It is known that summation of excitation in the normal nerve does not occur. As already stated, the nerve is a system in which the “all or none law” is operative. Such isobolic systems do not summate, having no power of summation because each individual stimulus brings about a maximum response. But we have seen that the nerve, as a result of depressing factors, such as deficiency of oxygen, narcosis, fatigue, etc., which decrease its irritability, can be transformed from an isobolic into a heterobolic system. In this state the nerve possesses the capability of summating excitations. _Waller_,[181] _Boruttau_,[182] _Boruttau_ and _Fröhlich_,[183] _Thörner_[184] and others have shown that the action current of the nerve during the application of tetanic stimulation becomes decidedly greater during a certain stage of narcosis or asphyxiation, so that the wave of negative variation is higher than when the nerve is excitated by a single induction shock. _Fröhlich_[185] first threw light upon this subject in that he made the observation that here a principle is involved which has far-reaching importance in the phenomena occurring in the organism. He showed that as a result of fatigue, cold and narcosis, etc., the course of excitation brought about by the single stimulation undergoes retardation. These conditions within certain limits become more favorable for the production of summation, because each succeeding stimulus meets with a more incomplete recovery of excitation than the one previously applied. In consequence of this, the irritability of the system in the beginning of fatigue, or narcosis, or immediately after the application of cold, is apparently increased. This “_apparent excitation_,” as it was called by _Fröhlich_, depends, however, in reality upon a beginning depression which is evident in that the course of the individual excitations are lengthened by this means. The irritability is likewise also reduced. _Reinecke_[186] later studied in further detail the retardation of excitation in the muscle and attributed to this the characteristic property shown in muscle in the so-called “reaction of degeneration.” Fatigue, asphyxia, cold, degeneration, in fact all factors which retard the course of excitation, are favorable to the summation of excitation, provided their influence does not exceed certain limits. [181] _Waller_: “Observations on isolated nerve.” Croonian Lecture, Philosophical transactions. 1897. [182] _Boruttau_: “Die Actionsströme und die Theorie der Nervenleitung.” Pflügers Arch. Bd. 84, 1901. [183] _Boruttau und Fröhlich_: “Electropathologische Untersuchungen. Ueber die Aenderung der Erregungswelle durch Schädigung des Nerven.” Pflügers Arch. Bd. 105, 1904. [184] _Thörner_: “Die Ermüdung des markhaltigen Nerven.” Zeitschr. f. allgem. Physiologie Bd. VIII, 1908, und Bd. N, 1910.