ill Mi i ill GENERAL PHYSIOLOGY GENERAL PHYSIOLOGY AN OUTLINE OF THE SCIENCE OF LIFE BY MAX VERWORN, M.D., Ph.D. A.O. PROFESSOR OF PHYSIOLOGY IN THE MEDICAL FACULTY OF THE UNIVERSITY OF JENA TRANSLATED FROM THE SECOND GERMAN EDITION AND EDITED BY FREDERIC S. LEE, Ph.D. ADJUNCT PROFESSOR OF PHYSIOLOGY IN COLUMBIA UNIVERSITY WITH TWO HUNDRED AND EIGHTY-FIVE ILLUSTRATIONS HontJon MACMILLAN AND CO, LIMITED NEW YORK: THE MACMILLAN COMPANY 1899 -xV V- RICHARD CLAY AND SONS, LIMITED, LONDON AND BUNGAY. TO THE MEMORY OF JOHANNES MULLER THE MASTER OF HIS SCIENCE THESE PAGES ARE BY A PHYSIOLOGIST ^ -\\ PKEFACE TO THE FIRST EDITION The elementary constituent of all living substance and the substratum of all elementary vital phenomena is the cell. Hence, if the task of physiology lies in the explanation of vital pheno- mena, it is evident that general physio- logy can be only cell-physiology. Modern physiology has arrived at a point in its development where it must constantly extend its inquiries to the cell, the elementary substratum of all life that exists upon the earth's surface. It appears more and more clear that the general pro- blems of life are cell-problems. This fact suggested to me the idea of examining from the cell-physiological standpoint these general problems, and the facts, theories, and hypotheses of the nature of life — subjects which thus far had never received compre- hensive treatment — and thus outlining a field in which the various branches of special physiology might unite. In the present book, therefore, I have made an attempt to treat general physio- logy as general cell-physiology. In dedicating this effort to the memory of Johannes Mtiller, I would express the obligation that we all owe to the work of our great master in physiology. But, more than all else, I would indi- cate Miiller's comparative-physiological standpoint, a standpoint that I have always strongly endeavoured to maintain in my own work. The comparative method of dealing with physiological problems, which Miiller's researches made so extremely fruitful, was unfortunately laid aside after his death, as physiology dealt more and more with the special problems of the human body. But it is now being shown constantly that the amount of material available for work in this latter field is too small in view of the variety of problems. Hence, if wrong and false generalisations viii PREFACE TO THE FIRST EDITION are to be avoided, and the science is to be allowed free develop- ment, it appears to me indispensable to return to Muller's method. For this reason I have dedicated the following pages to the memory of that great physiologist. The plan of the present book first assumed fixed form during a journey which I made in the year 1890 to different points on the Mediterranean Sea and the Red Sea for the purpose of making comparative-physiological researches. After my return my uni- versity lectures in Jena gave me an opportunity to present the collected material in connected form. But the greater part of the labour remained to be performed, and in the summer of 1892 I began the writing of the book. Although for nearly ten years I have been busy with the problems of general physiology and have endeavoured to contribute something to their solution, so much labour has been associated with the collection, examination, selec- tion, completion, and arrangement of the much scattered material, that the book has progressed slowly — and with varied feelings on my part. I have often wondered whether the result would accord with the enthusiasm and love with which the task was undertaken. Only the criticism of my colleagues can decide this. It is not to be expected that a book which brings together for the first time in a unified form a mass of material hitherto regarded as hetero- geneous, shall upon its first appearance pretend to completeness. I cherish no illusions that I have succeeded more than approxi- mately. I am fully aware that many faults and errors must have crept in, and these I beg my colleagues in friendliness to correct. It has afforded me especial satisfaction that one of my American colleagues, Professor Frederic S. Lee, of New York, in an address before the New York Academy of Sciences ('94), has developed simultaneously and independently the same ideas regarding the claims of modern physiology as are presented in detail by myself in the first chapter of this book. These ideas have also been expressed by me elsewhere, especially in an article in the Monist (Chicago, '94). If a book is to reach a wide circle of readers, its language must be neither too technical nor too prosaic. I have endeavoured to comply with this requirement. I wished to write something that would appeal first to my fellow physiologists, and offer them, besides certain new facts and ideas, a summary of our scattered knowledge. But at the same time I wished the work to give to any interested scientific reader, whether a student of medicine, PREFACE TO THE FIRST EDITION ix philosophy, botany, or zoology, an outlook over the problems, facts, theories, and hypotheses of life ; in other words, I wished to give him an introduction to general physiology, and thus afford him an idea of the important theoretical basis of his study. It is not easy to adapt oneself to these diverse aims. How far I have succeeded in doing this, only the judgment of the reader can decide. I bespeak his indulgent criticism. I gratefully acknowledge my obligations to all my friends who have taken active part in the planning, developing, and com- pleting of my task, and especially to Mr. Gustav Fischer, who has shown great liberality in the publication of the book. THE AUTHOR. LONDON, November 4, 1894. PREFACE TO THE SECOND EDITION In offering the second edition of this work to the public, I feel it obligatory upon me to express my warmest thanks for the extremely favourable reception given the book upon its first appearance, by readers and especially by critics. I have been pleasantly surprised to realise — as I have been made to realise by personal talks, by letters, and particularly by the criticism of pro- fessional journals both at home and abroad — that the subject of general physiology excites active interest and receives abundant recognition in the circles not simply of theoretical natural science, but of practical medicine. It gives me much satisfaction to perceive in this a sign that the practical medicine of the day acknowledges the profound importance of a knowledge of the general physiology of cell-life for an understanding of the physiological and pathological phenomena exhibited in the cell- community of the human body. I am encouraged in this view by the gratifying fact that cell-physiological researches have increased greatly in number during the last few years. In this second edition I have endeavoured to note the more important of the later results. Unfortunately, because of lack of space, I have been obliged to treat many of these with more brevity than I desired, and to curtail the amount of attention given in the first edition to some of the older work. But by the introduction of a considerable number of new figures, and the replacement of certain faulty ones by better, I trust that the whole has been made more comprehensible. I cannot expect the present edition to be free from errors and faults ; but I trust that every critic will recognise the great difficulties involved in the treatment of such a large amount of material, and will be indulgent towards mistakes. I am sincerely grateful to my critics for having called attention to errors in the first edition. So PREFACE TO THE SECOND EDITION xi far as these were errors of fact, I have endeavoured to correct them ; so far as the points raised were based upon differences in conception, or points of view, I have conscientiously tried to allow them their full value. Translations of the book into English and Italian are in course of preparation, and a Russian edition has recently appeared. Since the latter was published wholly without my knowledge, and has not been seen by either my publisher or myself, I am forced to disclaim all responsibility for it. I cannot forbear expressing my warmest thanks to Dr. Gustav Fischer, for the pains taken by him in issuing the present edition. THE AUTHOR. UNIVERSITY OF JENA : THE PHYSIOLOGICAL INSTITUTE, June, 1897. PREFATORY NOTE TO THE ENGLISH TiUNSLATION The first comprehensive treatment of general physiology was contained in Claude Bernard's now classic Lemons sur les pMnom&nes de la me communs aux animaux et aiix vfyetaux, which was pub- lished in 1878-79. Since that time the only adequate work upon the subject has been Professor Verworn's Allgemeine Physiologic. The first edition of this book appeared in 1894. This was followed in 1897 by a second and revised edition. The work has been welcomed by European and American biologists, who have felt the need of a review and summary of the rapidly accumulating details of cell-physiology, and its ability and suggestiveness have been widely recognised. Many of the special views of the author have encountered opposition — a fact that perhaps is indicative of their value — yet, however much we may agree or disagree with him upon special points, we all must acknowledge his breadth and be grateful to him for presenting such a wealth of facts, and for pointing out so clearly the possibilities of research. With Pro- fessor Verworn's consent I have undertaken the task of trans- lating and editing the book ; first, with the hope that in its English form it may enable English-speaking biologists and general scientific readers to realize more fully than before the wide scope of the science of Physiology ; and, secondly, because the book presents in a form convenient for the use of students suggestive and stimulating discussions of vital physiological questions. FREDERIC S. LEE. COLUMBIA UNIVERSITY, NEW YORK, March 1, 1898. CONTENTS PAGE CHAPTER I THE AIMS AND METHODS OF PHYSIOLOGICAL RESEARCH I. THE PROBLEM OF PHYSIOLOGY 2 II. THE HISTORY OF PHYSIOLOGICAL RESEARCH 6 A. The Earliest Times. B. The Period of Galen. C. The Period of Harvey. D. The Period of Haller. E. The Period of Johannes Miiller III. THE METHOD OF PHYSIOLOGICAL RESEARCH 28 A. The Past Achievements of Physiological Research. B. The Relation of Psychology to Physiology. 1. The Question of the Limits of a Knowledge of Nature. 2. Physical World and Mind. 3. Psycho-monism. C. Vitalism. D. Cell-Physiology CHAPTER II LIVING SUBSTANCE I. THE COMPOSITION OF LIVING SUBSTANCE 55 A. The Individualisation of Living Substance. 1. The Cell as an Elementary Organism. 2. General and Special Cell-consti- tuents. 3. Multinucleate Cells and Syncytia. B. The Morpho- logical Nature of Living Substance. 1. The Form and Size of the Cell. 2. Protoplasm, a. The Solid Constituents of Proto- plasm, b. The Ground-substance of Protoplasm. 3. The Cell- Nucleus, a. The Form of the Nucleus. 6. The Substance of the Nucleus, c. The Structure of the Nucleus. C. The Physical Properties of Living Substance. 1. The Consistency of Living Substance. 2. The Specific Gravity of Living Substance. 3. The Optical Properties of Living Substance. D. The Chemical Pro- perties of Living Substance. 1. The Organic Elements. 2. The civ CONTENTS PAGE Chemical Compounds of the Cell. a. Proteids. b. Carbohydrates, c. Fats. d. The Inorganic Constituents of Living Substance. e. The Distribution of Substances in Protoplasm and Nucleus. II. LIVING AND LIFELESS SUBSTANCE 118 A. Organisms and Inorganic Bodies. 1. Structural Differences. 2. Genetic Differences. 3. Physical Differences. 4. Chemical Differences. B. Living and Lifeless Organisms. 1. Life and Apparent Death. 2. Life and Death. CHAPTER III ELEMENTARY VITAL PHENOMENA I. THE PHENOMENA OF METABOLISM 137 A. The Ingestion of Substances. 1. Food-stuffs. 2. The Mode of Food-Ingestion by the Cell. B. The Transformation of In- gested Substances. 1. Extracellular and Intracellular Digestion. 2. Ferments and their Mode of Action. 3. Assimilation and Dissimilation, a. Assimilation, b. Dissimilation. C. The Out- put of Substances. 1. The Mode of Output of Substances by the Cell. 2. Secretions and Excretions, a. Secretions, b. Ex- cretions. II. THE PHENOMENA OF FORM-CHANGES 177 A. Phylogenetic Development. 1. Heredity. 2. Adaptation. B. Ontogenetic Development. 1. Growth and Reproduction. 2. The Forms of Cell-division, a. Direct Cell-division, b. In- direct Cell-division. 3. Fertilisation. 4. The Development of the Multicellular Organism. III. THE PHENOMENA OF TRANSFORMATION OF ENERGY 209 A. The Forms of Energy. B. The Introduction of Energy into the Organism. 1. The Introduction of Chemical Energy. 2. The Introduction of Light and Heat. C. The Production of Energy by the Organism. 1. The Production of Mechanical Energy. a. Passive Movements, b. Movements by Swelling of the Cell- walls, c. Movements by Change of the Cell-turgor. d. Move- ments by Change of the Specific Gravity of the Cell. e. Movements by Secretion. /. Movements by Growth. v a-io\oyoi," the conception of uo-£9 being extended to all nature. Later, with the separation of physics as an independent science in its present sense, the con- ception became again narrow, but different from the original one, being limited to non-living nature and thus possessing a significance the exact opposite of the original one. If the word (f>vcris be conceived in its proper original sense, the term " Physiology " expresses fully the essence of the science to -which the term is now applied, and it is unnecessary to replace it with the later word " Biology," with which at present very different ideas are associated. Physiology is the science of the phenomena of living nature, and, accordingly, its task is the investigation of life. In spite of the apparent simplicity of its task, the science has already laboured for centuries upon this problem. A little con- sideration will make its difficulties evident. It is only necessary to attach ideas to the expressions " life " and " investigation," which in this combination appear at first as empty words. We will consider first the subject-matter of physiology, namely, life. The untrained person associates usually with this word a METHODS OF PHYSIOLOGICAL RESEARCH 3 mass of ideas that concern phenomena of a secondary nature, because he thinks only of the remote results, constantly observed in daily life, of primary vital phenomena. With him life is characterised by various occupations, labours, pleasures, walking, travelling, reading, speaking, eating, drinking, etc., one or another activity appearing as the essential part of his own life according to his vocation and individuality : to one person, life is labour, to another a constant festivity. But the various occupations of daily life are combinations of a few primary vital phenomena. If the development of the conception of life be followed back to early antiquity, when mankind had no presenti- ments of all the occupations that accompany a highly developed culture, when he was unacquainted with fire, when he did not know how to make even the most primitive tools, the conclusion is reached that the conception sprang from the combination of a number of simple phenomena, which early man discovered by self-observation, especially those phenomena that are associated with evident move- ments, such as locomotion, breathing, nutrition, the heart-beat, and others. In fact, it is not difficult to analyse into their primary •constituents the complex occupations of our present life, and to recognise that its diversity is produced by various combinations of a few elementary phenomena, such as nutrition, respiration, growth, reproduction, movement, and the production of heat. If life be thus conceived as a sum of certain simple phenomena, the task of physiology is to determine, investigate, and explain the latter. It must be remembered, however, that such a conception of life is limited to the vital phenomena of human beings, while the field of life is far greater. Animals and plants likewise exhibit vital phenomena, and it may be asked whether these latter are the same -as or different from the phenomena that prevail among men. It is evident that all living organisms must be included in the .sphere of physiological investigation, the flower and the worm equally with man. Hence the first duty of physiology is to mark out the field of the living, to determine what is living and what is not living — an undertaking that is more difficult than it appears. The conception of life has not always been the same. It has experienced fundamental changes in the course of the develop- ment of the human species. Formed first with respect to man- kind, it was early extended to other objects. With primitive races, the conception was much wider than at present, and they termed living what is no longer regarded as such. With them stars, fire, wind and waves were beings endowed with life and mind, and they were personified in the image of man. The remains of these ideas are still found in the mythology of the classic and modern races. In the course of time the distinction between living and lifeless has been made constantly sharper, but even to-day a child regards •a steam engine as a living animal. The child is guided more or B 2 4 GENERAL PHYSIOLOGY less consciously by the same criterion as the primitive races, who from the fact of motion, considered as living the dancing flame of a fire or a moving wave. In fact, of all vital phenomena, motion is the one that gives most strongly the impression of living. It may be said that only primitive races and children are misled by the criterion of motion, and that the civilised and adult man, who is versed in a knowledge of life, is capable of deciding easily in any given case between the living and the lifeless. But this is not always true. For example, are dried grains living or lifeless ? Is a lentil that has lain unchanged in a chest for years living ? Scientific men themselves are not agreed upon this point. The lentil, when dry, does not show phenomena of life, but, if placed in moist earth, it can at any moment be induced to do so. It then sprouts and grows into a plant. The decision between the living and the lifeless becomes, how- ever, much more difficult with objects that are not commonly seen in daily life, e.g., certain microscopic things. Long observation and very detailed investigation are frequently required in order to> determine whether certain bodies that are found in a liquid by microscopic examination are living or not. If a drop of the dregs be taken from a bottle of weissbeer and examined with the micro- scope, it will be found that the liquid contains innumerable small pale globules, often clinging together in groups of two or three,, completely at rest so long as they are observed, and showing no trace of movement or other change. Very similar small globules, may be observed with a microscope in a drop of milk. The two kinds of globules can be distinguished from one another by strong magnifying powers only. No trace of vital phenomena can be found in either by the most patient and continued microscopic examination, yet the two objects are as widely different as a living organism and a lifeless substance ; for the globules from the beer are the so-called yeast-cells (Saccharomyces cerevisicz), the active agent in the fermentation of the beer and fully developed, unicellular, living organisms, while the globules from the milk are lifeless; droplets of fat, which, by their abundant presence and their reflec- tion of light from all sides, give to the milk its white colour. As a counterpart to these two objects, we may consider a third. In the body-cavity of the frog on either side of the spinal column between the transverse processes of the vertebrae there lie small y yellowish-white masses. If a bit of the contents of one of these be removed with a knife and placed with a drop of water upon a slide, and the whole be covered with a cover-glass, there may be seen with strong powers of the microscope a mass of minute granules and short rods of different sizes, which are trembling and dancing in constant motion, the smaller particles very actively, the larger ones more slowly. Every untrained person, brought before these three preparations and asked which of the three objects- METHODS OF PHYSIOLOGICAL RESEARCH 5 appears to him living and which lifeless, would invariably pronounce the yeast-cells and the fat-droplets lifeless, the dancing granules living ; but the latter are nothing more than minute calcareous •crystals, so light that they are put into trembling motion passively by the excessively delicate motion that the particles of every liquid possess. The manifestation of motion, which, because we see no external source, we are inclined to ascribe to an internal cause, here misleads to the assumption of life. Such examples may be found in unlimited number. Hence, under certain circumstances it is not at all easy to dis- tinguish the living from the lifeless, and it is accordingly clear that the first duty of physiology must be to inquire after the criteria of such a distinction, i.e., mentally to circumscribe the :subject-matter, life, in relation to non-living nature. Not less great are the difficulties that we meet when we •consider the second idea that is included in the task of physio- logy, that of investigation. What is meant by investigation or •explanation ? Civilised man appears to be distinguished essentially from primitive races by a great desire, namely, that of seeking after the •causes of phenomena, or, in other words, a craving for causality. This longing in all things to ask " why," from a pure desire for knowledge apart from any practical aim, appears to be an acquisi- tion of civilisation, and its origin and development can be seen clearly in children of a certain age. When we have discovered a cause for any phenomenon, the craving for causality in that respect is satisfied ; we have investigated and explained the phenomenon. This is true of investigation in all departments of science, of historical and philological science as well as that of nature, in so far as the development of the science has progressed beyond the .stage characterised by the mere accumulation of facts. But when we have discovered the immediate cause of any phenomenon, we have satisfied the craving for causality only relatively, for the cause itself is a phenomenon that must be explained. Thus gradually and systematically we put individual phenomena and series of phenomena into causal connection with one another, and constantly reduce larger and larger groups to their causes. Ultimately, how- ever, the question arises how far this reduction may be carried .successfully. Is there a final cause for the phenomena, or may the reduction be continued to infinity ? In all fields of non-living nature, especially in physics and chemistry, investigation has shown that all phenomena thus far known and investigated may be reduced in the last instance to a single common cause, namely, the movement of very small material elements. The whole physical world is conceived as consisting of separate, indivisible, extremely small, elementary particles called 6 GENERAL PBYSIOLOGY atoms, and the various motions of the atoms, which fill universal space, are regarded as producing all phenomena in nature. If it be the task of physiology to explain the occurrence of vital phenomena, i.e., to investigate their causes, it then becomes a question whether, in living nature likewise, all phenomena can be reduced to the motions of atoms, or whether it is necessary to take refuge in another principle. Next to determining the boundaries of the field of investigation, the chief task of physiology lies in answering this question. Since early times mankind has been conscious of the great gap that exists between two groups of vital phenomena, the physical and the mental. Hence the above question is a double one. If it be possible actually to reduce the physical phenomena of life to the same elementary causes as the phenomena of the lifeless world, the result will not necessarily hold good for psychical phenomena, and the relations between the physical and the psychical must be analysed. If it be impossible to trace psychical phenomena to the same ultimate cause as the events of the physical world, another explanation must be sought, and the important question will then arise whether psychical phenomena can be explained at all. But if it be allowed that they can be brought into causal relations with the phenomena of the physical world, the question will still remain. What are atoms ? The question of the possibility of answering this will then arise. If it can be answered, will our craving for causality then be satisfied ? The investigation of life is thus confronted with a multitude of questions, which tax to the uttermost the capabilities of the human mind. II. THE HISTORY OF PHYSIOLOGICAL RESEARCH1 An examination of the history of physiological research is not only interesting, but important for a correct judgment of the present condition of physiology and the future course which it has to take in order to accomplish its established purpose. A. THE EARLIEST TIMES The earliest traces of naive physiological ideas are lost in the impenetrable obscurity of prehistoric times. A picture of them has been handed down in the mythology of the early civilised races. This represents .a condition in which all knowledge and all formation of ideas are grouped about the veneration of higher 1 The account of the earlier epochs in the development of physiology is based upon the following works : K. Sprengel, Versuch einer pragmatischen Geschichte der Arzneikunde ; H. Haeser, Lehrbuch der Geschichte der Medicin. In his Elemente der allgemeinen Physiologic, Preyer gives a short sketch of the history of physiology based upon the latter book. METHODS OF PHYSIOLOGICAL RESEARCH 7 beings. The primitive worship of the early races and the know- ledge associated with it may be regarded as an indivisible whole, from which, in the course of the hundreds and thousands of years, theological, philosophical, scientific, and medical conceptions gradu- ally and slowly have been crystallised out as independent groups of ideas. The early notions of life were very naive and crude. All that moved was living and was endowed with mind. The property of motion was the criterion of life. Wind, water, fire and stars were personi- fied. Meteorites which moved through the air, called " bsetyli," were regarded by the Phoenicians as endowed with mind, and were believed to be healing, while Susruta, the author of the Yajurveda, the most ancient Indian work upon the art of healing, represented all motile bodies as living, in distinction from non- motile, or lifeless, bodies. The art of healing, which was almost wholly a doctrine of drugs, and in primitive ages was developed especially upon the Pontus, where witchcraft flourished and where Hecate was reverenced, was crudely empirical, was in league with magic and mystery, and wholly lacked a physiological basis. In these earliest times only one class of phenomena received detailed consideration, namely, the higher psychical phenomena, which reveal man's life most directly to himself. A doctrine of the mind was developed even in ancient Egypt, probably under Indian influence, which had for its basis the dualism of body and mind, and reached its culmination in the idea of the passage of the mind after the death of the body into other bodies. Later, this notion was transplanted to Greece by the Greek philosophers, especially Pythagoras. In general, from the earliest times onward, the phenomena of mental life served as a peculiar stimulus for priests and philosophers, the earliest theorisers, and in antiquity, of all fields of investigation, psychology was cultivated the most. While physiological notions were scarcely influenced by medicine until long after Hippocrates, in Greece they were enriched in a significant manner by the first blooming of philosophy as a distinct discipline independent of the priesthood. The oldest Greek philosophers, the Ionic " physiologists," the Eleatics, as well as the Atomists and the independent thinkers of the same time, whose aim was the development of a cosmology, were forced in the pursuit of this aim to reflect upon the origin of living nature. Whatever judgment may be passed upon the unbridled character of the specu- lations of these ancient thinkers, the correctness of their notions regarding many of the phenomena of life will always remain a very surprising fact. Among many of these early philosophers it is singular to meet with ideas which, after more than two thousand years, have again become current and are reckoned among the most important foundations of the present science of life. This is par- ticularly true of opinions concerning the origin and development of 8 GENERAL PHYSIOLOGY the organic world. The notion of the derivation of man from animal- like ancestors originally inhabiting the water, is found clearly ex- pressed by Anaximander (b. about 620 B.C.); and Heraclitus (about 500 B.C.) had an idea of the significance of the struggle for existence (epts). But the theory of Empedocles (b. 504 B.C.) upon the origin of living things is the clearest and most surprising. According to him, plants appeared first, then the lower animals, and from them the higher animals and, finally, men were developed by a process of perfection. The effective principle in this perfecting process he perceived in the fact that ill-adapted individuals are destroyed in the struggle for life, while those that are capable of living produce offspring. Almost twenty-five hundred years elapsed before this simple conception of the descent and natural selection of organisms, clearly expressed by Empedocles, was empirically grounded by Darwin and was established as the natural explanation of the otherwise marvellous multiplicity of organic forms. Many ideas, more or less correct, regarding special physiological phenomena are found also among the early Greek philosophers. But these scattered truths are mingled with so many fantastic and purely arbitrary notions that, from their associations, they lose their real value. No coherent, systematic observations or reflections concerning vital phenomena exist before Aristotle. From the side of practical medicine, likewise, the investigation of life experienced no considerable advance, even when medical art, hitherto without a critic, was placed by Hippocrates (460-377 B.c.) upon a sound basis. A physiological doctrine appeared first among the followers of Hippocrates, probably under the influence of Plato's philosophy, and it was soon perfected and controlled all the medical ideas of that time. This is the doctrine of the spirits (trvevfia), in the main thought of which can be found the first germ of a fundamental physiological truth. This doctrine asserts that the pneuma, an excessively subtile material agent, is attracted by the human lungs, passes from the lungs into the blood, and is distributed by the latter throughout the body. All vital phenomena depend upon the action of this agent. This conception, which, naturally, was adorned with all sorts of absurd accompaniments, suggests strongly our modern ideas concerning the role of oxygen in the organism. B. THE PERIOD OF GALEN The first intimation of an attempt to explain vital phenomena appears in the early Hippocratic doctrine of the pneuma. This was expanded, especially in the Alexandrian school, by Herophilus (about 300 B.C.) and Erasistratus (d. 280 B.C.), the latter of whom distinguished a 7rvev/j,a ^COTIKOV (vital spirits) in the heart and a (animal spirits) in the brain. From this it is METHODS OF PHYSIOLOGICAL RESEARCH 9 evident that the problem of physiology, the explanation of vital phenomena, had already begun more or less clearly to be recog- nised. Hitherto, individual physiological facts had been observed, and physiological questions had been discussed incidentally. But now, the more clearly the problem of physiology began to be formulated, the more the treatment of physiological questions began to assume the character of scientific investigation. Aristotle (384-322 B.C.), the great polyhistor of antiquity, estab- lished the preliminary conditions for this advance by accumulating .a vast mass of material in the form of facts. The significance of Aristotle's relation to physiology does not lie in explaining vital phenomena — very often his explanations are uncritical, and, more- over, they do not appear prominent in his work — but rather in observing and recording a great number of physiological phenomena. In the midst of this material by the side of striking and acute researches, there occurs, as might have been expected, much erroneous observation ; such, for example, is the origin of eels and frogs from mud by spontaneous generation. Nevertheless, his recorded observations form the basis of the new stage of develop- ment into which physiology passed after Aristotle, and which is •characterised by the clear recognition of the physiological problem and its vast importance in practical medicine. After Aristotle, by his systematising work, had laid a broad empirical foundation for natural science, the doctrine of the pneuma received a wider extension among the later pneumatic physicians, especially through the efforts of Athenaeus and Aretaeus (both about 50 A.D.). It is in the nature of this doctrine, that it must endeavour to comprehend and explain the phenomena of life from a single point of view ; and, accordingly, we find now for the first time a clear, conscious recognition of the physiological problem and a systematic comprehension of physio- logical phenomena. The man who first clearly perceived the nature and significance of physiology was Galen (131 — about 200 A.D.). Galen saw that practical medicine could not thrive unless it were based upon a very detailed knowledge of the normal vital phenomena of the human body. The investigation of the vital functions of the body must be the first pre-requisite of an art of healing. This practical aim was the first incentive to the develop- ment of physiology, and controlled the science almost exclusively until the eighteenth century. Galen was also the first to recognise clearly the importance of a knowledge of the anatomy of the body in an understanding of the functions of its parts, and laid great value upon the dissection of animals ; he himself dissected pigs and monkeys especially. Moreover, he perceived the im- portance of animal experimentation in the investigation of physio- logical phenomena ; and, although the experimental method did not assume under him that exact form and that fundamental 10 GENERAL PHYSIOLOGY % importance which many centuries later Harvey knew how to give it, Galen himself practised vivisection upon pigs and monkeys. Along with general recognition of his immortal service, Galen has often been reproached with the charge that he was not content with collecting physiological facts, making observations and devis- ing experiments, but that he felt strongly the necessity of arrang- ing his collected material into a complete and comprehensive system of physiology, in which he allowed hypothesis and philo- sophical speculation a place that exact investigation ought to have filled. Nothing can be more unjust than this reproach. If Galen had been satisfied with ascertaining disconnected physio- logical facts, physiology and with it all medicine would not have been advanced one step farther than Aristotle had already brought them. Galen's greatest importance lies in the union of scraps of physiological knowledge into a coherent system. Isolated observations obtain value only in connection with other facts, and only a survey of the relations of facts makes possible further systematic progress. It is only natural that, in this first attempt to put together the material of physiological observation into a coherent picture of the life of the human body, recourse must now and then be had to hypothesis, even much bold hypothesis. The single fault from which Galen's system suffers is not its binding cement of philosophical speculation, but the peculiar dualism that misled him, in accordance with which, in explaining vital phenomena, he strove to give at the same time a place both to the rigid idea of necessity, which sprang from his exact scientific investigations, and to teleology, which was derived from the Aristotelian philosophy. Nevertheless, in a just estimation of his time, when Aristotelian ideas had already begun a universal sway that was to last more than a thousand years, Galen can scarcely be reproached for this, the less when it is recalled that the teleological idea of a final purpose in all things appears here and there in modern natural science even to-day, quite independent of philosophy. Galen's system is based upon the doctrine of the spirits (pneuma). The causes of all the vital phenomena of the human body, which is composed of the four fundamental juices, viz. : the blood, the phlegm, the yellow and the black gall, are the three different forms of spirits, of which the animal spirits (irvevfjia ^V^LKOV) have their seat in the brain and the nerves, the vital spirits (irvevfjua fari/cov) in the heart, and the natural spirits (Trvev/jia (frvo-i/cov) in the liver. These three forms, which must be regenerated continually by the receipt of vital spirits from the air, are the agencies that maintain the functions of the respective organs. The body possesses many functions, but they may be arranged, according to the forms of the spirits, into three classes, and each function is carried on by a faculty (SiW/zt?) corresponding to its respective METHODS OF PHYSIOLOGICAL RESEARCH 11 pneuma. The psychical (animal) functions comprise thinking, feel- ing, and voluntary motion ; the sphygmical (vital) functions, the heart-beat, the pulse, and the production of heat ; the physical (natural) functions, nutrition, growth, secretion, and reproduction with its related activities. The blood is formed in the liver, and the veins arise there. Through the veins the blood goes to the right ventricle of the heart, where the useful part is separated from the useless ; the former is carried to the left ventricle, while the latter goes through the pulmonary artery to the lungs. In the lungs, the useless part is regenerated by the spirits and made useful. It is remarkable with what prophetic gift Galen pointed to a constituent of the air as the spirits, the nature of which he could not yet divine. He expresses clearly the supposition that it will be possible at some time to isolate that constituent of the air that forms the spirits. More than fifteen hundred years elapsed before Galen's supposition was confirmed by the discovery of oxygen by Priestley and Lavoisier. The blood, regenerated by the receipt of spirits in the lungs, flows through the pulmonary veins into the left heart, whence, together with the rest of the useful blood, it is carried by the aorta and its branches throughout the whole body. Galen's views upon the nervous system are equally interesting. In the brain and the spinal cord are the origins of the sensory and the motor activities of the nerves. The motor nerves act by pulling like a string upon the motor organs. In the special physiology of nerves, Galen investigated particularly the action of the vagus and the intercostal nerves upon respiration and the action of the heart, and he cut the spinal cord transversely and longitudinally — experiments which show how deeply he had penetrated into an understanding of the mutual relations of the individual organs of the body. Galen's physiological system was for that time a monumental work, and the fact that Galen's views continued for thirteen hundred years as the unassailable code of medicine is surely not to be ascribed simply to the decay of the ancient culture and to the complete barrenness of the middle ages in scientific matters. The development of physiological investigation took not a single step forward during the middle ages. The Arabians, who had come to possess the ancient culture, were, indeed, prominent as physicians, but Islam forbade them alike independent investigation and philosophical thought. Even Avicenna (Ibn Sina, 980-1037), who was the most prominent of the Arabian physicians and showed philosophical tendencies, performed no original work. With slight changes his system was the system of Galen, whose glory he obscured by his own powerful authority in the civilised world of that time. Moreover, the many famous medical schools which arose at that time in Italy, France, and Spain trained many able physicians, but did not advance beyond Galen's ideas, not- 12 GENERAL PHYSIOLOGY withstanding the fact that here and there an isolated physiological observation was made. This condition of stagnation continued until into the sixteenth century. C. THE PERIOD OF HARVEY An independent advance in physiology is first met with in the •sixteenth century. One of the first to abandon Galen's system was Paracelsus (1493-1541), who developed a complete system of nature. It was permeated with theosophical notions, a tendency that appeared still stronger in his followers and drove them wholly over to mysticism. Nevertheless, it contained many original, although frequently absurd, ideas. Paracelsus opposed the weak echoes of Galen's system and its outgrowths which had appeared during the middle ages, and this was at that time an important advance. The foundation of his system is the unity of nature. Nature is a unit, the macrocosm. In man as the centre of nature all forms of existence are contained. Hence, man is to be regarded as a microcosm. Nature, however, must not be considered as com- plete but as for ever becoming. The more special aspects of his system are arbitrary and unimportant, and, as is usual in such cases, this first beginning of independent investigation was com- paratively crude ; before all other things it lacked a purely empirical and experimental basis. At the same time, in France and in Italy a freer tendency began to appear in the medical schools. Fernelius (1497-1558) had many new ideas, although they were based wholly upon Galen's system. From the various forms of Galen's pneuma he separated the anima. The former consists of the most subtile material .substance ; the latter is the soul, which is to be recognised only by its effects. He advanced the further idea that the pheno- mena within the organism depend finally upon certain mysterious causes. Special physiological investigation received an impulse from the great anatomical discoveries in the schools of France and Italy, where knowledge of the anatomy of the human body was placed upon a wholly new and strictly empirical basis by Vesalius, Eustachio, Faloppio, arid others. Researches upon the structure of the heart and the course of the vessels were the most fruitful for physiology. The doctrine of the circulation of the blood, as founded by Galen, underwent fundamental changes. By proving the imperviousness of the interventricular septum, Serveto •(1511-1553) refuted Galen's idea that the blood goes from the right ventricle of the heart directly into the left ventricle. His followers, Colombo (d. 1559) and Cesalpino (1519-1603), added to this new facts upon the circulation of the blood in the lungs ; and Argentieri (1513-1572), who opposed the doctrine of the animal METHODS OF PHYSIOLOGICAL RESEARCH 13 spirits, and happily thought to put in its place heat as the cause of vital phenomena, emphasized the fact that the nutrition of the whole body is provided for by the blood alone. By these special investigations into the physiology of the blood, the path was made easy to the greatest discovery of this period, that of the circulation of the blood by Harvey (1578-1657). The importance of Harvey's discovery lies in the fact that he first established the physiological connection of the arteries and veins peripherally, and the passage of the blood from the arteries into the venous trunks and thence to the heart ; he thus laid a basis for the fact that all the blood passes through the heart and moves in a closed circuit through the whole body. He added to this a great number of special facts concerning the mechanism of the circulation, all of which — and herein lies the great significance of his work — rested upon keen observation and an exact experimental basis. Following the exact tendencies of his time — the time which brought forth also a Copernicus, a Galileo, a Bacon, and a Descartes — Harvey, by his brilliant discovery, raised the experimental method again to an honourable position in physiology, after it had remained in complete oblivion for thirteen centuries. The spirit of the conscientious investigator and great logical acuteness characterise Harvey's personality and stamp him as the first real physiologist after the long night of the middle ages. A second doctrine " de generatione animalium" stands with equal honour by the side of his doctrine of the circulation of the blood. In this he put forward the dictum, " omne vivum ex ovo" which has since obtained vast significance in the science of life, and in the various forms in which it has been ex- pressed in recent times controls all modern physiological views of organic reproduction. Of the adherents of the great theosophical school which Para- celsus instituted, one only is important in the history of physiology, namely, van Helmont (1577-1644), since, in spite of the mysticism that characterised the whole theosophical tendency, he made thoroughly accurate observations. Starting with the Paracelsian doctrine of the unity and the constant development of nature, he conceived all natural bodies to be composed of matter and " archeus " (energy). Things exist and live only in this combination. As a result of it, all things are living. There are, however, different grades of life, and the so-called lifeless bodies exist at the lowest grade. Among van Helmont's special physiological ideas, his chemical doctrine of ferments is especially interesting. He rejects Galen's idea that digestion goes on in the stomach through the action of heat, and puts in its place the correct conception, that digestion is performed by a " ferment " associated with the gastric juice. The philosophical systems of Francis Bacon (1561-1626) and Descartes (1596-1650) exercised a great influence upon the further 14 GENERAL PHYSIOLOGY • development of physiology. Bacon's monistic philosophy, which, because of its vigorous accentuation of the inductive method of investigation, has become the basis of all modern natural science, inaugurated the great series of new and exact physiological ob- servations, founded upon experiment, which has continued from that time to enrich our knowledge of vital phenomena. The philosophy of Descartes, although purely dualistic, was full of importance for the physiology of the senses and the theory of knowledge, because of the theory of sense-perception which formed its starting-point. Descartes was the first to maintain the pro- position that the only thing in the universe of which we have certain knowledge is subjective psychical sensation. Mind, sensa- tion, thought, is the only fixed point from which the universe can be surveyed and discovery proceed. " Cogito, ergo sum!' Sense- perception, therefore, gives us no information concerning things, for it is deceptive ; and things, i.e., bodies, are in reality wholly different from what they appear through our sense-organs to be. These propositions are capable of the widest application. Further, they are so well grounded and so precisely and clearly expressed, and give so admirable a basis for a philosophical system, that one must wonder how it is possible for Descartes, who was usually a clear and consistent thinker, to be so inconsistent as to arrive finally at the complete dualism of body and mind. It is a tempta- tion to believe that he maintained ultimate consistency secretly ; but that, for practical reasons, he allowed the pressure of the ecclesiastical conditions of his time to give this unexpected turn to his philosophy, while content with the feeling that the un- predjudiced thinker would note and correct the evident incongruity. Of the greatest physiological importance, however, is his clear dis- cernment in his dualism that the bodies of animals and men act wholly like machines and move in accordance with purely mechanical laws. But here again dualism comes in as a disturbing element, for Descartes ascribes the impulse to all movement to the soul, which, from its seat in the only unpaired organ of the brain, the pituitary gland, controls the individual parts of the body. Nevertheless, the general physiological ideas of Descartes have been of great value to physiology, and the gifted thinker also made many very important special physiological observations, which markedly advanced our knowledge of physiological optics and acoustics. Descartes' notion that, as regards its vital activities, the human body is to be regarded as a complicated machine, was especially fruitful for physiology in the ingenious application which Borelli (1608-1679) made of it in the science of animal movement. Borelli undertook for the first time to reduce the movements of the organic motor apparatus to purely physical principles, and thus laid the foundation of our present mechanics of animal motion. METHODS OF PHYSIOLOGICAL RESEARCH 15 The chief result of this undertaking found expression in the inauguration of a peculiar school founded upon Borelli's doctrine, the iatromechanical school (called also iatrophysical and iatromathe- matical), which played a considerable role in the further develop- ment of physiology, since it endeavoured to explain other vital phenomena of the animal body upon purely physical principles. At the same time, some of Borelli's followers, especially Glisson, by regarding contractility as a property residing within muscle- substance itself, became the precursors of the later doctrine of the irritability of muscle. Almost contemporaneous with the founding of the iatrophysical .school there arose another school, the iatrochemical, which for a time flourished by the side of the former. Its founder was Sylvius (1614-1672). Dissatisfied with the narrowness of the iatro- physicists, but recognising the importance of their principle in •explaining vital phenomena, Sylvius emphasized the chemical side in addition to the physical, and in accordance with this elaborated •chiefly the physiology of digestion and respiration by extending van Helmont's doctrine of the ferments. In the theory of respira- tion also, Mayow (1645-1679) expressed very pertinent thoughts upon the analogy between respiration and combustion. At this time physiology derived considerable assistance, the value of wtjich for physiological investigation, however, has not been completely taken advantage of even to the present day, from the invention of the compound microscope and the microscopic discoveries made by means of it by Leeuwenhoek (1632-1723), Malpighi (1628-1694) and Swammerdamm (1637-1685). The knowledge of the physiology of reproduction and development, more than all else, was thus markedly advanced. The first micro- scopic discoveries in this field naturally led to many excusable •errors. When, for example, aqueous infusions of decomposable sub- stances were made and the appearance of Infusoria in immense numbers was observed in them, spontaneous generation from lifeless substances was believed to have taken place, contrary to Harvey's dictum, " omne vivum ex ovo," but in accordance with Aristotle's •earlier assumption even for higher animals. On the other hand, Harvey's dictum became the starting-point of important discoveries ; for Malpighi followed the development of ova with the microscope, while Leeuwenhoek's pupil, Ludwig van Hammen, discovered spermatozoa, the importance of which Leeuwenhoek immediately recognised. These and a great number of special physiological discoveries which active investigation brought forth give to the period of the seventeenth and eighteenth centuries after Harvey's appearance the character of the dawn of exact investigation in physiology, just as the influence of exact methods pervaded and animated all science of that period. Yet, as is constantly happen- 16 GENERAL PHYSIOLOGY ing in the history of science, systems appeared at that time as evidence of a reaction against excessive specialisation, which fell into the opposite extreme of lacking all exact foundation and resting upon pure speculation. Boerhaave (1668-1738) skilfully avoided this pitfall in his eclectic system, which was put together from the various dogmas of his time and assumed as the source of all vital phenomena a "principiwni nervosum " in the form of a very subtile fluid. But the systems of Hoffmann (1660-1742) and of Stahl (1660-1734) did not escape it. Hoffmann's "mechanico- dynamical " system is purely teleological. and arose under the influence of the philosophy of Leibnitz. Hoffmann regarded the ether as the ultimate cause of all vital phenomena ; its movement follows mechanical principles, but it receives its immediate impulse from the idea of the purpose of its own existence, that resides in every ether-atom. But Stahl's " animistic system," which com- bated Hoffman's doctrines, rests still more upon a speculative basis. At the foundation of Stahl's system there lies a dualism of body and mind, according to which the body in its activities follows mechanical laws, but is animated and preserved from decay and destruction by the " anima." Upon the nature of the anima Stahl expresses himself in very uncertain and contradictory terms. In spite of its unsupported speculations and its many contradictions,, animism obtained numerous adherents, which may be explained by the facts that the innumerable details acquired by the many special researches of the period were not properly sifted, and there was. no coherent understanding of vital phenomena. D. THE PERIOD OF HALLER Haller (1708-1777) responded in a genuinely scientific manner to the need of a unitary arrangement of the details, and, as it had once been with Galen and, later, with Harvey, a new epoch in the development