The chemical stimulus to the cells does not reside in the amino-acids themselves, for there is no accumulation of amino-acids in the tissues after the ingestion of meat in large quantities. (See Van Slyke, Wishart, p. 80.) Also when protein is deposited in the form of new tissues these amino-acids exert no specific dynamic influence. Rubner3 gives the following example of the stage of the deposit of protein without a rise in the metabolism of a dog:

The researches of Hoobler4 have shown the same to be true of the baby, as appears from the following data:

Such facts demonstrate that the mere absorption of amino-acids and their rebuilding into new protoplasm does not increase the metabolism.

Since the hours of the highest heat production after giving glycocoll and alanin are the hours of the maximal metabolism of these amino-acids, it is obvious that the metabolism products, such as glycollic or lactic acids (see pp. 190-194), are indicated as the probable chemical stimuli which act upon the protoplasm of the cells, causing them to oxidize materials in increased measure.

1 Lusk: "Archives of Internal Medicine," 1913, xii, 485.

2 Grafe: "Deutsches Archiv fur klin. Med.," 1915, cxviii, 1. 3 Rubner: "Gesetze des Energieverbrauchs," 1902, p. 256.

4 Hoobler: "American Journal of Diseases of Children," 1915, x, 153.

One recalls in this connection the permanently increased metabolism in phosphorus-poisoning, in severe anemias, and in persons living at high altitudes, under all of which conditions lactic acid is found in increased amounts in the blood and often in the urine. (See Chapter XV (Metabolism In Anemia, At High Altitudes, In Myxedema, And In Exophthalmic Goiter)).

That the chemical stimulus acts on protoplasm directly and not through excitation of the nervous system is to be inferred from the experiments of Tangl,1 who noticed an increase in the heat production of curarized dogs after giving them protein.

External cold acts reflexly through the nervous system to increase metabolism in a fasting animal and thus prevents a fall in body temperature through the "chemical regulation" of body temperature. According to Rubner's hypothesis, the "free heat" liberated in the intermediary metabolism of protein can be used in lieu of that derived from the increased metabolism induced through the effect of cold. In the light of the newer researches, however, the extra heat necessary to preserve the body from a fall in temperature may be derived from an increased metabolism of the cell itself, whether this be induced by nerve action or by direct chemical stimulation.

It may be that the mass action of the various fragments produced in the breakdown of protein in metabolism is also a contributory factor in the higher production of heat, but that it is the main factor is negatived by contrasting the different effect of 20 grams of glutamic acid with that of 20 grams of glycocoll, the effect of the first being nil and that of the latter powerful.

The influence of meat ingestion in man is given in the following table:

1 Tangl: "Biochemische Zeitschrift," 1911, xxxiv, 1.

Table Showing The Percentage Increase In Metabolism Each Hour After The Ingestion Of Meat By Man

* Chopped meat 725 grams +100 grams fat.

In the last-named experiment protein furnished between 25 and 40 per cent, of the total calories of metabolism instead of the average normal of 15 per cent. When Grafe3 administered 80 grams of alanin or 50 grams of glycocoll to a man the specific dynamic action caused an increase in the oxygen absorption of 7 and 14 per cent, respectively. The specific dynamic action of protein is not usually as great in man as in the dog. Du Bois4, however, has seen a rise of 55 per cent, in the metabolism of an achondroplastic dwarf after giving him 750 grams of meat.

1 Magnus-Levy: "Pfluger's Archiv," 1894, lv, 87.

2 Gephart and Du Bois: "Archives of Internal Medicine," 1915, xv, 835. 3 Grafe: Loc. cit.

4 Unpublished.