Chapter II: Preface

The lectures on irritability here published were held at the University of Yale in October, 1911. When the authorities of that University honored me by an invitation to give a course of Silliman memorial lectures, I accepted with the more pleasure as it furnished me with the opportunity of summarizing the results of numerous experimental researches carried out with the assistance of my co-workers during the course of more than two decades in the physiological laboratories of Jena, Göttingen and Bonn, to unite therewith the results obtained by other investigators and thus present a uniform exposition of the general effects and laws of stimulation in the living substance. I have long entertained this plan and this for the following reason:

The physiologist, the zoölogist, the botanist, the psychologist, the pathologist, have to deal, day in, day out, with the effects of stimulation on the living substance. No living substance exists without stimulation. In the vital manifestations of all organisms the interplay of the most varied stimuli produces an enormous and manifold variety of effects. Experimental biological science employs artificial stimulation as the most important aid in the methodic production of certain effects of stimulation. The number of researches in which special effects of stimulation are treated is endless. Nevertheless the systematic investigation of the effects of stimulation have, curiously enough, been strangely neglected. Although countless results of individual effects of stimulation have been studied, the attempt has never been made to establish a general physiology of the laws of stimulation and consider it as an independent problem. This circumstance induced me to systematically investigate the general laws of the effect of stimulation. In the fifth and sixth chapters of my book on general physiology the results of these studies are recorded for the first time. Since then, especially during our own researches on the general physiology of the nervous system, a great number of new facts of importance for the general physiology of the effects of stimulation have been obtained. All these results I have endeavored to combine and elucidate in the following lectures.

The text of the lectures in its present form was written in German in 1911. The English translation was made by my wife, with the help of our friend, Dr. Lodholz of the University of Pennsylvania, who also undertook the reading of the proofs. We wish here to thank him once again and express our deep appreciation of the great sacrifice of time and labor involved in this task. I am likewise much indebted to Dr. Julius Vészi for his assistance unstintingly given, especially in obtaining a number of curves. Finally, I wish to take this opportunity to render warmest thanks to the authorities of Yale University, and especially to President Hadley and Professor Chittenden, as well as to my special colleagues, for the hospitality and cordial reception extended to me in New Haven and for the pleasant hours I was privileged to spend in their midst.

MAX VERWORN.

Bonn.

Physiological Laboratory of the University.

CONTENTS

I

_Contents_: Introductory. Earliest period. _Francis Glisson_ as
founder of the doctrine of irritability. _Albrecht von Haller._ The
vitalists. _Bordeu_ and _Barthez_. _John Brown’s_ system. _Johannes
Müller_ and the specific energy of living substance. _Rudolf
Virchow’s_ doctrine of the irritability of the cell. Discovery of
the inhibitory effects of stimulation. _Weber_, _Schiff_, _Goltz_,
_Setschenow_, _Sherrington_. _Claude Bernard_ studies on narcosis.
Tropisms. _Ehrenberg_, _Engelmann_, _Pfeffer_, _Strassburger_,
_Stahl_. _Semon’s_ speculations on mneme. 1

II

_Contents_: Principles of scientific knowledge and research. Origin
and meaning of the conception of cause. Cause and condition.
Criticism of the conception of cause. The conditional point of view.
Conception of cause. The conditional point of view applied to the
investigation of life. Conception of vital conditions. Definition of
the conception of stimulation. 18

III

_Contents_: The quality of the stimulus. Positive and negative
alterations of the factors which act as vital conditions. Extent of
the alteration in vital conditions or intensity of the stimulus.
Threshold stimuli, sub-threshold, submaximal, maximal and
supermaximal intensities of stimulus. Relations between the intensity
of stimulus and the amount of response. The _Weber_ and _Fechner_
law. All or none law. Time relations of the course of the stimulus.
Form of individual stimulus. Absolute and relative rapidity in the
course of the stimulus. Duration of the stimulus after reaching its
highest point. Adaptation to persistent stimuli. Series of individual
stimuli. Rhythmical stimuli. The _Nernst_ law. 39

IV

_Contents_: Various examples of the effects of stimulation.
Metabolism of rest and metabolism of stimulation. Metabolic
equilibrium, Disturbances of equilibrium by stimuli. Quantitative and
qualitative alterations of the metabolism of rest under the influence
of stimuli. Excitation and depression. Specific energy of living
substance. Qualitative alterations of the specific metabolism and
their relations to pathology. Functional and cytoplastic stimuli.
Relations of the cytoplastic effects of stimuli to the functional.
Hypertrophy of activity and atrophy of inactivity. Metabolic
alterations during growth of the cell. Primary and secondary effects
of stimulation. Scheme of effects of stimulation. 65

