Max Verworn

“ No function other than the physiological, even under the greatest pathological alterations, exists in any structure of the body. “The muscle does not perceive, the nerve moves no bone, the cartilage does not think.” In this way Virchow rediscovered in the domain of pathology the law that his great teacher, Johannes Müller, had already clearly established in the field of physiology. But this law can no longer be applied to all pathological disturbances of the nutritive and formative activities of the cell. ”

“ For if every thing in the world were the condition for every other, the conception of relation would lose its value in special states or processes. Should the conception of condition have a meaning in regard to a certain state or process, then we should only look upon that part of a complex upon which the other is directly dependent as a condition. When, however, we meet with a factor for a process or state, which can apparently be replaced by another factor, we have not carried the analysis far enough. ”

“ When we study the vital process metabolically, we can, as shown in the above-mentioned instance, divide the processes into a metabolism of stimulation in contradistinction to a metabolism of rest.
The comprehension of the metabolism of rest demands a closer consideration. On closer observation we must say that this much-used conception is merely an abstraction nowhere realized in a strict sense. In truth, there is nowhere in nature a metabolism of rest. No cell exists which in a mathematical sense remains for even two successive moments under absolutely the same external conditions. ”

“ In the preservation of metabolic equilibrium, we have a process before us, the principle of which is nowadays restricted to living substance. In my “Biogen hypothesis,”75 I have associated the self-regulation of metabolism with the chemical equilibrium in interreacting masses. I have considered the metabolic self-regulation as the expression of the formation of a mass equilibrium between the quantity of foodstuffs and the quantity of a hypothetical combination of living substance, the biogen, which continuously disintegrates and builds up again of its own accord. ”

“ For if we could analyze the irritability of living substance to its essence, then the nature of life itself would be fathomed. The analysis of irritability of living substance offers us, therefore, a path to the investigation of life and herein lies the importance of the study of irritability. ”

“ If we follow the course of the changes from that of the normal state of equilibrium of metabolism, wherein oxygen is sufficient to bring about complete disintegration of the molecules to the formation of carbon dioxide and water, we must assume in spite of the great explosive rapidity of this process on the basis of our chemical knowledge, that first a series of intermediate products are produced before finally the end products are formed. In this way the oxydative disintegration produced by a stimulus becomes more and more prolonged by an increasing want of oxygen. ”

“ Hence this mere increase of volume of the cell in growth forms the source of an infinite mass of alterations in the activities of cell metabolism, which we briefly term its “development,” and which by constant progression, leads either to a process of cell division, and with this to a correction of existing disorder, or finally to irreparable disturbances ending in death. In this way an inseparable relation exists between increase of volume and the development of living substance. ”

“ It is more precise, however, to speak of conductivity of excitation, for it is not the primary influencing external stimulus which is conducted in the living substance, but the excitation which it has produced. I have intentionally considered only the excitating effects of stimulation, and not those of the depressing reactions, as only excitations, not depressions, are conducted by the living substance. ”

“ If only one condition is absent, then life does not exist. It is then expedient to reserve the expression “life” for the entire sum of the vital conditions. When we speak of the individual constituent processes as “vital processes” in the plural, we must bear in mind that in reality each is not in itself life. Only the whole complex “lives,” not an individual constituent of the same. Living substance is rather the whole system, and not a constituent part of the same, not a piece of protoplasm, not a nucleus and not a specific protein combination in the cell. ”

“ Consequently the extreme irritability of the nerve is a manifestation of its decrementless conductivity. If we study the course of a process of excitation and its conduction in its molecular details, the fact of the decrementless conduction indicates that in excitation, produced by a stimulus, the same number of specific molecules capable of disintegration are broken down in the same manner at every following cross section, as at the point of stimulation; or in other words: an equal amount of energy is set free at every cross section, which, in its turn, acts as stimulus to the next, etc. ”

“ The nature of our sense perception, and consequently the knowledge derived therefrom, is such that we are obliged to arbitrarily take into consideration merely fragments from the endless interdependence of all things in the world, and so we separate the vital conditions of the organisms from their surrounding factors, as though they were independent. A conscientious theoretical analysis requires that we should never forget that in reality such an isolation does not exist. ”

“ In presenting the conception of stimulation from a conditional standpoint, I desired to show what difficulties stand in the way of a theoretical isolation of a fundamental conception in the field of physiology, which indeed is used in our practical research work at every step. “Natura non facit saltus.” I wished to demonstrate that the sharp separation of the conception of stimulation, like all artificial divisions which we make in nature, must always contain an arbitrary note, as in reality isolated systems do not exist in the world. ”

“ If we suppose a living system in a state of metabolism of rest influenced by an instantaneously excitating stimulus, the entire course of excitation extends from the first alteration produced by the stimulation until the complete restitution of the metabolic equilibrium, and we will, therefore, differentiate individually the successive stages of this whole process. ”

