In order to examine these facts once more on an extensive scale, and at the same time obtain an understanding of the development of the decrement in the narcotized stretch, I have requested Dr. Lodholz to register as many accurate curves as possible in which the positions of the secondary coil of an inductorium are the ordinates indicating the threshold of stimulation at four points of a nerve stretch. Of these points three are situated at prescribed distances from each other in the narcotized or asphyxiated stretch; the fourth is centrally placed. (Figure 24.) As might be expected the result was the same as in former investigations. They show however even more strikingly the abruptness of the disappearance of conductivity simultaneously for the weakest and the strongest stimuli. The curve produced by the centrally placed electrode remains at the same height for a considerable period, then suddenly abruptly declines. Those of the electrodes within the chamber likewise sink, at first slowly, then with increasing rapidity in successive order corresponding to the distance which they are situated from the point of exit of the nerve, so that the curve of the most distant electrode reaches the abscissa first, that of the electrode nearest the muscle in the chamber, last. The experiments demonstrate with complete clearness that in contrast to all those points within the affected stretch, where the conductivity, though already obliterated for weaker stimuli, still exists for stronger, that with stimulation of a point towards the center above the affected stretch, conduction ceases simultaneously for all different strengths of stimuli. This last state at the points within the affected stretch might be ascribed to the diminution of the excitability of this stretch, and the idea entertained that the weak stimuli no longer produce excitation capable of further conduction.

This assumption is contradicted, however, by the fact that subsequently to the disappearance of the response at a point situated at the greatest distance from the place of exit, an effect of stimulation can be obtained at the nearest point to the exit with the same or even less strength of the current. As the irritability in the affected stretch is reduced at all points in equal measure, the fact of a weaker stimulus becoming inoperative whilst a stronger remains effective can only be attributed to the circumstance that the wave of excitation set free at some point of the influenced stretch by a weaker stimulus is sooner obliterated on its way to the muscle than that produced at the same point by a stronger stimulus. These experiments, in which the manifestations of the nerves in response to stimuli applied centrally above the chamber in the normal stretch are compared to those in response to a stimulus acting on the affected stretch, clearly demonstrate the totally different effect in both cases. In stimulation of the centrally situated normal stretch, the wave of excitation, which enters from here into the influenced stretch, is obliterated at the same point simultaneously for the weakest as well as for the strongest stimulus; stimulation of the affected stretch, the wave of excitation which is set free at one point by a weak stimulus, is obliterated sooner and after passing through a shorter stretch than that which is produced by a stronger stimulus. It is self-evident that in the first instance, in which the stimulus acts on the centrally situated normal stretch, the wave of excitation, thereby set free, must in passing through the affected stretch undergo a decrement of its intensity. If, therefore, the wave of excitation, coming from above, is obliterated exactly at the same point, whether brought about by weak or strong stimuli, the inevitable conclusion must be drawn that, whether either a weak or a strong stimulus is operative, the wave of excitation must have entered into the influenced stretch from the normal stretch with exactly the same intensity. In other words: the weakest as well as the strongest stimuli produce excitations of equal intensity in the normal nerve, that is, the “all or none law” is valid for the nerve.

This information can no longer be doubted in the presence of such evidence as was presented above. This indeed is a fact of far-reaching importance in the understanding of the functional activity of our nervous system, for it is evident that the difference of intensity in the conduction of excitation is not, as has been assumed until now, the result of the conduction of varying strengths of a single excitation in the same elementary fibers, but rather the involvement of a various number of fibers, and that a series of processes which we have to the present attributed to the varying intensities are now to be explained by difference in the duration and form of excitation. This gives us an entirely different but nevertheless a more definite picture of the physiological character of the processes in the nervous system. Still, this question belongs to another chapter of physiology. Here we are interested in the fact that we have in the nerve a form of living substance, in which irritability has reached a high degree, and every stimulus which is at all operative brings about disintegration of all the material involved in excitation, and consequently the property of conductivity in the nerve reaches the state of highest development of all living structures, in that the medullated nerve conducts with the greatest rapidity on the one hand, and on the other, there is no decrement of the velocity and intensity of excitation. All these characteristics: the existence of the “all or none law,” the rapidity of the conduction of excitation, the absence of a decrement in the velocity, the absence of a decrement of the intensity of the excitation wave, the want of the capability of summation of excitation, are all dependent upon one another, for they are the combined expression of one and the same factor, that of the high state of irritability. When the irritability is artificially reduced, then the nerve approaches more and more, depending upon the amount of reduction, to the series of living substances in which we found the protoplasm of the rhizopoda to occupy the other extreme. Between the normal medullary nerve with its maximal, and the pseudopods of the rhizopods with their minimal capability of reaction, we find innumerable gradations in groups of living substances. Whether or not other forms of living substances follow the type of the nerve, whether for example the “all or none law” can be applied to the skeletal muscle as the investigations of Keith Lucas112 seem to show, requires further investigation.