V

_Contents_: Indicators for the investigation of the process of
excitation. Latent period. The question of the existence of
assimilatory excitations. Dissimilatory excitations. Excitations of
the partial components of functional metabolism. Production of energy
in the chemical splitting up processes. Oxydative and anoxydative
disintegration. Theory of oxydative disintegration. Dependence
of irritability on oxygen. Experiments on unicellular organisms,
nerve centers and nerve fibers. Restitution after disintegration by
metabolic self-regulation. Organic reserve supplies of the cell.
The question of a reserve supply of oxygen of the cell. Metabolic
self-regulation as a form of the law of mass effect, and metabolic
equilibrium as a condition of chemical equilibrium. Functional
hypertrophy. 87

VI

_Contents_: Only processes of excitation are conducted, not
processes of depression. Conduction of excitation in its two extreme
instances. Conduction in undifferentiated pseudopod protoplasm of
rhizopoda. Conduction of excitation with decrement of intensity
and rapidity. Conduction of excitation in the nerve. Rapidity of
conduction. Conduction of excitation without decrement. Relation
between irritability and conductivity. Conduction of excitation with
decrement of the nerve after artificial depression of irritability by
narcosis. Theory of the decrementless conduction of the normal nerve.
Proof of the validity of the “all or none law” in the medullated
nerve. Theory of the process of the conductivity of excitation.
Theory of core model (Kernleiter). Electrochemical theory of
conduction based on the properties of semi-permeable surfaces. 118

VII

_Contents_: Conception of specific irritability. Alteration of
specific irritability during and after excitation. Refractory
period in various forms of living substance. Absolute and relative
refractory period. Curve of irritability during refractory period.
Dependence of the duration of the refractory period on the rapidity
of the course of the metabolic processes in the living substance.
Dependence on temperature. Dependence on supply of oxygen. Theory of
refractory period. Refractory period as basis of fatigue. Fatigue as
a form of asphyxiation. Alterations of irritability and the course
of excitation in fatigue. Recovery from fatigue. The rôle played by
oxygen in recovery. Fatigue as an expression of the prolongation of
the refractory period conditioned by the relative want of oxygen.
Fatigue of the nerve. 154

VIII

_Contents_: Examples of effects of interference of stimuli in
unicellular organisms. Interference of galvanic and thermic
stimuli in Paramecia. Interference of galvanic and thermic stimuli
and narcotics. Interference of galvanic and mechanical stimuli.
Interference of galvanotaxis and thigmotaxis in Paramecia and hypotin
infusoria. Real or homotop interference, apparent or heterotop
interference. The two effects of homotop interference of excitations:
Summation and inhibition of excitations. Theory of the processes of
inhibition. _Hering-Gaskell_ Theory. Inhibition as an expression
of the refractory period. Individual possibilities of interference
of two stimuli. Interference of an excitating and a depressing
stimulus. Interference of two depressing stimuli. Interference of two
excitating stimuli. Analysis of the interference of two excitations.
Interference of two single stimuli. Conditions upon which the
result of interference is dependent. Heterobole and isobole living
systems. Intensity of the two stimuli. Interval between the stimuli.
Specific irritability and rapidity of reaction of the living system.
Latent period. Interference of single stimuli in a series. General
scheme of the development of the effect of interference. Summation
and inhibition. Apparent increase of irritability. Conditions of
summation. Tonic excitations. Conditions of inhibitions. Various
types of inhibition. Interference of two series of stimuli. Relations
in the nervous system. Peculiarities of the nerve fibers. Conversion
of the nerve by relative fatigue from an isobolic into a heterobolic
system. 189

IX

_Contents_: Necessity of cellular physiological analysis of toxic
depressions by pharmacology. Apparent variety of processes of
depression. Depression of oxydative disintegration as the most
extended principle in the processes of depression. Asphyxiation,
fatigue, heat depression, as a consequence of restriction of
oxydative disintegration. Narcosis. Theories of narcosis. The
alteration of specific irritability and conductivity in narcosis.
Depression of oxydative processes in narcosis. Asphyxiation of
living substance when oxygen is present during narcosis. Persistence
of anoxydative disintegration in narcosis. Increase of the same by
stimuli. Depression by narcosis as a form of acute asphyxiation.
Hypothesis on the mechanism of depression of oxygen exchange by
narcotics. Possibility of combining the facts with the observations
of _Meyer_ and _Overton_. 235

IRRITABILITY