of physiological investigation dates from his appear- ance. As Galen had first recognised the practical significance of physiology and had made the knowledge of vital phenomena the basis of practical medicine, and as Harvey by the introduction of exact experimental investigation had created the fruitful method, the employment of which in the sixteenth and seventeenth centuries called forth the enormous mass of individnal discoveries, so Haller for the first time brought together as a whole all the extensive material of facts and theories in his " Memento, physiologiac corporis humani." He thus made physiology an independent science, which was not simply to serve practical purposes in the interest of the art of healing but also to pursue purely theoretical aims for itself alone. In this circumstance lies Haller's great importance in the development of physiology. The grouping of a heterogeneous- METHODS OF PHYSIOLOGICAL RESEARCH 17 mass of facts into a closed and intelligible whole is always stimulating and fruitful, and this explains the immense authority and powerful influence which Haller exercised in the develop- ment of physiological investigation. His own physiological re- searches, however, while very conscientious and exact, as, e.g., those upon the respiratory movements and the theory of irritability, contain no epoch-making discoveries, and some of them even had the misfortune to play an obstructive role in the further develop- ment of the science. This is especially true of two doctrines which he advocated — the so-called theory of preformation, and the theory of irritability. The theory of preformation (theory of incasement) arose in connection with the microscopic observations upon the development of the ovum which were made in the seventeenth century. When it was seen how from a single small egg a complete animal was developed by the gradual maturing of one organ after another, the idea arose that all organs appearing in the course of development and, in brief, the whole animal, are preformed or already enclosed as such within the egg, and are made visible to the eye only by a process of growth and unfolding ; that, therefore, the human egg or, as some believed, the spermatozoon, is a minute but a completely formed homunculus. The necessary consequence of this idea was the assumption that at the creation of the world all coming generations were contained, already preformed, in the egg of each animal. The preposterousness of this view led a young physician, Caspar Friedrich Wolff (1733-1794) to maintain a new theory in opposition to that of preformation. Wolff's " theoria generationis" which later became the basis of all our modern ideas of the development of organisms, denied incasement and put in its place epigenesis. This asserted that all organs of the body are formed one after another in the course of development, in other words, that they originate as entirely new parts and have never pre-existed as such in the egg. Haller could not accept the idea of epigenesis, but opposed it energetically ; and, supporting the dogma of pre- formation with his whole authority, he retarded progress in the doctrine of animal development for more than half a century. Haller's theory of irritability influenced the development of physi- ology in a somewhat different manner. Haller's own researches in this direction were experimental and very exact, and materially advanced the general theory of irritability ; but they were mis- interpreted in various respects and extended by his followers, and formed the chief starting-point of a doctrine that confused all physiology down to the middle of the present century, and even now emerges again here and there in varied form. This is the doctrine of vital force. The fact of the irritability, or the direct excitability, of muscles had been emphasized by the earlier iatro- physicists, especially by Glisson (1597-1677). Haller took up the 18 GENERAL PHYSIOLOGY question, and added the experimental proof of the fact that the muscle-fibre possesses the property of contracting upon stimula- tion independently of nervous influence, a quality which he sharply distinguished as irritability from the sensibility belonging to nerves. This sharp distinction affirmed a difference between the excitation of nerve and that of muscle which did not correspond wholly to reality, and awoke in many of Haller's adherents and followers the need of demonstrating irritability to be a uniform phenomenon. This was attempted most successfully by an Englishman, John Brown (1735-1788), a gifted but careless thinker. Brown recog- nised in general a single excitability common to the nervous and muscular system, which system he regarded as a unit. The ca- pacity of becoming excited by stimuli is possessed by all living nature, and is, indeed, the fundamental characteristic by which living beings, animals and plants, are distinguished from lifeless. Regarding the nature of excitability, Brown, like all other physi- ologists of the time, had little to say. The hopes of the iatromechanics and iatrochemists of being able completely to resolve vital phenomena into physics and chemistry were not fulfilled. In irritability there existed a phenomenon which, as was believed, distinguished all organisms from lifeless bodies, and appeared to mock at a physico-chemical explanation. The unexplained conception of irritability, therefore, in union with the dynamical systems of Hoffmann and Stahl still prevailing, became the starting-point of vitalism or the doctrine of vital force, which in its most complete form asserted a distinct dualism of living and lifeless nature. This tneory appeared first in France, especially in the School of Montpellier, and later in Germany, and its hazy notions of vital force soon controlled all physiology. In France vitalism was founded by Bordeu (1722-1766), developed further by Barthez (1734-1806) and Chaussier (1746-1828), and formulated most distinctly by Louis Dumas (1765-1813). The vitalists soon laid aside more or less completely mechanical and chemical explanations of vital phenomena, and introduced, as an explanatory principle, an all-controlling, unknown and in- scrutable "force hyper me'chanique." While chemical and physical forces are responsible for all phenomena in lifeless bodies, in living organisms this special force induces and rules all vital actions. In Germany vitalism did riot reach this degree of clearness. Its founder, Reil (1759-1813), differed from the French vitalists, and in his treatise " Ueber die Lebenskraft " expressed fairly clearly the view that the phenomena of living organisms are chemico-physical in nature, but that principles are at the same time in control which are conditioned exclusively in organisms by the characteristic form and composition of living substance. Later vitalists, however, attempted no analysis of vital force ; they employed it in a wholly mystical form as a convenient explanation of all sorts of vital phe- METHODS OF PHYSIOLOGICAL RESEARCH 19 nomena, and they distinguished several varieties. The " nisus formatiwis" e.g., or peculiar " formative effort," offered a simple explanation of the forms of organisms, accounting for the facts that from the egg of a fowl a fowl and no other species always developed, and that the offspring of dogs are always dogs. In place of a real explanation a simple phrase, such as " formative effort," or " vital force," was satisfactory, and signified a mystical force belonging to organisms only. Thus it was easy to " explain "the most complex vital phenomena. But some investigators were not content with this kind of explanation, and, while indifferent to the doctrine of vital force, continued to search for a chemico-physical explanation of vital phenomena. They received a strong stimulus from the new discoveries of Galvani (1737-1798), who proved that electricity is produced by the living animal body, especially by the nerves. Naturally the value of this fact was very soon overestimated, and under the ban of the prevalent philosophy of nature, particularly as a result of the researches of Ritter (1776-1810) and partly also those of Alexander von Humboldt (1769-1859) and others, who extended Galvani's experiments, the idea arose and later became very popular, that the galvanic current is the cause of all vital phenomena, and even that all phenomena of all nature may be explained in general by galvanic polarity. The great chemical discoveries of the previous century also influenced the development of physiology. Vegetable physiology was especially advanced by Ingenhouss (1730-1799), who developed the theory of the consumption of carbonic acid by plants. The discovery of oxygen by Priestley (1733-1804) and Lavoisier (1743- 1794), which was so momentous for physiology, bore its first fruits when Girtanner (1760-1800) showed that venous blood receives oxygen in the lungs from the inspired air. Thus the old doctrine of the pneumu, which controlled physiological ideas for centuries, was justified in modern form, and at the same time the ingenious idea of Mayow, who had compared respiration to a process of com- bustion, was raised to the rank of a fundamental physiological fact. Besides the physical and chemical discoveries of that time, those in anatomy led also to important physiological results. Most prominent among these was the fundamental law of special nerve- physiology, announced by Charles Bell (1774-1842), and later proved experimentally by Johannes Miiller, which affirms that the posterior roots of the spinal nerves are sensory (conducting centripetally), while the anterior roots are motor (conducting centrifugally). Finally, in microscopy Spallanzani (1729-1799), and later especially Treviranus, obtained the distinction of having dis- proved experimentally by careful researches the theory of the c 2 20 GENERAL PHYSIOLOGY ^ spontaneous generation of animalcules in putrid infusions ; they snowed that these lowest of all living things develop only from germs which are to be found everywhere in the air and the water, and that even here Harvey's dictum " omne vivum ex ovo " admits of no exception. England and France produced the most of these exact researches, while in Germany the most prominent thinkers, such as Oken, were swept on by the philosophy of nature with its powerful tendency toward pure speculation in the fields of natural science. E. THE PERIOD OF JOHANNES MULLER Johannes Miiller 1 (1801-1858) is one of those monumental figures that the history of every science brings forth but once. They change the whole aspect of the field in which they work, and all later growth is influenced by their labours. Like the other investigators of his time Miiller was a vitalist, but his vitalism had an acceptable form. To him vital force was something different from the forces of lifeless nature, but its ad- ministration rigorously followed physico-chemical laws, so that his whole endeavour was to explain vital phenomena mechanically. In doing this he went over the whole field of vital activities uni- formly, neglecting no part, and by his own investigations, which were always original, he laid the foundations upon which we work to-day. He always kept his attention directed towards the whole ; he never undertook special investigations which would not help him to solve some large general problem. His ingenuity — and it is this that is so much missed in the more recent physiology — was expressed in the manner in which he attacked problems. He did not recognise one physiological method alone, but employed boldly every mode of treatment that the problem of the moment demanded. Physical, chemical, anatomical, zoological, microscopic and embryo- logical knowledge and methods equally were at his disposal, and he employed all of these whenever it was necessary for the accomplishment of his purpose at the time. The philosophy of nature experienced its most luxuriant growth during this time under the influence of the ideas of Schelling and Hegel, and with its unbridled speculation, which lacked all basis of fact, seriously threatened scientific investigation. But it exer- cised only the most beneficent effect upon the rigorously critical mind of Miiller. He recognised in the ambitious tendencies of the natural philosophers a germ of truth, and under its influence fashioned his own manner of scientific investigation into a genuinely philosophical type. While keeping constantly in view the large 1 The most important estimate of Johannes Miiller is to be found in the memorial address upon him given by du Bois-Reymond ('59). METHODS OF PHYSIOLOGICAL RESEARCH 21 problems and the goal of science, he regarded critically the special methods and questions only as means to an end, as means for arriv- ing at a harmonious comprehension of nature. Throughout his whole life he remained steadily true to this philosophical concep- tion of science, which he had set forth with energy in his inaugural address, " Von dem Bedurfniss der Physiologie nach einer philoso- p'kischen Naturbetrachtung" It is remarkable that, notwithstand- ing the unalloyed admiration aroused by the figure of Mtiller, the later physiology has often wholly neglected this element. This is particularly noticeable in two fields in which from his youth up he took the most active interest, — that of psychology, and that of com- parative physiology. Psychology is avoided by the physiology of to-day almost with fear, an attitude that is in peculiar contrast with that of Mtiller. He regarded physiology as essential to advance in psychology by empirical methods, and in his examination for the doctorate he defended the thesis, " Psychologies nemo nisi physiologus" Un- doubtedly, the science of psychology ought not to be considered as simply a part of physiology. But the achievements of physiology in the field of the nervous system and the sense-organs are of so fundamental significance for psychology, that it may be said that the former science is more nearly related than any other to the latter. Mtiller 's own labours show very clearly with what success physiology is capable of handling psychological problems, for scarcely any physiological discovery has a more important bearing upon all psychology and the theory of knowledge — although un- fortunately it is not generally appreciated — than the doctrine of the specific energy of the nerves or organs of the special senses. This doctrine affirms that different stimuli of whatever kind, when applied to the same sense-organ, e.g. the eye, are capable of calling forth only one and the same kind of sensation, namely, that sensa- tion that is mediated by the sense-organ in question under the influence of its natural stimulus, in the case of the eye, light. Vice versa, one and the same stimulus, when applied to different sense- organs, calls forth entirely different sensations according to the nature of the organ upon which it works. This doctrine is founded upon two fundamental facts: first, that in reality the external world is not what it appears to us to be when perceived through the spectacles of our sense-organs ; and, second, that by the path of our sense-organs we cannot arrive at an adequate knowledge of the world. Besides this fundamental proposition, however, Mtiller discovered many other important psychological facts, which he has presented in his works ; " Zur vergleichenden Physiologie des Gesichtssinnes des Menschen und der Thiere," " Ueber die phantastischen Gesichtserscheinungen" and the section " Vom Seelenleben " in his " Handbuch der Physiologie des Menschen!' Miiller's teacher Rudolphi had said : " Comparative anatomy is 22 GENERAL PHYSIOLOGY the surest support of physiology ; without it physiology is scarcely conceivable." Miiller was incited by this idea, and the result was the foundation of a wholly new science in his comparative physiology. Throughout his whole life he defended the position expressed in the words, " Physiology can be only comparative," and among the very large number of his physiological works there are few in which the comparative principle is not more or less clearly expressed. He presented the results of his own investigations together with practically all the physiological knowledge of his time in his " Handbuch der Physiologic des Menschen" This work stands to- day unsurpassed in the genuinely philosophical manner with which the material, swollen to vast proportions by innumerable special researches, was for the first time sifted and elaborated into a unitary picture of the mechanism within the living organism. In this respect the " Handbuch " is to-day not only unsurpassed, but unequalled. Naturally many of its details are incorrect according to present ideas ; later researches performed with a more perfect technique have greatly extended and transformed some depart- ments ; even many of Miiller 's general physiological ideas, such as that of vital force, have been completely abandoned by the later physiology ; nevertheless, it remains that of all the numerous hand- books that have since appeared none has reached that of the great master as regards the mode of dealing with the material. Most of the later Hand-books, Text-books, Elements, etc., although intended almost exclusively for the use of students, do not take the trouble to point out even briefly the aims, the problem and the purpose of physiological science, let alone giving to the matter as a whole a philosophical treatment in Mtiller's sense. Such a lack must be regarded as a serious detriment by thinking students who do not learn simply by rote. Only a very few text-books form an exception to this, as, e.g., Briicke's admirable " Vorlesungen uber Physiologic." The tireless physiological activity of Mtiller, which won for him the fame of being the greatest physiologist of all time, did not prevent him from giving himself up in the later years of his life with equal enthusiasm to morphology, especially zoology, com- parative anatomy, and paleontology, and of acquiring the name of the greatest morphologist of his time. So many-sided and comprehensive was he that by his own fundamental labours he mastered two large sciences, either one of which a single person is at present hardly able to survey unaided. It is no wonder that so large a realm could not be held together as a unit after the death of its ruler. Like Alexander's universal empire, it became divided into many small territories, each one of which controlled itself; and with the present boundary of science it would be difficult to find a worthy successor to Miiller, even METHODS OF PHYSIOLOGICAL RESEARCH 23 if he were endowed with the latter's superhuman power of labour. Morphology had become independent long before Mtiller. Soon after his death the course of physiology became divided and directed along purely chemical and purely physical paths. Movement in the chemical direction was guided by Wohler (1800-1882) and Liebig (1803-1873). In the year 1828 Wohler gave the theory of vital force its death-wound by his epoch-making synthesis,out of purely inorganic substances,of urea, a body produced in nature only by organisms. It had been believed that substances that were produced by the organism were produced only through the activity of vital force ; but here for the first time a very charac- teristic material product of the animal body was manufactured artificially in the chemical laboratory. This synthesis was soon followed by others. Justus von Liebig established new views regard- ing the metabolism of organisms ; and later Voit, Pfltiger, Zuntz, and others, advanced the theory of metabolism further, though not in entire agreement with one another. Physiological chemistry became more and more independent, partly under the influence of Mulder and Lehmann, who first made a survey of the field, and especially under that of Kuhiie, who by his original methods and investigations, particularly upon the chemico-physiological relations of the proteids, diffused new light and expressed his conception of the science in his text-book. Finally, most recently, through the labours of Hoppe-Seyler, Hammersten, Bunge, Halliburton, Baumann, Kossel, and others, physiological chemistry as an inde- pendent science has quite cut itself loose from physiology, to the detriment of the latter. E. H. Weber (1795-1878), Volkmann (1801-1877), Ludwig (1816-1895), Helmholtz (1821-1894), du Bois-Reymond (1818- 1896), Marey, and others, led the movement in the physical direc- tion. Ludwig mechanically transmitted the rhythmic changes of pressure of the pulse to a moving writing-lever, and made them record themselves upon the smooth surface of paper moved at a uniform rate (Fig. 1). He thus surpassed all others in creating a method of the greatest value in the investigation of the purely physical activities of the animal body. This graphic method proved so extremely fruitful that it found wide employment in physiology. It was used for the graphic representation of muscle-contraction, of respiratory movements, of the heart-beat, etc. In France, Marey developed it to unexpected completeness ; so that now it serves as the most important method of investigation in all researches that deal with the phenomena of macroscopic movement. One other method became fundamentally important in physical physiology, namely, that of the comprehensive and ingenious technique of galvanic stimulation, which was created by E. du Bois-Reymond's classic researches upon the general physics of muscle and nerve. 24 GENERAL PHYSIOLOGY By the perfection of this technique du Bois-Reymond made the galvanic current of all stimuli the most convenient to employ and H FIG. 1. — /. Lud wig's kymograph. One limb of the manometer is connected with an artery at A ; the blood-pressure is transmitted to the column of mercury (represented in black), thence to the float upon the mercury in the other limb, and puts this float with its writing-lever in motion. The writing-lever inscribes its movements upon the drum, C, which is kept in constant rotation by a clock-work, B. (From BrUcke). 11. Pulse-curve from a rabbit. The small waves represent the variations in blood-pressure that constitute the pulse ; the large waves, the variations that the blood-pressure undergoes as the result of respiration. the most capable of fine gradation and easy localisation for nerves and muscles; for these reasons it now holds the first place stimulation-experiments. in METHODS OF PHYSIOLOGICAL RESEARCH 25 The wide applicability of this ingenious physical method is due to the perfection of the technique of vivisection on the part of the great French physiologists, Magendie (1783-1855) and Claude Bernard (1813-1878). Claude Bernard guided operative physi- ology to its highest development, without at the same time becoming narrow. He was a philosophical investigator who in his researches kept in view the general problems of life. It is no wonder, there- fore, that all French physiology of to-day must be considered as of Claude Bernard's school. In comparison with the chemical and physical features of physi- ology, after Johannes Mliller's death other features receded into the background, or were entirely neglected. Psychological research was advanced especially by discoveries regarding the physiology of the sense-organs, in which the ingenious investigations of Helm- hoi tz and Hering led to most important results, and the physiology of the central nervous system of higher vertebrates, knowledge of which was perfected by the epoch-making labours of Flourens (1794-1864), Hitzig, Munk, Goltz, Horsley, and others. Preyer's endeavour to follow the development of the psychical phenomena of human beings through the early years of life has been followed by a few others. At first little attention was paid to the general questions of physiology. Lotze's Allgemeine Physiologic des korper- lichcn Lebens (1851) was purely speculative, and treated physio- logical questions from the standpoint of philosophy ; nevertheless, it necessarily would have proved a valuable stimulus to the experimental physiology of that time in the investigation of important questions, if in exact science interest in general problems had been greater. Although the striking works of Charles Robin, Chimie, anatomigue et physiologique (1853) and Anatomic et physiologic cellulaire (1873), presented a coherent summary of the anatomy and physiology of the cell, unfortunately they were little appreciated from the physiological side. So also the cell-pathological researches and ideas of Rudolf Virchow (Cellularpathologie, 1858), which quite overturned medical ideas, until very recently and in spite of their showing very clearly the enormous practical importance of general physiological researches upon the cell, have had scarcely the slightest influence upon the development of physiology, because the latter science was capti- vated by questions of a more special kind. More attention was excited by Claude Bernard's Lecons sur les phenomenes de la vie communs aux animaux et aux vegetanx (1878), which treated a number of general questions concerning life in a classic manner, although somewhat unequally. Preyer endeavoured to discuss the questions of general physiology more uniformly in his Elemente der allgemeincn Physiologic (1883), but unfortunately the book contains only a schematic summary of the subject. Finally, the researches of the histologists and the zoologists afforded many 26 GENERAL PHYSIOLOGY contributions to the physiology of the cell, and in our own time, from this side especially, the physiology of reproduction, fertili- sation, development, and heredity has been taken away from physiology proper, and developed into a fruitful and independent subject.1 The comparative method has not been employed in physiology since Johannes Miiller's time, unless the few researches that have been conducted upon other animals than the usual dogs, rabbits, and frogs are to be considered as comparative. Plant physiology, however, has developed quite independently into a nourishing science ; and the distinguished labours of Hofmeister, Nageli, Sachs, Pfeffer, Strasburger, Berthold, and others have made this in recent times the most complete branch of physiology. This is due partly to the fact that all vital relations are much simpler and more easily surveyed in plants than in animals, and partly to the fact that plant physiology has made use of certain acquisitions of science that have thus far found little or no application to the physiology of animals. There are three of the greatest discoveries of this century, from the further expansion of which physiology is justified in still expecting great results. One of these is the law of the conservation of energy, which was definitely expressed by Robert Mayer (1814-1878), and was estab- lished most comprehensively by Helmholtz. Modern chemical investigations had led to a recognition of the law of the conservation of matter, by showing that the quantity of matter, of atoms, in the universe is constant, and that the smallest atom cannot by any agency be destroyed or recreated. The law of the conservation of energy expresses the same fixedness for the sum of the energy of the universe. Energy, like matter, can be neither destroyed nor recreated ; when it seems to appear or disappear, it merely passes from one form into another. Among the recognised forms of energy two varieties are distinguished : energy of motion, or kinetic energy, when power is in action, i.e. is pro- ducing motion ; and energy of position, or potential energy, when it is latent but under certain conditions can come into action. Thus, e.g., the potential energy that was produced in the Carboniferous age by transformation of the kinetic energy of the sun's rays through the activity of plants and was stored up as chemical affinity in vast strata of coal, passes over into heat upon combustion of the coal. The heat is transformed by steam engines which are heated by the coal, into the energy of 1 Rdsumes of what has been accomplished in this field are given by the following books: Die, Zelle und die Gewebe, by O. Hertwig (1892) [authorised English trans- lation, The Cell: Outlines of General Anatomy and Physiology, 1895]; Gesammelte Abhandlungen iiber EntwicUungsmechanik, by W-. Roux (1895); La structure du protoplasma et les theories sur Vheredite, etc., by Yves Delage (1895) ; [and The Cell in Development and Inheritance, by E. B. Wilson (1896)]. METHODS OF PHYSIOLOGICAL RESEARCH 27 mechanical work, and this can be changed by means of a dynamo into electricity and be made to serve finally for the production of the electric light. Thus we perform daily the remarkable experi- ment of re-transforming, after millions of years, into its original form, the kinetic energy of the sun's rays which the plants of the Carboniferous age employed for storing up carbon, and thus illuminating our nights with the radiance of the sun that shone upon the surface of the earth in immemorial times (Cf. Bunge). The application of the law of the conservation of energy to the energetics of organisms was attempted by Robert Mayer, and has since been undertaken many times. By the calorimetric researches also of Dulong, Helmholtz, Rosenthal, Rubner, and others, the proof has been afforded experimentally that this law is as true in living nature as in lifeless. But our knowledge is extremely scanty concerning the mode of action of energy in the various performances of the body, concerning the transformations undergone by the energy in its path through the living substance. In this respect plant physiology, which is indebted especially to the striking researches of Pfeffer upon the energetics of the plant-cell for important discoveries and suggestions, is relatively farther advanced than animal physiology. In this subject of the energetics of living substance the future offers a wide field of labour, which is full of reward. The second of the great discoveries, which also has yielded chiefly to plant physiology its most important results, but has not yet been employed at its full value in the science of the physiology of animals, is the fact that organisms are composed of cells. The be- ginnings of the cell-theory are to be found in botanical studies. The microscopists of the seventeenth and eighteenth centuries, es- pecially Malpighi, Treviranus,Mohl,and Meyen found that plants are composed of small microscopic chambers, or cells, and elongated tubes which have liquid contents. The elongated tubes soon proved themselves to be structures that arise from series of cells by a dissolution of the transverse walls. Brown found next a more solid nucleus as a wide-spread structure in the liquid cell- contents. But Schleiden first put into general form the idea that all plants are composed of cells, and he distinguished as an essential constituent of the cell-contents, besides the cell-sap and nucleus, the semi-liquid motile plant-slime, which was termed by Mohl protoplasm. In the meantime the wide occurrence of cells in the animal kingdom had become recognised, and, soon after Schleiden, Schwann founded the cell-theory for the animal kingdom by showing that animals are composed of cells or cell-products, and in their development progress from forms that contain only a few similar cells. Later, embryology established the fact that in general all organisms are developed from a single cell, the egg- cell, into a cell-community which may become large and powerful, 28 GENERAL PHYSIOLOGY and in which the various parts, tissues, and organs consist of specific forms of cells. Although this knowledge carried with it the fact that the cell is the element of the living organism and the place where the life-processes occur, nevertheless, the cell, except in botany and embryology, has not yet been made a subject of special physiological study. We shall see presently that precisely in this direction is to be expected an essential advance in the physiology of the future. The third discovery, which thus far has not been fruitful in physiology, is that of descent in the organic world. The theory of descent, sketched in its outlines by Lamarck, and firmly founded by Darwin upon the principle of selection, has produced a great revolution in all morphological research, and impressed upon modern morphology its characteristic stamp. The theory shows that all the varied forms of organisms stand in genetic relation- ship to one another by descent, and that ultimately all have been derived from the simplest organisms. The theory of selection ascribes the enormous variety of forms to natural selection con- ditioned by the struggle for existence ; in this struggle only those individuals of a generation survive that are best adapted to existing external conditions — in other words, those that are best fitted to live. Thus, after an oblivion of more than two thousand years the ancient idea of Empedocles of the descent and gradual change of the organic world by selection has celebrated its resurrection in the present century by the empirical foundation - work of Darwin. Embryology, so far as it relates to the develop- ment of form in organisms, has flourished to an unexpected degree from the powerful stimulus given it as the result of Darwin's theory, especially by Haeckel and his pupils, but so far physiology has not availed itself of the evolution idea. The evolution of vital activities, the origin and development of the many functions possessed by the individual parts of the living body, is thus far almost a terra incognita. During the last few decades but one physiological problem of evolution, the problem of heredity, has been very actively discussed, and this almost exclusively from the zoological side. But the point has now been reached where experimental physiology alone is able to bring about further advance. III. THE METHOD OF PHYSIOLOGICAL RESEARCH It has been learned that the problem of physiology lies in the explanation of vital phenomena, and it has been seen, in its main features, how physiological research has developed in the course of history. It is now incumbent upon us to summarise with reference to the development of science what physiology has METHODS OF PHYSIOLOGICAL RESEARCH 29 already accomplished in the direction of its established goal, and to inquire by what path it may reach this goal. A. THE PAST ACHIEVEMENTS OF PHYSIOLOGICAL RESEARCH The aim of Physiology is to explain vital phenomena, i.e., to discover their elementary causes, to put them into causal relation with one another, to see whether their elementary causes are the same as those of the phenomena of inorganic nature. What has been accomplished in this direction ? The answer brings little encouragement, for, when the various branches of physiology are carefully reviewed, it is found that thus far practically nothing has been learned beyond the gross mechanical and chemical activities of the vertebrate body. The causes upon which these activities depend are, for the most part, a complete puzzle. We know that respiration depends upon the laws of aerodynamics; by the rhythmic diminution and increase of pressure of the air in the lungs, as a result of the contraction and relaxation of the respiratory muscles, the air streams passively in and out ; oxygen is removed from it by the red corpuscles of the blood and is chemically united with the substance of the corpuscles. But we have scarcely an idea as to how the contraction of the respiratory muscles comes about, or what events call forth the change of form, termed contraction and relaxation, and the performance of work in the individual muscle-cells. We know that the circulation of Hood in our bodies follows the laws of hydrodynamics, that it is conditioned by the rhythmic variation of differences of pressure within the vascular system, which are brought about by the contraction and relaxation of the heart-muscle. We have here again exactly the same problem as in respiration, for, although Engelrnann has recently proved that the causes of the rhythmic contractions of the cardiac muscle lie in the living substance of the muscle-cells, as to the manner in which the contractions come about physiology has enlightened us very little. We know that the digestion of the ingested food takes place strictly in accordance with chemical laws ; the chemical substances secreted by the gland-cells of the digestive canal transform the food chemically, exactly as we can imitate the processes by the help of those digestive secretions outside the body in the test- tube. But physiological chemistry leaves still unexplained how the gland-cells come to secrete their specific substances, why the cells of the salivary glands produce only ptyalin, and the cells of the gastric glands only pepsin, although the same food is brought to both by the blood. We know that in resorption the food-stuffs, changed chemically 30 GENERAL PHYSIOLOGY by the digestive juices, are taken up through the cells of the intestinal wall into the body. We know, moreover, that a great part of the ingested fat, after being divided into microscopic globules, is taken into the protoplasmic bodies of the intestinal epithelium-cells by their own activity, while the same cells do not take up other particles of equal microscopic size, such as granules of pigment. But Physiology has not yet learned how this selective faculty of the intestinal epithelium-cells is to be explained mechanically. We have seen how in the development of the human body the succession of definite morphological stages up to the complete man, which previously was so mysterious, may be understood naturally from the fundamental law of biogenesis. But it is still a much-debated question how in this development of the cells that arise from the segmentation of the egg some become gland-cells, others nerve-cells, and others epidermis-cells. We have learned that the movements of the skeletal bones, the arms, the legs, and the joints, follow purely mechanical and mathematical laws, especially the laws of the action of levers. But the action of the skeletal muscles which causes the move- ment of the skeletal bones is the same puzzle that is mentioned above, namely, the contraction of the muscle-cells. From the law of the conservation of energy we know that the heat and the electricity produced by the living body are derived from chemical changes which the ingested food undergoes in the body-tissues. But we do not know at all with what chemical pro- cesses the cells of the various tissues are concerned in the production of this heat and electricity. We know, finally, that the higher sense-organs of man are constructed in accordance with the principles of physical apparatus ; the eye, e.g., according to the principle of a camera obscura, so that a reduced inverted image of an object in the external world is formed upon its background according to the laws of the refraction of light. But it is a constant puzzle as to what occurs in this process in the retinal cells and how from them by the mediation of the optic nerves the ganglion-cells in the brain are excited to pro- duce in us the idea of the image. This enumeration might be long continued, but what has been said suffices for the recognition of a general fact. Every- where, to whatever branches of physiology we may turn, wherever the gross activities of the body are traced to the activity of the individual cells, we always come upon an unsolved problem. The pessimist, indeed, might be led to maintain with Bunge ('94): " All processes in the organism which may be explained mechanically are no more phenomena of life than are the movements of the leaves and branches of a tree that is shaken by the storm, or the movement of the pollen that the wind wafts from the male poplar to the METHODS OF PHYSIOLOGICAL RESEARCH 31 female." But, if we despair of a chemico-physical explanation of vital phenomena, nothing remains but to take refuge again in the long-buried doctrine of vital force. In fact, very recently this idea has again appeared in various places, notably in the writings of Hanstein, Kerner, Bunge, Rindfleisch, and other men of science. We might, however, be much more inclined to despair if we should look at the field of psychical phenomena. In the physiology of the brain and the sense-organs, indeed, much has been cleared up concerning the physical relations of certain psychical processes. But the old riddle of the causal relations between body and mind, which occupied so fully the thinking intellect even in earliest times, remains apparently wholly untouched by natural science. Under such disheartening conditions the investigator is constantly oppressed by the questions : Are there limits to our knowledge of vital phenomena ? If so, where do these limits lie ? Or are we upon a false path ? Was our attitude of inquiry into nature a mistaken one, so that we have not understood her answer ? B. THE RELATION OF PSYCHOLOGY TO PHYSIOLOGY 1. The Question of the Limits of a Knowledge of Nature Are there limits to our knowledge of nature ? And if so, where do they lie ? These questions have repeatedly arisen in the present generation, which is proud of its achievements in natural science, and have been treated in various ways. We can most fittingly consider them in connection with the well-known address of E. du Bois-Reymond ('84), " Ueber die Grenzen des NaturerJcennens," in which the recently deceased author, who was a master of lan- guage among German naturalists, discussed this theme in his accomplished style. With the lack of philosophical methods of thought which un- fortunately is so wide-spread in the science of to-day, the most re- markable ideas upon the basis of our knowledge of nature are often met with. This circumstance unfortunately justifies specula- tive philosophy in looking with contempt upon science, its rival in the recognition of truth. It is, therefore, necessary to examine these questions somewhat carefully, and, first, to inquire concerning the limits of knowledge, not only in organic, but in all nature. Modern science, especially physics and chemistry, is here the leader, and endeavours to reduce all the phenomena of the physical world to motions of atoms. Accordingly, du Bois- Reymond, in order to obtain a fixed point upon which to base his considerations, defines a knowledge of nature as follows : " A knowledge of nature — more accurately expressed, scientific know- 32 GENERAL PHYSIOLOGY ledge or knowledge of the physical world, with the aid and in the sense of theoretical natural science — is the reduction of changes in matter to the motions of atoms, which motions are accomplished by the intrinsic forces of the atoms independently of time ; in other words, it is the resolution of natural events into the mechanics of atoms." Recent science has, in fact, succeeded in showing in gross outline how natural phenomena may be derived from definite motions of atoms. We know that in all bodies the atoms are moving, in gaseous bodies very actively, in liquids more slowly, in solids very little. We know that light, heat and electricity depend upon regular, excessively rapid vibrations of atoms ; that sound is caused by definite modes of atomic vibration : and that chemical changes of bodies are conditioned likewise by characteristic movements and rearrangements of atoms. Following a fanciful conceit of Laplace, who imagines a human mind perfected to the highest degree and possessing such a know- ledge of atomic motions as we have in astronomy of the motions of the stars, du Bois-Reymond continues : " If we were to imagine all changes in the physical world to be resolved, into the motions of atoms, which are due to constant intrinsic atomic forces, the universe would be known in the scientific sense. The condition of the world at any period of time would appear as the immediate result of its condition during the previous period and the immediate cause of its condition during the following period. Law and chance would be merely other names for mechanical necessity. A stage in the knowledge of nature can be conceived in which the whole world-process would be represented by one mathematical formula, by one immeasurable system of simultaneous differential equations, from which could be deduced the place, direction of movement, and velocity of every atom of the universe at every moment." The human mind is only " a feeble image," it is true, of such a mind fancied by Laplace, but it differs from the latter only in degree, and in the achievements of the latter we can perceive the ideal which the human mind in its development is constantly ap- proaching. Let us imagine for once that we had reached this ideal and were in possession of the " world-formula." What would then be gained ? In order to explain a definite phenomenon of nature, we would need only to introduce into the world-formula certain values re- sulting from observation, and by computation we would be able to prove the phenomenon in question to be a necessary consequence of our known observations. Our craving for causality would per- haps be captivated for awhile by this play, but soon it would be- come free again and would call to us with louder and louder voice. So far so good ; we can now understand all phenomena of the physical world in their causal relations to each other ; we can explain them as perfectly definite motions of atoms ; but what is an atom ?' METHODS OF PHYSIOLOGICAL RESEARCH 33 Here, according to du Bois-Reymond, we stand at one limit of our knowledge of nature. What an atom is, i.e., what matter endowed with energy is, the world-formula does not explain. If we ask how we arrive at the conception of an atom, we find that we conceive it as an exces- sively small, indivisible, elementary part of a body, derived by con- tinued division of the body ; but if a body be continually divided until its atoms are reached, nothing but body is obtained. Atoms are bodies, and have the general characteristics of bodies. We cannot, therefore, expect to obtain by division something that elucidates the nature of the body. When we explain an unknown phenomenon by the motions of atoms, we merely resolve it into unknown phenomena. What an atom is, we do not learn, for it has only the properties which we attribute to it on the basis of the sense-perception of what large bodies show us, i.e., it is hard, im- penetrable, possesses form, and moves. But we obtain not the slightest information regarding the nature of the matter that is endowed with energy, i.e., that of which the physical world con- sists. Our craving for causality remains, therefore, in this respect unsatisfied, and as the result of our analysis we find ourselves at the first limit of our knowledge. But this is not the only limit. If, again, we possessed " astro- nomical knowledge " of the physical world, as du Bois-Reymond expresses it, i.e., the same mathematically exact knowledge of the motions of atoms that we have of the motions of the heavenly bodies, we would then, indeed, understand all phenomena of the physical world, but we would not understand how consciousness arises, how in general a psychical phenomenon, even the very simplest, comes to be. If we had, e.g., astronomical knowledge of our brain, we would know the position and motion of every atom at every moment ; we could also follow definitely the specific physical changes, rearrangements, and motions of atoms insepar- ably associated with specific psychical phenomena, and " it would be," as du Bois-Reymond says, " of unbounded interest, if with our mental eye turned inward we could observe the cerebral mechanics of an arithmetical problem, like the mechanics of a calculating machine ; or if we could know what dance of the atoms of carbon, hydrogen, nitrogen, oxygen, phosphorus and other elements, cor- responds to the delight of musical sensation, what whirl of such atoms to the acme of sense-enjoyment, what molecular storm to the frantic pain resulting from maltreatment of the nervus trigeminus." We could know all these if we possessed " astronomical know- ledge " of the brain. We could thus convince ourselves by self- observation that consciousness is inseparably associated with atomic motion. But with all this it would remain for ever con- cealed from us how consciousness arises, how the simplest psychical D 34 GENERAL PHYSIOLOGY phenomenon comes to be. However carefully we might follow the motions of individual atoms in the brain, we would see only motions, collisions, and again motion. Thus, it is evident that a mechanical explanation of consciousness, of psychical phenomena, from the motions of atoms is an impossibility for us, and we find ourselves at a second limit of our knowledge of nature, which ap- pears not less impassable than that of a knowledge of matter and energy. But supposing the first to be passed, and the riddle of matter and energy to be solved, how would it be with the second limit ? Would it be passed at the same time or would it still be impass- able ? We can evidently imagine consciousness, or rather the simplest form of mind, to be inherent in the nature of an atom, and, therefore, to be known when the nature of matter is known. In fact, this idea would be the only one that could be adopted by a monistic science, which seeks to explain all phenomena by one principle ; and Haeckel especially, who is an energetic advocate of monism among men of science, has always maintained it. du Bois-Reymond alludes to such a possibility only briefly when he says : " Finally, the question arises, whether the two limits of our knowledge of nature may not perhaps be the same, i.e., whether, if we understand the nature of matter and energy, we may not also understand how under certain conditions matter may have sensa tions, desires, and thoughts. This idea is, of course, the simplest one, and according to the known principles of investigation is pre- ferable to its opposite, according to which, as before said, the world appears doubly inconceivable. But it lies in tfye nature of things that we cannot elucidate this point, and all further words concern- ing it are idle." Therefore, " as to the riddle of matter and energy and their conceptions," du Bois-Reymond decides upon complete renunciation and proclaims to science not only a temporary " ignoramus," but an eternal and demonstrative " ignorabimus" 2. Physical World and Mind We have followed du Bois-Reymond's course of thought thus in detail, in order to show that the knowledge assumed by him as the starting-point of his considerations very soon encounters obstructions, in view of which the world appears incomprehensible. But eternal renunciation falls heavily upon the indefatigable thinker, and he is bound to ask whether this assumed path of knowledge is a right one, whether the definition of a knowledge of nature as a resolution into the mechanics of atoms is correct or justified. We will, therefore, test this basis of our considerations and inquire what knowledge is. For this purpose we will take the conception " knowledge " in METHODS OF PHYSIOLOGICAL RESEARCH 35 its widest and most general sense. One indispensable condition of the conception is the assumption that something exists. If we make this assumption, if we have something real or actual, a fixed point, then knowledge is simply the causal reduction of all phenomena to this reality. We have a measure for knowledge in the satisfying of our craving for causality ; and the latter will necessarily be satisfied, when once we have placed all phenomena in causal relation to the one reality. Nevertheless, an objection may here be raised. Let us suppose that we have succeeded in reducing all phenomena to the one reality. (This reality appears in the different philosophical systems under very different names, such as God, thing-in-itself, the unknown, etc. — the terms are equivalent and without material significance.) The question would then arise, whether our craving for causality would be satisfied, or whether it would not force us still farther to ask, What is this thing which exists, this reality, the unknown, the thing-in-itself, God, or whatever it is termed ? In the latter case, here, again, would be a limit to our knowledge. If we understand it rightly, however, this limit would be a logical error, a false conclusion. Our craving for causality arose and became established in the course of evolution by the continual reduction of effects to causes, and it is easily possible that in the present case it would continue for awhile from inertia to hold before us the question, why ? But it is evident that we would thus be guilty of an error of reasoning ; for, if all phenomena were reduced to the one reality, it would be a complete contra- diction to wish to know that reality in terms of non-reality. The demand that, after complete knowledge of the world, we must know the world still more involves an evident absurdity. Hence, the above objection is only an apparent one. We assume, therefore, the desire to reduce all phenomena to that which is real. Then the question arises, What is real ? Here we come in contact with a mistaken view which is espe- cially wide-spread in science and has been faithfully handed down from primitive time as an heirloom from the childhood of the human mind. This is the view that the physical world existing outside of us and independent of our own mind is real, and that, accordingly, we must reduce all phenomena to its laws. The impossibility of such an undertaking is plainly shown in the above argument of du Bois-Reymond. Yet a great many men of science — among those who, like du Bois-Reymond, have reflected upon the limitations of human knowledge, we need mention only the gifted botanist Nageli ('77) — have held it to be possible that even psychical phenomena may be resolved into the processes of matter. Hence it is useful to clarify our ideas as to what matter really is. At first sight bodies appear to us as actual objects outside of D 2 36 GENERAL PHYSIOLOGY our own minds. Any doubt as to the existence of a physical world outside of mind, will appear absurd to one who has not reflected upon it : a body, e.g., a stone, a tree, a man, which we look upon, really exists, no one will deny this ; we actually see the body, others see it ; and we say it exists. We are right ; without a doubt it exists, but it does not exist outside our mind; for, when we examine carefully the grounds for speaking as we do, we find that what we believe we see or feel as a body outside our mind is actually something quite different. Let us prove this. We have created our knowledge of a physical world by means of sense-perception. The question as to what can and does give us this knowledge is, therefore, one belong- ing to the physiology of the senses. Now the physiology of the senses shows that all that comes in through the door of our senses affords us, simply and solely, sensations. The many features that constitute the image of a body, e.g., a piece of gold, are so many different sensations, e.g., a yellow colour, hardness, weight and cold- ness. Persons with an innate defect in a sense, in whom a certain group of sensations is not mediated, e.g., persons born blind, have, therefore, an idea of the physical world that is wholly different from that of normal persons. This is clearest in those interesting cases in which persons who are born blind and have constructed their physical world solely by means of the senses of touch, hearing, smell, taste, etc., have been made to see by surgical operations. If objects that such persons have often had in their hands be brought for the first time before their eyes without their examining them by the other senses, e.g., by touching, they do not recognise them: a ball appears to them as something wholly new, and only when they touch it do they realise to their surprise its identity. At that moment a new world begins to arise in them. The physical world depends, therefore, wholly upon the development of our sense-organs ; to animals with sense- organs developed differently from ours it must appear very different, in proportion as they receive other sensations. With our death, with the destruction of the senses and the nervous system, the physical world in its previous form disappears. These facts are of far-reaching significance. They show that what appears to us as matter is in reality our own sensations, or ideas, our own mind. When I see a body or perceive it by means of my other senses, in reality I have not a body outside of myself but only a number of sensations in my mind. Beyond these I know nothing concerning it and can only form hypotheses. It is necessary that we accustom ourselves to this fundamental truth, and that we get rid of the error of the existence of a physical world outside of mind. In order to facilitate this let us consider the consequences of this truth. If the physical world is only my own sensation, or, better, since METHODS OF PHYSIOLOGICAL RESEARCH 37 it involves a complexity of sensations, my own idea, I must assume that a reason for this idea exists. Hence the question arises, What is the thing outside of my mind that produces in me through the senses this idea ? In other words, what is the external world ? This question contains an error. As is well known, natural science has shown that every phenomenon in the physical world has as its cause another physical phenomenon. This is only an expression of the law of cause and effect, 'i.e., the law of causality. Hence the cause of my sensation of the physical is another sensation or idea, which is located not outside of but within my mind. This is nothing but a paraphrase for the fact that our conception of causality has arisen out of a combination of separate experiences, which our mind has obtained by observation of the regular sequence of its own elements, its sensations and ideas. In other words, causality itself, like all other sensations, ideas, conceptions, or whatever we may term it, exists only in our own mind. If, therefore, the cause of my idea of the physical is located within, the supposition of a reality without is wholly un- justified. Various philosophers have, in fact, endeavoured to base the reality of an external world upon the causality of phenomena. But both rest upon the same error, and the argument presents the rare spectacle of an attempted proof of something by means of that which is to be proved. It is not to be denied that to every one who follows this line of thought for the first time the above result must appear paradoxical, and he will immediately raise the objection that besides himself many other men exist, possessing minds and capable of making •exactly the same assertions concerning themselves and their own minds. But here the delusion is again evident. To me, other men are bodies, I perceive in them nothing else. Hence they are only my idea. And when they tell me that they have a mind like myself, that they likewise feel and think, it is true ; but what they say to me, their speech, their movements, are only physical phenomena and, therefore, only my own ideas According to our scientific mode of expression, their mind has its seat in their brain, but if, by a surgical operation upon a living man, I am ever •enabled to examine the brain, I learn that nothing is to be found there but physical elements. I am thus forced to the conclusion that what I regard as the mind of another is also only my own idea. In short, whatever path I take, I come constantly to the conclusion that all that seems to be outside of me, whether it be a lifeless body, a living man or a human mind, is in reality only my own mind. Beyond my own mind I cannot go. My own individuality, indeed, is only an idea of my mind, and, therefore, I cannot finally say, the world is my idea, but I must say the world is an idea, or a sum of ideas, and what appears to me as my 38 GENERAL PHYSIOLOGY individuality is only a part of this complex of ideas, just as is the individuality of other men and the whole physical world. Although this reasoning will appear to every one at first sight strange and unusual, it is by no means new. More than two hun- dred years ago Descartes made the fundamental fact, that the whole physical world is only an idea, the starting-point of his philosophy. Later, Berkeley and, still later, Fichte and Schopenhauer employed it as the basis of their systems, which were widely different in other respects. More recently among men of science Mach ('86) has adopted a similar view as the nucleus of his views regarding the theory of knowledge. It is to be hoped that this monistic con- ception will gain ground more and more in science ; it alone holds strictly to experience, it is not hypothetical, and it necessarily sets aside the ancient doctrine of the dualism of the body and the mind, a doctrine that reached its highest development in the Egyptian theory of the wandering of the soul and has continued through the whole history of philosophy. 