nounced fatigue; and the same is true of his individual muscles, which are incapable of performing as many contractions as the muscles of a normal animal. Feeding such an animal with sugar restores his energy and makes his muscles capable of greater labor. This latter experiment has its counterpart in the common practise, by soldiers, guides and explorers, of consuming sweets, such as maple sugar, chocolate and raisins, when on long marches; while for the farmer in the hayfield nothing is more gratifying than a sweetened drink. It is quite possible that future research will discover other substances, besides oxygen and carbohydrate, the loss of which to the tissues is conducive to the production of fatigue.
Oxidation and destruction of carbohydrate result in the formation of at least two waste substances, both of an acid character, namely, 
Fig. 5. Series of contractions of the two gastrocnemius muscles of a frog, excised and stimulated at intervals of two seconds; the one muscle normal, the other under the influence of carbon dioxide. The longer, or, in the later contractions, the lower curves are those of the poisoned muscle. Every fiftieth contraction of the two muscles is recorded from the same base line. The augmenting action of the fatigue substance is visible in the first two hundred contractions: its fatiguing action in the subsequent ones. carbon dioxide and lactic acid. Now it is an interesting fact, derived from laboratory investigation, that both of these substances, when in any but small quantity, are inimical to protoplasmic activity, and, furthermore, that a muscle under their influence shows the very same physical symptoms that are shown by a muscle fatigued through work. A fresh muscle to which has been given a moderate or considerable quantity of either one of these substances is a muscle already fatigued, although it may have performed no work (Fig. 5). These two metabolic products are thus believed to be important factors in the causation of fatigue, and to them has been given the name, "fatigue substances." Fatigue substances are poisonous, or toxic, to protoplasm; they diminish its irritability, so that a given stimulus calls out a less response than before. Certain other substances, besides carbon dioxide and lactic acid, are thought to belong to the class of fatigue substances, some of which are probably produced normally, while others occur only in diseased conditions. Among these pathological fatigue substances may be mentioned β-oxybutyric acid, which is present often in large quantities in a body suffering from diabetes—and it is a well-known fact that a person afflicted with diabetes is incapable of any considerable labor without extreme fatigue. β-oxybutyric acid occurs also in a starving body. The weakness of a person in starvation is associated