Finally, there arises the important question as to the finer mechanism of conductivity. The progression of excitation from cross section to cross section in a living system is brought about by the decomposition of the molecules in one region acting as a stimulus and producing a disintegration of the molecules in another region, etc. We have already seen that the intensity is dependent upon the amount of energy produced by the disintegration of the molecules following the stimulus, that is, upon the amount liberated in a definite space in a definite time. The question which now arises is this: What form of energy is produced by the stimulus at the point of stimulation, which acts upon the neighboring molecules? The conduction of excitation is a property of all living substance, and we may presume that this occurs in all living systems in the same manner. If one examines the forms of energy which are produced in a living substance by the breaking down of the molecules, we find that chiefly three forms of energy may be taken in consideration in the problem of conductivity: heat, electricity and osmotic energy. Light cannot be looked upon as a form of energy which is produced by all living substance, and the other forms of energy, as the chemical energy and surface tension, remain local. At a first glance one is inclined to assume that heat is the form of energy which is liberated by the breaking down of the stimulated molecule and which spreads to the neighboring molecules and brings about their decomposition. For we know that heat facilitates dissociation, and the analogy between living substance and explosive material is very close. In both instances the decomposition, which extends over a great mass of molecules, is accomplished by the heat produced in the breaking down of a few molecules. In fact, the conduction of excitation of a nerve can in many respects be compared with the burning of a fuse.113 Nevertheless, it must not be forgotten that this analogy, which on first glance seems so apt, upon closer observation presents serious difficulties. It can be experimentally shown that an increase in the temperature in the living substance follows stimulation, but it is also known that in momentary excitation following a single stimulus, as in the muscle after the application of an induction shock, the heat production is extremely small. This difficulty becomes particularly apparent if we endeavor to gain an approximate idea of the numerical proportions of the irritable, that is the disintegrating molecules to the remaining mass of a living system. The water content above all represents an enormous proportion. If we calculate this to be for the nerve, for instance, roughly about 75 per cent., which is a low estimate, only 25 per cent. of dry substances remain. Even of this 25 per cent. by far the largest part is apportioned to connective tissue, for which 15 per cent. is certainly not too high a figure. Neither can the remaining 10 per cent. of dry substances be regarded as consisting entirely of molecules capable of decomposition. For in this is also included the organic reserve material of the axis cylinder protoplasm, which is doubtless of very considerable amount. Further, the salts and products of disintegration, for which the estimate for the sum total would probably not be too low if we assume the amount to be equal to that of the group specially concerned in the process of excitation. As, however, a constant metabolism of rest takes place, these last molecules or atom groups are certainly not at the moment of entrance of the stimulus in their entirety in a condition capable of decomposition. It is quite certain, therefore, that we are still overestimating the amount of the molecules capable of disintegration, if we put them down as 5 per cent. of the entire nerve substance. If we now suppose that this 5 per cent. of irritable molecules are broken down as a result of stimulation, 95 per cent. of nonirritable substance, separating these irritable molecules, must become heated to such a degree by the disintegration of the latter that the amount of heat suffices to bring about decomposition of the nearest surrounding molecules or atom groups, for otherwise conduction of disintegration could not take place in this manner. This condition presents a serious difficulty for the assumption that heat is the form of energy responsible for the conduction of disintegration. It is true that we cannot reject this view at once as being completely incorrect, as the possibility of conduction does not depend upon the absolute amount of heat which reaches the next molecule capable of decomposition, but upon the relative amount of heat in regard to the degree of lability of the irritable molecules, of which we cannot even approximately make an estimate. However, by a comparison with other highly explosive substances, such as iodide of nitrogen, we find that a slight trace of water applied to the iodide of nitrogen suffices to prevent the extension of the disintegration process, and with this the explosion of the whole mass. Nor does the view of Pflüger remove this difficulty, which assumes that the atom groups capable of breaking down are joined together by a chemical linking of atoms to long fiber-shaped giant molecules through the whole nerve fiber, for this assumption of a firm structure can hardly be reconciled with the principles concerned of metabolism.

In consideration of this difficulty it seems easier to assign the rôle of mediator of disintegration not to heat but to electricity. Production of electricity is likewise a property of all living substance. Differences of electrical potential between two points may be equalized in the stretch by conduction through the intervening space. Electricity would then fulfil the important conditions, which must be demanded for the form of energy, acting as mediator for the conduction of disintegration from cross section to cross section.

Physiologists even at an early date, misled by the apparent likeness in the conduction of excitation, especially in the nerve, to that of electricity in a metal wire, regarded both processes as identical. When, however, Helmholtz first demonstrated experimentally the rapidity of the conduction in the nerve, the thought that electrical conduction was concerned, such as takes place in a metal wire, had to be abandoned, as the velocity shows too great a difference in the two cases.