3. Psycho-monism When the history of the problems that have kept the human intellect busy during the long course of its evolution is studied, it is found that many problems that perplexed the ancients have con- tinued unchanged and unsolved down to the present day ; others have been solved ; while still others that have been prominent even for centuries have afterwards disappeared without finding a solution. The ancient question of the squaring of the circle, over which many a brain has puzzled in vain, that of perpetual motion, which since early times has been prominent in physics, and many others, have quite disappeared, although no one has ever squared the circle and no one has constructed a machine for per- petual motion. If it be asked how it happens that this is so, the answer is, because it is recognised that the basis of these supposed problems is false, and they are, therefore, insoluble. If the attempt be made to divide all the numbers of a series by 2 without a remainder, it is found impossible to do it. So it is with the above problems, which for centuries have harassed one generation of thinkers after another. So it is also with the attempted explanation of psychical by physical events. It still engages unremittingly the attention of those who are not pleased with having limitations to their conception of the world, yet no one, however earnest his thought, comes nearer a solution. Only gradually will the conviction force its way, that this problem, like those above mentioned, will always resist solution because the question is falsely put. That the attempted explanation is wrong is at once clear from METHODS OF PHYSIOLOGICAL RESEARCH 39 the preceding considerations. It was found that the sole reality that we are able to discover in the world is mind. The idea of the physical world is only a product of the mind, and with the altera- tion of an old sentence of the sensualists, it can be said : Nihil est in universe, quod non antea fuerit in intellectu. But this idea is not the whole of mind, for we have many mental constituents, such as the simple sensations of pain and of pleasure, that are not ideas of bodies. The task of psychology, i.e., the investigation of mind, consists in the analysis of all mental constituents. By investigating the contents of mind, by decomposing the higher psychical phenomena, the more complex groups and series of ideas, into their simple constituents, psychology arrives, finally, at the most primitive psychical phenomena, the psychical elements, and in the same degree discovers the laws of the arrangement of these elements into the higher groups and series of ideas. Just as in mathematics the endless variety of numbers is formed according to laws out of the numerical unit, so psychology reduces the end- less variety of psychical phenomena to their formation, according to laws, out of the psychical elements. But the idea of matter, or, better, of an atom, is not a psychical element, it is a great com- plex of highly developed ideas. An atom is nothing but a thing possessing all the properties of a body, such as hardness, impene- trability, form, and extension, all of which presuppose very complex psychical processes. The endeavour of natural science to reduce the phenomena of the physical world to the mechanics of atoms is justifiable ; it is an endeavour to derive the phenomena of large bodies from the properties of their material parts. But the attempt to reduce to the motions of atoms all psychical phenomena, not only ideas of the physical world but others, such as simple sen- sations, is precisely as absurd as the endeavour to reduce all numbers in the numerical series to 2 instead of to the numerical unit, for the complex notion of the atom is not a unit, not a psychical element. Herein lies the fallacy of the problem, and hence, as the history of human thought has shown so strikingly, all attempts to explain the psychical by the physical must fail. The actual problem is precisely the reverse. It consists not in explaining psychical ~by physical phenomena, but rather in reducing to its psychical elements physical, like all other psychical, phenomena. In natural science the view is frequently met with, that knowledge of the world falls into two sharply separated categories, namely, metaphysics and science. Metaphysics is left to philosophy, and science is limited to the investigation of the physical world. But the fact is often overlooked or intentionally neglected, that every process of knowledge, including scientific knowledge, is merely a psychical event, that science also deals with " metaphysics," as in accordance with an ancient and unfor- tunate manner of expression it is customary to term it, and even 40 GENERAL PHYSIOLOGY that science cannot exist without metaphysics. This fact cannot be banished by the well-known method of the ostrich. It thtfs appears to be a contradiction to contrast nature (0u,. Clepsidrina blattarum, a unicellular gregarine from the intestine of a cockroach ; the protoplasm is entirely filled with granules. protoplasm to certain constituents of the cell is wholly inadmissible and leads to evil consequences. The conception of protoplasm, therefore, should be maintained under all circumstances strictly in its original sense as a comprehensive morphological conception ; proto- plasm is a sum, a mixture, of very different morphological elements. Even if by degrees its individual constituents become known mor- phologically and chemically, the comprehensiveness of the term will not thereby be set aside. Whatever significations the various substances may have in the vital process of the cell is a wholly dif- ferent question, and does not affect the conception of protoplasm. LIVING SUBSTANCE When the contents of protoplasm are investigated, upon super- ficial examination two groups of constituents may be distinguished, namely, various well-defined bodies, such as grains, droplets, etc., and a uniform, semi-liquid, apparently homogeneous ground- substance, in which the former, like the nucleus, lie embedded. But, while in many cells the ground-substance contains only a few solid bodies, as, e.g., in many epithelium-cells (Fig. 22, a), in others it can scarcely be seen because of the abundant granular consti- tuents, as is frequently the case in many plant-cells, and especially in certain parasitic unicellular organisms, the Gregarince (Fig. 22, V). a. The Solid Constituents of Protoplasm The solid constituents of protoplasm are material elements of very various natures ; they are special constituents, and do not occur in all cells. Among them occur bodies that are of the highest significance for the life of the cell in which they are contained, that impress upon the cell a characteristic feature; and also elements that play no role whatever in the vital process, such as the indigestible residue of food. There are found, further, food- constituents which are not yet changed, other substances which have been regularly transformed from the food by the vital process or have been formed anew, and, finally, in many cells independent organisms which live continually in them as symbionts or parasites and under cer- tain circumstances play a definite role in the life-process of the cells. Among the solid protoplasmic constitu- ents which are especially significant in the life of the cell, and which, therefore, can be considered as organs of the cell, or, better, since we understand by organ a structure composed of many cells, as cell- organoids, the chlorophyll-bodies of plant- cells are especially important. These small, usually roundish, sometimes band- shaped bodies, which lie embedded in the ground-substance of the protoplasm (Fig. 23, a), give to the plant-cell and thus to the whole plant its magnificent green colour, for their delicate albuminoid bodies are saturated with an intensely green colouring-matter. The chloro- phyll-bodies are of the greatest importance for the plant-cell, for in them occurs a considerable part of its characteristic vital process. Other organoids, which in many cases are likewise of great import- ance for the cell-life, are the drops of liquid, or vacuoles, as they are G Fia. 23.— a, A plant-cell contain- ing chlorophyll-bodies. 6, A chlorophyll-body undergoing division. (After Sachs.) 82 GENERAL PHYSIOLOGY commonly but inappropriately termed. Of the vacuoles two kinds may be distinguished. Some collect only occasionally in the protoplasm in a place where a substance lies that attracts water. Others are permanent structures, and are present frequently in such great numbers that the mass of the protoplasm is small in proportion to them and merely forms thin walls for them ; the protoplasm then presents a frothy appearance, as, e.g., in many plant-cells (Fig. 24, a) and Eadiolaria (Fig. 24, &). Among the constant vacuoles that serve as cell-organoids there are the so- called contractile or pulsating vacuoles, drops of liquid that dis- FIG. 24.— a, Plant-cell from a stamen-hair of Tradescantia. (After Strasburger.) b,Thalassicolla nucleata, a radiolarian cell, c, Paramaicium aurelia, a ciliate-infusorian cell, which cc within the protoplasm at each end a pulsating vacuole. appear and appear again at the same spot, usually rhythmically, while the liquid rhythmically mixes with the protoplasm and again accumulates. Many of these pulsating vacuoles have special efferent canals and a constant wall, as is the case in many uni- cellular free-living organisms, especially the ciliate Infusoria (Fig. 24 c\ In addition to such constant elements, in many cells solid constituents are met with that are present as such only tempo- rarily. Here belong especially the food-bodies that are found in cells that nourish themselves by taking in solid food-constituents. Unicellular naked organisms, such as Amceba, white blood-cells, LIVING SUBSTANCE 83 infusorian cells, and others, not rarely show in their body- contents small Algce, Bacteria, and Infusoria, which they have taken up from the outside (Fig. 25, 7), and which sometimes are scarcely to be distinguished from other solid constituents of the protoplasm. These food-organisms become gradually digested and disappear. There appear also frequently in the cell-body as products of digestion, both in the cells that ingest solid, and those that ingest only liquid food, definite granules, usually roundish, and varying greatly in nature (Figs. 7 and 22, &), which Altmann has grouped in part under the name gramda, and which, as has already been Fio.25.-7, Prog's leucocytes, or white blood-cells, each containing a bacterium. (After Metschnikoff .) //, A plant-cell containing starch-grains. HI, Starch-grains isolated — a, from the potato ; b, from corn ; c, from the pea. seen, he regards as elementary organisms, the ultimate living elements of the cell. The composition and significance of most of these metabolic products of living substance which in the form of granules help to constitute the protoplasmic body, is not yet known. But some are characterised very exactly and are easily recognised, such as the concentrically stratified starch-granules in plant-cells (Fig. 25, // and III), the fat-droplets in the cells of the lacteal glands, the glycogen-granules in liver-cells, the pigment- granules in the pigment-cells of the skin of many coloured animals (Fig. 17, d), the aleur one- grains, consisting of proteid, in the cells of sprouting plant-seeds, the crystals of calcium oxalate in plant- cells, of calcium guanin in pigment-cells, and many others, special mention of which would lead us too far. G 2 84 GENERAL PHYSIOLOGY In the contents of many cells there occurs a fourth group of solid elements, which either do not take part at all in the life- Gcess of the cell, or have ceased to do so. These are indigestible ies which are taken in occasionally, such as sand-grains (Fig. 26), which are met with in many Amoebce, the indigestible residue of food-stuffs, such as shells, skeletons, and the capsules of food-organ- isms, and excretory substances, which remain for some time in the cell -body as useless by-products or as end-products of metabolism, to be excreted later. Finally, among the solid elements of the protoplasm in certain cells, especially in aquatic animals, there occur not rarely symbiotic or parasitic unicellular organisms which strictly do not belong to the protoplasm of the cell in question, but in individual cases play an important role in the life of their host. Among such symbiotic organisms are especially many algae, the Zooxanthellce and the FIG. 26. — Amceba-eell containing in its protoplasm one diatom shell and two sand-grains. FIG. 27. — Paramcecium bursaria, a ciliate- infusorian cell, the exoplasm of which is filled with small parasitic alga-cells (Zoochlorellce). Zoochlorellce, the nature of which as independent organisms has been for a long time in dispute. They occur abundantly in the cells of lower animals, particularly in many Infusoria and Eadiolaria, to which by the activity of their chlorophyll-bodies they furnish oxygen, so that as regards respiration their hosts are largely independent of the oxygen of the medium in which they live (Fig. 27). We shall not enumerate exhaustively the solid components that are to be met with in cells. Such a list would fill many pages. It is only important here to understand how different in nature are the various solid constituents of protoplasm that may occur in in- dividual cells, and how unjustified is the idea of the unitary character of protoplasm. We will now leave the solid elements, and turn to the consideration of the homogeneous ground-substance. LIVING SUBSTANCE 85 b. The Ground-substance of Protoplasm As already noted, the ground-substance of protoplasm, in which the granules, etc., are embedded, appears upon superficial examina- tion completely homogeneous. This can be seen best in cells that contain only a few solid constituents stored in their ground - substance ; it is especially evident in many Amcebce, which are free-living cells possessing naked protoplasmic bodies that creep about at the bottom of stagnant water, constantly changing their form, and represent the lowest and simplest organisms inhabiting the surface of the earth. These interesting elementary organisms usually form upon their surface pseudopodia which are wholly free from granules, broad, finger-shaped, or lobate, and appear com- pletely hyaline and structureless (Fig. 16, p. 75, and Fig. 28). In fact, in the Amoeboe the hyaline protoplasm not rarely is completely structureless. All investigations up to the present time which have been undertaken with the best microscopic methods agree in this. But this actual homogeneity of the ground- substance of protoplasm is not the rule ; on the contrary, the employment of high magni- fying powers shows that by far the majority of cells possess in reality in their apparently homogeneous ground-mass an extremely fine and characteristic structure. Remak ('44) observed that not only nerve- fibres but also the ganglion-cells of the central nervous system possess a very fine fibrous or fibril lar structure— an observation that was confirmed and extended by a large number of investigators, especially by Max Schultze (71). A striated structure was later found in the protoplasm of various other cells, gland-cells, epithelium-cells, muscle-cells, etc., and thus the idea was formed by various investigators that a fibrillar struc- ture is wide-spread in protoplasm ; this view is still defended to- day, especially by Flemming, Ballowitz, and Camillo Schneider. But this theory early underwent a modification. Beginning in 1867, Frommann especially endeavoured to show by a long series of researches that the finer structure of the protoplasm of all cells is not properly fibrillar, but reticular; this view was adopted almost at the same time by Heitzmann, and soon obtained wide acceptance. According to this idea, protoplasm forms a network, or, better, a mesh work, the nodal points of which appear as indi- vidual granules. The whole mesh work of the cell is open to the Fia. 28.— An amoeba-cell containing completely hyaline and homogene- ous pseudopodial pro- toplasm. In the endo- plasm by the side of the nucleus lies a pale con- tractile vacuole (droplet of liquid). 86 GENERAL PHYSIOLOGY outside, and between its threads exists a liquid, which, however, is different from the liquid of the medium in which the cell lives, i.e., the water, the body-juices, etc. It is difficult to understand why, as the adherents of the theory of the reticular structure of pro- toplasm hold to be possible, the internal cell-liquid in cells that possess no membrane, such as the leucocytes of the blood and Amoeba, the reticular structure of which has been described by Heitzmann in great detail, does not continually mix with the sur- rounding medium in spite of its great proportion of water. But attempts to stain such living protoplasmic masses by certain staining-solutions show clearly that the staining-fluid does not penetrate into the living protoplasm. This and similar difficulties which arise in connection with the idea of protoplasm as a mesh- work open upon all sides have led many investigators to take a very sceptical attitude toward the theory of a reticular structure, although in various ways the reticular appearance of the protoplasm of many cells has been confirmed. The striking researches with which in recent years Biitschli ('92, 1) has been surprising the scientific world, have completely clarified our ideas upon the real nature of the protoplasmic struc- tures so much observed. The protoplasm of a cell that contains so many vacuoles or droplets of liquid that its contents have a foamy appearance, presents with high powers of the microscope a picture, not of many vacuoles or bubbles pressed tightly together, but of a network, the threads of which form the cross-sections of the thin walls of the vacuoles. This is due to the fact that with strong powers surfaces only, and never bodies, are seen. The microscope shows only optical cross-sections of bodies. But the optical cross-section of a foam is a network. This fact led Biitschli to the conviction that the finer reticular appearance of protoplasm which appears homogeneous by feeble magnification, as has been observed in so many cells, is merely the optical expression of an extremely finely vacuolated foam-structure. In order to confirm this idea, Btitschli endeavoured artificially to produce microscopic foams of a fineness equal to the hypothetical protoplasmic struc- tures, and he succeeded in this in a most gratifying manner. He employed for his experiments oil which was very finely rubbed up with potash or cane-sugar. Small droplets of this oil-mixture, when placed upon a slide with a drop of water, covered with a cover glass, and observed under a microscope, immediately took on an extremely fine foam-structure. This was due to the fact that the particles of potash or sugar, which were finely divided in the oil-droplet, attracted particles of water ; the latter passed from the outside through the oil by diffusion, accumulated as extremely fine droplets closely about the former, and transformed the oil into a very fine foam. The oil-foams obtained in this way show such a remarkable similarity to the structure of protoplasm that they can LIVING SUBSTANCE 87 scarcely be distinguished from the latter. From the accompany- ing figures (Fig. 29, a and b), which are taken from Biitschli, the identity in structure of the two objects may be recognised at a glance. After the very careful and comprehensive investigations, the results of which Btitschli has published in his book, doubt can no longer exist that the problematic fine structure of protoplasm is in reality foam-structure, which depends upon the presence within a uniform ground- mass of a large number of extremely fine FIG. 29. — a, Foam-structure in the intracapsular protoplasm of Thalassicolla nucleata. b, Foam from olive oil and cane-sugar, c, Protoplasmic structure in a pseudopodial extension of a foraminifer-cell (Miliola). d. Protoplasmic structure of an epidermis-cell of an earthworm. (After Biitschli.) vacuoles, lying almost at the limit of microscopic visibility, and so close together that their walls consist of relatively thin lamellae. Further, Biitschli has demonstrated this foam-structure in so many wholly different forms of cells (Fig. 29, a, c, d) that its wide distribution can be disputed no longer. As the result of these recent investigations the following picture can be formed of the finer morphological structure of protoplasm. Protoplasm consists of a ground-mass, in many cases completely homogeneous, in most cases very finely foam-like or honey-comb- like, in which lies embedded a greater or less quantity of very 88 GENERAL PHYSIOLOGY various solid elements, or granules. In the foam-like protoplasm the- granules always lie at the corners and angles where the foam- vacuoles come together, never in the liquid of the bubbles themselves. We have already spoken 1 of the idea of Altmann, who regards the granules as the sole elementary parts of protoplasm, and the intermediate substance between the granules as non-living. In the light of Blitschli's investigations this view appears all the more untenable. 3. The Cell-Nucleus In recent years the cell-nucleus has become a favourite object of morphological investigation. And here a psychological phe- nomenon is to be noted, which has constantly repeated itself in the history of the human mind, since mankind began to reflect upon things — this is the tendency toward exaggeration. The earlier investigators of protoplasm, especially Max Schultze, had convinced themselves that protoplasm shows important vital phenomena, and at once by excessive generalisation the view was promulgated that protoplasm is the sole bearer of vital phenomena, while the nucleus possesses an accessory significance. Since then it has been recognised that the nucleus participates prominently in certain vital phenomena ; several investigators have shown that it plays a very important role in reproduction, fertilization, secre- tion, etc. Immediately the original view of the all-importance of the protoplasm has by an extreme reaction become exchanged for its opposite, that of the all-importance of the nucleus. As will be seen in a later section, here, as so often, the truth lies between the two. But every reaction is exaggerated. Opinions, like a pendu- lum> go first to the two extremes, and only after some time does the proper mean come to be maintained. Biology is indebted to these investigations upon the nucleus for the fact that our knowledge of it has been greatly extended.2 a. The Form of the Nucleus The form of the nucleus is very different in different cells. The first conception of the nucleus was formed from cells in which within a circumscribed protoplasmic mass a single, more or less spherical nucleus exists, which as regards its refractive power and its consistency differs essentially from the surrounding proto- plasm. It was found later that the nucleus stands in sharp con- 1 Cf. p. 63, etfolg. * A. Zimmermann has recently made a comprehensive survey of the results of research upon the nucleus, especially in plant-cells, in his book, Die Morphologic und Physiologic des pflanzlichen Zellkernes : Eine kritische Litteraturstudie. Jena, 1896. LIVING SUBSTANCE 89 trast to the protoplasm by its characteristic behaviour toward certain reagents, especially colouring-matters. Nuclear masses possessing these characteristics are the most wide-spread in the organic world. The nuclei of a majority of free-living and most tissue-forming cells among animals and plants are of this type. In it the relation of the volume of the nucleus to that of the protoplasm varies greatly. There are cells in which a relatively small nucleus is surrounded by a large mass of protoplasm, as, e.g., many Foraminifera, while in other cells, the mass of the protoplasm, in comparison with the nucleus, is extremely small, as in most spermatozoa. From the type of the single, more or less spherical nucleus deviations in very different directions occur. First, as regards the number of nuclei: As has already been seen, there are organisms that con- sist of a unitary protoplasmic mass in which lie embedded a large number of nuclei, such as multinucleate cells and syncytia. In such cases the number of the nuclei can be so great and their size so ex- cessively small that, as Gruber ('88) has observed in certain Rhizopoda from the harbour of Genoa, especially Pelomyxa pal- lida, the nuclei lie distributed through the whole protoplasm as a fine powder (Fig. 30). With such a division of the nuclear mass as is present in multinucleate forms, the nu- clear surface naturally is con- siderably larger than with the same quantity contained in a single large nucleus — a fact that is particularly important from the physiological point of view. The same principle of surface-enlargement is seen also in the differentiation of the form of the single nucleus. The most mani- fold and extreme deviations from the typical spherical form occur. Rod-shaped, band-shaped (Fig. 31, a,) and moniliform (Fig. 31, &) nuclei are very common among ciliate Infusoria.. Going still fur- ther, the same principle leads to star-shaped and branched nuclei, which are found in certain cells in the bodies of insects, and reach their highest development in antler-like branched forms in the cells of the spinning-glands of many caterpillars (Fig. 31, c). It seems noteworthy that it is the nuclei of secreting cells, i.e., cells FIG. BO.— Pelomyxa pallida, a rhizopod-cell from the harbour of Genoa, containing finely- divided nuclear substance in the protoplasm. (After Gruber.) 90 GENERAL PHYSIOLOGY characterised by lively activity, in which the principle of surface- enlargement by branching is especially expressed. b. The Substance of the Nucleus As regards the nature of the substance of the nucleus, exactly the same is true as in the case of the protoplasm. The nucleus is no more a unitary substance than is the protoplasm. It is a morpho- logical structure, an organoid of the cell, which consists of several FIG. 31.— Cells containing different forms of nuclei, o, Vorticella, a ciliate infusorian, possessing a rod-shaped nucleus, b, Stentor, a ciliate 'infusorian, possessing a moniliform nucleus, c, c, Cells of the spinning-glands of the caterpillar possessing antler-like branched nuclei. (After Korschelt.) different constituents that may be distinguished from one another microscopically more or less clearly, and all of which are not present in all cells at all times. Because of the exceeding minute- ness of the objects, it is often difficult sharply to characterise the individual constituents. Therefore, their identity in two separate species is not always beyond doubt, and extended investigations are still needed before it will be known clearly what constituents. LIVING SUBSTANCE 91 of one nucleus correspond exactly to those of another. Neverthe- less, a number of constituents, which apparently are wide-spread, are even now fairly well characterised. The following substances occur most constantly : — 1. The nuclear sap constitutes the liquid ground-substance, in which the solid nuclear constituents are contained (Fig. 32). M. Heidenhain, Reinke, and Korschelt have lately demonstrated that in many cells, even during life, it presents an extremely finely granular appearance. 2. The achromatic nuclear substance forms in the ground-substance a supporting-structure of fine threads, which are characterised, like the nuclear sap in which they are suspended, by not staining with the typical nuclear stains, such as the carmine stains, haemotoxylin, etc. 3. The chromatic nuclear substance is distinguished from the achromatic by its property of staining with these reagents. It is contained in the strands of the achromatic substance, as a rule in the form of small granules and irregular particles, and upon its FIG. 32. — Various nuclei from the mother-cells of the spermatozoa of the thread- worm of the horse. (After Hertwig.) staining-power chiefly rests our knowledge of the finer structure of the nucleus. 4. The nucleolus is a homogeneous granule which is present comparatively rarely in nuclei ; it consists of a strongly refractive substance which appears to be closely related to the chromatic substance. Since, as a rule, the substance of the nucleoli may be stained by the nuclear stains like the chromatic substance, the nucleolus has been considered by many investigators as a special accumulation of chromatic substance — a view which, however, because of the different relations of the two substances toward certain chemical reagents, cannot strictly be maintained. All of these substances, to which with advancing knowledge of the nucleus others will perhaps be added, are present in very dif- ferent quantities in different cells. A substance that is abundant in one nucleus may be insignificant in another, and it even appears as if certain substances can be wholly wanting in certain nuclei. In many cases the nuclear substances are surrounded and marked off from the protoplasm by a special nuclear membrane, which, how- ever, like the cell-membrane in relation to the cell, is not a general constituent of the nucleus. 92 GENERAL PHYSIOLOGY Recently, Zacharias ('81-'87) and Frank Schwarz ('87) have en- deavoured to replace the customary names of the individual sub- stances by other names. Thus, the chromatic substance has been termed nuclein, the achromatic substance linin, the nucleolar substance paranuclein or pyrenin, the nuclear sap paralinin, and the substance of the nuclear membrane amphipyrenin. The adoption of these names is not recommended, for they may so easily be confounded with chemical notions as to lead to the error of seeming to deal with chemical entities, while the nuclear substances in question are purely morphological. If the term nuclein were to be employed in a chemical sense, the chromatic nuclear substance would be placed in a chemical contrast with the other nuclear substances that does not really exist, for the majority of other nuclear substances likewise belong chemically to the so- called nucleins, representing different kinds of the latter. There- fore it is more fitting to employ the original names above mentioned for the morphological nuclear constituents, and not to confuse the latter with chemical substances. One more phenomenon relative to the differentiations of the individual substances is of interest. This is the fact that, of the substances that occur together within the nucleus in most cells, some have become differentiated in many cells into separate masses within the protoplasm, so that two entirely different forms of nucleus occur side by side within the same cell. This condition is almost universally realised in ciliate Infusoria, which possess, in addition to a larger nucleus, the macronucleus, which in some species and at certain periods seems to consist chiefly of chromatic substance, one, several, or often a great number of the so-called accessory nuclei, or micronuclei, which likewise in some species and at certain periods seem to consist mostly of achromatic sub- stance. The claim of the two elements in the infusorian cell to be regarded as two different nuclear substances is based upon the phenomena which, according to the striking investigations of R. Hertwig ('88-'89), appear in the conjugation of two individuals. Here the chief nucleus goes to pieces completely in the protoplasm, and after conjugation a new rudiment of it is differentiated from the substance of the accessory nuclei. While in the ciliate Infusoria the two forms of nucleus remain throughout life, in the Difflugice of the PJiizopoda a localised differentiation of two nuclei appears only during the period of conjugation and gives place afterwards to the uninucleated condition.1 c. The Structure of the Nucleus It has been seen that the achromatic substance forms in the ground-mass of the granular nuclear sap a supporting-structure, in 1 Cf. Verworn ('90, 1). LIVING SUBSTANCE 93 the strands and nodal points of which the chromatic substance and the nucleoli lie embedded in precisely the same manner as the solid elements, the granules, etc., lie in the alveolar walls of the proto- plasm. Indeed, as Biitschli has shown, the similarity of the relation even goes so far in in- dividual cases that the achromatic substance in the nucleus shows precisely the same alveolar struc- ture that the ground-mass of the protoplasm as a rule possesses (Fig. 33). All these structures are char- acteristic Only Of the SO-Called FlG. 33._Alveolar structure of the nucleus resting-stage OI the Cell. As SOOn of a ganglion-cell. (After BUtschli.) as the latter prepares to multiply by division, very peculiar and very complex changes in the structure of the nuclear substance appear ; these will be considered in detail in another chapter. C. THE PHYSICAL PROPERTIES OF LIVING SUBSTANCE 1. The Consistency of Living Substance Although the earlier investigators of the cell, such as Schleiden, Mohl and others, as the result of direct observation, considered the contents of the cell to be liquid, and compared its con- sistency with that of slime, later the idea found wide accept- ance that protoplasm is at bottom a solid substance. This idea arose from purely theoretical considerations. Briicke ('61 ), especially, thought that the cell-contents cannot be liquid, for the reason that vital phenomena cannot possibly be associated with a liquid substratum, but presuppose a definite organisation, and the latter is not compatible with the nature of a liquid. Briicke's view soon obtained many adherents, and appeared to be supported par- ticularly by the theory of the reticular structure of protoplasm, as maintained by Frommann and Heitzmann. It was believed that the solid supporting-structure, with the organisation of which vital phenomena are associated, was represented by the network. It has turned o«t, however, that the supposed reticular structure is an optical delusion, and thus this basis for the view of the solid consistency of protoplasm has been taken away. In reality, with the present methods of microscopic investigation, only a strong prejudice in favour of other and untenable theories can overlook the fact that, with the exception of individual differentiations in certain cells, protoplasm behaves physically like a liquid. The idea that vital phenomena can be associated with a solid 94 GENERAL PHYSIOLOGY substratum only is not only unjustified, but even untenable. Not only is it unsupported on any acceptable ground, but it even contradicts facts that may easily be observed. E.g., it is quite impossible to understand how protoplasm in the more or less stiff condition of a framework or network can be capable of streaming and flowing, as can be observed so easily in certain plant-cells and in Amoeba. It is impossible for a solid network to flow in such a manner that the individual particles of its mass mix continually with one another, as may be seen so clearly in Amoeba. If at first sight the theory of the solid consistency may not be incompatible with the behaviour of cells that possess a constant form, it is absolutely so with the phenomena exhibited by naked protoplasmic masses. Hence various investigators, especially Berthold ('86) and Btitschli ('92, 1), have recently defended strongly the idea of the FIG. 34.— a, Vaucheria tube cut open at the upper end ; the protoplasm is flowing out and taking the form of globules. (After Pfeffer.) b, Amceba-cell containing a pale vacuole and various small fat-droplets. liquid nature of the cell-contents, and no investigator who is familiar with the phenomena need hesitate to accept this view. Observation of a few facts is convincing of its truth. The phenomena of movement, already mentioned, are the strongest proof of the liquid nature of protoplasm. In the protoplasmic strands of plant-cells and in the pseudopodia of Rhizopoda the living substance may be seen flowing like the water of a quiet stream, now slower, now faster, and in different places at unequal rates, so that, as can be observed easily in the constituents enclosed within the ground-mass, the granules, fat-droplets, etc., the particles continually mingle with one another. How would it be possible for a stiff ground-mass to flow like water in a stream ? Another thing that throws light upon the liquid consistency of protoplasm is the fact that protoplasmic masses, when oozing out of the cell after its walls have been crushed or cut, form drops and globules. The formation of such drops and globules can be observed very beautifully in the protoplasm of the alga Vaucheria LIVING SUBSTANCE (Fig. 34, a). They can be observed also in the streaming proto- plasmic strands of the uninjured plant-cell, when the electric current is sent through them. The protoplasm then collects at once into globules and small spindle-shaped masses, which, if the current be interrupted, become again extended and united, their substance flowing on (Fig. 35). The same can be seen in the pseudopodial filaments of many marine Rhizopoda upon shaking them strongly or continually (Fig. 36), and likewise in many other objects. A third phenomenon that points to the liquid consistency of protoplasm, and one that can be observed in very different forms of cells, is the assumption of the globule- or drop-shape ~by accumulations of liquid enclosed within the protoplasm, such as the so-called vacuoles, and the fat- and oil-droplets, which ap- pear here and there, increase in size, and under certain circum- stances disappear (Fig. 34, 6). Were the ground-mass of pro- toplasm stiff, it would be incom- prehensible that these droplets of liquid of very different sizes always assume the spherical form and preserve it during their growth, as oil-droplets do. In such cases a spherical form is mechanically possible only when the surrounding medium exer- cises upon all sides equal pres- sures and yields equally, i.e., when it is itself a liquid. Innumerable phenomena of this kind may be cited, which are compatible only with the liquid nature of protoplasm. But those mentioned suffice completely to show that vital phenomena can very well be associated with a liquid substratum. Of course the liquid and the solid conditions of a body cannot be separated from one another by a sharp limit, but are united by imperceptible transitions. According to our present physical ideas the difference between the gaseous, liquid and solid conditions of a body depends solely upon the fact that in the first the molecules are in rapid FIG. 35. — Tradescantia. Cell of a stamen-hair. A, Containing quietly streaming proto- plasm. B, The same cell stimulated by an induced current. The protoplasm in the strands has become rounded into single globules (c, d). (After Kiihne.) 96 GENERAL PHYSIOLOGY motion, in the second they are moving somewhat more slowly, and in the last still more slowly. Since, therefore, only a gradual difference exists, it is impossible to establish a sharp limit. In living substance also there are different grades of mobility among the particles,, i.e., in one case the substance is like thin, in another case like thick liquid. In general, it possesses the consistency and mobility of raw white of egg, but it may be firmer, and certain constant differentiations of protoplasm may possess even the con- sistency of a soft jelly approximating a solid condition, without losing, however, the power of shifting its particles. Such a condi- tion exists in muscle-fibres, flagella, cilia, the nucleus, and upon the surface of many protoplasmic masses that do not possess a. FIG. 36. — Orbitolites. Piece of the many-chambered calcareous disc, bearing outstretched pseudo- podial filaments. A , Undisturbed. B, By strong shaking the protoplasm of the pseudopodia has been stimulated to form globules and spindles. membrane, such as infusorian cells. The term . solid is applicable to such cases only, if at all. But these cases of a more viscous con- sistency are always locally restricted within the cell ; the rest of thfe cell-contents is always a thinner liquid. Finally, it should not be forgotten that within the liquid there may be deposited all sorts of solid elements of very various con- sistencies, and that, therefore, the whole constitutes, not a homo- fBneous liquid, but a mixture, or, as Berthold terms it, an emulsion, or this reason it appears inadmissible to speak of an " aggregate condition " of protoplasm, as many observers do. Strictly speaking, the term " aggregate condition " can apply only to a homogeneous substance, not to a mixture containing substances that possess in themselves very various aggregate conditions. LIVING SUBSTANCE 97 The liquid nature of living substance is its most important physical characteristic. It requires that in its physical relations living substance must obey the laws of liquids. Accordingly, and in opposition to the idea that vital phenomena are associated only with a solid organisation, it will be seen that such phenomena may be understood only upon the supposition that their substratum is in a condition in which the particles are more or less capable of shifting. The structures that have a rigid consistency, like tendons, connective-tissue fibres, cell-membranes, and the ground- substance of bone and of cartilage, show no active vital phenomena, and the old dictum, " Corpora non agunt nisi soluta," although its universality may be attacked here and there, applies perfectly to living substance. 2. The Specific Gravity of Living Substance Among the physical properties of living substance its specific gravity possesses an important value for the understanding of certain vital phenomena. If cells of different kinds or pieces of tissue as pure as possible be allowed to fall into distilled water, it is observed that usually they sink to the bottom. It follows, therefore, that the cell-contents, as a whole, is in general heavier than water, i.e., possesses a specific gravity greater than 1. Very recently Jensen ('93, 1) has made a careful determination of the specific gravity of the one-celled ciliate infusorian, Paramcecium aurelia, in the following manner. It is well known that the specific gravity of a liquid can be raised by the addition of soluble salts, and can be graduated very finely by increase of the concentra- tion. Jensen placed Paramcecia in a weak solution of potassium carbonate, the strength of which he raised until they no longer sank to the bottom, but remained suspended in the solution — a sign that the solution possessed the same specific gravity as the bodies of the Paramcecia. Then the specific gravity of the solution was determined by means of an areometer. It was thus found that the cell-body of Paramcecium possesses a specific gravity of approximately 1*25. In general, the specific gravity of living substance cannot be much greater than this. So far as our knowledge at present extends, it is always a little greater than 1. But there are certain cases in which the aggregate weight of the cell deviates from this general principle, in which the specific gravity of the cell as a whole is less than 1. These cases can be understood at once, if it is recalled that protoplasm is not a homo- geneous substance. E.g., in the case of cells in which fat-droplets are stored in the ground-substance of the protoplasm it is possible that, although the ground-substance is heavier than water, the cell as a whole possesses a less specific gravity, since the accumulation of fat, which is considerably lighter than water, reaches such an H 98 % GENERAL PHYSIOLOGY extent that it overcomes the weight of the rest of the protoplasmic body. Such cases are realised in the fat-cel]s of the subcutaneous connective tissue in man and many animals ; if such tissue be thrown into water, it floats upon the surface. For this reason fleshy men, in swimming, have to make less effort to maintain themselves above the water than thinner persons. Other substances in the cell-body can play the same rdle as fat, particularly bubbles of gas, which under certain circumstances can lower the specific gravity of the whole body of the cell enormously — a phenomenon that occurs in many shell-bearing fresh-water Rhizopoda (Arcella, Difflugia). It follows from this fact that by the accumulation of lighter or heavier substances the cell under certain circumstances can actively diminish or increase its specific gravity, and, therefore, can actively rise or sink in water without employing locomotive organs. Under many conditions, e.g., when the vital conditions become unfavourable in the place where the organism lives, such a power is of great importance for the life of the organism. In all cases, however, where cells are found that are lighter than water, certain elements only are lighter, the whole protoplasm never. The ground-mass of the protoplasm appears always to be slightly heavier than water. 