“ By far the greater number of all diseases furnish examples of this kind. Disease is nothing else but reaction to stimulation. Should a constant stimulus persist and if the development of a new equilibrium of this system is not established, the result is premature death.
In most cases, as, for instance, the nerve impulses which move toward an organ, or better still the electrical stimuli as used for experimental purposes, it is not a question of a permanent but of a temporary alteration in the external vital conditions. The stimulus starts, then ceases after a longer or shorter period. ”

“ It is scarcely necessary for further comments upon the value of the conception of cause for the scientific explanation of a state or process. If we do not seek to introduce into exact science the antiquated symbols which have become useless and belong to a primitive phase of development of human thought, there cannot be a moment’s doubt that a strict scientific analysis in whatever field of investigation it may be carried on can consist only in the study of all the conditions concerned in a state or process. ”

“ 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. ”

“ Although the explosion of the impulse is an alteration within the body, nevertheless, as far as the muscle is concerned, it may be looked upon as an external vital condition, therefore as a stimulus. As the conception of stimulus involves the relation to a given state, it likewise involves at the same time the relation to a given living system, upon which it acts from the exterior. ”

“ When, however, the assumption is made, and this would appear to me as inevitable, that living substance contains in itself a certain even though a very slight quantity of oxygen, which in low temperature is greater, in a high temperature less, the recovery from narcosis, when oxygen is withheld, is not at all surprising. The comparatively rapid setting in of depression in narcosis finds a simple explanation in the violent manner in which the oxydative breaking down, notwithstanding the presence of oxygen, is suddenly suppressed by the flooding by the narcotic. ”

“ If a living organism is the subject of consideration, to which the “all or none law” is applicable, as, for instance, the heart at the moment of the beginning of excitation, irritability is completely obliterated, as shown by the fact that the second stimulus of any strength remains without response, for during the excitation there is a complete breaking down of all the substances capable of decomposition. ”

“ If we observe the occurrences in a living system at various moments of the cycle of life, we will find that the condition differs qualitatively at each period. The progressive alteration of the system is such that every state of living substance conditions another, by which it is followed. ”

“ Alterations in those factors which act as vital conditions compose the great mass of physiological stimuli which act continuously on every living organism. The first point to be considered in every alteration is its direction. The alterations produced by stimuli may be of two different kinds, either positive or negative. The quantity of foodstuffs, water or oxygen, in the surrounding medium, can undergo an increase or diminution; as may the temperature, intensity of light, the atmospheric and osmotic pressure. The strength of the electric current, which may be applied, can also be regulated. ”

“ It is true that every stimulus is followed by an alteration in living processes, but this is to be expected when one clearly understands the nature of vital conditions. A stimulus is in all cases an alteration in vital conditions and, in that each of the vital conditions is necessary for the continuance of life, it follows of necessity that every alteration in the vital conditions, so intimately connected with the living processes, will also be followed by an alteration in the processes occurring in the living system. ”

“ Nevertheless the assumption of the existence of a small oxygen supply in the cell can hardly be evaded. It must not be imagined that the moment the blood of the frog has been replaced with an oxygen-free solution, there is not a trace of oxygen left in the organism. Were such the case, the irritability, if measured by the extent of the response, would sink momentarily to a very low level, for the anoxydative disintegration processes are associated with an incomparably smaller production of energy than those of oxydative disintegration. ”

“ In considering the two stages of metabolism, assimilation and dissimilation, in their entirety, it appears as a very remarkable fact, that nearly all stimuli produce primarily a dissimilative excitation. We are only acquainted with a primary assimilative excitation, that is, an augmentation of the building up processes, in short, the formation of living substance, occurring as a primary result of stimulation, following increased introduction of foodstuffs extending over a prolonged length of time. ”

“ A stronger primary stimulation must also secondarily produce a stronger stimulus in the neighborhood. In other words: the conduction of excitation is a function of irritability. The greater the irritability, that is, the greater the number of molecules broken down in a unit of time and space by a stimulus of a certain intensity, the greater also is the conductivity of the living system, that is, the stronger, the more rapidly and the further excitation is extended. Conductivity of excitation is, therefore, unthinkable without irritability. ”

“ In the cases, for instance, where we have recovery, we have the same rhythm of stimulation as that of response. When recovery does not occur, interferences of the response are developed, which are of great physiological importance, with the analysis of which we shall later on find occasion to occupy ourselves in detail. The physiological example for these stimuli is the rhythmical discharge of impulses of the nerve centers; the physical method, which is most widely used for experiments, is the faradic current. ”

“ When there is interference of two series of stimuli, there are two resultant possibilities. In one type the stimuli of the one are active simultaneously with that of the other. In this instance both stimuli would act as a single stimulus of greater intensity, and we have essentially the same condition as exists when a single series is operative. Nevertheless, such cases are practically hardly realized in the physiological happenings of the organism. More often a state exists wherein the single stimuli of one series occur in the intervals of the stimuli of the other. ”