The observations, on the other hand, on the conductivity in the so-called “core model,” seemed to offer another possibility of attributing the conduction of excitation in the nerve to electric processes. Matteucci, later Hermann and finally Boruttau114 have endeavored to apply the results obtained when electricity is introduced in a wire covered with a moist envelope (saline solution), to the explanation of conductivity in the nerve. (Figure 25.) The fact has been shown, that in such a model the application of electricity to a point, as a result of polarization between the moist envelope and the metal, produces a weak local current, which in turn disturbs the electrical potential in the next cross section and consequently a new local current is produced and so on through the whole length of the wire. (Figure 26.) This fact, in connection with the apparent similarity in the differentiation of the axial fibers and peripheral envelope in the nerve, has led Boruttau to apply the principles of conductivity in the “core model” to that of the nerve. Then, however, Nernst and Zeyneck brought forward their theory, according to which the galvanic current is operative as a stimulus in that it brings about an alteration in the concentration of the ions at the junction of two different electrolites which, in turn, produce local currents. Boruttau then dropped the assumption of the existence of a simple physical polarization between the wire and the envelope and replaced it by the assumption of an alteration in the concentration of the ions at this position. Thereby the “core model explanation” was already altered in principle, in that only the differentiation of a central fibrilla and a peripheral enveloping substance was appropriated. It seems to me that this factor can likewise be considered as completely dispensable and may, therefore, be omitted; thus nothing remains of the “core model explanation” of the conduction of excitation in the nerve.

The results of continually increasing numbers of investigation in recent times make it appear almost as a certainty that the elementary fibrillæ in the axis cylinder are nothing else but skeletal substances. Wolff,115 Verworn116 and others have first expressed the view that the neurofibrillæ must be looked upon as skeletal fibers for the soft neuroplasm, and more recently Lenhossek117 and especially Goldschmidt118 have confirmed this assumption in detail. Goldschmidt has shown by extensive comparative studies of cell mechanism the rôle played by the neurofibrillæ in a physical connection as internal skeletal formations, and has proved at the same time, in complete unanimity with other investigators, their continuity with other undoubted skeletal fibrillæ. By this the numerous combinations and speculations of Apathy and Bethe concerning the part taken by the neurofibrillæ have been rendered untenable. In no case is there the slightest justification to regard the apparent “Kernleiterstructur” of the nerve as the principal condition for the process of conductivity, for should we dispense completely with this point for the theory of the conduction of the nerve, we can obtain, solely by the aid of the facts known today in physical chemistry, the foundations for a theory of the conductions of excitation which not merely renders the specific case of the conduction of the nerve intelligible, but contains at the same time the principles of the process of the conduction of excitation for all living substance.

On the basis of investigation in the physical chemistry on the properties of semi-permeable membranes, we know that such membranes produce an elective effect on the diffusion of dissolved substances. This is in the way that the two different solutions, separated by a semi-permeable surface, do not follow the known laws of diffusion, but are altered in that certain substances in contrast to their rapidity of diffusion pass through the membrane or are prevented from entering by the latter. This applies likewise to the two kinds of ions, which are dissociated in diluted substances. If the surface exercises a selection in the way, for instance, that the positive kations are allowed to pass through, whilst the negative anions are held back, a difference of potential must exist between the two. In this manner, wherever two different solutions are separated from each other by a semi-permeable surface, an opportunity occurs for the taking place of galvanic currents. As we know, living protoplasm by reason of its colloidal components possesses, in common with all colloidal substances, on its surface the properties of semi-permeable membranes. Between the cell and the medium, therefore, there is always the opportunity for the occurrence of differences of electric potential. But more. We likewise know that protoplasm itself represents a mixture of colloid substances and actual solutions. Frequently, if not always, living structure presents a morphological differentiation of two types, when seen under the microscope, in the form of a foam structure described by Bütschli. (Figures 27 and 28.) If we suppose that with the disintegration of complex molecules, which we must assume as taking place in the material of the walls of the protoplasm network, substances are formed which are subjected to electrolytic dissociation, the anions and kations hereby liberated must be diffused from the place of their separation into the surroundings. Their diffusion, however, is restricted by the protoplasmic network. The positive ions may pass through, but the negative ions may not. As a result: the reticulated substance is the seat of electric discharge, which in turn gives the impact to the breaking down of new molecules and with this to the occurrence of new potential differences, and so on, consequently the disintegration is extended further and further through the connected masses of the protoplasmic framework.

This theory, founded on facts gained entirely from investigation, would involve those forms of energy which play the rôle of activator in the extension of the breaking down of the molecule from cross section to cross section, namely, the osmotic and the electrical energy. Based on the general properties of physical chemistry and those of morphology of the living substances, they would be applicable to all vital systems. It would be premature to attempt to extend this assumption and further develop its specific details, above all to make it responsible for the specific differences in the process of the conduction of excitation in various forms of living substance. For this our knowledge of the properties of living substance is still far too incomplete. Nevertheless, it furnishes us even now with various points of view for the further analysis of a series of vital manifestations, as, for instance, the facts concerning the production of electricity, of galvanotaxis, chemotaxis and so on. This, however, exceeds the limits of the task we have here mapped out. We are concerned here solely with the general principle on which the conductivity of excitation in the living substance is founded.