3. The Optical Properties of Living Substance In most cases protoplasm is entirely colourless or grey ; in thin layers free from solid contents it is transparent, in thick layers opaque. It refracts light somewhat more strongly than water. As regards details, the various forms of living substance behave differently according to the condition of their constituents. Some solid elements, such as fat-droplets, drops of water, and chlorophyll grains, can be intensely coloured, so that the cells in which they are present in great quantities appear yellow, red, green, etc., as, e.g., in plant tissues. The power of refracting light also differs with the individual constituents, that of water-droplets in the vacuoles is less, that of fat-droplets greater than that of the ground-substance. It would carry us too far to examine all the individual cases, but it is of interest to consider somewhat in detail the behaviour of one form of living substance, viz., the so-called contractile substance, i.e., amoeboid protoplasm, cilia, and muscle-fibres, which execute definite changes of form, called contractions. In the first half of the century Boeck found that certain elements of the cross-striated muscle-fibre are doubly refractive, i.e., are able to divide a ray of light into two rays, which are transmitted with different velocities. Later, Briicke, especially, investigated this property in detail. Still later, Engelmann (75) LIVING SUBSTANCE 99 observed that not only the discs of cross-striated muscle, but in general all fibrous contractile substances, such as those of smooth and cross-striated muscle-cells, the contractile fibres or myoids of the infusorian body, and the cilia and flagella of all ciliated cells, exhibit positive uniaxial double refraction, in such a way that their optical axis coincides with the direction of the fibres. This fact indicates that the molecular structure of all these fibrous tissues must be different in the direction of the fibres from that in other directions — an inference that is important for the under- standing of the phenomena of contraction in these objects. Engelmann has not been able to find double refraction in the naked contractile protoplasm of Bhizopoda, e.g., Amoeba. He, ob- served it only in the straight, radiating pseudopodia of Actino- sphcerium Eichhornii, a delicate fresh-water rhizopod ; but here it belonged most probably, not to the contractile protoplasm, but to the stiff rays that occur as supporting-organs in the axis of the pseudopodia, and apparently have nothing to do with the contraction. D. THE CHEMICAL PROPERTIES OF LIVING SUBSTANCE 1. The Organic Elements Of all the natural sciences, chemistry, in dealing with the atoms, penetrates deepest into the composition of the physical world. It must hence be employed in elucidating the composition of living substance, and thereby completing the preparation for an under- standing of vital phenomena. It is well known that chemistry has arrived at the point at which it recognises the vast variety of substances in the physical world to be composed of the atoms of a small number of relatively simple substances, which thus far it has not succeeded in decomposing. But, although by means of its analytical methods the division of the sixty-eight chemical elements has so far not been accomplished, and their composi- tion out of still simpler substances cannot yet be proved ex- perimentally, no chemist entertains longer any doubt that in reality these elements are not final units. Accordingly, many attempts have been made to arrange them in a genetic relation to one another, and to establish the relationship that is expressed in the analogies of the chemical behaviour of individual elements and their compounds, as a natural relationship arising by the direct derivation of one from another. Especially Mendelejeff, Lothar Meyer, and, most recently, Gustav Wendt and Preyer, arguing chiefly from the relations of the atomic weights of the elements and the similarity of certain elements as regards their own behaviour towards one another and the behaviour of their compounds, have attempted this with success ; the result is shown H 2 100 GENERAL PHYSIOLOGY by the subsequent discovery of previously unknown elements, whose existence they had predicted from certain gaps existing in the genealogical table of the elements. According to Wendt ('91) and Preyer ('92), the elements have been developed in the course of the earth's history by gradual condensation from a primitive element, hydrogen, in such a way that those having a higher atomic weight have been derived from those having a lower one; finally, all have been derived from hydrogen, the element possessing the lowest atomic weight. But here scientific theory ceases and hypothesis begins. Whether hydrogen is really the ultimate unit, and in what relation its atoms stand as ponderable or mass-atoms to the imponderable universal ether, the existence of which physics finds it necessary to assume from the phenomena of light and electricity, for the present is not known. But if we confine ourselves to ponderable matter, to which living substance, like all other bodies, belongs, chemical analysis shows that of the sixty-eight elements of which the physical world consists, twelve only are found constantly in living substance. These twelve elements which occur in every cell are :— Name. Symbol. Atomic Weight. Carbon C 12 Nitrogen N 14 Sulphur S 32 Hydrogen H 1 Oxygen O 16 Phosphorus P 31 Chlorine Cl 35 Potassium K 39 Sodium Na 23 Magnesium Mg 24 Calcium Ca 40 Iron Fe 56 Besides these twelve general organic elements, a small number of special elements occur which are not met with in all cells, and some of which are found only very sporadically. These are : — Name. Symbol. Atomic Weight. Silicon Si 28 Fluorine Fl 19 Bromine Br 80 Iodine I 127 Aluminium Al 27 Manganese : . . . Mn 55 Among these, silicon is wide-spread and fluorine is infrequent, while the others, which likewise have a very limited occurrence, LIVING SUBSTANCE 101 and certain metals, such as copper, which are occasionally found in traces in living substance, perhaps possess no importance at all for the vital processes of the organisms in which they have been observed. But no one of all these organic elements is limited exclusively to organic nature. Carbon occurs in the air, combined with oxygen, as carbonic acid, and in large masses in the calcium carbonate of sedimentary rocks. Hydrogen, likewise combined with oxygen, as water, covers the greater part of the earth's surface. Oxygen occurs both free as a gas in the atmospheric air, of which it constitutes about 21 per cent., and also combined with a large number of other elements. Nitrogen occurs likewise both in the free state in the air, com- prising about 79 per cent., and also combined with hydrogen and oxygen in the compounds of ammonia, both ammonium nitrate and nitric acid. Sulphur is wide-spread in combination with oxygen in sulphates. Phosphorus behaves similarly, and is to be found everywhere in the phosphates of the alkalies and the alkaline earths. Chlorine is very widely distributed, combined with sodium, as common salt. Potassium occurs in combination with chlorine as potassium chloride, and with acids as nitrates, sulphates, and phosphates. Soditim, chiefly in the form of sodium chloride or common salt, is found everywhere on the surface of the earth ; it is in solution in the sea, in the earth, and forms large solid masses in salt strata. Magnesium is a constant accompaniment of' potassium and sodium, and is similarly combined, occurring as magnesium chloride, carbonate, sulphate, and phosphate. Calcium, in the form of calcium carbonate, silicate, sulphate, and phosphate, occurs in the vast limestone strata of the sedi- mentary rocks. Iron is very wide-spread over the earth's surface in the form of sulphur compounds, oxides and their salts. Silicon appears almost exclusively combined with oxygen in the form of silicic acid and its salts in igneous rocks. Fluorine occurs chiefly in combination with calcium as fluor spar. Bromine and iodine are present in many salt strata, as well as in sea-water, as sodium bromide (iodide), and potassium bromide <(iodide). Aluminium is spread over the whole earth in combination with oxygen as clay, and in the latter form, combined with silicic acid, as feldspar. Manganese and all the other'metals that are observed occasionally 102 * GENERAL PHYSIOLOGY here and there in the living organism are met with everywhere in rocks in the form of their oxides, sulphur compounds, and various salts. This survey shows that all organic elements help at the same time to constitute the inorganic portion of the earth's surface. Since, moreover, chemical analysis of living substance has shown that no constituents but these organic elements are to be found in the organism, the important fact follows that an elementary vital substance exists no more than a specific vital force. The conceptions of a " vital ether," a " stpiritus animalis" a " vital matter," etc., with which the earlier physiology so freely dealt, have, therefore, in harmony with the advanced development which analytical chemistry has undergone at the present time, com- pletely disappeared from the present theory of life; living substance is composed of no different chemical materials from those occurring within lifeless bodies. Nevertheless, one fact deserves mention, viz., that the few general organic elements are not scattered irregularly here and there through the natural system of elements, but they occupy a definite position, being remarkable as elements having very low atomic weights. Hence the conclusion may with great probability be drawn that in the evolution of the elements the organic elements arose by condensation very early, and therefore existed in the very early stages of the development of our planetary system, at a time when other elements, such as the heavy metals, had not yet been formed. 2. The Chemical Compounds of the Cell Living substance must be killed before its chemical composition can be learned. Paradoxical as this may sound, at present it is the only way by which a knowledge of the chemistry of living sub- stance can be obtained. The biting sarcasm that Mephistopheles pours out before the scholar upon this practice of physiological chemistry must be quietly endured. It is not possible to apply the methods of chemistry to living substance without killing it. Every chemical reagent that comes in contact with it disturbs it and changes it, and what is left for investigation is no longer living substance, but a corpse — a substance that has wholly different properties. Hence ideas upon the chemistry of the living object can be obtained only by deductions from chemical discoveries in the dead object, deductions the correctness of which can be proved experimentally in the living object only in rare cases. This alone is responsible for the excessively slow advance of the knowledge of the chemistry of the vital process. It is evident that the greatest foresight is necessary in applying results obtained upon the dead object to conditions in the living, and it must con- LIVING SUBSTANCE 103 stantly be borne in mind that the chemical relations of the latter are to be distinguished sharply from those of the former. Although there is no fundamental difference between the ele- ments composing living and those composing lifeless substance, in other words, although no special vital element exists in the organic world, some of the elements in living substance form unique com- pounds which characterise it only, and are never found in lifeless substance. Thus, there exist in the former, besides chemical compounds that occur also in the latter, specific organic complexes of atoms. Many of these organic compounds, especially those that are of special importance to living substance, possess so complicated a constitution that thus far chemistry has not succeeded in obtain- ing an insight into the spatial relations of the atoms in their molecules, although the percentage composition of the molecules is known to a greater extent. There are especially three chief groups of chemical bodies and their transformation-products, by the presence of which living sub- stance is distinguished from lifeless substance ; these are proteids, fats, and carbohydrates. Of these only the proteids and their deri- vatives have been demonstrated with certainty as common to all cells ; hence they must be set apart among the organic constitu- ents of living matter as the essential or general substances, in contrast to all special substances. a. Proteids The proteids play the most important rdle in the composition of living substance, since they are absolutely indispensable to all life that exists at present upon the surface of the earth, and quan- titatively they constitute the chief constituent of all the organic compounds of the cell. Without exception they consist of the elements carbon, hydrogen, sulphur, nitrogen, and oxygen ; of these, nitrogen especially distinguishes proteids from the two other chief groups of organic bodies, carbohydrates and fats, so that the former, as nitrogenous bodies, are to be contrasted with the latter two as non-nitrogenous. The stereo-chemical composition of the proteid molecule is not yet known, but from analyses, in which the molecule is split up into a large number of still very complex molecules, it is known that it must have an excessively complex constitution ; although it contains only the five elements C, H, N, S, and O, the number of its atoms often reaches far beyond a thou- sand. In the year 1866 Preyer made the first analysis of haemoglobin, the proteid that gives the characteristic colour to the blood, more exactly to the red corpuscles, and, as a carrier of oxygen from the lungs through the blood to the cells of the tissues, 104 GENERAL PHYSIOLOGY plays an extremely important role in the animal body. found the composition of haemoglobin to be — Preyer Although at first this formula caused surprise, a number of later analyses have since given quite similar results.1 Thus, according to Griibler's investigations ('81), the compo- sition of the crystallised proteid which occurs in the squash-seed may be estimated as — ZinofFsky ('85) found the formula of hsemoglobin from horse blood even still larger than Preyer — Similarly complex formulas have been derived for the proteid that constitutes the white of the hen's egg. From all these analyses it follows that because of the mass of its constituent atoms the proteid molecule must be enormous. The great size of the molecule explains an important character- istic of proteids, viz., that, in contrast to other bodies, they do not diffuse from solutions through animal membranes or artificial parchment. If an aqueous solution of common salt or any other soluble salt be placed in a wide glass tube, the lower end of which is closed by a membrane, preferably artificial parchment (Fig. 37), and the tube be suspended in a vessel of pure water, it is found after a short time that the concentration of the salt solution in the inner tube has de- creased considerably, while the water in the outer vessel has come to have an equal percentage quantity of salt. Hence salt has diffused from the tube through the membrane into the outer water until its percent- age composition has become equal in the two liquids. But if instead of the solution of salt a solu- tion of egg albumin be employed, which can be obtained by rubbing up thoroughly the white of a hen's egg with about 100 cubic centi- metres of water and filtering, the solution can be allowed to stand in the dialyzer (as the apparatus is called) for hours and days without a trace of albumin diffusing from the inner tube into the outer water. This phenomenon may be explained very simply from 1 Cf. Bunge ('94). FIG. 37.— Dialyzer. LIVING SUBSTANCE 105 the size of the albumin molecule ; the latter is too large to pass through the excessively fine pores of the membrane, while no obstruction stands in the way of the small molecules of salt. This property is of practical importance in the chemical investigation of proteids, for by dialysis the proteids can always easily be sepa- rated from the salts that may be present with them in solution. The fact that proteids and a host of other substances which behave similarly do not diffuse through membranes, has led to the idea that these bodies, in contrast to diffusible substances, dissolve in water only apparently, and form no real solutions ; their appa- rent solubility may be only a largely developed power of swelling. Proteids in a dry state are, in fact, capable of taking up very large quantities of water, and thereby gradually swelling. In 1861 Graham contrasted these bodies as colloid substances from crystalloid substances ; and this distinction has been handed down and been generally accepted. The colloids are said to be capable of swelling only, not of crystallising ; the crystalloids, on FIG. 38.— Crystals of haemoglobin. /, From man, //, from the guinea-pig, ///, from the squirrel. (After Kirkes.) the other hand, to be really soluble and capable of crystallisation. But such a sharp distinction is scarcely admissible ; for in the first place, proteids are known that can form genuine crystals, like the above-mentioned proteids in squash-seeds, which occur wide- spread in plant seeds as aleurone-grains, and like the haemoglobin of the red blood-corpuscles. If, e.g., whipped blood from the guinea- pig be shaken for a time with ether, by which the haemoglobin is extracted from the substance of the red corpuscles and driven out into the blood-serum, and a drop of this liquid be allowed slowly to evaporate upon a glass slide, very delicate tetrahedral crystals gradually separate (Fig. 38, //), which consist of pure haemoglobin. In the second place, under the influence of certain reagents, proteids can pass over into modifications that diffuse through membranes, without losing in the process the chemical characteristics of proteids. These modifications, which, e.g., proteids undergo in the body under the influence of the digestive juices of the stomach and the pancreas, are termed peptones : it is known 106 GENERAL PHYSIOLOGY that they arise by the hydrolytic cleavage of the original proteid molecule, so that the peptones represent the hydrates of the original proteids. Important conclusions follow from this fact. Since the proteid molecule, which was originally not diffusible on account of its enormous size, is split up in the peptonising process into the peptone molecules, which are much smaller and therefore diffusible, but which have the chemical characteristics of proteids, it follows that the proteid molecule is not simple but polymeric, i.e., it consists of a chain-like combination of many similar groups of atoms. In the transition to the peptone condition the proteid molecule is broken up with hydration into these single, similar atomic groups, all of which, however, have the chemical characteristics of proteids, but represent much smaller molecules. The inability of proteids to diffuse through membranes depends, therefore, solely upon their polymerism. Wholly analogous cases occur in inorganic nature ; e.g., certain forms of silicic acid are unable to diffuse through membranes because of their polymerism. Hence it is evident that no fundamental difference exists between solutions of simple molecules, as found in peptones, and those of polymeric molecules, as in ordinary albumin. A further physical property, which is perhaps connected with the polymerism of the ordinary proteid molecule, and which belongs to almost all proteids with the exception of their hydrates, the peptones, is their capacity of clotting, or coagulating. Coagula- tion consists in the passing of the substance from the dissolved to the solid condition within the solvent medium. Boiling is a method that causes coagulation in almost all proteids. In the fresh hen's egg the proteid is present in a thick clear viscous solution. In the boiled egg it has become a solid white opaque mass ; it is coagu- lated. By boiling, proteid can be separated out of thin solutions in the form of fine curdled flakes. Other methods, such as the use of inorganic acids and alcohol, also cause proteid in solution to be coagulated and precipitated, the result being indicated by a clouding of the liquid. That the power of coagulation is in some way connected with polymerism is indicated by the fact that in- organic polymeric molecules, such as the above-mentioned silicic acid, in aqueous solution can likewise be coagulated into a jelly. If, e.g., hydrochloric acid be added to a solution of sodium silicate, free silicic acid and sodium chloride are produced ; the silicic acid may then be separated from the salt by dialysis, since, in contrast to the salt, the former, like a polymeric body possessing very large molecules, does not diffuse through membranes. By the addition of a few bubbles of carbonic acid this solution of silicic acid may be changed at once into a coagulated jelly-like mass. Since our knowledge of the chemical composition of proteids is at present very incomplete, it is not easy to produce definite chemical reactions with them. Nevertheless, a number of tests have been empirically LIVING SUBSTANCE 107 determined, which are characteristic for proteids and in doubtful cases make known their presence. What chemical transformation the proteid molecule undergoes in these tests is of course prac- tically unknown. The best-known tests are the following, any one of which alone is riot sufficient to prove with absolute certainty the presence of albumin : — 1. The xanthoproteic test : a solution of proteid is coloured yellow by boiling with nitric acid ; by the addition of ammonia the colour changes to orange. 2. The biuret test : if a solution of proteid be made alkaline by causic potash or soda, it takes on in the cold, by the addition of a drop of cupric sulphate solution, a clear violet colour. 3. Milton's test : coagulated proteid, boiled for a time with a solution of mercuric nitrate, and a little nitrous acid, becomes rose-red. 4 The hydrochloric acid test : boiling with concentrated hydrochloric acid dissolves coagulated proteids and colours the clear liquid violet. 5. The potassium ferrocyanide test : a solution of proteid to which acetic acid has been added shows by the addition of a solution of potassium ferrocyanide a white cloudiness. 6. The iodine test : the addition of tincture of iodine, or a solution of iodine in potassium iodide, serves as a good microscopic method for recognising proteids ; the clot becomes yellowish-brown. Besides these tests, a great number of others have been sug- gested by different investigators, but they fail in individual cases. According to their different solubilities in water, three groups may be distinguished among the simple proteids — viz., the albumins, the globulins, and the vitellins.1 The albumins are directly soluble in pure water. To them be- long egg-albumin, which forms the great mass of the white of eggs ; serum-albumin, an albuminous body contained in blood-serum ; muscle-albumin, the proteid of muscle-cells, soluble in water ; and plant-albumin, which is dissolved in the sap of plant-cells. The globulins are soluble in water only when it contains neu- tral salts, but in less quantity than in saturation. If a solution of globulin be saturated with salts, the globulin is precipitated in a flocculent mass — a phenomenon that is termed " salting out." The globulin is likewise precipitated if the solution be wholly freed from salts by diffusion in a dialyzer. To the globulins belong serum-globulin, which is dissolved in the blood-serum ; fibrinogen, also a proteid of blood, which coagulates spontaneously into flakes and threads of fibrin when the blood is allowed to stand outside the blood-vessels ; myosin, the globulin of muscle, which likewise 1 Neumeister ('93}. 108 GENERAL PHYSIOLOGY coagulates spontaneously upon standing — a phenomenon that appears in dying muscle in rigor mortis ; and, finally, plant- globulin, which gives to kernels of grain their glutinous quality, and hence has been termed glutin. The mtellins are likewise soluble in neutral salt solutions only, but, in contrast to the globulins, they are not precipitated by satura- tion of the solution with salts. Among them are the so-called yolk- plates of the yolk of eggs, and the already-mentioned aleurone grains of plant seeds, both of which are proteids capable of crystal- lization. The above-mentioned proteids occur in a free state in living substance. A very large number of proteids, however, are not free, but are chemically combined with other substances. In these com- pounds, which have been termed combined proteids in distinction from the simple proteids, the proteid molecule behaves in general like a feeble acid, and by the addition of stronger acids it can frequently be forced out of its compounds/ the stronger acid taking its place. The proteid then becomes free. We have already become acquainted with one of these compounds, haemoglobin, which plays in blood so important a role and is a compound of proteid and iron. But the most important compounds, in which proteids appear with- out exception in every cell, are the nucleins. The nucleins, as Altmann ('89) has shown, are compounds of proteid with nucleic acid, an acid which is itself a compound of phosphoric acid with peculiar basic bodies, the so-called nuclein bases — guanin, adenin, xanthin and hypoxanthin. The nucleins are capable of entering into further combinations with a second proteid molecule, and these ex- tremely complex compounds are termed nucleo-proteids or nucleo- albumins. Casein, a body which for a long time has presented difficulties to the physiological chemists, is such a nucleo-proteid, combined with calcium. Casein is the calcareous nucleo-proteid of milk that is manufactured into cheese ; it has the peculiarity of not coagulating when the milk is boiled, while it is immediately precipitated when separated, as by acetic acid, from the calcium. A fourth group of combined proteids is that of the glyco-proteids, in which proteid is combined with a carbohydrate ; prominent among these is mucin, which is contained in the cells of mucous glands. Besides the genuine proteids which we have just described, there exist a number of bodies which behave in many ways similar to proteids and, therefore, have been termed albuminoids. The group of albuminoids is a true omnium gatherum ; it contains a very large variety of .bodies. These are partly compounds of pro- teids and partly bodies of similar constitution to the proteids, but which show in their chemical behaviour much less similarity and are much less known than the proteids themselves. Especially prominent among albuminoids are many of those substances that are produced by cells to serve as skeletal substances for the support LIVING SUBSTANCE 109- of the more delicate parts of the organism. A detailed examination of the known reactions which the numerous albuminoid bodies present would lead too far and be superfluous for our purpose.1 It is sufficient here to cite some of the most important members of the group, all of which occur in the solid undissolved state. Such are keratin, which is contained in most horny structures produced by the epidermis-cells of the skin (horns, hoofs, hairs, feathers, and nails) ; elastin, which composes the elastic fibres of the cells of connective tissue and the strong yellow ligamentum nuchce ; collagen, which composes the organic ground -substance of bones and car- tilage, and in boiling passes over by hydrolysis into gelatine ; spongin, the skeletal substance of bath-sponges ; conchiolin, the organic substance of the shells of mussels and snails ; cornein, that of the skeletons of corals ; and many other substances that form skeletons, especially in invertebrates. With the albuminoids also is classed a series of highly complex nitrogenous bodies which at least are derivatives of proteids and possess the greatest importance in the life of the organism, especially in digestion. These are the unformed ferments or enzymes, such as pepsin, produced by the gland-cells of the stomach ; ptyalin, by the cells of the pancreas and the salivary glands ; trypsin, produced likewise by the pancreatic cells ; and many others. Tihe properties of these bodies and their roles in the life of the cell will be considered more fully elsewhere. There appear in living substance, as constant accompaniments of proteids, certain decomposition-products of them which can be divided into two groups — the nitrogenous and the non-nitrogenous cleavage-products. The former constitute a series of substances whose chemical constitution is more exactly known. They are the products of retrogressive proteid-metamorphosis. Among them belong especially the substances excreted in considerable quantity by the higher animals in the urine. Among them urea, (NH2)2CO, holds the first rank ; it is the richest in nitrogen of all the nitrogenous end-products of proteid-decomposition, and its artificial synthesis was accomplished by Wohler in the year 1828. Next to urea, uric acid, C5H4N4O3, contains the most nitrogen ; next to uric acid come in order hippuric acid, creatin, which originates in the muscles by the decomposition of proteid, and creatinin. Further, the nuclein bases, xanthin, hypoxanthin or sarkin, adenin and guanin are met with as end-products of the decomposition of nucleins in the living organism. Of these, especially the last in combination with calcium occurs very frequently in the skin-cells of Amphibia and of fishes, in the latter of which its crystals produce the well-known silvery sheen. Finally, there is one more group of nitrogenous bodies, the lecithins, 1 A review of the subject and the bibliography of it may be found in Neu- meister : Lehrbuch der physiologischen Chemie. 2nd edition, Jena, 1897. 110 GENERAL PHYSIOLOGY which stand near the fats, but contain phosphorus ; they are pro- bably present in every living cell and, according to Hoppe-Seyler, are to be regarded as cleavage-products of proteids, especially of nucleins, with which they occur. Among the non-nitrogenous end-products of proteid-decompo- sition carbonic acid, which is produced by every cell, comes first in importance. Lactic acid, oxalic acid, and sulphuric acid are im- portant. The cholesterins also are to be regarded at least as deriva- tives of proteids ; they seem to occur in all living substance, but appear in great quantity only under certain circumstances in the form of iridescent scales, as upon the surface of the skin and the beak of birds, and in pathological conditions as gall-stones in the bile. Chemically the cholesterins are univalent alcohols, which with fatty acids can form fat-like compounds. Finally, there appear as decomposition-products of proteids certain carbohydrates, particu- larly grape-sugar and glycogen, and fats, which must be considered somewhat in detail in connection with allied substances. I. Carbohydrates In contrast to its presence in the proteids, nitrogen is wanting in the carbohydrates. The latter contain only the three elements, carbon, hydrogen and oxygen ; in the natural carbohydrates the number of carbon atoms within the molecule is always six or a multiple of six, while the number of hydrogen atoms is always double that of the atoms of oxygen ; hence hydrogen and oxygen are present in the same relative proportions as in water — a foct which led to the designation " carbohydrates." The carbohydrates are very wide-spread and are of great importance, especially in the manufacture of living substance in plant-cells; but there are varieties of living substance in which they cannot be demonstrated ; in other words, they are not general constituents of such substance. They present far simpler chemical relations than the proteids, and a brief glance will show their most essential features. The natural carbohydrates may be divided into monosaccharids, disaccharids and polysaccharids, of which the two latter groups are different anhydride forms of the first group. The monosaccharids all have the formula C6H12Og, and are, there- fore, isomeric ; but they are not all stereo-isomeric, that is, their individual atoms are not grouped alike in all. To the mono- saccharids belong chiefly grape-sugar (dextrose or glucose) andfruit- sugar (Isevulose), both of which are wide-spread in plant juices, the former in great quantity also in animal tissues. One of the most remarkable characteristics of the monosaccharids is that they readily take up oxygen from their surroundings and thus reduce bodies that are rich in oxygen, a peculiarity upon which depend the most important tests for their recognition. The most re- LIVING SUBSTANCE 111 liable of these reduction- tests are Trommer's test and Bottger's test. They may be performed very simply in a test-tube. The former consists in the reduction of cupric hydroxide to cuprous oxide by an alkaline solution of grape-sugar. If a few drops of a very dilute solution of cupric sulphate be added to a sugar solution, made alkaline by caustic potash or soda, until a blue flocculent pre- cipitate of cupric hydroxide appears, on boiling the latter is reduced to red cuprous oxide or yellow cuprous hydroxide. In Bottger's test a few drops of a solution of basic nitrate of bismuth is added to the alkaline solution of grape-sugar ; the former is then reduced to black metallic bismuth. A further very characteristic property of the monosaccharids is their power of fermentation. They become decomposed by the action of yeast-cells (Saccharomyces) into alcohol and carbonic acid — C6H1206 = 2C2H5OH + 2C02. Such an experiment can be carried on best in a fermentation - glass (Fig. 39), by introducing into it a solution of grape-sugar FIG. 39.— Fermentation-tube— a, newly filled ; b, with carbonic acid developing. At the top of the straight limb a quantity of carbonic acid has already accumulated. mixed with fresh yeast, so that the liquid fills completely the long closed limb of the glass. At a temperature of c. 30° — 40° C. there appears a fairly energetic cleavage of the grape-sugar, small bubbles of carbonic acid rising continually as in a glass of cham- pagne, and accumulating at the upper end. The more carbonic acid accumulates above, the more the liquid is forced out of the long limb into the spherical part of the vessel, until finally the former may be entirely filled with the gas. The presence of alco- hol may be recognized at once by the odour of the liquid. One more characteristic of the monosaccharids may be mentioned, 112 GENERAL PHYSIOLOGY which they share with all soluble carbohydrates — viz., the power of rotating the plane of polarised light. As their names indicate, dextrose rotates it to the right ; Isevulose, to the left. The disaccharids may be regarded as having arisen from the monosaccharids by the combination of two molecules of the latter and the loss of a molecule of water ; this would yield the formula — C12H22On. Among the disaccharids are to be noted especially cane-sugar (saccharose), which is contained in large quantities in the cell-sap of the sugar-cane ; and milk-swgar (lactose), the carbohydrate of milk. By certain methods, as by boiling with dilute inorganic acids or by the action of certain bacteria, the disaccharids can be made to undergo hydrolytic cleavage, so that they pass over into the monosaccharids. This change is termed inversion. In contact with certain fermentation-agents, especially Bacterium lac- ticum, the disaccharids are induced not to ferment directly, but to pass over into monosaccharids, which are themselves subject to the fermentative action of these organisms. If Bacterium lacticum be employed as the fermentation-agent, lactic acid results — C6H1206=2C3H603 — a process which, in contrast to alcoholic fermentation by the yeast, plant, is termed lactic acid fermentation ; to it is due the souring of milk exposed to the air. Finally, under the influence of another fermentation agent, Bacillus butyricus, lactic acid can be still further decomposed into butyric acid, carbonic acid and hydrogen — 2G3H603 = C4H802 + 2C02 + 4H ; thus a butyric acid fermentation is recognised. The polysaccharids are anhydride stages of the monosaccharids. still further removed ; in them several monosaccharid molecules combine with the loss of a molecule of water, so that their formula is a multiple of C6H10O5. Among the polysaccharids occurs a series of bodies that play an important role and are wide- spread, some in the life of the plant-cell, others in many animal-cells. They are, first, starch, which occurs in all green cells of plants in the form of granules, in which the layers are arranged concentrically (Fig. 40) ; secondly, glycogen, which occurs as flakes and irregular particles, especially in the cells of the liver, but in smaller quantities in many other tissue-cells; thirdly, cellulose, which constitutes the cell-membranes of all plant-cells, and has been demonstrated also in the leathery mantle of the Tunicates. These members of the group of polysaccharids may be distin- guished from one another in a very characteristic manner by their behaviour towards solutions of , iodine : by iodine starch is coloured an intense blue, glycogen a mahogany brown, and cellulose LIVING SUBSTANCE 113 not at all ; the latter, however, becomes blue in the presence of iodine and sulphuric acid. In addition to the free carbohydrates, combinations of carbohydrates exist in living substance — e.g., combinations with proteids, as an example of which mucin has already been mentioned. The most important decomposition-products of carbohydrates have also been mentioned, such as lactic acid, butyric acid, carbonic acid, etc., all of which are met with in living substance. c. Fats The fats likewise do not belong to the general constituents of living substance, but they are wide-spread, chiefly in animal cells. Like the carbohydrates, the fats are non-nitrogenous, and contain only the elements car- bon, hydrogen and oxygen. But chemically they differ funda- mentally from the carbohy- drates. For example, they re- present the so-called compound ethers, or esters — i.e. compounds in which an acid has combined with alcohol with the loss of water. The alcohol that is the basis of all fats is glycerine, C3H5(OH)3, and the acids that are combined with glycerine belong to the series of fatty acids, whose general formula is CUH211O2. Since the glycerine represents a trivalent alcohol, in the neutral fats three atoms of fatty acid are always combined with one atom of glycerine into tri-glycerides. The general formula of the fats is, therefore— C3H5(OH)3 + 3CnH2n02-3H20. As examples of the fatty acids there may here be mentioned palmitic acid, stearic acid, butyric acid, valeric acid and capronic acid. In addition to these, oleic acid, which does not belong to the normal series of fatty acids, occurs in the various oils combined with glycerine. In correspondence with their composition, the neutral fats may by certain methods be split up by hydrolysis into their constituents — i.e., into glycerine and free fatty acids ; this process takes place in the organism as the result of the action of the digestive juices. It I i it FIG. 40. — /. Plant-cell containing starch-grains. II. Starch-grains isolated — a, from the po- tato ; b, from the corn ; c, from the pea. 114 ' GENERAL PHYSIOLOGY occurs also when neutral fats are boiled with alkaline liquids, such as caustic potash or soda. The fatty acids thus set free combine with the alkali to form the so-called soaps, which may be distin- guished as potash soaps, sodium soaps, calcium soaps, etc. The fats are all lighter than water and do not dissolve in water, but they are easily soluble in ether. A characteristic property, which is important for the microscopic recognition of the fat-drop- lets in cells, is their power of reducing perosmic acid to metallic osmium, the latter forming a black coating to the fat-droplet. This osmic acid reaction is not to be employed alone as a sure test in the diagnosis of fat ; for doubtless other reducing substances exist, which, under certain circumstances, can be blackened by osmium; hence it should be used only in conjunction with other tests, solubility in ether, strong refracting power, etc. The fact that fats, like carbohydrates, can appear as cleavage- products of proteids has already been mentioned. d. The Inorganic Constituents of Living Substance In the case of the organic compounds of the cell the general con- stituents (proteids) and the special constituents (carbohydrates and fats) can be contrasted ; the same distinction can be made with the inorganic compounds. Here, also, the greater interest is associated with the general inorganic constitiients, among which there are distinguished water, salts, and gases. ' Water is that constituent of living substance that gives to it its liquid nature and thus renders possible the easy shifting of its particles, which is so necessary for the occurrence of vital phenomena. It is contained in the cell, in part chemically combined as water of constitution, and in part free, as the solvent medium of all sorts of substances. Accordingly, water is present in abundant quantity, constituting upon the average more than 50 per cent, by weight of living substance. If, e.g., the whole water contents of the human body be investigated, which with the great variety of the forms of tissue affords a good average, approximately 59 per cent, of water is found; this is shown especially by the detailed investigations of Bezold. The different tissues vary very greatly in this respect. Thus, bones contain only about 22 per cent, of water, the liver 69 per cent., muscles 75 per cent., and the kidneys 82 per cent. Hence it is not strange that the water contents of living substance varies much more in different species of animals, and that all intermediate stages in percentage composi- tion are met with between the slight traces of water contained in a rotifer when dried but still capable of life, and the water-contents, amounting to more than 99 per cent., of certain pelagic Cteno- phora. LIVING SUBSTANCE 115 Many salts occur dissolved in water, and they are present in all living substance. The compounds of chlorine appear to be espe- cially important, as well as the carbonates, sulphates, and phosphates of the alkalies and alkaline earths, particularly sodium chloride (common salt), potassium chloride, ammonium chloride, and sodium, potassium, magnesium, ammonium, and calcium carbonates, sul- phates and phosphates. Finally, as regards gases, there occur in all living substance oxygen and carbonic acid. When not in chemical combination, they are usually absorbed in water, and rarely, as in many uni- cellular organisms, e.g., Rhizopoda, in the form of bubbles of gas. The special inorganic constituents of cells comprise a great variety of substances, but for present purposes it is unnecessary to discuss them. It is remarkable that in certain cells even free mineral acids appear, such as hydrochloric acid, which is produced by certain cells of the gastric glands in vertebrates, and sulphuric acid, which in many marine snails is secreted by the cells of the salivary glands. e. The Distribution of Substances in Protoplasm and Nucleus Although during the last few years our knowledge of cell- morphology has increased greatly, and microscopic investigation of the cell has revealed its finest structural relations, comparatively little is known of the chemical nature of its individual morpho- logical constituents. Here is the point where physiological micro- chemistry must institute its work. The combination of microscopic observation and chemical reaction alone is able to bridge the gap between that which has become known morphologically as ground- substance and solid constituents in the protoplasm and the nucleus, and that which gross chemical analysis has shown to be the constituents of living substance. The building of the bridge be- tween the morphology and the chemistry of the cell is a difficult undertaking, since the majority of reactions that can be employed conveniently and easily in the test-tube, under the microscope on account of the minuteness of the objects either give very indistinct results, or are entire failures. Hence, first of all, delicate and re- liable micro-chemical methods need to be devised. The first steps in this direction have already been taken, and we have begun to obtain here and there an insight into the distribution of the chemically known substances within the cell-contents. It has been shown that the bodies that have been found as morphological differentiations in the cell- contents, differ also chemically. Especially the investigations of Miescher, Schwarz, Zacharias, Altmann, Kossel, Lowitt, Malfatti and others have proved that characteristic chemical differences exist between the [ 2 116 GENERAL PHYSIOLOGY constituents of the two essential cell-elements, the protoplasm and the nucleus. The proteids, which are the sole general chemical constituents of the cell, occur in both the protoplasm and the nucleus, but a very remarkable difference between them has been discovered. It has been found that the compounds of proteids, containing phosphoric acid, the so-called nucleins, preponderate greatly in the nucleus,1 while in the protoplasm they seem to be wanting entirely, or at least to appear only in combination with other pro- teids as nucleo-albumins ; the protoplasm, on the other hand, is constructed chiefly of simple proteids and proteid compounds that lack phosphorus. The employment of a simple chemical method confirms this fact. As Miescher ('74) has shown, the nucleins, in contrast to all other proteids, resist the digestive action of the gastric juice. If, therefore, cells of very different kinds be brought under the influence of artificial gastric juice, all other proteids are digested, while the nucleins remain. It is then found that the whole protoplasmic body is digested, while the nuclei are left with an inconsiderable decrease in volume and a somewhat ragged contour. If, now, the remaining substance of the nuclei be tested with the known nuclear stains, it is shown that what is wanting is the nuclear sap,2 and perhaps the achromatic substance also, for the whole remaining mass takes up the nuclear stain more or less strongly. It follows, therefore, that the chromatic substance and the nucleoli consist of nucleins, while the pro- toplasm of the cell is composed of other proteids. Lilienfeld and Monti ('93), in Kossel's laboratory, have endeavoured to prove by means of a micro-chemical reaction that phosphorus is localised especially in the nucleus. If ammonium molybdate be added to a substance containing phosphoric acid, a compound is formed, phospho-molybdic acid, which with pyrogallol takes on a dark brownish-black colour. Lilienfeld and Monti were able to show that in a great variety of cells the nuclei stain black because of this reaction, while the protoplasm is left unstained ; but it should be mentioned that soon after the publication of their results Raciborski, Gilson and Heine raised the objection against the re- action that there was simply an accumulation of ammonium molybdate in the nucleus, which is analogous to the accumulation there of nuclear stains. Hence caution is still necessary in drawing conclusions from this reaction. The carbohydrates appear to be limited to the protoplasm ; at least, thus far no carbohydrates have been found in the nucleus. In the protoplasm they appear not rarely as solid constituents, e.g., glycogen in the form of scales and irregular particles in the proto- plasm of liver-cells, starch-grains in general in the protoplasm of 1 Gf. Kossel ('91). a Cf. Haifa tti ('91, '92). LIVING SUBSTANCE 117 all green plant-cells, and cellulose as a protoplasmic product upon the surface of cells. The fats also appear to be limited to the protoplasm. Without •exception they seem to be wanting in the nucleus, but are very wide-spread in the protoplasm as fat- and oil-droplets. They may always be recognised by their great refracting power, or, in dubio, by their blackening with perosmic acid and solubility in ether. Concerning the distribution of the inorganic constituents of the cell almost nothing whatever is known. As to the potassium com- pounds, however, the investigations of Vahlen appear to show that they are to be found exclusively in the protoplasm, and not in the nucleus. These are the few facts thus far known. The chemical composi- tion of the great mass of substances in the protoplasm that are termed granules, as well as that of the substances in solution, is thus far wholly unknown. Here an unbounded field is open to the physiological chemists of the future, and in a more distant future shall we have to look to the micro-chemical investigation of living substance for the solution of the final riddle of life. The main points of the above examination of living substance may be summarised as follows : Living substance, as it now exists upon the surface of the earth, appears solely in the form of elemen- tary organisms, the cells, some of which live separately, while some Are united together into coherent communities. Each cell is a bit of liquid substance, usually microscopic in size, in which various constituents, partly solid, partly in solution, are stored Only the liquid ground-mass, the protoplasm, and the somewhat more solid nucleus contained within the former can be regarded as general cell-constituents. A bit of protoplasm containing a nucleus is a complete cell, and, vice versa, there are no cells that do not possess nucleus and protoplasm. Just as very different morpho- logical constituents may be distinguished in living substance, so very different chemical bodies are present. The elements of which they consist are only such as exist in the inanimate world also, but their number is small, and it is chiefly the elements having the lowest atomic weights that compose living substance. A special vital element does not exist, but the compounds in which these elements occur are characteristic of living substance, and in great part are absent from the inorganic world. They are, first of all, proteids, the most complex of all organic compounds, which consist of the elements C, H, O, N, and S, and are never wanting in living substance. Further, there occur other complex organic compounds, such as carbohydrates, fats, and simpler substances, all of which either are derived from the decomposition of proteids or are necessary to their construction ; and inorganic substances, 118 GENERAL PHYSIOLOGY ' such as salts and water; the latter gives to living substance its requisite liquid consistency. In its main outlines the above is the picture that the anatomical, microscopic, physical, and chemical investigation of living substance has afforded. II. LIVING AND LIFELESS SUBSTANCE But the picture of living substance is still incomplete. In the above pages there have been presented the details of its composi- tion as known at present, but the most essential point is still wanting. In what does the characteristic difference between living and lifeless substance consist ? This question is weighty, for it contains nothing less than the problem of all physiology — namely, the problem of life, which since the earliest times has had an irresistible fascination for inquiring minds. As has already been seen, the conception of life has not been always the same. Since its origin among primitive peoples, it has become changed in diverse ways. We will now inquire whether it is possible to outline the conception scientifically by considering the differences between living and lifeless substance. Because of the sharp distinction between objects that never have lived, such as stones, and those that have lived and died, or corpses, this undertaking must be extended in two directions — first, to the differences between organisms and inorganic sub- stances, and, secondly, to the differences between living and dead organisms. A. ORGANISMS AND INORGANIC BODIES 1. Structured Differences In comparing organisms with inorganic substances, the mistake has been made of contrasting the organism with a crystal, instead of with a substance that has a consistency, and, in general, physical relations similar to those of living substance, i.e., with a semi- liquid mass. Because of this mistaken comparison, a host of differences have been set up, the incorrectness of which is evident. Thus, it has been said that inorganic bodies have forms con- structed according to simple mathematical laws and possessing perfectly definite angles and edges, while organisms have bodily shapes that cannot be represented mathematically. It is not necessary to cite in refutation the " crystallised human folk " which Mephistopheles claims to have seen in his years of travel ; the untenableness of this distinction becomes clear when it is recalled that, in the first place, mathematically simple body-forms do actually occur among organisms, as in the Kadiolaria, which are LIVING SUBSTANCE 119 provided with extremely delicate silicious skeletons, in many tissue-cells when pressed close together into polyhedral forms, and in many spherical egg-cells ; and, in the second place, in inorganic nature the mathematically fixed body-form is wanting in all fluids. Farther, it has been maintained that inorganic bodies, such as crystals, have no organs, while the presence of these distinguishes all organisms. This also is incorrect. There exist not only organisms without proper organs, such as Amoeba and all other Rhizopoda, in which the whole liquid protoplasmic body is an organ for all things, but also inorganic structures with real organs, such as machines, in which the individual parts are provided with perfectly definite functions. Yet no one will seriously regard Amaebce as inorganic bodies, or steam-engines as living organisms. Another difference has been sought in the claim that, in con- trast to all inorganic bodies, organisms are composed of the charac- teristic structural elements of all living substance, cells. It is true that the cell is a specific element of the whole organic world. But that which characterises this elementary constituent, that which distinguishes it from the whole inorganic world, is not its morphological character. Objects that are composed of separate form-elements can easily be manufactured out of inorganic sub- stances. Nature has manufactured such objects in great quantity in rocks wrhich consist of innumerable separate crystals, such as granite. That which characterises the cell is rather its chemical properties. Hence the presence of cells is not a sign of absolute structural difference. Finally, it has been said that inorganic bodies possess a very simple uniform structure, while organisms possess a highly complex " organisation." If by "organisation" there is understood simply the more or less complex composition of organisms out of different kinds of elementary structural particles, the cells, this state- ment, within certain limits, is true ; although, in contrast with composite rocks, the difference is merely one of degree. But the cell must be employed for comparison, for it is in itself a complete organism. If, however, the conception of complex " organisation " be applied to the cell, it signifies merely the gross morphological variety and chemical complexity of its constituents, and such a condition can be established in a test-tube in a complex chemico- physical mixture. If by "organisation" a special kind of associa- tion of the individual constituents is understood, such as would not occur in inorganic nature, then the conception carries with it more or less mysticism, which has always been a favourite aid in explaining vital phenomena. Such a process cannot be followed in science, for science and mysticism are mutually exclusive. Thus it is seen that a comparison of the structural relations of living and of inorganic substance does not reveal essential 120 GENERAL PHYSIOLOGY differences between the two. If the former be compared with a liquid rather than with a crystal, it is found that in its structural relations it differs no more from lifeless liquid mixtures than these differ among themselves, and, indeed, not so much as they differ from a crystal. 2. Genetic Differences A second series of differences which, it is believed, have been found between organisms and inorganic substances has reference to reproduction and derivation. These differences likewise are not fundamental, and it is easy to perceive that between the two groups no real contrast in this respect exists. It is regarded as a characteristic sign of difference that organisms reproduce, while inorganic bodies cannot do so. This is not an absolute difference, for many organisms are known that live and yet can never reproduce.