not the direct cause of the transformations taking place in the body. As one looks over the history of progress in our knowledge of nutrition from the time of Lavoisier to the present, it is easy to note the gradual change of view regarding oxidation in the living organism. Step by step, it has been demonstrated that there are many factors involved in this breaking down of complex substances; that while oxygen is an ever present requirement, there are other equally important factors to be taken into account. The contrast between the older views and those now current is clearly shown by the difference in attitude regarding the place in the body where oxidation occurs. Thus, in the earlier days, when the view was gradually gaining ground that nutritional changes were mainly the result of oxidation, and that the oxygen drawn into the lungs in inspiration was a primary factor, then, as we have seen, the lungs were considered as the laboratory where the transformation takes place. This view, however, was soon exploded, and next we find the blood, the lymph, and other fluids, but especially the blood, looked on as the locality where oxidation occurs. This was indeed quite a natural view to hold, since the blood is the carrier of oxygen, but we now know, in harmony with the fact that the breaking down of complex food material is a complicated process, involving various kinds of chemical change, that these katabolic processes are not located in any one place, but occur all over the body wherever there are active tissues. As has been previously stated, the human body is a "nation" of cells, all of which are more or less active, and it is in these miniature laboratories mainly that oxidation and all the other nutritional changes coincident to life take place. Muscle tissue and nerve tissue, the large secreting glands, such as the liver, stomach, and pancreas, all are the seat of oxidative and other changes which we class under the broad term of nutritional. To these cells, therefore, we must look for an explanation of the causes of oxidation, and the other transformations of a kindred nature that take place in the body.