- Thus, it is well known that the power of reproduction is wanting throughout life in the so-called workers, those individuals in communities of ants and bees which form the great majority of the community and in which the sexual organs are undeveloped ; notwithstanding this latter fact they must be regarded as living organisms. Further, reproduction in organisms consists simply in a giving-off of a certain portion of the body-substance, a division of the individual body. This fact shows most distinctly, i.e., is less masked by accompanying accessory phenomena, in unicellular organisms. An Amoeba, for example, constricts itself into halves, and each half continues to live as a new Amoeba. But if reproduction in its essentials con- sists merely in the division of substance, no fundamental difference exists between the process in a living cell and that in an inorganic body. A drop of mercury that falls upon the floor is divided, into a number of small globules, all of which are drops of mercury. It has been said, further, that organisms are always derived from other organisms, while inorganic bodies can be derived from both organisms and inorganic bodies. Thus, it is impossible to manu- facture even the simplest organism artificially from inorganic substances, while it is not difficult to obtain inorganic bodies — e.g., water — in a variety of ways from both organic and inorganic substances. This appears to be an absolute difference, for it is true that in spite of all endeavours no one has succeeded in demonstrating that organisms can be formed from inorganic matters either in nature or in the laboratory. Nevertheless, this difference cannot be regarded as really absolute, for it can be replied that organic substance is constantly being built out of in- organic substance in the plant-body, this being the exclusive method of construction in plants. To this it has been rejoined in LIVING SUBSTANCE 121 turn that this origin of organic out of inorganic substance is pos- sible only with the help of living organisms ; Preyer ('80) has said that organisms are distinguished from inorganic bodies by the fact that they always presuppose the existence of living substance. Only in this form does the distinction hold good, at most, for the present time. Virchow's dictum, " Omnis celhda e ccllula" which is the generalisation that has become necessary in the course of time from the old dictum of Harvey, " Omne vivum ex ovo" holds good only for the conditions that now prevail upon the earth's surface. If we go backward in the development of the earth, we soon come to a time when the earth was an incandescent mass, upon which no cell could exist. Cells must, therefore, have arisen at some time from masses of matter that were not cells. At this point the following alternative is presented : Either, as the theory of spontaneous generation assumes, organisms have arisen at some time out of inorganic substances, or, as the theory of the continuity of life demands, the conception of life must be applied also to those bodies from which cells have developed, although they were totally different from the living substance of present organisms. If the former be accepted, the difference in the derivation of the two groups of bodies disappears of itself, for then not only inorganic, but also organic nature is derived from non- living substance. Preyer decides upon the second assumption ; he considers as living the mass of matter out of which cells have developed, and even the whole incandescent mass of the earth itself; and he extends still further Harvey's dictum to " Omne vivum e vivo" thereby expressing the idea that life has never originated, but has existed from eternity. But the difficulty of establishing a fundamental difference between organisms and inorganic bodies upon the ground of their derivation is not thus set aside. For, in harmony with his idea that the whole incandescent mass of the earth is to be considered as living, Preyer assumes that the inorganic has arisen out of the organic. Hence, not only does organic nature, but also inorganic, pre- suppose the existence of living substance, and it is clear that the above-mentioned difference in the derivation of the two great groups of matter disappears. It is seen, therefore, that even by such an extension of the conception of life as Preyer's the difference in derivation cannot be maintained for the earlier period of the earth's development. Just as little absolute difference exists between the organism and the inorganic body in their development as in their repro- duction and derivation from like bodies. By development is understood a series of changes undergone by the new-born organism, which make it finally like its parents. Such changes occur in inorganic nature likewise, and are there not funda- mentally different from those in organisms. E.g., if a piece of 122 GENERAL PHYSIOLOGY sulphur be melted in a vessel and the melted mass be poured into water, there is obtained a tough, brown, gummy substance which has not the least external resemblance to the piece of sulphur from which it came. But if it be left for a day or two, it becomes gradually harder and more solid, its brown colour fades and changes to a yellowish, and after some time the whole mass takes on again the appearance of common hard yellow sulphur. Here the sulphur has gone through a development which has made it again like the piece from which it was derived. But even on the part of organisms development is not an absolute sign of difference, for there are organisms that live without developing. The two equal parts into which Amoeba constricts itself are complete Amcubce, without any further process, and are dis- tinguished by their size only from the individual from which they are derived. Finally, an endeavour has been made, but with similar slight success, to find a distinction between organisms and inorganic substances in the manner of growth. The unfortunate contrast of the organism and the crystal, again, has led to the assertion of this difference. It has been said that the crystal grows by the apposition, the organism by the intussusception of particles ; i.e., the crystal grows by laying one particle after another upon its surface, the interior remaining fixed and unchanged, the organism, on the contrary, by taking particles into its interior and storing them between those already present. If a cell as a whole be con- trasted with a crystal, this is not to be disputed ; but it has already been seen that as regards its physical characteristics the living substance of organisms in its essentials ought to be com- pared with a liquid. Liquids, however, grow solely by intussus- ception, i.e., if a soluble body be added to a liquid, e.g., salt to water, the latter dissolves the former and stores the molecules of the soluble body by diffusion between its own molecules — that is, there is here exactly the same process as in the growth of the organism. Hence, the comparison of the genetic relations of organisms and inorganic bodies reveals no more fundamental difference between them than the consideration of their structural relations, and it is necessary to search further. 3. Physical Differences A third group of differences which have been asserted to exist between organisms and inorganic bodies comprises the phenomena of movement. Movement, the most evident of all vital phenomena, was regarded in early times as a characteristic sign of life, and primitive people, in holding consistently to this idea, regarded winds and waves as living things. But the sea is no longer LIVING SUBSTANCE 123 called living, and, on the other hand, in the resting plant-seed there is seen a condition of the organism in which, while it is not dead, not the slightest movement can be recognised. Thus the significance of movement in its primitive form has now dis- appeared, and in place of it more special motile phenomena have been sought as distinguishing marks between organisms and inorganic bodies. It has been thought that a difference must be recognised in the causes that produce movements, on the one hand, of organisms, and, on the other, of inorganic bodies. The former, such as muscle- movements, are said to result from internal causes — those that have their seat in the organism itself; the latter, such as the movement of waves and clouds, from external causes — those that, like the wind, act upon the object from without. The mystical vital force is here more or less evident. But we have already become convinced of the non-existence of such a force, and the claim of such a difference in the causes of movement cannot be maintained. Moreover, in many cases it is difficult to draw a sharp boundary between internal and external causes. E.g., if a steam-engine, and not winds and waves, be considered, it can be said of it, with as much right as of the organism, that it works from internal causes, for the pressure of the steam which drives the piston and puts the wheels in motion is in the interior of the boiler. But it has been said that the difference between the causes of motion in the steam-engine and those in the organism lies in the fact that the former cannot work unless it is heated from the out- side, while the latter works of itself. This is wholly untrue. The organism also must be heated if it is to continue in activity, i.e., in life, exactly as the steam-engine. Its heating is by the introduction of food. The analogy between the heating of the steam-engine and the nutrition of the organism goes very far. The carbon-containing food is burned in the organism in great part as is the coal in the steam-engine — i.e., the food-stuffs are oxidised by the oxygen taken in in respiration, as the coal is oxidised — and in both cases there is obtained as the end-product carbonic acid. If the introduction of food be interrupted, the activity of the organism ceases after a time when all the ingested food is consumed, similarly as with the steam-engine ; in both, movement is stopped. The comparison of the organism with the steam-engine allows the untenableness of the claim of another difference, closely associated with the previous one, to be at once recognised. It has been said, namely, that organisms are in dynamical equi- librium— i.e., the same quantity of energy that is introduced into the organism leaves it again in some form — while in- organic bodies are in stable equilibrium. It is true that organ- isms in the adult state are in dynamical equilibrium. But, when this is put forward as a real difference in comparison with 124 -v^ GENERAL PHYSIOLOGY inorganic bodies, the crystal alone is again in mind. The steam- engine, however, is an inorganic system in which dynamic equi- librium exists very clearly; for by the mediation of heat the system gives off to the outside as mechanical energy exactly as much energy as is introduced by the burning of the coal. Finally, irritability has been brought forward as a general characteristic of organisms in contrast to inorganic bodies. In reviewing the history of physiological investigation it was seen that at first very indefinite ideas were associated with the word " irritability," and, in order to guard against misunderstandings, the conception must be definitely formulated. It can be said in general that irritability is the capacity of a body to react to an external influence by some kind of change in its condition, in which the extent of the reaction stands in no definite proportion to the extent of the influence. As a matter of fact, irrita- bility, or excitability, is a property of all living substance, whether the organism responds to the external influence by the production of definite substances, as with secreting gland-cells, or definite forms of energy, as with muscle-cells, phosphorescent cells, and electric cells, or whether it responds by depression or even standstill of its vital activities. But irritability is not the exclusive property of organisms, for lifeless substances are likewise irritable and respond to external influences by definite changes, e.g., by the production of definite substances or of energy, in which process the extent of the production by no means corresponds always to the extent of the external impulse. The clearest examples of such cases are afforded by explosive substances. By a slight shock nitroglycerine is decomposed into water, carbonic acid, oxygen and nitrogen, the process being accompanied by a powerful evolution of energy; in other words, nitroglycerine responds to an external influence by an enormous production of energy and a change of material. Hence irritability is not an absolute sign of difference between organisms and inorganic bodies, and it is seen that a fundamental contrast between the two is afforded no more by their dynamical than by their structural and genetic relations. We will, therefore, search still further. 4. Chemical Differences It is by a comparison of their chemical relations that a dif- ference is finally found to exist between organisms and inorganic bodies. It has been seen that a specific vital element exists in the organism no more than a specific vital force. The chemical elements that compose the organism occur without exception in inorganic nature also. Therefore, a fundamental chemical con- trast between organic and inorganic substance is not to be LIVING SUBSTANCE 125 expected, i.e., a contrast that rests upon a difference as regards chemical elements. But a difference does exist in the kind of combinations into which the elements enter. It was seen above that chemical compounds are present in living substance, that never occur in the inorganic world; such are proteids, carbo- hydrates and fats. Of most importance is the fact that one group of these chemical bodies, the proteids, belong to all organisms without exception. Just as there is no single organism, whether living or dead, in which proteids are wanting, so there are no inorganic bodies in nature in which even an approximately similar substance is present. The possession of the highly complex proteid molecule is, therefore, a definite mark of distinction of the organism in its relation to all inorganic bodies. But some have gone still further and have endeavoured to find an absolute difference between the two bodies, not only in the existence of certain compounds, but also in the order of the chemical processes in the active organism. It is said that living substance is characterised by its metabolism, in which definite compounds are formed continually, are broken down, give off* their decomposition-products to the outside, and are reformed at the expense of the substances taken in from the outside as food ; hence a continual streaming of matter through the living substance takes place, being conditioned by the construction and destruction of the compounds in question. Metabolism is, indeed, a characteristic process of the living organism, and it will be seen later that upon it the vital process rests; but it is solely a process that distinguishes the living organism from the dead organism and not from inorganic substance, for it is not confined to organisms, but occurs also among inorganic bodies. A simple example of this is found in the behaviour of nitric acid in the production of concentrated sulphuric acid. If nitric acid be mixed with sulphurous anhydride, which is obtained in the manufacture of sulphuric acid by roasting sulphur ore, the sulphurous acid withdraws oxygen from the nitric acid and passes over into sulphuric acid, while the nitric acid becomes nitrous acid. If the constant entrance of fresh air and water be provided, the nitric acid is constantly reformed from the nitrous acid and gives a part of its oxygen again to new quantities of sulphurous acid, so that the molecule of nitric acid is continually being alternately broken down with loss of oxygen and built up with absorption of oxygen. In this manner with the same quantity of nitric acid an unlimited quantity of sulphurous acid can be changed into sulphuric acid. Thus here in a simple form, i.e., in a simple chemical compound, is a regular metabolism, a succession of destructions and constructions of a substance along with the gain and loss of substances, which corresponds in principle, even 126 GENERAL PHYSIOLOGY to its details, to the metabolism of organisms ; nevertheless, nitric acid is an inorganic compound, Such phenomena are relatively rare and occur in free nature, where their conditions are not artificially established by human agency, only very seldom. Nevertheless, they do not permit the presence of a metabolism to be maintained as an absolute difference between living organisms and inorganic bodies. Thus the fact has been established that a fundamental con- trast between living organisms and inorganic bodies does not exist. In contradistinction to all inorganic nature, however, organisms are characterised solely by the possession of certain highly complex chemical compounds, especially proteids. B. LIVING AND LIFELESS ORGANISMS 1. Life and Apparent Death In India, where mystery and magic have always prevailed, the belief seems to have existed for a long time, that many men, especi- ally the so-called fakirs, whose existences are full of privation and self-inflicted torture, and who are supposed to possess special holi- ness, have the remarkable power of voluntarily putting a complete stop to their lives for a time and later resuming them undis- turbed and unchanged. A great number of such cases, in which the fakirs have been buried in this condition of suspended animation and after some time have been taken from their graves, have been reported by travellers from India. James Braid ('50), the well- known discoverer of hypnotism, has collected some of the most authentic cases, and supported them by the testimony of witnesses. One of these cases, which may serve as a type, is the following : At the palace of Runjeet Singh, in a square building which had in the middle a closed room, a fakir, who had voluntarily put him- self into a lifeless condition, had been sewed up in a sack and walled in, the single door of the room having been sealed with the private seal of Runjeet Singh. (To judge from the account, the air, as in all such cases, was not absolutely excluded.) In order to exclude all fraud, Runjeet Singh, who was not himself a believer in the wonderful power of the fakirs, had established a cordon of his own body-guard around the building ; in front of the latter, four sentries were stationed, who were relieved every two hours and were continually watched. Under these conditions, the fakir remained in his grave for six weeks. An Englishman, who was present during the whole event as an eye-witness, reported as follows concerning the disinterment, which took place at the end of six weeks : When the building was opened in the presence of LIVING SUBSTANCE 127 Run jeet Singh, the seal and all the walls were found uninjured. In the dark room of the building, which was examined with a light, the sack containing the fakir lay in a locked box, which was provided with a seal likewise uninjured. The sack, which pre- sented a mildewed appearance, was opened, and the crouching form of the fakir was taken out. The body was perfectly stiff. A physician who was present found that nowhere on the body was a trace of a pulse-beat evident. In the meantime the servant of the fakir poured warm water over the head, laid a hot cake upon the top of the head, removed the wax with which the ears and nostrils were stopped, with a knife forcibly opened the teeth, which were tightly pressed together, drew forward the tongue which was bent backward and which repeatedly sprang back again into its position, and rubbed the closed eyelids with butter. Soon the fakir began to open his eyes, the body began to twitch convulsively, the nostrils were dilated, the skin, heretofore stiff and wrinkled, assumed gradually its normal fulness, and a few minutes later the fakir opened his lips and in a feeble voice asked Kunjeet Singh, " Do you believe me now ? " Similar cases are reported in great number by more or less reliable witnesses. An analogous instance was observed in Europe, and is cited likewise by Braid. It is the well-known case of Colonel Townsend, of whom Dr. Cheyne, a physician of Dublin, well-known in scientific circles, narrates as follows : " He could die or expire when he pleased, and yet, by an effort or somehow, he could come to life again. He insisted so much upon us seeing the trial made that we were at last forced to comply. We all three felt his pulse first : it was distinct, though small and thready, and his heart had its usual beating. He com- posed himself on his back, and lay in a still posture for some time : while I held his right hand, Dr. Baynard laid his hand on his heart, and Mr. Skrine held a clear looking-glass to his mouth. I found his pulse sink gradually, till at last I could not feel any, by the most exact and nice touch. Dr. Baynard could not feel the least motion in the heart, nor Mr. Skrine perceive the least soil on the bright mirror he held to his mouth. Then, each of us, by turns, examined his arm, heart, and breath ; but could not, by the nicest scrutiny, discover the least symptom of life in him. We reasoned a long time about this odd appearance as well as we could, and finding he still continued in that condition, we began to conclude that he had, indeed, carried the experiment too far ; and at last we were satisfied that he was actually dead, and were just ready to leave him. This continued about half an hour. By nine in the morning, in autumn, as we were going away, we observed some motion about the body, and upon examination found his pulse and the motion of his heart gradually returning : he began to breathe heavily and speak softly. We were all astonished to the last 128 GENERAL PHYSIOLOGY Q* degree at this unexpected change, and after some further conversa- tion with him, and among ourselves, went away fully satisfied as to all the particulars of this fact, but confounded and puzzled, and not able to form any rational scheme that might account for it." It is not to be denied that a priori these tales, especially those of the Indian fakirs, are calculated to awaken distrust, and a sound scepticism is the basis of all good criticism. The mistrust is increased when cases happen in which the fakirs are exposed as swindlers, as at the Hungarian Millennium Exposition in Budapest. But from the standpoint of an unprejudiced science we must say that it would be an entire mistake superciliously to regard a thing as untrue merely because at first sight the reports appear strange, and because an impostor employs it for purposes of gain. It is rather in accordance with the liberality of scientific research first carefully to test the phenomenon and to see whether genuine scientific grounds for its impossibility may be brought against it. If from all the known stories their more or less sensational accom- paniments be removed, the simple statement remains that certain men can voluntarily put themselves into a state in which no vital phenomena are demonstrable by a more or less superficial examina- tion, and can awaken later to normal life. Now, sufficient cases are known where physicians by the usual methods of their practice are able to discover absolutely no traces of vital phenomena, where pulse, respiration, movement, and irritability are not to be observed ; and yet where the person, supposably dead, has after a time re- turned to life. These phenomena are usually termed " apparent death," and are connected with those of normal sleep by a series- of transition phenomena. Such transition phenomena are the continual sleep in which persons, such as the " sleeping soldier " and the " sleeping miner," continue in a state of depressed vital activity and incapable of being awakened, and, especiallv, the phenomena of the winter sleep of warm-blooded animals. If the fact of apparent death cannot be disputed, the mysterious- and mystical in the reported tales constantly diminish and become limited solely to the power of going into such a state voluntarily. As regards this, we know that it is possible by exercise to bring under the influence of the will bodily activities, such as the move- ment or inhibition of certain muscles, which once took place only involuntarily. And it is known that in certain pathological con- ditions, especially in cases of profound hysteria, many phenomena, which are never associated with the will in normal persons, can be brought under its influence. Hence it is not justifiable to assert, a priori, the impossibility of the reported phenomena, al- though the reports, which come almost exclusively from the English military and civil officials, concerning fakirs that are buried alive must be received with great caution and criticism. It will be an LIVING SUBSTANCE 129 interesting task for the physiologists to investigate carefully these phenomena, heretofore so ill-defined, to prove by refined methods what vital phenomena are really depressed and to what degree, and finally to show how this voluntary apparent death, which, it is widely believed, has in it absolutely nothing mystical, is to be explained physiologically. How little justification there is in doubting the power of certain organisms to retain the capacity of life without exhibiting the slightest vital phenomena, and even for so long a time that the usual duration of their life is greatly surpassed, appears when we turn from the vertebrates to the invertebrates, which have been very carefully investigated in this respect. Leeuwenhoek (1719) made the very remarkable observation that in the dust of eaves-troughs animalcules exist which are capable of drying up completely without losing the power of awakening to active life upon being moistened with rain- FIG. 41. — Macrobiotus Hufdandi, -A tardigrade, a, Creeping, in the living state. (After [R. Hertwig.) b, Dried, in the state of apparent death. water. Since their discovery by Leeuwenhoek this fact has been confirmed by a great number of observers and its details have been more fully described. It is not difficult to convince one's self of its truth. If some of the crust be scraped from an old eaves-trough or from the moss-covered side of an old tree-trunk, and the dry powder be covered with pure rain-water, often in the course of some hours a number of small animals can be seen by the aid of the microscope, actively creeping about among the particles of mud. They are mostly representatives of the wheel- is 130 GENERAL PHYSIOLOGY animalcules, or Rotatoria, whose bodies, extended like a telescope, have at their anterior end a locomotor organ provided with stout cilia, which on account of the apparently wheel-like motion of the cilia has been termed the wheel-organ. Besides the Rotatoria there are found chiefly the so-called bear-animalcules, or Tardi- grada, clumsy mite-like animals provided with four pairs of short stumps of feet, bearing claws ; like the Rotatoria they are provided with a nervous system, digestive apparatus, etc. (Fig. 41 a). So long as this latter peculiar animal is in water, it performs all its vital phenomena like other animals. But if it be isolated and allowed to dry slowly upon a slide, it is seen that the more the water evaporates, the slower become its movements, until finally they cease entirely when the drop is dried up. Then the body gradually shrinks, the skin becomes wrinkled and folded, the form becomes gradually indistinguishable, and some time after the animal has become dried up it can scarcely be dis- tinguished from a grain of sand (Fig. 41 fr). In this dried con- dition it can remain for many years without undergoing the slightest change. If it be moistened again with water, the return of life to the desiccated body after its sleep can be followed with the microscope. The awakening of the tardi- grade, or the anabiosis, as Preyer ('80) has termed the process, takes place somewhat as follows: The body swells up and becomes extended, the folds and wrinkles slowly disappear, the extremities project, and the animal soon assumes its normal shape. At first it remains quiet ; then, after a time, varying, according to the duration of the drying, from a quarter of an hour to several hours, movements, at first slow and feeble, begin and gradually become stronger and more frequent, until after some time the animal, unaided, creeps away to resume life at the point where it was interrupted. These highly remarkable phenomena of anabiosis are not limited to the Rotatoria and the Tardigrada. They have been noticed likewise in various other organisms in the course of investigations which in great number followed Leeuwenhoek's discovery. They have been observed in the so-called paste-eels, or AnguUlulidce, the small eel-like worms that live in diseased wheat-grains, in Infusoria and Amoeba, and in Bacteria, In the same group of facts belongs also the long-known capacity of plant-seeds to remain dry for many years unchanged without losing their power of sprouting ; indeed, it has even been believed that this power can continue for an unlimited time. The state- ments are well known that wheat-grains found in the graves of Egyptian mummies after a rest of many thousand years have sprouted and bloomed. It has been settled, however, that these reports rest upon a delusion, for Mariette, the well-known Egypto- logist, has shown that with genuine mummy wheat these experi- ments always fail, since all wheat-grains taken from the graves LIVING SUBSTANCE 131 have a charred appearance, and, when brought into water, dis- integrate into a clayey pulp. Nevertheless, from several observa- tions it appears certain that many plant-seeds, when completely dried, can retain their power of sprouting for more than a hundred, perhaps for more than two hundred, years. These rare facts are of great importance in forming a conception of life, and demand exhaustive investigation. The question to be considered is whether it is allowable to regard organisms in this peculiar condition as really lifeless. Theoretically, in its most general expression, the distinction between living and lifeless organisms meets with no great diffi- culties. Our conception of life has been formed from the observa- tion of certain phenomena which appear only in living organisms, in other words, vital phenomena. Wherever we observe vital phenomena we speak of a living organism. This characterisation of the conception of life can be simplified still more. If, for example, all the varieties of vital phenomena be recalled, it is found that they arrange themselves into three great groups, — those of metabolism, or change of substance, those of change of form, and those of transformation of energy. Every living organism exhibits changes in its component materials, since it continually takes in substances from the outside and gives off others to the outside ; it exhibits changes of its form, since it develops, grows, and reproduces by constricting off certain parts ; and it exhibits changes of its energy, since it transforms the chem- ical energy received with its food into other forms of energy. But these changes are not three wholly different processes, which are independent of one another ; they are, rather, different kinds of phenomena of one and the same process. No substance exists without form or energy. Substance, form, and energy are simply the three phases in which the physical world can manifest itself in phenomena, in which matter can be considered. Every change of substance necessitates a simultaneous change in the two other phases, although in a given case one phase is more evident to the senses than another. Hence it can be said that in a general sense the vital process, the outward expression of which is perceived in the various vital phenomena, consists in changes of substance, or, in brief, metabolism. Accordingly, it is meta- bolism in which the living organism differs from the lifeless. Practically, i.e., in a concrete case, this distinction is not always so simple, as is evident from the case of desiccated organisms. In accordance with the above considerations, it is a question whether these organisms in their peculiar condition possess really no meta- bolism, or whether their metabolism is simply depressed to so slight a degree that it is not apparent to our unaided senses in the form of vital phenomena, i.e., whether the life-process is at an actual standstill, or whether only a vita minima exists. The decision of this question is possible only by means of the most K 2 132 GENERAL PHYSIOLOGY refined and careful methods of research. The majority of investi- gators have always believed that in such dried organisms there is really a complete standstill of life ; but the objection has always been possible that the metabolism in this condition may be so slight that with the minuteness of most of the objects it cannot be proved by the usual methods of investigation. The experiments carried on recently by Kochs ('90) are likely to refute this ob- jection completely. Dried animals, isolated upon a clean glass slide, take in no solid or liquid food, and direct observation shows likewise that no outgo of liquid or solid matters takes place. But Kochs has demonstrated in the following way that a respiration, i.e., an in-take of oxygen and an out-put of carbonic acid, is never present. He selected for his experiments various plant seeds, completely dried, and placed a considerable quantity of them in a wide glass tube ; he extracted the air as much as possible by means of the air pump and then sealed the tube by melting. If only a slight metabolism were present in the seeds, with their considerable quantity at least a trace of expired carbonic acid could have been found. But, when after several months Kochs investigated the contents of the tube by the most delicate methods, he found not the slightest trace of expired carbonic acid or any other product of metabolism. These experiments were repeated always with the same result. Nevertheless, the seeds remained capable of life and sprouted upon being sown. From the results of these experiments it can no longer be doubted that in desiccated organisms there is a complete standstill of life. Can organisms in this peculiar condition be termed dead ? In reality they are lifeless but not dead, for anabiosis is possible after the application of water, while nothing can bring dead organisms back to life. The distinction between the dried and the dead organism lies in the fact that in the former all the internal vital conditions are still fulfilled, and only the external conditions in part have disappeared, while in the latter the internal vital condi- tions have experienced irreparable disturbances, although the external conditions can still be fulfilled. Preyer illustrates this distinction very happily. He compares the dried organism to a clock that has been wound but has stopped, so that it needs only a push to set it going, and the dead organism to a clock that is broken and cannot be made to go by a push. Hence a sharp distinction must be made between dried and dead organisms. But dried organisms cannot be called living, for they exhibit no vital phenomena, and, as has been seen, vital phenomena are the criterion of life. It is best, therefore, to apply to them the ex- pression " apparently dead." Claude Bernard has termed the condition of apparently dead organisms " vie latente " (latent life), an expression which Preyer has replaced with " potentielles Leben " (potential life), in contrast to the . usual or " actuelles Leben " (actual life) of the normal organism. To use a German expression, LIVING SUBSTANCE 133 it may be said that such organisms exist in the condition of " Scheintod " (apparent death). 2. Life and Death It has been seen that the determination of the difference between life and apparent death is beset with practical difficulties, since it is not easy to decide experimentally whether the life-process in reality is at a complete standstill in dried and apparently dead organisms. It is still more difficult to determine theoretically a sharp limit between life and death. In daily life it is easy to distinguish the dead organism from the living ; for from the human body and from the higher animals we have formed a general conception of death, and are accustomed to consider it as occurring at the moment when the heart, hitherto never quiet, stands still, and the individual ceases to breathe. But we here follow the superficial habit of daily life and take into consideration only the gross differences that make their appearance at that time, without noticing the continuance of certain phe- nomena after this all-important moment. The criterion of life is formed only by the vital phenomena, i.e., by the various phases in which the vital process, or the metabolism, becomes evident to the senses. But if this criterion be applied to the human being at the moment usually termed the moment of death, it is found that in reality he is not then dead. A careful examination shows at once the truth of this statement. It is true that the spontaneous gross muscular movements cease, the man becomes relaxed and quiet. But the muscles frequently remain for several hours sensitive to external influences, responding to the latter with twitchings and movements of the limbs, in other words showing vital phenomena. A moment even comes when the muscles gradually contract once more spontaneously, this is the death -stiffening (rigor mortis). Not until this has passed is the life of the muscles extinguished. Nevertheless, even then the body is not entirely dead. Certain parts only, certain organs or cell- complexes, such as the cells of the nervous system and of the muscles, no longer show vital phenomena ; but other cells and cell- complexes continue to live unchanged long after rigor mortis has passed. As is well known, the inner surface of the air-passages, the larynx, the trachea, and the bronchial tubes, is covered with a ciliated epithelium, a layer of cylindrical cells pressed tightly together and bearing upon their surface fine hair-like appendages, with which they perform a continual, rhythmic, beating motion (Of. Fig. 20 a, p. 78). These ciliated cells continue their normal activity in the corpse for days after the cessation of the heart, and thus survive after the so-called death. But even after several days the whole body is not always dead. The white blood-corpuscles, or leucocytes, the amoeboid cells that are not only carried about passively in the 134 GENERAL PHYSIOLOGY blood-current but also wander about actively in all the tissues of the body and play an important role in the organic household, re- main in great part living, and, if kept under favourable conditions, can live still longer. What moment then shall be designated as the moment of death ? If the existence of vital phenomena be employed as the criterion, then the moment when spontaneous muscular movement, espe- cially the activity of the heart, ceases, cannot consistently be regarded as the moment of death, for other cell-complexes con- tinue to live for a long time thereafter. We see, therefore, that there is no definite point of time at which life ceases and death begins ; but there is a gradual passage from normal life to complete death which frequently begins to be noticeable during the course of a disease. Death is developed out of life. The history of death is very different in the different classes of animals. In the warm-blooded animals death develops relatively rapidly after the standstill of the blood-circulation, as a result of the great dependence of all tissue-cells upon nourishment from the blood-current. The cold-blooded organism passes from life to death as a rule much more slowly ; the definitive death, i.e., the state in which no further vital phenomenon can be perceived in the body, appears in many cases only months after the animal has experienced an irreparable, fatal injury. In harmony with the greater independence of the individual organs in respect to the blood-circulation and one another, in many cold-blooded animals individual parts also, when severed from the rest of the body, can survive for a long time, — a peculiarity upon which depends the special usefulness of such animals, e.g., frogs, for many physio- logical investigations. It is well known that a muscle with its nerve can be removed from a frog's body, and under proper conditions can be maintained for experimentation alive and in an irritable condition for days. The fact appears here much more clearly than in the case of man, that death is not a condition that is established in a moment, but is developed very gradually. It may be said that in all the cases mentioned multi- cellular animals are under consideration, and in them one kind of cell suffers death earlier, the others later ; but how is it with the single cell, which in itself represents a living organism ? The history of cell-death corresponds exactly with the development of death in the multicellular organism, except that in the former the various important points appear much more clearly. We see here also that death does not occur suddenly, but that normal life is united with definitive death by a long series of transition-stages, following one another uninterruptedly, and frequently extending through several days or, not rarely, several weeks. We have already become abundantly acquainted with the fact that non- nucleated protoplasmic masses that have been cut off from a cell do not continue living. If such a separated piece of protoplasm r LIVING SUBSTANCE 135 which possesses no nucleus and whose fate is therefore sealed, be observed with the microscope, it can be seen that it passes from its normal behaviour to complete standstill of all its vital phenomena only very gradually.1 Certain marine species of Rhizopoda, e.g., Orbitolites, are well fitted for this observation; they stretch out through the pores of their calcareous shell clusters of naked non-nucleated protoplasmic threads, or pseudopodia, of considerable length, and by means of them they move, seize food- organisms and digest food. If such a mass of pseudopodia be cut off from an Orbitolites under the microscope, the network of threads first flows together into a roundish droplet, which thereupon immediately stretches out new pseudopodia of the same form as in the uninjured organism, and moves as if in connection with the nucleated body. The new pseudopodia also seize food- organisms, but are not able to digest them. This latter fact is very important, for from it follows the fact that the non-nucleated protoplasmic droplet is not able to manufacture new body-substance. The move- ments of these microscopic bodies continue normal for hours, and their irritability is also maintained. But the pseudopodia are very gradually drawn in, while new ones are no longer protruded, and as a result the mass draws itself more and more into a spherical lump. It cannot yet be said that the protoplasmic mass is dead, for even upon the next day, if the object be observed at intervals of several hours, extremely slow, feeble changes of form can be perceived. Only after several days does the protoplasmic droplet swell up and disintegrate into a loose mass of granules. Thus, death does not come to the cell immediately, but is the end-result of a long series of processes which begin with an irrepar- able injury to the normal body, and lead by degrees to a complete cessation of all vital phenomena. Since during the course of this process vital phenomena are still noticeable, while death as a result of the injury is unavoidable, it is advantageous to character- ise by a name the time from the receipt of the fatal injury up to the definitive death as a time of uninterrupted transitions. Ex- tending a conception introduced into pathology by K. H. Schultz and Virchow ('71), I shall term it necrobiosis. It is seen, therefore, that is impossible to draw a sharp line between life and death, that life and death are only the two end- results of a long series of changes which run their course success- ively in the organism. But if, after having established this fact, the transition-stages be left out of consideration for the moment and only the two end-results be considered, on the one side, the uninjured living organism and, on the other, the same organism killed and preserved in alcohol by the modern technical methods, a sharp distinction between these two can be recognised in the fact that in the former the life-process goes on undisturbed, as is 1 Cf. Verworn ('91). 136 GENERAL PHYSIOLOGY evident from the appearance of all vital phenomena, while in the latter it is for ever at a complete standstill, as is shown by the absence of even the slightest phenomena of life. We are now in position to add a capstone to our characterisa- tion of living substance — in other words, to characterise in general terms the vital process itself. It has been shown that a fundamental difference — i.e., a difference in the elementary materials and the elementary forces — between organisms and inorganic bodies does not exist. The vital pheno- mena of organisms must, therefore, depend upon the same general mechanical laws as the phenomena of the inorganic world. But a difference does exist between the two great groups of bodies in respect to the kind of chemical compounds in which the element- ary materials are associated, since in organisms generally certain highly complex compounds occur, especially proteids, which are never wanting in living substance, and are never found in the inorganic world. It is evident that this difference is of the same kind as the differences that exist between the various inor- ganic bodies themselves as regards their chemical composition. Nevertheless, in the possession of the complex proteids organisms have something in common in contrast to all inorganic bodies. Further, it has been shown that living differ from lifeless organisms, whether the latter be apparently or really dead, by their metabolism — i.e., by the fact that their substance continually breaks down spontaneously, is regenerated, and accordingly continually gives off substances to the outside and receives other substances from the outside. The kind of product arising from this decomposition shows that nitrogenous compounds, especially proteids, are involved in it. Since it is known that the nitrogenous proteids, with their allies, which in part are derived from the proteids and in part are necessary to their formation, are the sole organic compounds that are never wanting in living substance, that everywhere they constitute its chief mass and alone are sufficient for its formation, it can be said that all living organisms are characterised by the metabolism of proteids. We can thus summarise our considerations so far, and at the same time give simple expression to the problem of all physiology. The life-process consists in the metabolism of proteids. If this be true, all physiological research is an experiment in this field ; it con- sists in following the metabolism of proteids into its details and recognising the various vital phenomena as an expression of this metabolism which must result from it with the same inevitable necessity as the phenomena of inorganic nature result from the chemical and physical changes of inorganic bodies. CHAPTER III ELEMENTARY VITAL PHENOMENA WHAT is called life is a series of vital phenomena very un- equal in importance. As regards most of the activities that con- stitute the daily life of mankind, some are composed of elementary phenomena, and some are secondary results of elementary pheno- mena. Even those that are apparently simple and direct, such as the circulation of the blood and respiration, are not elementary. The elementary phenomena are the contraction of the heart and the respiratory muscles, which secondarily accomplish the circulation of the blood and the exchange of air in the lungs ; for muscle-contraction cannot be reduced to the activity of other elements, it is the direct expression of the life of those cells in which it appears. If we wish to become acquainted with the elementary vital phenomena, we must go back to the cells in which they appear. If all complex activities and secondary phenomena be traced back to the elementary vital phenomena that lie at their founda- tion, three great groups of the latter are found, which in some form are peculiar to all living substance, to every cell ; these are the phenomena associated with changes of substance, of form, and of energy. All living substance without exception, so long as it lives, shows continual changes of its material, alterations of its form, and transformations of its energy ; and all vital phenomena whatsoever, when resolved into their elements, may be placed in one or more of these three great groups. In this chapter we shall endeavour to obtain a comprehensive view of vital phenomena by recording the facts, and shall leave to a later chapter the reduction of them to mechanical causes. I. THE PHENOMENA OF METABOLISM A. THE INGESTION OF SUBSTANCES ' Nourishing," in the widest sense, signifies the whole process involved in the taking-in of food-stuffs from the environment. In 138 ^ GENERAL PHYSIOLOGY the case of the compound organism, eating and drinking constitute merely an extrinsic part of the process ; whatever is thus brought to a single organ, the stomach, is for the good of each one of the many millions of cells that constitute the body. If the life of the body is to be maintained, all cells must take in certain food-sub- stances. The following consideration must, therefore, cover two points — first, the nature of the substances that every cell needs in order to maintain its life, and, second, the mode of ingestion of those substances. 1. Food-stuffs All living matter is continually undergoing decomposition and, hence, must take in substances that contain all the chemical elements of which it is constructed. While it is a vital phenomenon of every cell to take in food- stuffs, the latter differ in kind with every form of cell. But in spite of all specific differences in the substances that each form of cell requires for its life, all organisms may be classified into a few large groups, within each of which a general agreement in the kind of nutrition prevails. A fundamental difference in the nutrition of plants and of animals was discovered early. All green plants take up from the earth and air simple inorganic materials from which to construct their living substance ; on the other hand, all animals without excep- tion, in order to be able to maintain life, require highly complex organic compounds. This fact is easily confirmed. In order to prove that animals cannot exist without organic food, it is only necessary to perform suitable feeding experiments. When fed with purely inorganic matters, such as water, salts, etc., even when these contain all the chemical elements of living substance in the correct proportion, animals always die after a longer or shorter time. On the other hand, it can be shown that plants live solely at the expense of inorganic substances, by allowing them to grow in so-called nutrient solutions, which possess in the form of inorganic salts the chemical elements that are necessary to the formation of living substance. Such a nutrient solution, which contains in soluble compounds the elements N, H, O, S, P, Cl, K, Na, Mg, Ca, Fe, i.e., with the exception of carbon, all organic elements, is composed, according to Sachs ('82), as follows : — Water 1,000 c.c. Potassium nitrate 1 gr. Sodium chloride 0*5 „ Calcium sulphate 0'5 „ Magnesium sulphate 0'5 Calcium phosphate 0'5 Ferrous sulphate 0'005 „ ELEMENTARY VITAL PHENOMENA 139 If the root of a grain of corn that has sprouted in water be placed in a cylinder containing this nutrient solution, while the upper parts project into the air (Fig. 42), the plant, when placed in the light, grows well, develops into a large stalk, flowers and produces seed with which the experiment can be repeated. If the iron salt be wanting in the nutrient solution, the plant grows likewise for some time, but remains colour- less, and microscopic examination of the leaves shows that the chlorophyll is wanting in the cells. Only after the addition of a trace of iron sulphate do the leaves become green. As a glance at the contents shows, no carbon is present in the nutrient solution. Since, how- ever, under all circumstances the plant requires carbon for building its organic substance, in its growth it must have taken carbon from the air ; hence it is necessary that the experiment be ar- ranged so that the upper parts of the plant pro- ject into the air. If the air be excluded by a bell-jar, in a short time the plant dies. Carbon is contained in the air only in the form of car- bonic acid ; hence the plant must withdraw it from this compound, and, in fact, it appears that, when a certain quantity of carbonic acid is left under the bell-jar, after a short time all is con- sumed. This important fact, that the plant supplies its need of carbon solely from the carbonic acid of the air, was discovered by Ingenhouss and de Saussure, and, after having been doubted for a long time, now forms one of the most important facts in all plant physiology. The plant's nitrogen, however, as an experiment analogous to the above shows, cannot be extracted from the air ; it is taken up solely from the nitrogenous salts of the water. It follows from these experiments that plants construct their living substance out of simple inorganic compounds, from the carbonic acid in the air, which is taken up by the leaves, and from the water containing salts, which reaches the plant through its roots. In contrast to this, no animal is able to build its living substance synthetically from simple inorganic compounds, even when all the chemical elements of its body are contained in them ; all animals without exception require organic material already prepared. This, contrast between animals and plants is very significant, for it expresses the important fact that the animal world cannot exist without the plant world. It is true that a great number of FIG. 42. — Corn-plant growing in a cylin- der containing a nutrient solution. N, Nutrient solu- tion ; S, grain of corn ; K, cork. (After Sachs.) 140 GENERAL PHYSIOLOGY animals exist, such as carnivora, which require only animal food- stuffs, especially flesh ; but, if the source of their food be sought, it is always found ultimately in herbivora, and the latter cannot live without plant-food. Thus, the carnivora depend ultimately upon the existence of plants. Without plants all animals would die, for plants alone are able to manufacture from inorganic substances the carbohydrate, the fat and the proteid that animals require for their existence. The old philosophy of nature, prevalent at the beginning of the present century, was, hence, not entirely incorrect when in this sense it termed the whole animal world parasites of the plants. For a long time it was believed that this difference in the nutrition of animals and plants is an absolute one, that all living cells, as regards their metabolism, can be divided simply into animal- and plant-cells. But it has been found that the difference exists only within certain limits, viz., only so far as animal-cells and green, i.e., chlorophyll-containing, plant-cells are concerned, for those constituents of the plant-cell in which carbonic acid is received and elaborated are exclusively the green chlorophyll- bodies. There are plants without chlorophyll — e.g., the fungi — which in their metabolism form to some extent a transition between animals and green plants. The fungi do not have the power of the chlorophyll-containing plants to extract carbon from the carbonic acid of the atmospheric air; in order to satisfy their need of carbon they require, like animals, organic substances, such as proteid, carbohydrate, etc. On the other hand, the fungi behave like plants in so far as they satisfy their need of nitrogen from the inorganic salts of the earth, while animals obtain their requisite nitrogen only from proteids and their derivatives. These facts follow from experiments with nutrient solutions, in which fungi do not grow when no organic material is at their disposal ; if, however, besides nitrogenous salts, sugar be added fco such a solution, they grow vigorously. Thus, the fungi constitute a group of organisms which, as regards their metabolism, combine half animal and half plant characters. But still other relations occur in nature ; for among micro-organ- isms numerous entirely similar transition-forms occur, and the more the very peculiar life-relations of these microscopic beings, especially the Bacteria, are investigated, the more it appears that in this group of lowest organisms the metabolic relations in general are not so sharply differentiated as in the higher organised animals and plants. Thus, very recently the clever investigator, Winogradsky ('90), has discovered Bacteria that live in the earth and construct their living substance entirely from inorganic material, chiefly ammonium carbonate and certain mineral sub- stances. These remarkable nitrogen-bacteria (Nitromonas), there- fore, although they possess no chlorophyll, behave exactly like ELEMENTARY VITAL PHENOMENA 141 green plants. Other forms of Bacteria cannot exist without organic food. To glance at the more special nutrition of animals, as regards the organic food-stuffs a considerable difference prevails between individual species. There are remarkable adapta- tions to single food-stuffs. Thus, the caterpillar of the fur-moth lives exclusively upon the hairs of fur, which consist of pure keratin. Keratin, which is closely allied to proteid, is, therefore, capable of furnishing all the elements for the formation of the living substance of the fur-caterpillar. In other cases, e.g., in carnivora, proteid alone suffices to supply all the elements necessary to the formation of the body ; and lately Pfltiger ('92) has shown by detailed experiments that even dogs, when forced to perform hard labour daily, can live continually upon pure proteid food. In such experiments, after a short time the dogs lose almost all their body-fat, but remain abundantly capable of work, strong and healthy. On the other hand, it is impossible to maintain an animal's life with carbohydrates or fats solely, or even with the two together. In spite of an abundance of such food, the animals consume their own body-proteid, as shown by the continual excre- tion of nitrogen in the urine, and finally grow weaker and die. The reason for this is evident, for, since the living substance is constantly breaking down of itself in a definite quantity, it must constantly be reconstructed if the animal is to live. But this cannot happen if no nitrogen, which is lacking in carbohydrates and fats, be given to the animal. Since, however, as has been seen, animals cannot take up nitrogen from inorganic compounds, it- follows that proteids, which alone represent the nitrogenous food- stuffs, are absolutely necessary for the maintenance of animal life. Hence we arrive at the important fact that of all organic sub- stances proteids alone are indispensable to the nutrition of animals, and in certain cases also they alone suffice to maintain the animal's life. Pfliiger, therefore, distinguishes proteid as the primitive food from the carbohydrates, fats, etc., which act only as substitute foods. In addition to food proper in the narrow sense, all organisms take in oxygen — a process that is termed respiration. Of course all organisms do not receive oxygen in the same form and from the same source. Terrestrial organisms take it in the form of gas from the air ; aquatic organisms use the oxygen dissolved in the water; and the tissue-cells of animals that are provided with a blood-circulation, as well as many parasitic organisms, withdraw it from chemical compounds — the tissue-cells from the haemoglobin of the blood, with which it is loosely combined, and certain para- sites from relatively fixed combinations. All organisms take only a certain quantity of oxygen, even when more is offered ; their consumption of it is not essentially increased in a medium of pure 142 GENERAL PHYSIOLOGY oxygen. Hence within certain limits living substance is fairly independent of the quantity of oxj-gen that is at its disposal. But all organisms without exception absolutely require for their life a certain quantity of oxygen. If separated from it they invariably die after a shorter or longer time. Without respiration no life exists. Finally, all organisms without exception take in water, and with it certain salts, which, in so far as they are not contained in the other food, are likewise essential to the maintenance of life, although wide differences prevail among the different organisms as regards the kind of salts required. Salts of sodium, potassium, magnesium, calcium, and iron, containing phosphorus, sulphur, carbon, and chlorine, appear to be essential to all organisms. We have thus reviewed the food-stuffs of organisms ; we will now consider how the individual cell takes in this food. 2. The Mode of Food- Ingestion ly the Cell Food-stuffs exist partly in the gaseous, partly in the liquid, i.e., dissolved, and partly in the solid condition ; but by no means all living cells are able to take in solid food. The great majority of all cells, almost all animal tissue-cells, a great number of plant- cells, and many unicellular organisms take in dissolved food only, the latter either primarily consisting exclusively of dissolved sub- stances, or being transformed from the solid to the dissolved state by the agency of certain secretions outside the cell-body. Only relatively few kinds of cells are fitted for the ingestion of solid food. The process of ingestion of gaseous and dissolved food-stuffs, which is termed resorption, is essentially different, according as the cells in question do or do not possess a cell-membrane. In cells that do not possess a membrane all dissolved food-substances of whatever kind pass directly into chemical relations with the mate- rials of the living substance at the surface of the protoplasm. W'here a membrane is present, it is necessary that the food-stuffs have the power of diffusing through membranes. The substances that cannot do this must, therefore, first be transformed into diffusible substances in order to reach the interior of the cell. Every cell, however, is capable of ingesting gaseous and dissolved food. In plants the carbonic acid and oxygen of the air come into direct contact with the cells of the leaves. A similar arrange- ment is found in the lungs of vertebrates. The finest branches of the bronchial tubes end in small blind sacs, the so-called pulmonary alveoli, which are formed by an extremely thin layer of epithelium-cells and are surrounded by a close network of likewise very thin-walled blood-capillaries. The oxygen of the air inspired ELEMENTARY VITAL PHENOMENA 143 into the lungs passes readily through the thin walls, to be eagerly sucked up by the red blood-corpuscles and transported throughout the whole body. Dissolved substances also always bathe the surface of the cells. In the plant they ascend along with the water in fine tube-like canals and thus are brought directly to the cells. In the compound animal body some of the cells, such as those of the intestinal epithelium, are in immediate contact with the dissolved food-stuffs of the intestinal tract, while all the other tissue-cells are bathed by the blood-current, which brings to them the dissolved food in a definitely elaborated form. In such invertebrate animals also as possess no proper blood-circulatory system, the cells either stand in immediate contact with the surrounding water or are supplied with juices that bathe the cells in fine intercellular spaces. The simplest relations, finally, exist in unicellular organisms, such as Algcv, Bacteria, and others, which live constantly in a nutrient solution, either in water containing salts or in organic liquids. The ingestion of solid food occurs in only a few cell-forms. Among unicellular organisms all Eliizopoda, most ciliate Infusoria, and some flagellate Infusoria, take in solid food. In the complex cell-community this power is possessed by the leucocytes or white blood-corpuscles, which, therefore, have been termed by Metschni- koff phagocytes (eating cells), by amoeboid wandering cells, which play in the lower animals the role of leucocytes, by amoeboid egg-cells, such as occur in sponges, and by the intestinal epithelium- cells. Among these forms of cells two types may be distinguished, according to the manner of ingestion of solid food. The one type is able to take the food-masses into its living substance at any desired point upon its surface — such are all amoeboid cells, to which belong Khizopoda, leucocytes and intestinal epithelium-cells ; the other type possesses a special, constant mouth-opening — such are the ciliate and the flagellate Infusoria, which have a definitely fixed body-form with a denser cutaneous layer. All cells, however, that take in solid food are able to do it only by means of active movements of the body. The ingestion of food by Amoeba may serve as an example of the first type. The process, which has been observed in full only relatively seldom, takes place somewhat as follows. An Amoeba, which is being observed in a drop of water under the microscope, creeps about the glass slide by letting the living substance of its formless protoplasmic body flow here and there into broad, lobate projections (Fig. 43). Suddenly it turns toward a small alga-cell lying in the vicinity, and creeps on until it touches the cell. Its protoplasm immediately begins to flow around the latter in the form of the usual lobate pseudopodia ; but the cell is shoved away by the encroaching protoplasm and the amoeba is obliged to make a new attempt to surround the cell. After several fruitless attempts it 144 GENERAL PHYSIOLOGY frequently succeeds in bringing the cell into such a position and so holding it fast by a delicate viscous secretion that its pseudopodia are able to grasp the alga completely. Then, by flowing more and more about the cell, the protoplasm encloses it gradually on all sides, and the alga finds itself surrounded by a thin covering of water, form- ing the so-called food-vacuole, in the interior of the amoeba, which then creeps on unhindered. Amoeba, therefore, takes in solid food by causing its protoplasm simply to surround the food-mass. But the act does not always go on so smoothly. The difficulties that arise before the food-mass, which yields continually to the pressure of the encroaching protoplasm, is so fixed that the proto- plasm can enclose it upon all sides, are frequently so great that not rarely the amoeba, with its pseudopodia flowing on continually in u b c d FIG. 43. — Amoeba devouring an alga-cell. Four successive stages of the process of food-ingestion. other directions, is taken away from its victim, and must creep toward it anew in order to seize it, if it has not been taken entirely out of the sphere of influence of the food-mass. The ingestion of food by other lihizopuda takes place exactly as in the case of Amoeba, whether they have pseudopodia that are thick and broad, fine and thread-like, or branched and tree- like. If the food-bodies are motile organisms, e.g., Infusoria, they usually cause the excretion of a viscous substance by stimulation resulting from their swimming against the rhizopod body ; this is in- creased by stimulation arising from their attempts to escape ; hence they stick firmly and can be drawn into the protoplasm. The amoeboid wandering-cells and leucocytes also, like Amoeba, ingest solid substances which exist in the blood or in the interstitial spaces between the cells. As the admirable work of Metschnikoff ('83, '84) has lately shown, they possess very great importance in the protec- tion of the body from infectious diseases by devouring the bacteria that have entered a wound; they thus prevent the increase of the bac- teria and protect the body from further infection (Fig. 44). Finally, the ingestion of microscopic fat- droplets on the part of the intestinal epithelium-cells represents the same mode of food-ingestion. In lower animals — e.g., in worms — these cells are really amoeboid cells, and by means of their pseudopodia flow around the fat-globules of ELEMENTARY VITAL PHENOMENA 145 the digested food (Fig. 45, A). In the higher animals, such as man and other mammals, however, the intestinal cells are somewhat modified. They are cylindrical cells that possess upon their free surface, turned toward the lumen of the intestine, a striated border. As Thanhoffer (74) has shown, this stri- ated border represents really nothing more or less than fine, pseudopodium- like, protoplasmic processes, which can be extended and retracted, and with which the cells, exactly like Amoeba, flow around the fat-droplet and draw it into its body (Fig. 45, £). The phenomena are wholly dif- ferent in the second type of food- ingestion, where the cell has a firmer superficial layer of a fixed form, and only a small opening, the cell -mouth, which. leads directly into the liquid endoplasm. Here the movement of the cilia and flagella of the cell exclusively mediates the ingestion of solid substances. The delicate Vor- ticella may serve as an example, a ciliate infusorian whose bell-shaped cell-body sits upon a contractile stalk and bears at its broad end a spiral-like circlet of cilia (Fig. 46). a b c FIG. 44. — Leucocyte from the frog de- vouring a bacterium. Three suc- cessive stages in the ingestion of food. (After Metschnikoff.) FIG. 45.— A. Intestinal epithelium-cells from the liver-fluke, possessing pseudopodium-like proto- plasmic processes for the ingestion of blood-corpuscles,a, &,and drops of chyle, c. (After Sommer.) B. Intestinal epithelium-cells from the vertebrate, ingesting fat. In the interior of the cells single microscopic fat -droplets are found. (After Thanhoffer.) At the bottom of this spiral-like ciliated funnel is a cell-mouth, which is prolonged a short distance into the protoplasm as the cell- pharynx, and then gradually disappears into the liquid endoplasm. 146 GENERAL PHYSIOLOGY The cilia of the ciliary wreath of the peristorne contract continually and rhythmically, and in this way produce in the water a whirlpool, which is so directed that it sucks small particles, such as detritus, mud, bacteria, alga3, etc., which are suspended in the water, into the cell-mouth ; from there, surrounded by a layer of water, they are shoved by contractions of the body into the cell-pharynx, and thence into the endoplasm (Fig. 46). The phenomena may be very easily observed, if, according to Ehrenberg's method ('38), granules of carmine or indigo be mixed with the water. It is seen at once how the Vorticella engulfs the red or blue granules and forms them in its protoplasm into balls which are surrounded by a cover- ing of water and constitute food-vacuoles. The mode of ingestion of food lay other Infusoria is entirely similar to that of Vorticella. The free-swimming forms frequently seek fixed FIG. 46. — Vorticella in four successive stages of the process of food-ingestion. An alga-cell is being engulfed into the cell-mo ath and taken through the pharynx into the endoplasm. food-masses and engulf them. Many Infusoria even, such as Goleps, a small, egg-shaped, ciliate form having a delicate lattice- like surface, take in large balls of food which are broader than their mouth-opening by pressing the latter upon the ball by the force of the ciliary contraction so that the mouth-opening, as in a snake, is gradually enlarged. Thus they really suck the food-balls into their bodies (Fig. 47). The ingestion of solid food on the part of the cell is, therefore, in every case brought about by active movements of the cell- protoplasm or its motile organoids. In the ingestion of substances by the living ceil, one phenomenon deserves special mention — namely, the fact of the selection of food. Of the various cells living in the same medium, each takes to itself different materials, and such as are necessary for the forma- tion of its characteristic substance. This is clear in the tissue- cells of highly organised animals, such as the human body. Here the blood-plasma is the common nutrient material for all tissue- ELEMENTARY VITAL PHENOMENA 147 cells. But from this common nutrient liquid each kind of cell removes the substances necessary for its life ; the mucous cell takes substances different from those taken by the ganglion-cell, the muscle-cell substances different from those taken by the car- tilage-cell, the liver-cell substances different from those taken by the sense-cell, and so on. The different cells choose entirely different materials, each one according to its need. This phenomenon of food-selection is, perhaps, more remarkable in certain free-living cells that take in solid food. Cienkowski FIG. 47. — Four individuals of Coleps hirtus swarming about and ingesting a ball of food. ('65), who has studied in detail the life of the lowest Rhizopoda, the naked monads, gives an interesting description of how Colpo- della and Vampyrella, two simple, naked rhizopod-cells, procure their food, which consists of living alga-cells. Cienkowski relates as follows : " Although the zoospore- and amoeba-conditions of the monads are only naked protoplasmic bodies, their behaviour in seeking and ingesting food is so remarkable that it seems to be the work of conscious beings. Thus, Colpodella pugnax pierces the Chlamydomonas, sucks up the chlorophyll that flows out, and L 2 148 GENERAL PHYSIOLOGY runs away. A second rare case of this kind is afforded by Vampy- rella Spirogyrce. The amoeba of this species applies itself to a healthy Spirogyra, bores through the cell-wall and devours the slowly escaping primordial utricle together with the chlorophyll- bands. It seems to be able to satisfy its hunger upon Spirogyra only." (Fig. 48.) But we need not search so far. In the human body there are cells that behave similarly. As Metschnikoff ('92) has shown by his researches extending over many years, the leucocytes or white blood-corpuscles, the amoeboid wandering-cells, devour and digest certain forms of bacteria present in the body, while they scorn and even directly avoid other bacteria; likewise, intestinal FIG. 48.—Vampyrella Spirogyrce boring into and suck- ing out a Spirogyra-cell. A. The Spirogyra-cell is pierced and the contents are passing out into the Vampyrdla. B. The Spirogyra-cell is completely emptied. At * a cell that has been pierced and A emptied. (After Cienkowski.) epithelium-cells, as has been seen, devour only fat-droplets, while they behave wholly passively toward other small particles that are brought into the intestine, such as granules of carmine. Finally, another very interesting phenomenon, which has to do with the ingestion, not of food, but of substances that likewise play a role in the life of the organisms in question, has also frequently been referred to, although incorrectly, as a power of selection on the part of the cell. This is the ingestion of material for shells and capsules on the part of certain shell-bearing rhizopods. The Difflugice, which are unicellular fresh-water Rhizopoda whose naked' protoplasmic bodies are fixed in a very delicate urn-shaped or flask-shaped capsule, take up the material for their tiny dwellings with their finger-like pseudopodia out of the mud of the pools and lakes at the bottom of which they live.1 The structural material of their shells is very varied, but in many 1 Cf. Verworn ('88). ELEMENTARY VITAL PHENOMENA 149 cases the shells are composed of one definite material (Fig. 49). Thus, forms occur that employ only cases of the silicious Algce or diatoms, whileothers em ploy only sand-grains of certain sizes, and still others particles of mud. It has been thought that the Difflugim select their material from substances at their command. But it can be proved, at least in some cases, that no real selection exists here in the same sense as in food-ingestion by the above-men- tioned cells. The fact that forms from one and the same locality employ only a certain material depends rather upon the circum- Fio. 49.— Various Difflugia-shells, constructed of : A, diatom-cases ; B, fine sand -grains ; C, fine and coarse sand-grains ; J), diatom cases and sand-grains ; £, coarse sand-grains ; F, the same form as E, but made of splinters of blue glass. stance that in the given locality only this one material is at hand. If, e.g., the dwelling-place of the form that constructs its shell out of mud or substance excreted from its body be examined, it is found that here other materials, perhaps diatom-cases or sand- grains, are wholly wanting. If, however, such forms be given the possibility of getting other material, by the introduction of very finely pulverised sand or, still better, very finely ground, coloured glass into the culture-vessel in which they live, it is found that the individuals arising by reproduction surround themselves with a delicate shell of sand or splinters of coloured glass.1 The circum- 1 Cf. Vervvorn ('90, 1). 150 GENERAL PHYSIOLOGY stance that some shells possess small sand-grains, and others considerably larger ones is likewise to be referred in part to the character of the material at their disposal, in part, however, to other external conditions, such as the narrowness of the opening of the capsule, which does not allow the protoplasmic body to draw through large sand-grains. It accordingly appears that in most cases the construction of the capsule by Difflugice involves no real selection of material, and thus far no case has become known where such a selection has really been established with certainty. There is, therefore, no justification in drawing a parallel, as is often done, between the ingestion of structural material in the building of the Difflugia-c&psule and the act of food-selection by _the living cell. B. THE TRANSFORMATION OF INGESTED SUBSTANCES The process of construction of living substance out of the in- gested food-stuffs can be designated best by generalising, as is frequently done, a conception of the botanists and employing the word assimilation. By assimilation in the narrow sense has been understood for a long time in botany the synthetic formation in plants of the first visible organic material, starch, out of the ingested inorganic compounds. But it is advantageous to extend the conception and employ it also for the construction of higher organic compounds, especially the proteids, and, indeed, not only in plants, but also in animals. By assimilation, therefore, is under- stood the sum of the processes that lead to the construction of living substance to the maximum of its most complex constitution, the syn- thesis of proteids. Construction, or assimilation, can then be contrasted with destruction, or dissimilation. 1. Extracellular and Intracellular Digestion " Corpora non agunt nisi soluta" This old dictum plays in the life of the cell a very great role. In order that the ingested food- stuffs may work chemically and be of use for the construction of living substance, they must be in a dissolved condition ; since, however, the food taken in by the organism is in part solid food, it must first be transformed into soluble form, and this process is termed digestion. It has been seen that only a few cells have the power of taking in solid food; in these there occurs so-called intracel- lular digestion, the transformation of the solid food into soluble com- pounds taking place in the interior of the cell. The great majority of cells, however, cannot take in solid food ; in them, therefore, the transformation of the solid into the soluble form must take place outside of the cell, in order that ingestion may be possible ; ELEMENTARY VITAL PHENOMENA 151 this transformation is, therefore, termed extracellular digestion, and the ingestion of the dissolved food, resorption. The change of solid food, such as coagulated proteids, starches and fats, into soluble compounds takes place through the action of definite secretions which the cell-body gives off to the outside. These characteristic secretions are called enzymes or unorganised ferments. The result of their action can be demonstrated outside FIG. 5Q.—lieberMhnia, a fresh-water rhizopod, from the egg-shaped shell of which branched pseudopodial filaments protrude. the organism by allowing an enzyme, e.g., pepsin, which is produced by the cells of the gastric glands, to act upon a bit of coagulated proteid. If, e.g., there be placed in a beaker a solution of pepsin in water to which has been added an equal volume of 0*4 per cent, hydrochloric acid, there is obtained an artificial gastric juice. If there be put into this digestive solution a flake of fibrin, i.e., the proteid the spontaneous coagulation of which causes the clotting of 152 C4ENERAL PHYSIOLOGY the blood outside the blood-vessels, and the beaker be warmed in a digestion-chamber to the body-temperature, it is found after some time that the solid flake of fibrin begins to swell, to become transparent upon the outside, and gradually to become dissolved in the liquid. Finally, the whole flake, as such, disappears, and in its place there is found dissolved in the liquid peptone, that modi- fication of proteid which, as has already been seen, arises by a hydrolytic cleavage of the polymeric proteid molecule, is soluble in water, and diffuses through organic membranes. Besides the peptone there are found also certain transition-stages between the native albumin and the peptone, which are likewise soluble in water and are termed albumoses. We shall presently discuss more in detail the peculiar manner of working of the ferments. That which happens, in extracellular digestion, outside the cell- body, and which can be imitated even in the test-tube, takes place in intracellular digestion within the protoplasm. Likewise here the process can be followed best in the naked protoplasmic body of Rhizopoda. Lieberkuknia is a large fresh-water rhizopod, from the egg-shaped, membranous shell of which thick, branching pseudopodial filaments protrude through an opening at the pointed pole (Fig. 50). When the Lieberkuhma seizes and digests1 an infusorian that carelessly swims against its pseudopodia, it can be seen with the microscope that the prey first becomes attached to the pseudopodia, entangles itself more and more firmly by its strong efforts to escape, and gradually becomes surrounded either wholly or partially by the pseudopodial protoplasm (Fig. 51). For some time the movements of the infusorian continue ; then they become feebler, and at the same time its body-form begins to change. It decreases in size constantly, while the liquid and granular parts of its protoplasmic body pass over into the pseudopodial protoplasm, mix with it, and are no longer seen to stream to the central body of the Lieberkuhnia. Thus, gradually, the whole body of the infusorian becomes dissolved and its liquefied contents mix with the protoplasm of its captor, until none of it is longer distinguishable. In other cases of intracellular digestion the food-body, e.g., in Amoeba and Infusoria, becomes surrounded by a food-vacuole within the endoplasm, and is dissolved in the same manner as in the exoplasm of the Lieberkuhnia. Further, the observations that have been made upon the Infusoria by Green- wood ('94) are very interesting. She followed the fate of the in- gested food-masses in the Vorticellinw, especially in Carchesium (Fig. 52), and found that, while they are undergoing digestion, the}r take a perfectly definite path within the cell-body — viz., from the cell-pharynx (Of. Vorticella, p. 146, Fig. 46) to the bottom of the cell and back to the mouth-opening, where the undigested masses are cast out. It is very noteworthy that the food-masses 1 Cf. Verworn ('89, 1). ELEMENTARY VITAL PHENOMENA 153 remain for a long time in the concavity which the sausage-shaped nucleus turns toward the interior of the cell, there chiefly to FIG. 51.— An elongated pseudopodium of Lieberkuhnia in which an ini usorian (Colpidium colpoda) has become caught ; o, b, c, d, e, /, various stages of digestion of the inf usorian. undergo destruction. This indicates that very probably the nucleus takes an important share in the digestion of the food-masses. Just as proteids are transformed by pepsin in an acid and by 154 GENERAL PHYSIOLOGY trypsin in an alkaline solution, so also the insoluble carbohydrates, such as starch, are changed into soluble forms both in intracellular and extracellular digestion by the action of certain enzymes. As has been seen, starch is a polysaccharid, which represents a com- bination of several sugar molecules in the anhydride form. By the action of the enzyme, e.g., the ptyalin of the saliva and the pancre- FIG. 52. — Carchesium polypinum, scheme of the path taken by the ingested food in digestion and expulsion of the excreta. The food enters through the pharynx and is transported downward (small circles), where it is stored in the concavity of the sausage-shaped nucleus (the latter is recognised by its containing darker bodies). It remains here for some time at rest (small crosses). Then it passes upward upon the other side (dots) and returns to the middle of the cell, where it undergoes dissohition. The excreta are removed to the outside, through the opening of the cell-mouth. The black line with arrows indicates the direction of the path. (After Greenwood.) atic juice in animals or the diastase in plants, the polymeric starch molecule is split up through hydrolysis into simple sugar molecules, maltose and dextrose, which are soluble in water. In the intracellular digestion of Infusoria, as M. Meissner ('88) has shown, starch -grains are slowly digested from the outside, so that they appear as if gnawed (Fig. 53), and finally are completely dis- solved. Yet from the striking researches of Greenwood ('86, '87) ELEMENTARY VITAL PHENOMENA 155 and Meissner (loc. cit.) it appears that Rhizopoda such as Amoeba, although occasionally taking in starch, are nevertheless unable to digest it. Finally, fats in extracellular digestion are split up, likewise with hydration, by the fat-ferment steapsin into glycerine and fatty acids, the latter uniting with alkalies to form soaps. Glycerine and soaps are soluble and can be resorbed. In the intracellular ingestion of the neutral fat-droplets as such, however, a direct digestion does not always take place. As FIG. SS.-Starch-grains which have been r. J. . -I * 7 devoured and digested by an infusorian. Meissner has observed, Amoeba (After M. Meissner.) and Infusoria retain ingested fat- droplets within their protoplasm for days unchanged, and Green- wood has found that Amoeba and Actinosphcerium do not digest ingested fat at all. 2. ferments and their Mode of Action The ferments are physiologically such an extremely interesting group of bodies that it is worth while to examine them somewhat in detail, and especially to become acquainted with their peculiar mode of working. By ferments there is understood a series of highly complex organic bodies belonging to animals and plants, which have the remarkable peculiarity of bringing about certain chemical transformations apparently ivithout undergoing changes themselves. When two substances act upon each other in an ordinary chem- ical reaction, both undergo a chemical transformation. With the ferment this appears not to be the case, for, when a large quantity of a chemical compound has been split up by a certain quantity of an enzyme, the original quantity of enzyme is found unchanged in the liquid. Theoretically, an unlimited quantity of material can be decomposed by a small quantity of a ferment. Practically, however, this is usually not possible, because the effectiveness of the ferment gradually becomes diminished by the accumulation of substances resulting from the cleavage. It is a question, however, whether the ferment, when acting upon other substances, really undergoes no decomposition or is it- self destroyed and constantly re-formed, so that in the end the same quantity of ferment is found as at first. In inorganic chemistry there are cases analogous to each possibility. By the terms catalytic action and contact -action in the original sense, chemists understand the property possessed by many sub- stances of decomposing chemical compounds by simple contact. Thus, Sainte-Claire Deville and Debray have found that formic acid can be split up into carbonic acid and hydrogen, not only by certain ferments, but also by finely divided iridium, rhodium and ruth- 156 GENERAL PHYSIOLOGY enium, the molecules of the metals undergoing no change. These facts are explained as follows : It is known that according to the mechanical theory of heat the atoms in every molecule are in con- stant vibratory motion — a phenomenon that is termed intra- molecular heat. Upon contact of the molecule of the metals in question with the complex molecule of formic acid this intra- molecular vibration of the atoms of the former is transferred to the latter, and combines with the latter's vibration in such a way that another arrangement of atoms results — i.e., a decomposition of the formic acid molecule. According to a different idea, it is the chem- ical affinity between the atoms of the molecule of the metal and certain atoms of the formic acid molecule that disturbs the intra- molecular vibrations of the formic acid atoms in such a way that a rearrangement, i.e., a decomposition, takes place, without, however, the occurrence of a real combination of the atoms of the metal with the corresponding atoms of formic acid. However it be, in every case the intramolecular motion of the atoms in the molecules that are to be broken up becomes disturbed, while the catalytic molecule of the metal remains intact. Such contact-actions are widely known in chemistry. Thus, hydrogen peroxide upon contact with finely divided platinum is changed into water and oxy- gen without the platinum itself being altered. In contrast to these pure contact-effects, chemistry recog- nises other cases in which the effective body remains unchanged only apparently. While bringing about transformations, it is continually altered chemically, but is immediately re-formed again. The end-results in the two cases must be the same, for even in the latter case at the conclusion the body in question is found in its original form. We have already become acquainted elsewhere with such a case. In the manufacture of concentrated sulphuric acid the nitric acid is continually reduced by sulphurous anhydride into nitrous acid, to be re-formed again into nitric acid with the aid of the oxygen of the air. Which of the two cases does the action of ferments resemble ? Thus far this question has not been decided with certainty. It is very probable, however, that among so-called ferment-actions both cases are present. In the large group of ferments two kinds are distinguished — dis- solved unorganised ferments, or enzymes, and solid organised ferments, or ferment-organisms ; the former comprise secretions which are given off to the outside by the living cell and remain constantly effective, the latter consist of the living substance of the cell itself, with the life of which the ferment-action is associated. While in ferment-organisms the ferment-action is extinguished with the life of the cell, the enzymes can be preserved as long as desired as chemical bodies, without losing their power. The cells of yeast (Soccharomycex), which cause the alcoholic fermentation ELEMENTARY VITAL PHENOMENA 157 of beer (Fig. 54), are ferment-organisms, decomposing grape-sugar into alcohol and carbonic acid.1 They produce, however, in addition an enzyme, invcrtin, which is able to convert cane-sugar into grape-sugar. The two actions can be separated from one another. If the yeast-cells be killed by chloroform or ether, it is no longer possible for them to decompose grape-sugar into alcohol and carbonic acid ; but the power of the inverting enzyme continues undiminished, so that the change of cane-sugar into grape-sugar goes on as well as before. In ferment-organisms the living sub- stance exercises the ferment-action only so long as it lives, i.e., its ferment-action is associated with metabolism. This evidently indicates that in ferment-organ- isms there is realised the second case mentioned above, that which is analogous to the action of nitric acid in the manufacture of sul- phuric acid ; while the peculiar fact that the action of the en- zymes may be replaced by other FlG> bi.-SaccharomyCeS) yeast-ceiis. (After substances, e.g., metals, suggests Remke.) the probability that they work also like finely divided metals by pure contact. At present, naturally, this question cannot be decided with absolute certainty. Like the organised ferments the enzymes are highly complex com- pounds, all of which probably contain nitrogen and are derived from the metabolism of proteids ; they are made ineffective by substances that enter into combination with proteids, as well as by boiling ; within certain limits, however, an increase of tem- perature is favourable to ferment-action, because thereby the intramolecular vibrations of the atoms are increased. If the action of ferment-organisms depends actually upon a continual destruction and rebuilding of their own substance, then all living organisms may be regarded as ferment-organisms ; for all living substance transforms food-stuffs in its metabolism while not disappearing itself. Hence the metabolism of living substance can be compared with the metabolism of nitric acid in the above case. 3. Assimilation and Dissimilation a. Assimilation The digestion of food-stuffs by the action of ferments is only a preparation for the process of assimilation. Only after the food- stuffs have been brought into the condition in which they can do chemical work, i.e., after they have become dissolved, can their 1 Cf. p. ill. 158 GENERAL PHYSIOLOGY function in the construction of living substance begin to be exercised. The process of assimilation naturally differs much according to the condition of the ingested food. Differences must be recog- nised also in assimilation by the two main groups of organisms, plants and animals, corresponding to the differences that have been recognised in their food. It is evident that the processes that lead to the formation of living substance in the plant-cell must constitute a much longer series than in the animal-cell, for the plant must construct the highly complex proteid molecule out of the simplest inorganic compounds, car- bonic acid, water, salts and oxygen, while the animal obtains, already formed, the proteid food without which it cannot live, and only needs to use this in its specific manner. We will follow the processes that lead to the assimilation of proteids somewhat in detail in the two series, so far as in general they are known. The lack of our knowledge is realised here as elsewhere. To consider first the plants, a simple experiment shows the first step which the plant takes in the series of pro- cesses that lead to assimilation. In a cylindrical tube, provided with a bulb closed above (Fig. 55) and gradu- ated, a green leaf is placed by means of a wire, and a certain measured quantity of carbonic acid is allowed to flow in. The lower end of the tube is closed by means of mercury, and the whole is allowed to stand for some hours in the sunlight. If then the contents of the tube be tested gaso- metrically, it is found that the car- bonic acid has disappeared, and in place of it an equal volume of oxygen is in the tube. Since the volume of the carbonic acid is equal to the volume of the oxygen contained in it, the experiment proves not only that the plant has taken up carbonic acid and given off oxygen, but also that it has given off as much oxygen as was contained in the carbonic acid. The first stage toward assimilation . in the plant is, therefore, a FIG. 55.— Apparatus for the investiga- tion of the cleavage of carbonic acid in the green parts of plants. (After Detmer.) ELEMENTARY VITAL PHENOMENA 159 cleavage of carbonic acid ; this takes place in the green plant-cell under the influence of sunlight. The plant gives off oxygen to the outside. As to the fate of the retained ' carbon, microscopic observation gives us information. It shows, namely, that in pro- portion to the destruction of the carbonic acid starch is formed in the chlorophyll-grains themselves, and is laid down in the form of small, highly refractive granules (Fig. 23, p. 81, and Fig. 56). More- over, by a series of experiments Sachs has shown that as soon as the breaking-up of the carbonic acid ceases in darkness the formation of starch also ceases, immediately to begin again in the light along with the destruction of carbonic acid. Since starch contains, in addition to carbon, only hydrogen and oxygen in the same relative proportion as in water, it can be derived only by syn- thesis from the carbon that is set free arid the water that is received through the roots. Starch is, therefore, the first assimilation-product to appear. " If," says Sachs, ('82)," starch is the first and sole visible product of assimilation, it follows directly that all other organic com- pounds of the plant must originate by chemical metamorphosis from it." It will be remembered that no carbon was present in the artificial nutrient solution in which plants were allowed to grow.1 If, therefore, laterthe plant manufactures other carbohydrates, fats, and finally pro- teids, all of which contain carbon, it can employ only starch as the starting-point. Of course almost nothing is known concerning the special chemical transformations which starch undergoes further. But an idea can be formed, at least in gross outline, of the further processes of assimilation. The fact that from the starch soluble varieties of sugar can be derived very easily by cleavage with hydration, is at once understood when it is borne in mind that starch is a polymeric molecule of the anhydride of sugar. Hence it can pass into the condition of the soluble carbohydrates, and this is necessary in order to make possible further chemical syn- theses. The formation of fatty oils out of starch can also be directly observed. If unripe seeds of certain plants, e.g., Pceonia, which contain carbohydrates and no fats, be allowed to lie in moist air, it is found after some time that all starch has disappeared, but fatty oil has appeared in its place. But much more complicated is the origin of proteid from carbohydrates. Since in addition to the atoms of carbohydrate proteid contains nitrogen and sulphur, 1 Of. p. 138. : ; FIG. 56. —Starch appearing as transparent scales in chloro- phyll-bodies. A, Chlorophyll- bodies lying in the cell. B, Chlorophyll-bodies undergoing division. (After Sachs.) 160 GENERAL PHYSIOLOGY 9 which the plant receives through its roots from nitrates and sulphates only, complicated transformations of these salts and then syntheses with the carbohydrate atoms must take place, the details of which are thus far wholly unknown. As to how, finally, the proteid molecule, synthetically formed, is employed further in the living substance for purposes of construction, at present, on account of our extremely scanty knowledge of the chemical constitution of proteids, we can say absolutely nothing. Here an enormous field is offered for future physiological investi- gation. In animals, the path from the ingested food to the living proteid molecule is of course essentially shorter, for all animals without exception need for their nutrition proteids already pre- pared. But what happens further to the proteids that have been peptonised by digestion is not fully known. After the investigations of Salvioli ('80), Hofmeister ('82), Neumeister ('90), and others, no doubt can be entertained that the peptones as such disappear in the cells of the wall of the intestine, in other words, they are transformed in the cell itself. If pieces of the intestinal mucous membrane of a rabbit be placed in a liquid that contains peptone, in which the cells of the intestinal wall exist during life, after some time it is found that all peptone has disappeared. If, moreover, a solution of peptone be injected into the blood of an animal, in a short time the whole quantity of peptone is excreted unchanged in the urine ; and in normal life the blood is always free from peptones. These two experiments prove undoubtedly that the peptones become changed on their way through the cells of the intestinal wall. But little is thus far known as to the kind of change within the cells. Perhaps some of the peptones are broken down immediately into simpler substances by a retrogres- sive proteid metamorphosis. It is certain that many are changed back into proteid and pass into the juices of the body along with the proteid resorbed directly without peptonisation. This dissolved proteid circulates throughout the body with the blood- current, bathes the cells of all tissues, and is withdrawn by the cells from the blood, to be broken down within them. Hence it happens that in a remarkably short time all the proteid taken into the body, beyond a certain quantity, appears as urea, uric acid, etc., in the urine. Voit ('81) thought that this proteid that is broken down ought to be distinguished as " circulating proteid " from the " tissue proteid/' which is employed for the formation of tissues, since he assumed that the destruction of the circulating proteid took place in the blood, in the liquids, of the body. But the reason for such a distinction has disappeared, since Pfliiger ('93) and Schondorff ('93) have shown recently by very careful investigations that the breaking-down of the proteid dissolved in the blood does not take place in the, blood itself, but in the tissue- ELEMENTARY VITAL PHENOMENA 161 cells. Under certain circumstances, however, the cells also retain a small part of the proteid dissolved in the blood, either employing it for the increase of its living substance, as in growth, or storing it up in the protoplasm, as in fattening, in the form of reserve, i.e., passive, proteid which is not ordinarily consumed in meta- bolism. Under certain conditions, as in fasting or during the development of eggs, such passive, indifferent, reserve-proteid can again be drawn into the metabolism. The vitellin in egg-cells is such a substance. Regarding the fate of the ingested fats and carbohydrates as few details are known as regarding the finer transformations of proteids. The fat which is taken as such into the cells frequently remains for a long time as reserve-material. Likewise the fat that is split up into glycerine and fatty acids and resorbed can be changed back into neutral fat in the cell ; this is proved by the striking experiments of J. Munk ('84), who, by feeding fat-free soaps or free fatty acids, was able to cause a storing-up of tissue-fat in dogs that had fasted and become extremely lean. In a similar manner the grape-sugar that is split off from the carbo- hydrates can be transformed synthetically into glycogen in the tissue-cells, especially in the cells of the liver and the muscles, and can be stored up as such. Regarding the further fate of this stored fat and glycogen, however, it is known only that they can be consumed during fasting and during excessive muscle-work, that, therefore, they represent a reserve-material which acts in cases of need as " compensation-food " in Pfltiger's sense. b. Dissimilation Our knowledge of the processes of dissimilation of living sub- stances is much more meagre than that of assimilation. We really know only that living substance is continually undergoing decomposition, for this is apparent from the output of decompo- sition-products. But as to the path from the complex proteid compounds to the end-products, as to the special chemical trans- formations that take place, our knowledge is very incomplete, since as yet the composition of proteids is known very slightly. But one fact at least is certain, namely, that the most of all those substances that result from the decomposition of the proteid mole- cule are not groups of atoms that were preformed as such in the molecule and are now simply split off, but they are derived from certain cleavage-products by successive syntheses ; this takes place either at the moment of decomposition by rearrangement of the atoms in the proteid molecule itself, as in the case of carbonic acid, or later outside of the proteid molecule by combination with other cleavage-products and a simultaneous rearrangement of atoms, as is the case, e.g., in the formation of uric acid. Thus far it is not known M 162 GENERAL PHYSIOLOGY that any product of proteid-decomposition originates by the simple cleavage of preformed groups of atoms. It is important to become acquainted with the most essential derivatives of the disintegrating proteid molecule. As has been found by the investigation of the substances that are contained in living substance,1 there can be distinguished among these products of proteid transformation two groups — those containing nitrogen, and those not containing nitrogen. Representatives of each group appear in every cell, but their special composition differs in indi- vidual cases according to the characteristic metabolism of the cell. Among the substances that contain nitrogen the most wide-spread are urea, uric acid, hippuric acid, creatin, and the nuclein bases — xanthin, hypoxanthin or sarkin, guanin, and adenin. Regarding the majority of these substances, thus far it is not known how they originate from the decomposition of proteids, but for some at least hypotheses concerning their immediate forerunners have been formed. Thus, from the fact, which Schroder discovered, that ammonium carbonate introduced into the fresh, excised, still-living liver of a dog leaves the liver as urea, it has been supposed that ammonium carbonate is the forerunner of urea, that from it the liver- cells prepare urea by a transformation of the atoms and the giving-off of two molecules of water : — (NH4)2C03 - 2H20 = (NH2)2CO. But this is not conclusive, it is only a provisional hypothesis, for the possibility is not to be excluded summarily that within the organism itself still other substances are employed for the syn- thesis of urea. With somewhat more certainty we know the forerunner of uric acid, which is that substance in which, in rep- tiles and birds, the greater part of the nitrogen that is derived from the decomposition of proteids leaves the body. Its forerunner is ammonium lactate. From experiments which Gaglio ('86) carried out upon dogs it follows that the lactic acid of the blood is derived from the decomposition of proteid, for the quantity of lactic acid in the blood increases and decreases together with the quantity of proteid food, and is wholly independent of the quantity of ingested carbohydrate. While lactic acid is always found in the blood, under normal conditions no trace of it occurs in the urine ; it must, therefore, undergo transformation before it is excreted. Minkowski('86) made these relations clear by an experiment, in which he showed that geese after the extirpation of the liver excrete very small quantities of uric acid but large quantities of lactic acid and ammonia, both of the latter in the quantitative relations of ammo- nium lactate. From this important fact Minkowski rightly concluded that ammonium lactate is a preliminary stage in the formation of uric acid, from which uric acid arises by rearrangement. We can also 1 Cf. p. 109. ELEMENTARY VITAL PHENOMENA 163 conjecture with great probability as to the synthesis of hippuric acid, which arises from the decomposition of proteids, especially in the metabolism of herbivora. By boiling with mineral acids or alkalies hippuric acid is split into benzoic acid and glycocoll by hydrolysis, and by heating under a high pressure these two sub- stances can again be united into hippuric acid with the loss of water. It is, therefore, supposed that in the body of the herbi- vore, where the possibility exists of the derivation of benzoic acid from proteid or the aromatic compounds of the food, and of glycocoll from gelatine-yielding substances derived from proteid, hippuric acid is formed synthetically from these two substances. As a matter of fact, not only in the body of the herbivore, but even in the carnivore, the formation of hippuric acid may be brought about artificially by introducing benzoic acid into the stomach, this acid then uniting with glycocoll into hippuric acid in an unknown manner in the tissues. In contrast with this, nothing whatever is known concerning the origin of creatin. Creatin, together with creatinin, which is derived from it with loss of water, is the sub- stance in which muscle-cells give off chiefly the nitrogen that comes from the decomposition of their proteid. Just as little is known concerning its fate as concerning its origin ; for, although it is found in muscles in considerable quantity, only small quantities of it appear in the urine ; hence it appears to undergo in some manner transformations in the body itself. Finally, regarding the nuclein bases, it is known only that they are derived from the decompo- sition of nucleins and their derivatives ; the details of the process are unknown. Among the non-nitrogenous transformation-products of proteids, the most important are fats, carbohydrates, lactic acid, and carbonic acid. These also are derived from the proteid molecule, not by a simple cleavage but by rearrangement and synthetic processes. The theory th&kfat can arise from proteid by transformation has been much disputed. The pathological process of the so-called fat- metamorphosis of cells, in which fat appears in the place of proteid, so that at the end of the process the cells are dead and filled with fat, necessarily led to the idea that here proteid is transformed into fat. But the objection was possible that in the course of the disease the proteid of the cell is forced out by the fat coming in from the outside. Notwithstanding this possibility, this important question has been decided experimentally in favour of the former view. Leo ('85) made experimental use of the fact that phos- phorus poisoning causes an extremely rapid fat-metamorphosis, especially of the liver-cells. From a number of frogs he selected six individuals of equal size and weight, killed them and deter- mined their fat-contents. He then took six other individuals, poisoned them with phosphorus and killed them after three days. The determination of fat revealed a considerably greater fat- M 2 164 GENERAL PHYSIOLOGY contents in the latter than in the former. This experiment proves that fat must actually have arisen in phosphorus poisoning. Franz Hofmann ("72), however, performed an experiment which showed directly the origin of fat from proteid. He took a quantity of eggs from the bluebottle fly (Musca vomit oria) and divided them by weight into two equal portions. One of these portions he em- ployed for the determination of the fat-contents, the other he laid upon blood, the small quantity of fat contained in which was like- wise determined. The larvae of the flies creeping out of the eggs fed upon the blood and grew. After they were grown, Hofmann determined the quantity of fat in them, and found that they con- tained ten times as much fat as the eggs and the blood together. On account of its minute quantity, the blood-sugar need not be considered in the fat-formation. Hence the fat could have come only from the proteid of the blood. After these experiments it is no longer doubtful that fat can originate from proteid. Neither can doubt exist concerning the origin of carbohydrates (grape-sugar and glycogen) from proteid. It has been known for a long time that in severe forms of diabetes mellitus, even with complete lack of carbohydrates in the food, the quantity of grape- sugar excreted in the urine is considerably increased by the consumption of an increased quantity of proteid. Likewise, Claude Bernard has observed that in dogs in which the glycogen had been used up by fasting, glycogen is stored in greater quan- tity when they are fed abundantly upon pure proteid food ; and in a dog that had been fed for four days with pure fibrin after fasting twenty-one days, Mering ("77) found more than sixteen grains of glycogen in the liver. Numerous similar observations have been made, and the origin of carbohydrates from proteids is now assured. The origin of lactic acid from proteid has been proved by the investigations of Gaglio ('86), which show that the lactic acid of the blood depends only upon the quantity of ingested proteid, not upon that of the carbohydrates. Finally, that carlonic acid also, which all living substance without exception expires throughout its life, is derived from the decomposition of proteid and not from that of non-nitrogenous substances, is at once evident from the fact that in carnivora life can be maintained continually with proteid food alone. This important fact proves in general that from proteid all those substances can be formed that are continu- ally excreted by the organism, as well as all the substances that are necessary to maintain life. Formerly a sharp distinction was drawn between animal- and plant-cells as regards the kind of chemical transformations that take place in them. It was said that in the plants synthetic processes take place almost exclusively, in the animals analytic processes only ; and this idea has persisted until recent times. But that such a fundamental difference exists was energetically dis- ELEMENTARY VITAL PHENOMENA 165 puted more than twenty years ago by Pfliiger (75, 1). As a matter of fact, as the above consideration has shown, the difference consists only in that the plant-proteid of the chlorophyll-bodies has re- tained from early times the property of assimilating inorganic material, while animals require for the construction of their living substance organic food-material already prepared. Nevertheless, synthetic and analytic processes take place in both the plant and the animal body. In the plant the decomposition of carbonic acid must precede the synthesis of starch ; in order that the starch may be further elaborated, it must first be decomposed into simple kinds of sugar, and so on. Finally, in the plant also there occurs the whole series of cleavages that are associated with the decom- position of the proteid molecule, with dissimilation, exactly as in the animal body. But syntheses take place in the animal body to a great extent. The further elaboration of the digested pro- teids, fats, and carbohydrates towards the construction of living substance involves extended synthetic processes, and it has been seen that the majority of the products of retrogressive proteid- metamorphosis are formed synthetically out of the cleavage- products of the proteids. Hence analytic and synthetic processes go hand in hand in the animal- as in the plant-cell, and the old distinction into analytic and synthetic organisms is merely the expression of an earlier stage of our knowledge of the chemical processes in living substance. C. THE OUTPUT OF SUBSTANCES Living substance excretes transformation-products in the same proportion in which it receives substances from the outside and transforms them ; the substances given out are as varied as those taken in. But with our slight knowledge of the transformations und with the overwhelming number of substances excreted by the various forms of cells, we can say in a very few cases only by what processes the substances are derived. As regards most of them, it is not known whether they are derived from assimilatory or dis- similatory transformations ; evidently a large quantity of by- products are formed in both the ascending and the descending portions of the metabolic series, whether by simple cleavage, or by synthesis from the cleavage-products or other substances which are excreted by the organism either for some further use or as useless products. This last point, as to whether the excreted substances are of still further use in the life of the organism, or are removed as useless products, as slag, has caused a distinc- tion to be recognised among the substances given off. Although it is difficult to make this distinction sharp, because of the ex- traordinary variety of different products, the use of it is advisable 166 GENERAL PHYSIOLOGY from practical considerations. The substances given off from the cell, among which occur gaseous, liquid, and solid substances in all grades of consistency, are distinguished as secretions when they play a still further useful role in the life of the organism, and as excretions when they are removed to the outside as useless residue. Accordingly, secretions are contrasted with excretions. We will look for a moment somewhat in detail at the two groups of sub- stances and at the mode of their output. 1. The Mode of Output of Substances ly the Cell Like the taking-in of food, so also the manner of output of substances varies, according as the latter are gaseous, dissolved or solid. The output of gaseous or dissolved substances evidently takes place under the same conditions and in the same manner as such substances are taken in, for here there is the same process reversed. In many cells, e.g., in many unicellular organisms, it is very probable that the so-called contractile vacuole (Fig. 57), a drop of liquid within the cell which is alternately emptied and filled by rhyth- mical contractions of the protoplasm of its wall, attends to the expulsion of dissolved substances. It is supposed that the latter, together with the water that during the diastole of the vacuole streams in from all sides out of the protoplasm, accumulate in the vacuole and at its systole are given off to the outside. It is clear that every cell excretes primarily substances that are derived from its own metabolism. But in the compound cell- community, especially of the animal organism, there exist also cells which in addition have undertaken for the whole body the excre- tion of certain other materials. Thus, the cells in the convoluted uriniferous tubules of the kidney excrete the urea that is prepared by the liver-cells and passed into the blood, by receiving it from the blood and giving it off to the outside. Other cells of the kidney, those of the so-called glomeruli, the microscopic capsules in which the blood-capillaries are twisted into knots, greedily suck up the water from the blood to excrete it as the water of urine into the pelvis of the kidney. In the mode of output of solid substances two types again are dis- tinguished. They are essentially different according as the excreted substances either occur in the cell itself in a dissolved condition, and become solid only at the moment of excretion, or lie within the living substance as solid masses, which are to be given off as such to the outside. In the former case, which is realised in the excretion of most skeletal substances, such as chondrin, chitin, and lime, the same conditions are present as in the excretion of dissolved sub- ELEMENTARY VITAL PHENOMENA 167 stances in general, except that sooner or later after their exit from the living cell the substances assume a solid form. The solidifying of the excretions at the surface does not prevent the repetition of the process, and thus eventually all substances of the kind become excreted and solidified upon the outside. Thus originate the cell-membranes of tissue-cells, the cellulose coats of plant-cells, the chitinous coats of insects, and the calcareous shells of Foraminifera. This process and at the same time the mode of growth of these superficial structures can be illustrated by an experiment which IG. 57.— A, Amoeba. A pale contractile vacuole lies in the endoplasm beside the dark nucleus £, Paramcecium. At each pole is a star-shaped contractile vacuole ; the upper is in the act of contracting, while the lower is beginning to fill itself from several small drops of liquid that are flowing together. was suggested by Traube, and was much discussed in his time. If a drop of a thick solution of gelatine be allowed carefully to fall into a solution of tannin, there appears about the drop a so-called precipitation-membrane of gelatine tannate, since at the surfaces of contact of the gelatine and the tannin the two substances undergo a chemical combination. This precipitation-membrane shows the peculiar phenomena of growth both in surface and in thickness, and on account of its similarity to a living cell Traube's drop of gelatine in the tannin solution has been termed an " arti- ficial cell." Since the gelatine solution attracts water to itself, tannin in solution comes constantly through the membrane to the 108 ' GENERAL PHYSIOLOGY drop. At the surface of the latter the tannin is united with the gelatine, and thus the continual apposition of new layers leads to the thickening of the membrane. The water, however, presses into the interior of the drop, so that this constantly swells and increases in size. By this process there appear continually in the precipitation-membrane extremely fine holes and cracks ; these, however, become closed by new precipitate at the moment of their appearance. Thus, the artificial cell grows continually and uniformly larger until all the gelatine is in combination. The formation and growth of the membrane, which in the large drop take place relatively rapidly, proceed very gradually in the small living cell. In botany a fruitless discussion has been going on for a long time over the question whether the cellulose-membrane of the plant-cell is formed by intussuscep- tion, i.e., by the deposition of new particles between the old ones, or by apposition, i.e., by the deposition of particles upon the outside.1 This discussion arose in connection with Nageli's unhappy com- parison of, or rather distinction between, growth in crystals and growth in organ- isms. Lately the view has been gradu- FIG. 58.— ceii-waii of a pith-ceil of ally accepted that both modes lead to £E£V<§S±g»>l"$£ the growth of the membrane-the one strasburger.) £o growth in surface, the other to growth in thickness. If the protoplasmic body of the cell itself is enlarged, the membrane is extended. In the process, as a rule, no actual cracks appear, as in the artificial cell, but as a result of the extension the spaces between the single particles of the membrane become wider and larger, so that new particles of protoplasm can enter in. But, on the other hand, the stratification of the membrane parallel to the surface, which is visible under high magnifying powers and with increasing thickness becomes constantly more distinct, shows that increase in thickness by apposition is also present (Fig. 58). If the cells in their metabolism produce substances and excrete them to the outside continually, extensive solid masses are gradually formed, which in multicellular tissues, where the products of the individual cells blend together, form the so-called intercellular substances, such as in cartilage and bone (Figs. 59 and 60). But the substances are not always excreted at once to the outside ; in many cases they are stored up as a solid mass in a vacuole in the cell itself, particle after particle being added to them as in a crystal. Thus, starch-grains in plant-cells, and calcareous needles 1 Of. p. 122. ELEMENTARY VITAL PHENOMENA 169 and stars in echinoderms and sponges, are formed within the cell itself, and only after they have reached a certain size are they given off to the outside by the customary mode of excretion of solid bodies (Fig. 61). Amoeba shows best the mode of excretion of substances that lie in the interior of the cell as solid masses. It has been seen that FIG. 59. — Cross-section of bone. The compact ground-substance lies between the star-shiped bone- cells. In the middle of the sec- tion is a cross-section of a bone- canal. (After Hatschek.) FIG. 60. ^Hyaline cartilage. Between the indi- vidual cells a solid, hyaline ground-substance has been excreted. (After Hatschek.) in the ingestion of food by Amoeba the food-ball enclosed in a food-vacuole lies finally within the protoplasm. In this vacuole, which may be termed a digestive vacuole, all digestible substance becomes dissolved, and passes into the protoplasm ; but the indigest- ible residue, such as shells of algae and of diatoms and the chitinous masses of rotifers, remain in the vacuole, and become excreted in the following manner : By the creeping of the Amoeba the digestive vacuole in the streaming protoplasm comes to lie very near the surface, so that its contents are separated from the medium merely by a thin delicate wall of protoplasm. In such a case the wall breaks very easily by the protoplasm flowing in all FIG. 61. — Formation of a triradiate calcareous star in an echinoderm cell. (After Semon.) directions away from the thinnest place, and the contents of the vacuole together with the solid mass are emptied to the outside (Fig. 62). This mode of removal of solid constituents from the protoplasm is found exclusively in cells that do not possess a membrane, and hence chiefly in amoeboid cells of all kinds. A transition between the method of output of liquids and that of solids is represented by the secretion of mucus. The mucous 170 GENERAL PHYSIOLOGY cells, which in the compound organism play so very important a role in protecting the internal surfaces and keeping them smooth and moist by their secretion of mucus, are always cylindrical. The nucleus, surrounded by somewhat more solid protoplasm, lies at the bottom of the cell-body, while the upper end of the cell, which borders the free surface of the membrane, is formed by a FIG. 62. — An Amosbain four successive stages of excretion of the undigested residue of food. substance, mucigen, that is continually being transformed into mucus. During the quiet activity of the cell a little of the secretion passes constantly to the thin liquid layer that covers the surface of the tissue. But during energetic, sudden secretion the whole mass that forms the upper part of the cell is shoved out (Fig. 63) and blends with the drops cast out of the neigh- bouring cells into a thick, gummy covering of mucus. The FIG. 63. — Mucous cells. A, Three isolated cells. S, Seven adjacent cells, of which the three at the left are full, the four at the right are empty. (After Schiefferdecker.) peculiarity of many holothurians, those cucumber-shaped forms of echinoderms, of transforming their thick, solid skins upon stimulation in a short time into a glistening, viscous slirne, is very remarkable and not yet explained. In general, the cell-physio- logical investigation of the process of secretion promises to afford many very interesting general physiological facts. ELEMENTARY VITAL PHENOMENA 171 2. Secretions and Excretions It is neither necessary .nor possible to examine here in detail the whole series of secretions and excretions which plant and animal cells afford in their metabolism ; our consideration shall therefore, be limited to the most important of these. a. Secretions Since it is characteristic of secretions to be of use to the organism, it is easy to understand that many secretions remain continually within the organism and are not given off to the outside. Hence two groups of secretions can be distinguished, according as after their formation they are at once given off or are retained continually in the organism, whether in the cell or upon its surface ; in neither case in the cell-community of the com- pound organism is it always necessary that the secretion be of use to that particular cell that affords it. Among the secretions that after their production learn the organism there are, in the first place, the ferments, which have to do with digestion and appear in both animals and plants. Thus, in animals the cells of the salivary glands produce ptyalin, which transforms starch into grape-sugar ; the cells of the gastric glands, pepsin, which peptonises proteids, and rennet -ferment or chymosin, which mediates the coagulation of casein ; and the cells of the pancreas ptyalin for the digestion of starch, trypsin for the pep- tonising of proteids, and steapsin for the splitting of fats. Ferments occur likewise in plants, such as the so-called carnivorous plants, which catch insects, hold them and digest them by the secretion of peptonising ferments. An example of such a plant is Drosera, which grows in the swamps. Whether the very effective ferments that are produced in the milky juice of some plants, such as Carica papaya, and are not cast out upon the surface, are to be regarded really as secretions in the present sense or only as excretions (by-products of metabolism) is thus far not decided, since the significance of these in the life of the plant has not yet been discovered. In unicellular organisms, further, the ferments are of great importance for the nutrition of the cell when these organisms, as is the case with the bacteria, come into contact with organic food and are obliged first to liquefy solid food-stuffs in order to be able to absorb them. Other secretions, such as the wide-spread mucin, of which mucus consists, are of great importance. Mucin protects the cell itself from external influences that can harm it, such as direct contact with objects; with strong stimulation the mucous cell produces a thick layer of mucus separating the former from the body that touches it ; this is the case with the mucous cells of the trachea 172 GENERAL PHYSIOLOGY when a foreign body comes into the throat. Further, the mucus of the saliva serves to make masticated food smooth, so that the masses of food can glide more easily through the narrow gullet. In this lies the chief importance of the saliva in man; here, on account of its too brief action, the ptyalin, which works only in an alkaline liquid, and hence in the acid gastric juice is made immediately ineffective, can hardly exercise its amylolytic power. Finally, mucus serves for attachment, especially in the lower animals and unicellular organisms. Rhizopoda secrete upon the surface of their protoplasmic bodies a delicate mucous covering with which they stick themselves to the bottom in order to creep about, and with which also they hold fast food-organisms that swim against them, in order to draw the latter into their own bodies and digest them. A similar importance as protective media is possessed by the fats which, such as the sebum, are produced by the sebaceous glands of the skin ; they protect the skin from too great evaporation and render it supple. Further, as Stahl ('88) has shown by a series of experiments, many secretions act in a different manner solely as protective media in animals and especially plants : such are ill-smelling or ill-tasting adds and ethereal oils. The organisms are protected by them from being devoured. Most of these cases present interest- ing phenomena of adaptation to definite conditions, which have arisen through natural selection and constitute contrivances advantageous to the organism. The same is true also of other cases in which plants, by means of good-smelling and good- tasting secretions, such as ethereal oils and honey, attract insects whose coming and going are useful, perhaps indispensable, to the plants ; the animals bear awray pollen upon their legs and deposit it upon the female flowers so that the latter are fertilised. Such adaptations, often astonishingly fitting, are especially common among plants, and the physiology of secretion touches here most closely the interesting field of the mutual relations of plants and animals. Finally, as secretions in the widest sense there may be recognised also substances produced in the cell, such as starch, aleur one- grains, fat-droplets, etc., which are stored in the cell for a time as reserve- material and later are used in metabolism. Among the secretions that after their production r&main in the organism, there belong almost exclusively pigments and substances that form skeletons. The former appear mostly in the form of fine granules, remain continually in the cell-body, and possess a special importance in the colour-changes of the animal, which is not yet entirely explained. The great majority of skeleton- forming substances are excreted to the outside. Sometimes they are laid down within the cell itself and later extruded, as are the calcareous needles and plates of the Holothuria ; sometimes they ELEMENTARY VITAL PHENOMENA 173 are secreted at once upon the surface of the cell in the form of membranes, shells, and coatings, such as cell-membranes, the c^te-membrane of plant-cells, the chitinous coats of insects, the silicious cases of diatoms, the delicate latticed skeletons of Radiolaria (Fig. 64), and the calcareous shells of Foraminifera ; A B FIG. 64.— Silicious skeletons of Radiolaria. (After Haeckel.) A, Dorataspis, B. Thcoconus. and sometimes they are stored in the tissues between the in- dividual cells as the so-called connective substances, such as chondrin in cartilage, glutin in bone, calciiim phosphate in bone, and the great number of supporting or skeletal substances which belong to the albuminoids and in the different groups of animals have compositions very different and as yet little known. b. Excretions The excretions are much fewer in number than the secretions. Chief among them are the products of retrogressive proteid- metamorphosis which are excreted by all living substance. Among gaseous excretions the most important one, whose pro- duction is associated with the life of every cell without ex- ception, is carbonic acid, the end-product of respiration ; it is produced chiefly by the oxidation and the decomposition of proteid, but under certain circumstances by the fermentation of carbohydrates. As has already been seen, in addition to carbonic acid, plants excrete oxygen, which is derived from the splitting-up of the carbonic acid received from their green parts. It has, therefore, been thought that the supposed contrast in the meta- bolism of plants and of animals, already spoken of, is to be found 174. GENERAL PHYSIOLOGY in the fact that plants take in carbonic acid and give out oxygen, while animals, vice versa, take in oxygen and give out carbonic acid. But later experiments have shown that, in reality, this contrast does not exist. It is true that animals inspire oxygen, employ it for the combustion of living substance, and expire carbonic acid as the product of such combustion. But plants do the same. In them this fundamental vital phenomenon of respiration is merely concealed by the consumption and the splitting-up of carbonic acid ; the latter, however, has nothing to do with respiration itself, but is preliminary to the construction by the plant of the first organic substance out of inorganic materials. If the metabolism of plants be examined at a time when no starch- formation is going on, when no carbonic acid is being split up, but when the life of the plant is being expressed in other ways, as in the night or in darkness, it is found, by gasometric experiments analogous to those above described, that the plant consumes oxygen and expires carbonic acid like the animal. In the plant, therefore, the process of respiration is not to be confounded with the process of assimilation of starch : the latter requires carbonic acid to be taken in and split up and oxygen to be given out, and thus conceals the respiration which is constantly taking place beside it. Respiration, i.e., the taking-in of oxygen and the giving-out of carbonic acid, is a general metabolic phenomenon. Among liquid excretions water occurs everywhere, and sub- stances dissolved in water. Because of the small quantity of these various excretions, in the present state of micro-chemical reactions it is usually not possible to demonstrate them for the individual cell ; hence they must be studied in the compound cell- community. In the plant, water is excreted and evaporated during transpiration through the so-called stomata of the leaves. By the action of special guard-cells the stomata can be closed and opened, and thus the output of water by the plant can be regulated very delicately. In animals there are special glands, the kidneys and sweat-glands, the cells of which excrete the water, together with the products of retrogressive proteid-meta- morphosis, out of the body-liquids, and pass them to the outside. Most of the non-nitrogenous products of proteid-decomposition are oxidised completely to carbonic acid and water, so that the latter leave the body as the almost exclusive end-products. But intermediate products also arise, which, excreted by certain cells, have a different fate within the body. This is true especially of lactic acid, which, among other things, is excreted by the muscle- cells into the blood and can be found there, but does not leave the body as such in the urine. That sarco-lactic acid or para-lactic acid is derived from the decomposition of proteids, and not from the ingested carbohydrates, is proved by the experiments of ELEMENTARY VITAL PHENOMENA 175 Gaglio ('86), already mentioned. But the sarco-lactic acid is still further transformed in the body, for, as has been seen, the experiments of Minkowski ('86) upon geese in which the liver was extirpated have shown that lactic acid, presumably combined with ammonia, is consumed in the synthesis of uric acid. The nitrogenous products of proteid-decomposition are the well- known substances which have already been met with frequently, especially urea, uric acid, hippuric acid, creatin, and the nuclein bases, xanthin, hypoxanthin or sarkin, adenin, and guanin. These are excreted chiefly in the urine and represent the compounds in which all the nitrogen taken in in the food leaves the body, apart from an inconsiderable quantity in the sweat and the faeces. The last fact, that, with the exception of the minute quantity in the sweat and the faeces, all the nitrogen is excreted in the urine, has assumed great importance in the physiology of animal organisms in connection with the circumstance that proteids and their derivatives are the sole nitrogenous substances in organisms. But, unfortunately, it has led to a false conclusion, which in itself would, perhaps, have had no immediate influence upon the development of fundamental physiological ideas, had not far-reaching and weighty deductions been drawn from it. It follows necessarily from the above-mentioned fact that all nitrogen excreted in the urine must be derived from the decom- position of proteid ; but the further conclusion which, it has been thought, must be drawn from it, does not follow, namely, that the nitrogen excreted in the urine is a measure of the proteid-trans- formation in the body. The latter conclusion would be justified only if it were known that all nitrogenous cleavage-products of the proteid molecule, without exception, leave the body. But there is no ground for such a belief ; on the contrary, no fact what- ever is known which contradicts the idea that nitrogenous cleavage- products of the proteid molecule can rebuild themselves syn- thetically again into proteid with the aid of new non-nitrogenous groups of atoms. This latter possibility has been overlooked, and in consequence views have arisen, especially in relation to meta- bolism in muscle, which, a priori, bear in themselves the stamp of improbability, but which have been accepted and handed down. Recently they have been attacked and criticised by Pfliiger ('91). To the excretory substances resulting from retrogressive pro- teid metamorphosis one more group can be added, the members of which likewise are derived from the transformation of proteids, chiefly in the metabolism of bacteria. These are the so-called ptomaines, some of which, on account of their very poisonous action, have lately been termed toxines. Upon their poisonous action chiefly depends the serious illness in the infectious diseases pro- duced by bacteria, such as cholera, dysentery, diphtheria, and 176* GENERAL PHYSIOLOGY typhoid fever. The chemical composition of these substances has become somewhat better known recently, especially through the comprehensive and exhaustive labours of Brieger ('85-'86). Some of them, the ptomaines that were first found, which are produced by the putrefaction of proteid substances through the metabolism of the putrefactive bacteria, as in dead bodies, are nitrogenous bases that are related to the so-called alkaloids or vegetable bases, which arise in the plant-body and likewise represent very poisonous excretory substances. Finally, we may refer here briefly to a very interesting series of substances which are produced, likewise, by the metabolism of bacteria chiefly, but also of very many other cells, and very recently have attracted the attention of investigators. These are the toxalbumins, poisonous proteids, which are produced in the metabolism of the cells by transformation from other bodies, and in the pathology of infectious diseases play an important role. Most of these toxalbumins are globulins and albumoses. Thus, the active constituent of tuberculin, which was obtained some time ago by Koch from the metabolic products of tubercle bacilli, is a toxalbumose, which in small doses is extremely poisonous. By the production of another toxalbumose the bacilli of diphtheria cause very characteristic phenomena of poisoning in the bodies of persons ill with diphtheria, the phenomena dis- appearing very slowly. The toxalbumose of the bacteria of diphtheria was the first toxalbumin which was recognised as such ; it was so recognised by LofHer ('90), and was obtained pure by Brieger and Frankel ('90). No little astonishment was caused when the first poisonous proteids were recognised, since the proteids had been known so long as harmless substances, and even as abso- lutely necessary food-substances. And the surprise was no less when later it was found that the poisonous effects of snake-bites, which are so greatly feared, and of the blood of many fishes, such as the lamprey, are to be traced, likewise, to the poison of such toxalbumins, which are produced by the metabolism of the tissue- cells and are excreted. Solid excretions are found almost exclusively in cells that take in solid food. In them the indigestible residue of the food is given off to the outside in the form of solid excretions in the manner already described. In a few cases the excretory substances which occur dissolved in the cell-contents are formed into solid con- cretions within the cell and are then cast out ; this is the case in the ciliate Infusoria, according to the investigations of Rhumbler ('88). At present it is not yet decided whether the concretions of yuanin and the crystals of calcium guanin which accumulate in many cells and are stored permanently in the protoplasm, such as in the beautifully iridescent crystalline plates and needles in the epidermis-cells of amphibians and fishes, are to be regarded as ELEMENTARY VITAL PHENOMENA 177 excretions or as substances that possess still further importance in the life of the organisms in question. If, now, the facts of metabolism be co-ordinated, it is found that from the entrance of substances into the living cell to their exit from it, metabolism consists of a long series of complicated chemical processes which can be represented in the form of a curve with an ascending and a descending limb. The ascending limb comprises all processes that lead to the construction of living substance ; the apex is formed by the synthesis of the most complex organic compounds, the proteids; the descending limb comprises the processes of the destruction of living substance into its simplest com- pounds. The beginning and end of the curve, i.e., the substances that enter into and go out from the organism, are best known ; the components that lie at the apex of the curve are known least, and in large part not at all. The green plant-cell, even the simple, unicellular, green alga, such as Protococcus, is a chemical laboratory in which, out of the simplest inorganic materials — carbonic acid, water, and salts — organic substance is manufactured, analytic processes and syntheses going on hand in hand in the process. First, starch appears. Starch with the help of nitrogenous salts serves to construct proteids, in which process very various kinds of by-products arise. But the green plant-cell does not complete this gradual con- struction of proteids for itself alone, it does it at the same time for all animal-cells, which in the course of evolution have lost the power of manufacturing organic material out of inorganic. The organic substances produced by plants serve as food for herbivora, the flesh of herbivora as food for carnivora. Carnivora can live upon proteid food alone. Hence it is seen that of the substances that appear in metabolism some, as in plants, lead to the construction of proteid, and some, as in carnivora, are derived from the transformation of proteid. But in plants as well as in animals a constant decomposition of proteid finally takes place, and there result again, as definitive end-products of metabolism, simple inorganic compounds, essentially the same materials with which the construction of living substance was carried on, namely, carbonic acid, water, and nitrogenous salts. All metabolism, therefore, is merely a series of processes which are related to the construction and destruction of proteids and their compounds. This is true as well of the plant as of the animal. II. THE PHENOMENA OF FORM-CHANGES The form of organisms is not unchangeable. Apart from the changes that are associated with motion, and which will be con- sidered elsewhere, organisms show profound changes of form that N 178 GENERAL PHYSIOLOGY are termed their development. Two great series of form-changes are recognised in living substance — phylogenetic or racial develop- ment, which comprises the form-changes of living substance in their totality during the earth's development ; and onto genetic or germinal development, which comprises the form-changes that a single individual goes through during his life. Haeckel ('66), who has done pioneer work of fundamental importance for the modern theory of evolution, has shown that the two series stand in intimate connection with one another; in general, germinal development is an abbreviated recapitulation of racial develop- ment. A. PHYLOGENETIC DEVELOPMENT The forms of living substance that inhabit the earth's surface have not always been the same. Modern palaeontology, the science of fossil organisms, has revealed an overwhelming number of forms which differ from those now living the more the older the strata from which they are derived. Critical research during the last decade has relegated to the realm of fable a large number of remarkable beings with which the earlier geology peopled the earth, and has shown them to be fanciful pictures which stand upon the same plane as the rare animal forms contrived by the curious creative fancies of the Indians, the Assyrians, and the Incas ; nevertheless, the discovery of well-authenticated fossil forms during recent de- cades has proved conclusively how utterly different from its present state was the organic world upon the earth's surface during the earlier periods of the earth's development. An overwhelming number of organisms have become known which inhabited the water and the land before man. The theory of descent has intro- duced a causal connection into this wealth of forms by showing that fossil organisms are not to be regarded as unique curiosities, lusus naturae, and the unsuccessful experiments of a Creator, as the previous century believed them to be. Rather are they the dead twigs and branches of a mighty, wide-spread trunk, of which the youngest and last shoots are the present living organisms ; the oldest branches have sprung from a common root, the Protista, whose direct descendants, little changed, now appear in the in- teresting groups of unicellular beings, Ehizopoda, Bacteria, Infiisoria, and Algce. Modern morphology has succeeded by critical research in drawing in gross outline a picture of the genealogical tree of organisms, and the conception of natural relationship, which was presaged by the use of the word by the earlier systematic mor- phology in a figurative sense, has obtained through phylogenetic research a very real significance. The present organic world is the product of an historic development stretching back over an enormously long space of time, in which some forms, such as the ELEMENTARY VITAL PHENOMENA 179 vertebrates, are the result of manifold and profound transforma- tions, while others, such as the Protista, have persisted from the earliest times in a form changed relatively little. The last fact, that in the unicellular Protista there is recognised a group of organisms that possess in almost absolute purity the characters of the ancient ancestors of all organisms, makes these micro-organisms appear particularly valuable physiologically. But let us go some- what more fully into the phenomena of the development of form in general. No substance exists without form. All substance has a definite form which is the expression of chemico-physical laws that pertain partly to the nature of the substance in question and partly to the influences that it receives from the outside. Living substance is only a portion of the matter that composes the earth, and is not different in its elementary nature from other substances. In assuming form, therefore, living substance must obey the mecha- nical laws of matter, as all other bodies do. If an organism has a definite form, however, there are two factors, the mutual working of which determines its further form-development — a conservative factor, which acts to maintain the form, and a mutative factor, which acts to change it. The factor that maintains form is the inheritance of present characteristics, the factor that causes change is adaptation to changed external conditions. 1. Heredity Heredity is one of the most familiar phenomena, so familiar that in daily life we scarcely notice it and become conscious of it only in special cases. By heredity is meant simply the fact that in reproduction characteristics of the parents are transmitted to the offspring, so that the descendants resemble in general the ancestors. The offspring of a beetle become beetles of the same form, and from the eggs of a fowl fowls develop ; a dog can produce only a dog, a human being only a human being and never other species. This transmission of the characteristics of the parents to the offspring pertains to the minutest details ; not only is the external form of the body transmitted, but special peculiarities of motion, attitudes, habits, etc. This is seen most clearly in human beings, since by practice in distinguishing them our gaze is sharpened even for minutiae. But, as a rule, the fact of heredity strikes us only when it has to do with specially characteristic signs, when we see transmitted from parents to children peculiar features, abnormalities of the body, such as supernumerary fingers, hair over the whole body or upon unusual parts, and physical defects. But not all peculiarities are always inherited. Many special characteristics are not inherited at all, others are transmitted N 2 180 GENERAL PHYSIOLOGY from the parents, not to the next generation, but to the second or the third. This transmission of characteristics to the second or third generation, with omission of the first, is known as reversion, or atavism. Thus, in man it is frequently observed that children have peculiarities of their grandparents which are wanting in their parents throughout life. Indeed, many pecu- liarities, after having remained latent for many generations, can suddenly appear again. This is frequently observed in domestic animals and cultivated plants which have been artificially bred from the wild forms and been gradually improved. When these are allowed to run wild, as a rule they go back again to the wild state ; every breeder of animals and every gardener is acquainted with many such examples. It would lead too far to discuss these facts in detail, and it would be superfluous, since a great variety of examples have become known through the immortal work of Darwin and the morphological studies that have been carried out in connection with the theory of descent. One interesting question in the problem of heredity has recently come into the fore-ground and has been discussed very actively, namely, the question of the inheritance of acquired characteristics in multicellular organisms. Are characteristics that have arisen during the individual life through the action of external influences, e.g., mutilations and diseases, inherited, or does inheritance deal with innate characteristics alone, i.e., characteristics that have become established during the germinal development of the organism? While Darwin ('59), Haeckel ('66), Eimer ('88) and others have defended the view that acquired characteristics are heritable, Weismann ('92, 1) has endeavoured to show in a long series of studies that only those characteristics are inherited the rudiments of which were already present in the germ-cells of the organism. At the first glance it seems surprising that such a question, which apparently is so easy to answer, can be the subject of such opposite views ; for nothing seems simpler than to decide by experiment whether mutilations, performed upon an adult animal, are transmitted to its offspring. In fact, such experiments have been made by Weismann and others. Weismann removed the tails of twelve white mice, of which seven were females and five males, and bred five generations of descendants, a total of 849 mice, from these tailless parents, but not a single one was born without a tail; and in all the adult animals the tails had their normal length. Many such experiments have been performed, but they prove only that in the cases in question the mutilations are not inherited, and not that no acquired characteristics at all are heritable. Upon the other side a number of examples have been brought forward, from which it would appear that certain acquired peculiarities have been transmitted. But Weismann has subjected all these cases to very careful criticism and has sought ELEMENTARY VITAL PHENOMENA 181 to show that for various reasons they ought not to be regarded as demonstrative. Hence, thus far, the question is not decided. A decision can be reached only by experiment, but not by such experiments as those performed upon mice. It is a priori improbable in the highest degree that injuries of the tail, the finger, or similar parts of the body are inherited, for it is hardly to be imagined that the organs in question stand in such a relation to the sexual cells, through which alone reproduction and inheritance occur, that their mutilation shall exercise a marked influence upon those cells, which is the first requisite of inheritance. In future experiments, therefore, mutilations must be performed upon such organs as stand demonstrably in correlation with the sexual organs, for only then would there be the possibility of hereditary transmission. Few such correlations, however, are known. In man, as is known, the development of the larynx is correlated with that of the sexual organs. Men who in their youth have lost the testes by castration retain throughout life a larynx retarded in its development and a high childish voice. The splendid sopranos in St. Peter's at Rome, whose artistic sing- ing is so attractive, have often afforded examples of this. Similar correlations ought first of all to be fully investigated and then to be employed for experiment, unless experimentation is to be a mere groping-about without plan, a process that leaves the decision to chance. That influences which affect the germ-cells, the ovum and the spermatozoon, influence the further develop- ment in a high degree, is a priori clear, and, moreover, has recently been shown, especially by the brothers Hertwig ('87), in a large number of striking experiments. If, now, mutilations that alter the germ-cells could be performed upon highly developed animals or upon plants, it would be possible to decide experimentally whether mutilations as such are transmitted by means of a definite action upon the germ-cells, or whether they influence the latter only in so far that offspring coming from those cells have other defects and abnormalities that are not like the mutila- tions. In the first case, there would be a real transmission of acquired characteristics, in the second not. Hence the question of the inheritance of acquired characteristics remains to be decided experimentally. Whatever has thus far appeared upon either the affirmative or the negative side is nothing but more or less probable supposition. Special characteristics are not necessarily inherited. But the general characters of every organism which for generations have been reproduced constantly, whether they are exclusively innate or are really acquired at some time by some predecessor, are constantly transmitted in their essentials. A change takes place so slowly that it can scarcely be perceived within the few genera- tions that come under observation during the life of one man or of 182 ' GENERAL PHYSIOLOGY several, or even within many generations ; this is evident from the identity of the animal world found in the Egyptian graves with that of the present. Heredity, therefore, represents an agency upon whieh depends in phylogenetic development the preservation of peculiarities of form that have once been present. 2. Adaptation Adaptation, which changes form, is not so immediately apparent as heredity, which maintains form. This is especially due to the fact that the phenomena of adaptation usually require long spaces of time for their observation, while heredity appears in every gene- ration of organisms. But the results of adaptation are seen daily, usually without this fact being recognised. The fact of purposefulness in living nature, which was so marvellous to men of science in early times, even down to the middle of the present century, forced them constantly to embrace teleology, i.e., the hypothesis of a fore-ordained plan of creation, such as dogmatic theology, preserving faithfully the ancient venerated ideas, accepts to-day. This purposefulness in nature is the simple expression — or, better, the result — of the adaptation of organisms to their vital conditions in the widest sense. Aquatic animals are adapted very perfectly to life in water, terrestrial animals to life upon dry land, flying animals to life in the air. Fishes have limbs in the form of fins, which function very perfectly as rowing-organs ; terrestrial vertebrates have in place of fins legs for walking and creeping upon dry land ; birds have wings constructed most fittingly, with which their light bodies, supported by bones containing air, soar through the air so perfectly that up to the present all inventors of artificial flying machines have tried in vain to imitate them. But only in single cases in the develop- ment of the individual can an adaptation to other conditions be traced. Thus, the larvae, of frogs, so long as they live in the water as tailed tadpoles, breathe like fishes by means of gills, which are constructed very simply and suitably for obtaining from the water the air dissolved in it. As soon as the small frogs come to the land, the tails shrink, the gills degenerate, and the lungs develop, by means of which, like all terrestrial animals, they take air directly into their bodies. If the tadpoles be prevented artificially from creeping upon dry land, they retain their tail and gills, and the lungs do not develop even though the animals reach a considerable size. Such examples prove that all organisms are adapted very fittingly to their vital conditions; and the later zoological and botanical investigations have shown that these adaptations extend frequently to the mi- nutest details, of which an untrained observer would never think. ELEMENTARY VITAL PHENOMENA 183 Since the conditions upon the earth's surface have slowly and con- stantly changed from the time of the incandescent nebula down to the present, since fairly rapid changes of the external conditions of life continually appear in locally restricted regions, and, finally, since all organisms are constructed even to the smallest minutiae in a manner corresponding perfectly to both general and special con- ditions, organisms must become adapted to their external conditions constantly and in proportion as the conditions themselves change. If this ratio between the change of external conditions and the change of the form of organisms had not existed in the past, there would have appeared within a conceivable time an extraordinary lack of fitness in the structure of organisms. But the cases in which an organ seems to be superfluous are relatively rare, and injurious mechanisms perhaps do not exist at all. The mode of adaptation of organisms is a double one : an indi- vidual, or personal, and a phyletic, or racial, adaptation may be distinguished. The two occur very differently. Individual adaptation acts only within very narrow limits, and in the phylogenetic changes of form has, perhaps, only a subordinate importance ; it has, indeed, no importance whatever in phylogeny, if the inheritance of acquired characteristics does not take place, for it consists in the fact that changes in the external environ- ment cause direct changes in the organism itself according to the different factors of the environment. Individual adaptation usually expresses itself much more clearly in habits, manner of life, etc., than in form. A man, put under other conditions than his customary ones, in another land and among other people, adapts himself to his surroundings gradually in the course of years, and gradually adopts the customs, usages, activities and mode of life of the new people. Much more seldom is there observed in organisms a change in body-form through individual adaptation to vital conditions, especially because much more profound changes in the conditions are necessary to cause it, and these are not so easily endured as the relatively slight changes that lead to adapta- tion in manner of life. A relatively slight change in the compo- sition of the water in which aquatic animals live, leads in most cases to death. Marine animals placed in fresh water and fresh- water animals placed in sea water usually die ; only a few forms have adapted themselves to both, especially such as live at the mouths of rivers, like certain fishes. A crustacean, Artemia salina, is very interesting in this connection. Schmankewitsch (77) established the very interesting fact that this small animal living in salt water can change itself, by slowly becoming accustomed to a higher or lower percentage of salt, into a dif- ferent form of crustacean — in water of greater concentration into Artemia Milhausenii, in fresh water into Branchipus stagnalis, two forms having wholly different characteristics (Fig. 65). Similar 184 GENERAL PHYSIOLOGY cases are known in single cells. Thus A. Schneider, Brass, and O. Zacharias ('85) have produced considerable changes of form in spermatozoa, intestinal epithelium-cells, and Amoeba, by the addition of various solutions to the medium. Unicellular organisms in general, especially Infusoria and Rhizopoda, afford many favour- able objects for the study of the changes that the body-form experiences as the result of changes in the surrounding medium. The following example1 is very interesting; it shows that the various forms of Amoeba, which are usually characterised by the shape of the pseudopodia, ought not to be regarded as distinct species in the systematic sense. Innumerable quantities of small amoebae are frequently found in the bacterial scum upon the sur- face of decomposing hay-infusions. When placed upon the slide, these have an essentially spherical form (Fig. 66, a). Broad, lobate pseudopodia begin gradually to be extended in various directions, so that the form of Amoeba proteus (princeps) (Fig. 66, &) is as- sumed. The creeping soon takes on one principal direction, the whole cell in a certain sense representing a single, long pseudopodium and assuming the form of Amoeba Umax (Fig. 66, c). In this form the amoebae creep about constantly, so long as they are not disturbed. If the composition of the medium be changed by making the water very feebly alkaline by the addition of potash solution, the following is observed. The amoeba? first contract into balls, but soon fine-pointed pseudopodia appear upon their surface (Fig. 66, d). These become longer and longer, and finally assume the appearance of long, pointed thorns. In the course of about 15 or 20 minutes the cells assume the very characteristic shape of Amoeba radiosa (Fig. 66, £,/), which is known by the systematists as a very well-defined species ; they remain in this condition and show the very sluggish movements of this species so long as the alkalinity of the medium continues. If they are put again into their accustomed water, their shape changes gradually to the usual Umax-form. Many moulds, which can be accustomed to concentrated salt-solutions when these contain sufficient food-stuffs for Mucor, behave similarly. The hyphae, as a rule, become considerably finer and slenderer than in the customary water. In many cases, however, changes in the vital conditions affect, not directly the form of the individual, but in a hidden manner the germ-plasm of the sexual cells, so that the offspring assume forms different from those associated with earlier conditions ; this, however, is rather to be considered under phyletic adaptation. 1 Of Verworn ('96, 4). FIG. 65. — A. Branchipus stag- nalis, fresh-water form ; B. Artemia salina, salt- water form of the same crustacean. (From Sem- per.) ELEMENTARY VITAL PHENOMENA 185 Phyletic adaptation, i.e., the gradual adaptation of the series of forms to existing vital conditions, has a disproportionate^ great, perhaps a determinative, significance in the form-changes of phylogenetic development. It takes place in a manner wholly different from that of individual adaptation. Darwin's immortal work ('59) consists in explaining naturally the surprising purposefulness in the organic world by revealing the mode of phyletic adaptation. According to Darwin's theory of selection the adaptation of organisms to external conditions takes place, not by the immediate change of the single individual, but by natural °6 FIG. 66. — Amceba Umax, a, Contracted ; I, at the beginning of the formation of pseudopodia, (proteus-foYTa) ; c, common Umax-form ; d, e,f, forms assumed after the addition of potash solution ; d, at the beginning of the action ; e, /, radiosa-forms. selection among many individuals in the same manner as in the improvement of the race by artificial selection on the part of the breeder. Starting from the fact of individual variability, i.e., the pheno- menon that in every generation of offspring from the same parents no single individual is wholly like another, although to ordinary observation the differences frequently appear very small, Darwin finds as a necessary consequence of the struggle for existence a choice, a selection, among the different individuals of every generation according to the measure of their vital power. It is known that in all organisms without exception more offspring 186 GENERAL PHYSIOLOGY are produced in germ than as adults would find sufficient vital conditions. To cite a striking example, it has been computed that, if of the several million eggs that a sturgeon lays only one million should develop into females and reproduce to an equal extent, the third generation would find no room upon the surface of the earth, while the fourth generation could produce a quantity of eggs greater than the volume of the earth ! But this re- markable condition is illusory, for only a very limited number of individuals can find the proper conditions for their existence, all others perish. But in this partly passive, partly active struggle for the means of existence it is not the chance individuals that perish, but almost exclusively those that can maintain the struggle less long, that are less adapted to the given conditions. On the other hand, those that are strongest, most powerful, most capable of life under the given conditions, will overcome in the competition and alone survive. Thus there takes place a se- lection of individuals most fitted for the given conditions of life ; and since this selection, as in breeding, continues for many and finally innumerable generations, while the selected individuals reproduce their characteristics by hereditary transmission, a gradual adaptation of individuals to their external conditions comes about, the result or expression of which is the purpose- fulness, reaching to the minutest details, of organisms in relation to the conditions under which they live. If the external con- ditions remain for a time unchanged, adaptation acts in a con- servative sense ; if they change, whether locally and suddenly, or generally and gradually, as in the development of the whole earth's surface, there occurs by selective adaptation in the struggle for existence a proportionate variation of form. The test of the correctness of this theory lies in the experiments of animal breeders, which have gone so far, especially in England, that by artificial selection toward definite aims in the course of a few years new varieties of domestic animals, especially pigeons, can be supplied to order, having these or those desired qualities. Here the artificial selection of the breeder plays the role of natural selection which in free nature consummates the struggle for existence. Darwin's theory affords a comprehensive and consistent picture of the origin of form-changes in living substance from the simplest species that previously inhabited the surface of the earth down to present organisms. If the effects of the few agents that determine form are recognised, it is easy to understand naturally the phylogenetic development of plants and animals from the unicellular protists, on the one side through cryptogams and monocotyledons to the highly developed flowering-plants, and on the other side through the coelenterates and worms to the highly developed arthropods and vertebrates. ELEMENTARY VITAL PHENOMENA 187 All living substance, like every physical body, must have some form, which is determined by its relations to the chemico-physical conditions of its environment. If the relations between organisms and the external world remained constantly the same, no change in the forms of organisms in the phylogenetic series would take place : and, since living substance has the property of reproduction, by heredity the descendants would always be exactly like the ancestors. Since, however, the conditions upon the earth's surface, as upon every physical body, are continually changing, and since the form of living substance, like every physical body, is under the influence of its surroundings, it must likewise continually change by adapting itself to the new conditions. Thus, there are the two opposing factors of heredity and adaptation, and the result of the action of these is expressed in the phylogenetic changes of form. B. ONTOGENETIC DEVELOPMENT The old myth of the metamorphoses of the multiform Proteus never found a more beautiful realisation than in the developmental history of the individual. Just as the organic world as a whole has undergone an unbroken change of form in the course of innu- merable centuries, so the single individual, especially the multicel- lular animal, during its development into the adult organism passes through in the briefest time a long series of manifold forms until it becomes like or approximately like its parents. It does not belong to the task of general physiology to follow the cycle of development of individual groups of organisms ; by the great growth of the fundamental ideas of Darwin and Haeckel our knowledge of indi- vidual or ontogenetic development has expanded into an indepen- dent science, embryology, the great importance of which for the understanding of the present organic world has been demonstrated during the last few decades. To-day no biologist or physician, who has not became a blind specialist, is unequipped with embryo- logical knowledge. But, although the study of the more special facts of the ontogenetic development of form must be left to the embryologist as his well-earned right, physiology has to deal with certain general and elementary vital phenomena, upon which the development of the individual rests. These are the phenomena of reproduction. As should be the case with all vital processes, these phenomena should be studied in the cell. The success of this method of treat- ment has already been demonstrated with reproductive phenomena ; morphology has laboured here intelligently and has illumined the whole field solely by means of cellular methods. As a result, we are now oriented as to the minute details of the visible events. 188 GENERAL PHYSIOLOGY 1. Growth and Reproduction Reproduction cannot be separated from growth, for in the widest sense it is only a special case of growth; the earlier embryology was prompted to regard reproduction as growth beyond the measure of the individual. The general process that consti- tutes growth is an increase of living substance, and the essence of reproduction likewise consists merely in an increase of living sub- stance. The difference between that which is usually termed growth in the narrow sense and the phenomenon of reproduction consists only in the fact that in the former case the newly formed FIG. 67.— SUntor polymorplms. N, Monilifonn nucleus ; o, mouth-opening, cv, contractile vacuole. /. Young individual extended. II. Older individual in the process of division, contracted. (After Stein.) living substance remains in constant connection with the original organism and helps to increase its volume ; while in the latter case a part of the substance separates itself from the original organism, either, as in most cases, being set entirely free, or, as in the increase of tissue-cells, being separated merely by a partition- wall and re- maining in place. Correspondingly, there is a large number of transitions between the growth, in the narrow sense, and the reproduction of the cell. Examples of such are afforded especially by many multinucleated cells, as, e.g., Opalina,the infusoriari living in the intestine of the frog, which at first is uninucleated and in growth becomes multinucleated by the repeated division of its nucleus. There occurs here a reproduction of the nuclei, while the ELEMENTARY VITAL PHENOMENA 189 protoplasm belonging to them remains in one mass ; the final result is a very large but multinucleate cell. Every cell exhibits, if not continually, at least at a certain time of its life, phenomena of growth ; the mass of its living substance increases. This can occur only by taking in material from the outside, or, in other words, by metabolism ; and the conception of growth can be rendered precise by bearing in mind that in meta- Fio. 68. — 7. Formation of eggs in the sea-urchin. A, Piece of a young ovary with the germinal epithelium within ; B, piece of an older ovary, in which the cells of the germinal epithelium are developing into eggs which are being constricted off. (After Ludwig.) //. Egg-tubes of the ovary of an insect. In the tubes lie eggs in different stages of formation. (After Hatschek.) bolism more living substance is built up than is broken down. But, as has been seen, the size of every cell is limited and does not surpass a certain measure. Particularly the size of every definite cell-form has a limit assigned for that particular form, which varies little. Hence, if the quantity of the living substance increases further by growth, this must lead to a " growth beyond the measure of the individual," the cell-mass must divide, i.e., it reproduces. The cell, therefore, multiplies by division ; and every one of the 190 GENERAL PHYSIOLOGY parts that arise, every daughter-cell, is correspondingly smaller ; it can then grow in turn until it has reached the limit of its indi- vidual measure. But in the reproduction of the cell by division, parts must pass over into the daughter-cells from both the essen- tial cell-constituents, the nucleus and the protoplasm, otherwise the daughter-cells would not represent complete cells, and hence could not continue to live. In another chapter in which we shall consider the mechanical explanation of vital phenomena we shall have to enquire after the deeper-lying causes of growth and of limitation in the size of cells. In this place it is necessary merely to obtain an outlook over the field of vital phenomena. If it be accepted provisionally that reproduction is merely further growth, while the size of the cell is limited, it follows that all repro- duction depends upon a division of the living substance of the cell. The widely different varie- ties of reproduction are nothing but cell-division ; and Virchow has rightly extended the old dic- tum of Harvey, " omne vivum esc ovo, " into that which forms the basis of all modern ideas of re- production, " omnis cellula e cellula" This is at once evident in unicellular organisms. They re- produce simply by the division of their cell-body, each daughter- cell assuming during the division the shape and form of the mother- cell ; and if, as in the Infusoria, the cells possess various kinds of appendages or organoidjs, the elements that are lacking become regenerated after the division of the body (Fig. 67). But in multi- cellular organisms, both animals and plants, special reproductive organs are developed, the cells of which become constricted off and as eggs develop by repeated cell-division into similar organisms (Fig. 68). In organisms that have separate sexes the sexual cells of the reproductive organs are different in the male and the female individuals. The male sexual cells are the sperm-cells, or sperm- atozoa, the female the egg-cells, or ova. For the production of a new individual a union of the two sexual cells, called fertilisation, must take place, except in certain cases where parthenogenesis is present, i.e., where individuals capable of life can develop from unfertilised eggs, as with many Crustacea and insects. Finally, in the lower multicellular animals, in addition to sexual repro- FIG. 69. — Myrianida, a worm in the process of fission. The single individuals are still hanging together like the links of a chain. a, The original animal ; 6, c, d, e, J, g, the buds from the oldest (6) to the youngest ((/). (After Milne-Edwards.) ELEMENTARY VITAL PHENOMENA 191 duction, there occurs asexual increase, by fission and gemmation. In both cases whole complexes of cells are separated off. In fission, e.g., in certain worms (Fig. 69), the whole body, after having reached a certain size by cell-division, is constricted into two or more parts which regenerate themselves again into complete individuals. In gemmation, e.g., in many coelente- rates (Fig. 70), there is formed in one part of the body by rapid cell-multiplication a bud, which contains cells from the essential body- layers and likewise becomes constricted off to regenerate into a new individual. In all cases, therefore, reproduction, whether asexual or sexual, takes place by cell-division alone, and this depends upon growth. We will now follow the different kinds of cell-division somewhat more in detail and consider the remarkable phenomena that take place in the cell. FIG. 70.— Gemma- tion in a polyp. (After Claus.) 2. The Forms of Cell-division In order that the daughter-cells of a cell-division may be capable of life, both the nucleus and protoplasm, as already remarked, must divide. But while the division of the protoplasm is very simple, the cell-body simply becoming constricted deeper and deeper by a groove until the protoplasm is separated into two halves, in most cases there appear in the nucleus extremely complicated changes, which in most cells, both animal and plant, agree remarkably in essentials. Regarding the more minute phenomena of cell-division a literature so large as to be almost beyond mastery has appeared during the last two de- cades, since investigators, misled by the very peculiar behaviour of the nucleus in cell-division, adopted the erroneous view that the nucleus is the sole essential cell-constituent and must be studied as exhaustively as possible in its " active " condition. The fundamental investigations of the phenomena of cell-division comprise the admirable ones of Biitschli (76), Flemming ('82), Strasburger, ('80, '88), O. Hertwig (76, 77, 78, '92), van Beneden ('87), Boveri ('87, '88, '90), and others, who have found objects best fitted for this purpose in the cells of young larvaB of sala- manders, in the pollen-cells of lilies, and in the transparent eggs of the sea-urchin and the round- worm of the horse. a. Direct Cell-division The simplest form of cell-division is the direct or amitotic cell- division, which, however, is comparatively rare and, beyond certain 192 GENERAL PHYSIOLOGY unicellular organisms and leucocytes, has been met with only in very few forms of cells. The division of Amoeba can serve as a type (Fig. 71). While the Amoeba is creeping, the original spherical nucleus becomes gradually lengthened, then biscuit- shaped, then constricted through the middle ; the connecting- piece becomes constantly slenderer and finally breaks ; and thus two new nuclei result, which immediately assume the spherical form. Then the division of the protoplasm begins ; the Amoeba -r.-JPL -, • • ."^sssw/ j •:• * *£•& $. ^ S/X"\' vl»" •'.* ' M W( <>m*M ^ >*C«^^ -p^ FIG. 71. — Amoeba polypodia in six successive stages of division The dark body surrounded by a clear area in the interior is the nucleus, the pale body the contractile vacuole. (After F. E. Schulze.) becomes constricted in a similar manner between the two nuclei like a dumb-bell and creeps towards the two sides, until only a thin thread of protoplasm unites the two halves , this finally breaks so that two new Amcebce, each with one nucleus, result from the division. The process requires a long time, usually several hours, and does not always proceed smoothly : the protoplasm often flows together into one mass after a considerable constriction has taken place, and then flows apart again, until, finally, the uniting bridge is torn through. ELEMENTARY VITAL PHENOMENA 193 I. Indirect Cell-division By far the great majority of all animal- and plant-cells follow the mode of the so-called indirect or mitotic cell-division, in which the protoplasm is simply constricted, while the nucleus undergoes very remarkable and typical changes of great regularity. Different authors have distinguished different stages and have designated them by different names. Two phases in nuclear division can be D E FIG. 72.— Scheme of mitotic cell-division. (After Flemming.) very generally recognised — a progressive one, in which the changes reach their height, and a retrogressive one, in which the two nuclear halves that arise from the division go back to the " resting-stage " of the nucleus, which latter term designates the condition in which the nucleus shows no phenomena of division. A picture will put before oar eyes the important phenomena of nuclear division better than all classifications and descriptions (Fig. 72> To begin with the resting nucleus about to undergo division, it is seen that the chromatic substance, which, as is well known, o 194 GENERAL PHYSIOLOGY consists of nucleins, arranges itself into threads which appear loosely rolled up into a coil (Fig. 72, A). The threads, which have given to this form of nuclear division the name of mitotic division and have approximately equal lengths, split lengthwise so that from each a double thread results. - At the same time the nuclear membrane becomes dissolved, and at the two opposite poles of the nuclear mass the centrosomes, or central bodies (p. 69), surrounded by their protoplasmic radiations, now become visible, the two being united to one another by a fibrous, spindle-shaped figure which is derived from the achromatic substance mixed with the protoplasm. The double threads form loops, and group themselves in the equator of the achromatic nuclear spindle in such a way that their angles are directed towards the centre (Fig. 72, B). Presently the spindle-fibres, streaming out from the centrosomes, by their own contraction divide the double threads in such a way that one half of each is turned to- ward one pole, the other half toward the other (Fig. 72, G). Thus two groups of threads separate from each other and from the equator of the spindle (Fig. 72, Z>). With this the progressive phase of nuclear division is ended and the retrogressive phase begins. The two groups of chromatic threads proceed further and further toward the two poles, so that the whole equatorial part of the spindle becomes free (Fig. 72, E). FIG. 73.— Centrosomes with Presently the spindle-fibres between the protoplasmic radiation * -i • , i -\ • , • m the division of the two groups begin to become indistinct, egg-ceii. (After Boveri.) and the threads become twisted again into a coil at each pole (Fig. 72, F). During this process the whole cell-body has become constricted by a circular groove, the plane of which stands at right angles to the axis of the two nuclear poles. The groove becomes deeper and deeper, until finally the whole cell divides into two equal halves, each of which possesses a nucleus ; the latter surrounds itself with a new nuclear membrane, the spindle-fibres completely disappearing, and thus returns to its resting-stage. Thus by the division of the mother-cell two daughter-cells have arisen, and these continue the growth on their own behalf (Fig. 72, F). But during the division a phenomenon has appeared in the protoplasm. Simultaneously with the appearance of the spindle, the poles of which are formed by the centrosomes, two star- shaped figures begin to appear in the protoplasm, by the latter arranging itself at each pole like rays around the centrosome as a centre ; the centrosomes thus become surrounded exactly like two suns by a closed circle of rays (Fig. 73). As the spindle- fibres become indistinct the protoplasmic rays also disappear. ELEMENTARY VITAL PHENOMENA 195 This mode of mitotic nuclear division is the same in the different forms of cells, almost without exception and even to the finest details. But the division of the cell as a whole does not always proceed in exactly the same manner. Deviations from the type occur in various cases, especially in the division of egg-cells that contain much nutrient material (yolk). With O. Hertwig ('92) FIG. 74. — /. Division of the frog's egg. P, Pigmented surface of the egg ; pr, protoplasmic pole ; d, pole rich in yolk ; sp, nuclear spindle. (After Hertwig.) //. Unequal division of the egg of a worm (Fabricia). A, Protoplasmic pole ; V, pole rich in yolk. (After Haeckel.) all known forms of cell-division can be conveniently classified under four types — I. Total division. a. Equal division, ft. Unequal division. c. Gemmation. II. Partial division. III. Multiple division. IV. Reducing division. In total division, the protoplasm of the daughter-cells is com- pletely divided by a partition, so that complete cells always result from the division. But certain differences are here noticeable. In one case, that of equal division, the daughter-cells are entirely equal, as in the type described above (Fig. 72, F). In another case, that of unequal division (Fig. 74), the two daughter-cells are o 2 196 GENERAL PHYSIOLOGY unequal in size and their contents differ ; the larger one contains the chief mass of the passive yolk, while the smaller one consists principally of active protoplasm. In this way differences arise which have an important bearing upon the subsequent divisions, and become constantly greater. In the third case, that of gemmation, only a very small portion of the egg-cell becomes divided off; this FIG. 75.— Formation of the polar bodies in the starfish ; sp, nuclear spindle ; rfc1, first polar body ; rib2, second polar body ; ek, egg-nucleus. occurs especially during the maturation of the egg in the forma- tion of the so-called polar bodies or direction-corpuscles, where the process occurs twice in succession (Fig. 75). In partial division the groove that separates the two daughter- halves extends not through the whole cell, but through a part FIG. 76.— Discoidal cleavage of the egg of a cephalopod. (After Watase.) only, so that in subsequent divisions the daughter-halves remain united on their under side by a common protoplasmic mass (Fig. 76). This form is termed discoidal cleavage. In multiple division, no division whatever of the protoplasm appears at first, but the nuclei alone multiply in the egg- cell ; later, however, they wander to the surface and there surround ELEMENTARY VITAL PHENOMENA 197 themselves with a separate protoplasmic covering. Thus there exists upon the whole surface an indifferent yolk-mass surrounded by a single layer of separate cells (Figs. 77 and 78) — a phenomenon that has been termed superficial cleavage. A special kind of multiple division is spore-formation, which is especially common in the Protista. The characteristic of this FIG. 77. — Superficial cleavage of the egg of an insect in three successive stages. (After Bobretzky.) form of cell-multiplication is that the nucleus breaks up into a very large number of tiny granules. Each of these small nuclei surrounds itself with a certain quantity of protoplasm, so that tiny cell-territories appear, which become free as amoebae or flagellated cells, while the rest of the protoplasmic body perishes. The swarm-spore, set free, represents a very small cell containing a nucleus, and slowly develops into the form of the protistan cell from which it was derived. Finally, in reducing division, as Weis- mann has termed certain processes that lead to the formation of the ova and the sperm-cells in the ovary and the testis, a slight deviation in the behaviour of the chromatic fibres of the nucleus appears during division. The sperm-cells arise by repeated division of other cells, the sperm mother-cells. The first division of the sperm mother-cells proceeds according to the type described above, but before the nuclei have returned to the resting-stage a second division takes places, each centrosome dividing into two halves which diverge from one another and attract to themselves on both sides the chromatic fibres that arise from the first division, without the latter being able to split lengthwise as in the normal division. Thus, one half of the chromatin-loops wander toward one pole, FIG. 78.— Multiple, division in the cleavage of the egg of an insect in two successive stages. (After Balbiani.) 198 GENERAL PHYSIOLOGY the other half toward the other pole, so that by this second divi- sion each nucleus obtains only one-half as many chromatin-fibres. as in a normal division (Fig. 79). FIG. 79.— Reducing division in the origin of the sperm-cell from the sperm mother-cell of the thread- worm of the horse. (After O. Hertwig.) These comprise the various forms of cell-division which have become known thus far. The only element common to them all is the transfer of both nuclear substance and protoplasm to the daughter-cells. 3. Fertilisation The act of fertilisation is intimately associated with that pro- found mystery with which mankind is wont to invest its most sacred feelings. The biologist recognises that fact that the un- conscious aim of normal sexual love, one of the most powerful factors that control organic life, is the microscopic act of fertilisa- tion of the female egg-cell by the male sperm-cell. At first sight it might seem strange that so powerful motives, as are those of love in human life, culminate in so tiny a phenomenon, which cannot be perceived by the naked eye ; but when it is borne in mind what the result of this act is, what an endless chain of com- plex processes and changes associated with the development of the new organism from the egg is caused by fertilisation, and what is the end-result of this long series of developmental processes — namely, the highly complex animal, man, with the immeasurable richness of his life — then this fact loses its strangeness, and we come to attribute to the tiny act of fertilisation an extraordinary significance, which it contains in potentia. It is no wonder, there- fore, that since early times physicians and men of science have made sexual reproduction the subject of deep research. Yet it was not till after Leeuwenhoek had constructed the microscope that his pupil, Ludwig van Hammen, discovered the sperm-cells, which because of their active intrinsic movements were called " sperm- animalcules " or " spermatozoa." And only the unlooked-for perfection of the microscope in the present time has made possible the brilliant work of Butschli, Fol, Hertwig, van Beneden, Boveri, ELEMENTARY VITAL PHENOMENA 199 and others, who have thrown light upon the minute details of the phenomena of fertilisation. In the human being and the higher animals the process of fer- tilisation cannot be observed, because it is concealed in the inte- rior of the female body, and it is not possible to keep the egg- cells alive outside of the body and there fertilise them with sperm. This latter method, however, succeeds with certain lower animals, and hence in eggs that are particularly large and transparent, such as those of the sea-urchin and the round-worm of the horse, the whole course of this interesting process has been carefully studied. As has already been seen, the male and the female germ-cells are differentiated very differently. While the ova usually are large, spherical or amoeboid cells consisting of a vesicular nucleus and much protoplasm, the latter containing the building-materials for the future development (Fig. 80), the spermatozoa are ex- FIG. 80.— Ova. /. Spherical ovum of a sea-urchin. (After Hertwig.) II. Amreboid ovum of a calcareous sponge. (After Haeckel.) tremely tiny in comparison with them. The spermatozoa consist chiefly of nuclear substance, and have only a thin protoplasmic covering; in most cases the latter is extended into a motile flagellum, the tail, which is distinguished from the rest of the body, the head, and serves for the movement of the spermato- zoon in seeking the ovum. The finer structure of the sperm-cell, as the detailed investigations of Ballowitz ('90) have recently shown, is very complicated, and very various differentiations occur among different animals. The accompanying illustrations present some examples of this (Fig. 81). But both the spermatozoa and the ova are always complete cells, and contain both the essential cell-constituents, protoplasm and nucleus — a fact upon which special emphasis should be laid. Before fertilisation takes place, in some cases also during the beginning of fertilisation, there occurs the maturation of the ovum, which consists in the formation, by means of two successive divisions of the nucleus, of two buds, the polar bodies or direction- 200 GENERAL PHYSIOLOGY corpuscles, and their subsequent extrusion (Fig. 75, p. 196). Fer- tilisation, therefore, consists in the union of a mature egg-cell with a sperm-cell, in which process the latter seeks the former by its own locomotion. We shall become acquainted with the mode of locomotion later in considering the phenomena of movement. The process of the union of two cells is a phenomenon that occurs not only in sexual reproduction but is constantly met with among unicellular organisms, where sexual differentiation cannot be said to exist. There, in the Protista, it is known by the name of conjugation. Conjugation occurs even among the unicellular shell-bearing Ehizopoda, e.g., in Difflugia, which is provided with a delicate capsule. In this genus two, and sometimes three, four, 0 0 FIG. 81. — Various forms of spermatozoa, a, From a bat ( J esperugo nocturna) (after Ballowitz) ; b and c, from the frog ; d, from the finch ; e, from the sheep ; / and 0, from the pig. (After Schweigger-Seidel.) h, From a medusa ; i, from a monkey (Cercopithecus) ', I, from a crustacean. (After Claus.) k, From the round-worm (after Boveri). or even more, of the sluggish protoplasmic forms creep closely together; their protoplasmic bodies lie in contact with one another, then coalesce into a common mass, and finally separate after the protoplasm of the various bodies has mixed and certain changes in the nuclei have taken place.1 The phenomena of conjugation in ciliate Infusoria have been studied very thoroughly by Butschli (76), Balbiani ('61), Maupas ('88), A. Gruber ('86, 2), and R Hertwig ('88 — '89). Paramoewum is an oblong infusorian, completely ciliated upon the outside, and constitutes an extraordinarily favourable object for cell-physiological investiga- tions of the greatest variety. Paramcecia, visible to the naked eye, may be cultivated in great quantity in decomposing hay- infusions and may be kept in stock. It is frequently observed that an epidemic of conjugation suddenly appears throughout the whole culture, so that almost none but conjugating individuals are found. The phenomena of conjugation are as follows : — Two indi- 1 Cf. Verworn ('90, 1). ELEMENTARY VITAL PHENOMENA 201 viduals apply themselves parallel to one another at their mouth - openings (Fig. 82, 1., o), their masses of protoplasm join together to form a bridge, and very characteristic changes in the nuclei begin. As above remarked, ciliate Infusoria have two forms of nucleus — •a macronucleus, or chief nucleus, and one or more micronuclei, or FIG. 82. — Conjugation of Paramcecium in the various successive stages ; A*, macronucleus ; n k, micronucleus. I. Beginning of conjugation. II. The micronucleus has divided twice in succession. III. Three of the four portions of the micronucleus perish, the fourth divides once more into a male m and a female w nucleus. IV. While the macronucleus is disin- tegrating, the two male nuclei, 1m and 5m, become exchanged and unite with the two female nuclei into a nucleus, V. t, which divides in turn into t' and t". VI. t' and t" divide. VII. From this division arise the rudiments of the new macronucleus pt and the new micro- nucleus nk'. The old macronucleus perishes. (After R. Hertwig.) accessory nuclei. During conjugation the macronucleus perishes, disintegrating and dissolving in the protoplasm. If the Paramce- cium be a form possessing one micronucleus, such as Paramcecium caudatum, where the relations are simplest, the micronucleus in each individual divides twice in succession, so that four partial nuclei arise. Three of these likewise dissolve in the protoplasm, 2°2 GENERAL PHYSIOLOGY but the fourth divides once more in each individual, and one half (the " male " nucleus) passes over the protoplasmic bridge into the other individual, so that each one of the pair now con- tains a " female " nucleus of its own, and a " male " nucleus from the other. These two nuclei immediately fuse together and then divide, one half becoming a new macronucleus, and the other half a new micronucleus. After such a mutual exchange of half-nuclei, the pair separate again and the conjugation is ended. The phenomena of fertilisation in sexual reproduction are derived phylogenetically from the conjugation of asexual unicellular FIG. 83. — Fertilisation of the ovum of the thread-worm (Ascaris megdlocephala) in six successive stages. The maturation of the ovum, i.e., the extrusion of the polar bodies, takes place simul- taneously. (After O. Hertwig.) organisms ; essentially the same facts are found in the former as in the latter. The process of fertilisation is not entirely the same in different species ; at least in the two species that thus far have been most fully investigated, the egg of the sea-urchin and that of the thread-worm of the horse, some slight differences have been observed, although the essential factors agree throughout. We shall consider, first, the fertilisation of the ovum of the thread- worm. The maturation of the ovum, i.e., the extrusion of the polar bodies, takes place while the sperm-cell is entering the egg. While the latter process is taking place (Fig. 83, 7), the egg- nucleus, which up to this time has lain in the middle of the egg> ELEMENTARY VITAL PHENOMENA 203 wanders to the surface (Fig. 83, 77), where it divides twice in succession and gives off the polar bodies (Fig. 83, III and IV). In the meantime, the protoplasm of the sperm-cell has fused with the protoplasm of the egg-cell and withdrawn from further ob- servation. The sperm-nucleus, however, has wandered into the middle of the egg. to which place also the egg-nucleus, after giving off the polar bodies, returns from the periphery. The two nuclei now apply themselves to one another, surround themselves with a transparent envelope, and show distinctly two large chromatic loops in each. At the same time, two centrosomes become visible and begin to surround themselves at opposite sides of the nuclei with a circle of rays (Fig. 83, V). In the thread-worm the nuclear substances do not fuse, but the well-known spindle of nuclear division develops, beginning at the two centrosomes, and the spindle-fibres on either side draw to their respective poles one chromatic loop from the egg-nucleus and one from the sperm- nucleus, so that each half of the egg-cell obtains one nuclear com- ponent from the egg and one from the spermatozoon (Fig. 83, VJ\ The fertilisation is thus ended, and at the same time the first division of the ovum is prepared for ; the latter now proceeds in the usual manner, the egg being constricted through the equator of the spindle, while the nuclei in the two halves assume their resting-form. As regards individual points, the fertilisation of the egg of the sea-urchin proceeds somewhat differently. The maturation of the ovum is completely ended when the spermatozoon enters. Further, the egg- and the sperm-nuclei fuse completely into a single nucleus before the division into the first two cleavage-cells of the ovum takes place. Fol ('91) supposed that he had made in the further course of the fertilisation -process an observation of special interest, because it appeared to shed some light upon the behaviour of the centrosome. What he saw was the following : With the sperm-cell, a sperm-centrosome enters the ovum, which still possesses, in addition, its own centrosome. After the union of egg-nucleus and sperm-nucleus the two centrosomes come to lie at the two opposite poles of the common nucleus, which is sur- rounded by a simple protoplasmic radiation. Each of the two centrosomes thereupon divides, constricting itself like a dumb-bell into two, each of which wanders across to the other of the opposite side, a phenomenon that was termed by Fol the " quadrille of the centrosomes." Thus, each half of the original egg-centrosome comes into union with one half of the sperm -centrosome and finally fuses with it, so that only two centrosomes are present again at the opposite poles of the nucleus ; each of these two, however, consists in half of the substance of the egg-centrosome and in half of that of the sperm-centrosome. These two centro- somes now form the poles for the following division of the nucleus 204 GENERAL PHYSIOLOGY and become surrounded each with its own protoplasmic radiation. Thus the fertilisation is ended and the division of the fertilised ovum into the first two cleavage-cells is introduced. But, unfor- tunately, this account by Fol concerning the course of fertilisation and the much-quoted " quadrille of the centrosomes " appears to rest upon incorrect observation. At least Boveri ('95) and, in harmony with him, Wilson and Mathews ('95) in sea-urchin eggs, and Mead ('95) in the eggs of tube-worms (Chcetopterus pergamentaceus), have found that such a quadrille of the centrosomes does not exist, that rather the centrosome of the egg-cell perishes and disappears (Mead) without playing any rdle, while that of the sperm-cell after fertilisation divides alone in the egg-cell into two centrosomes, each of which becomes a centre for the protoplasmic radiation and the succeeding division of the fertilised ovum. A re'sume' of the essential factors of the phenomena of fertilisa- tion leads to the following statement : Fertilisation consists in the union of two cells, the egg-cell and the sperm-cell, in which protoplasm fuses ivith protoplasm and nucleus with nucleus ; thus, in the succeed- ing division of the fertilised egg-cell each half obtains material from both the fused cells, and from both the protoplasm and the nucleus. 4. The Development of the Multicellular Organism Development may be defined in a general sense as a continuous series of changes. If we leave out of consideration the repro- duction of the multicellular organism by the constriction of entire parts of the body, as in gemmation and fission, where the essential cell-groups of the individual systems of organs are transferred directly from the parent organism to the buds or products of fission, the formation of the multicellular organism consists only in its development from the egg-cell. The multi- cellular organism develops gradually from a single cell, whether the egg develops without fertilisation, as in the interesting- phenomenon of parthenogenesis (which occurs in certain lower animals and affords a real background for the ancient legend of the immaculate conception), or whether the egg has previously been fertilised, as is the general rule in the development of animals and plants. Development is present in unicellular organisms, but here the whole cycle proceeds in a single cell. The development of the Protista forms an interesting analogy to that of multi- cellular organisms, both animals and plants. In the lowest forms, such as Amceba, development is identical with simple growth. An Amoeba changes simply by increasing in mass and then dividing. The halves then grow again until they become so large that they again divide. The whole developmental cycle of Amceba consists in growth up to cell-division. We see, therefore, that growth and ELEMENTARY VITAL PHENOMENA 205 cell-division are the simplest elements that development demands ; in fact, in the whole living world there is no development without growth and cell-division. In all Protista that reproduce by spore- formation, there occurs a development expressing itself in com- plex changes of form. In this case the spores, which are totally unlike the mother-cell, must pass through a series of changes of form until they become like it. The development of the Protista has been little studied. Nevertheless, Rhumbler ('88) has followed completely and with great care that of the infusorian genus Colpoda. Colpoda is a small bean-shaped infusorian, the surface of whose whole body is ciliated (Fig. 84, A). In spore- FIG. 84.— Development of Colpoda cucullus. (After Rhumbler.) formation the body surrounds itself with a thick envelope or cyst (£), within which by giving off water the body constantly diminishes its volume. Finally it extrudes all undigested food- particles and draws itself together into a ball ((7), which loses its cilia and surrounds itself by a second smaller envelope (D). The contents of this second envelope (E) break up into single spores, which together with a remnant consisting of useless material burst the capsule and freely wander out (F). From each spore (£) a new individual develops by the spore transforming itself into a small amoaba-like being which creeps about, takes food, grows (H, J, K, L\ develops a long flagellum with which it swims (M), and finally contracts into a small spherical cell (N), which covers its surface with cilia (0), and by further growth gradually assumes the form of a Colpoda (P, Q, R). Thus the developmental cycle is completed. 206 GENERAL PHYSIOLOGY That which comes to pass among the Protista in a single cell, takes place in an aggregate of cells in the development of the multicellular organism. In accordance with the above considerations concerning reproduction, the development of the multicellular organism from the unicellular egg can take place by continued cell- division only. But in this process two factors play important rdles : first, the products of the division of the egg-cell do not separate as in most Protista, but remain in connection with one another; and, second, the products of division are not always alike, but by unequal division two forms of cell, wholly different from each other and from the mother-cell, can arise. In this manner is FIG. 85. — A. Eudorina elegans, B. Magosphcera planula, two multicellular organisms consisting of similar cells. (After Haeckel.) rendered possible the origin, not only of a multicellular organism, but of such an organism with differentiation of various kinds of tissues and organs. If the first factor alone were present, there would result a cell-community consisting of many cells, all of which, however, would be alike. Such organisms exist among Protista (Fig. 85), and are regarded as cell-colonies that have a republican constitution, i.e., in which every cell is exactly like every other. These forms are the intermediate links be- tween the really unicellular organisms and the animals or plants. In the bodies of animals and plants, even the lowest, the cells are not all alike, and this differentiation, through which alone the development of a complex cell-community becomes possible, depends upon the efficiency of the second factor, unequal cell- division. Hence, cell-division, both equal and unequal, and cohesion of the cells are the factors that bring about the develop- ment of a differentiated cell-community. ELEMENTARY VITAL PHENOMENA 207 We cannot go further into the special phenomena of the individual development of animals and plants, and must refer the reader to the detailed works of Haeckel ('91), 0. Hertwig ('90), and Korschelt and Heider ('90), who treat embryology as an independ- ent science. We must, nevertheless, glance at that important law which, as has already been seen, prescribes a definite path to individual development, namely, the fundamental law of biogenesis. Karl Ernst von Baer, the founder of embryology, discovered that in the embryonic development of widely different forms of animals, stages occur that appear strikingly similar; and after Darwin's epoch-making labour Fritz Miiller ('64) expressed clearly the fact that the developmental history of the individual is a short repetition of the whole course of development which the corres- ponding species has undergone during the development of the earth. It was Haeckel's service to formulate more exactly the fundamental law of biogenesis and emphasise the existence of a causal relation between ontogeny and phylogeny. Haeckel ('66) showed that individual development, or ontogeny, is only in gross outline a repetition or palingeny of the racial develop- ment or phylogeny, but that this repetition is frequently blurred or falsified by the appearance of phenomena that are not present in the phylogeny of the corresponding form and which, therefore, he termed the phenomena of falsified development or cenogeny. Hence, in the individual development of every organism, two elements may be distinguished : first, the palingenetic phenomena, which recapitulate in brief the racial development of the form in question, and, second, the cenogenetic phenomena which have arisen supplementarily by adaptation and have altered and blurred the course of the palingenetic phenomena. The causal explanation of these facts lies in the two factors which, as has been seen, control the whole development of organic life, namely, heredity, which maintains form, and adaptation, which changes it. The characteristics of an organism comprise more than those which it shows at any single moment of its development or as an adult animal. To them belong the whole sum of pe- culiarities and changes which it has shown from its simplest beginnings ; for the later characteristics do not represent any- thing new and spontaneous, but proceed immediately and continu- ously from the earlier ones. If, therefore, heredity conveys the characteristics of the parents to the offspring, it must convey to the latter, not only the characteristics possessed by the parents at the moment of the production of the offspring, but the whole sum of parental characteristics, and among them those that the parents have shown during their development. Hence the peculiar course of development that the parents have gone through must be transmitted to the children, and the latter must 208 GENERAL PHYSIOLOGY go through the same development. Since this is true of every generation of parents and children, it must be true also of all the ancestors of the race, even the earliest, i.e., the children are the historic product of the whole racial development and in their developmental history must pass through the whole history of the race. But this is true only on the condition that heredity is the sole factor that determines form. In such a case every minute pecu- liarity that was once present in the ancestral series of the organ- ism would repeat itself with painful exactness in the development of the latter. Since individual development demands a relatively short time and racial development shows an inconceivable variety of changes in form, the remarkable spectacle would be presented of the ontogeny of a higher animal appearing like the picture in a constantly turning kaleidoscope, which never remains the same but presents to the eyes at every moment a different form. It is well known that this is not the case, but that the racial development is recapitulated only in bare outlines and under- goes manifold changes ; these latter are the cenogenetic phe- nomena, which are caused by the second factor that determines form, namely, adaptation. It has been seen that the form of every organism is determined in a certain degree by external conditions. Any form that lived at a certain geological period in the racial series of an animal is, therefore, determined among other things by the conditions that prevailed upon the earth's surface at that period. The conditions now are entirely dif- ferent. But not only have the conditions upon the earth become different, but the animal in its development is under wholly differ- ent conditions from the completed animal, especially if the first developmental stages are passed through within the mother's body. Since, however, these external conditions must effect an adaptation of the organism in question, it is explained why in the ontogenetic recapitulation of the phylogenetic series there appears not only a simplification but also an alteration of certain phenomena. Simplification comes about because developmental stages which at the time of their appearance represented special adaptations to certain conditions become bred out as useless and disturbing factors now when those conditions are wanting; alteration occurs by the adaptation of certain developmental stages themselves to the new conditions. It is clear that here also selection controls the change of form, and that characteristics arising cenogenetically become transmitted like original ones. Accordingly, with Haeckel (75), the fundamental law of biogenesis may be formulated in brief as follows : " Germinal de- velopment is an epitome of racial development ; the more complete, the more the abridged development is maintained ly heredity ; the less complete, the more a falsified development is introduced ~by adaptation. ELEMENTARY VITAL PHENOMENA 209 III. THE PHENOMENA OF TRANSFORMATION OF ENERGY A. THE FORMS OF ENERGY For a long time natural science has distinguished different forces which bring about the phenomena of motion in nature. In the scientific sense force is nothing but an expression for the cause of motion, for we know nothing concerning it except that it causes motion. Sense-perception is not force, it is merely motion. Accordingly, since early times, wherever different kinds of motion have been seen, different kinds of force have been assumed. It thus came about in time that a large number of forces were distinguished, which could not in any way be compared with one another, because some kinds were only special cases of others, some were combinations of several kinds, and some were not forces at all. The force of gravity, muscular force, and the force of will were all spoken of. This condition of things has not yet wholly dis- appeared. The forces that physics still recognises are not equivalent things, and little light has been thrown, even yet, upon the rela- tions of certain ones to others. In recent times, in accordance with the usage of Th. Young and Thomson, the old and easily misunderstood name " force " has been replaced by the term " energy," and what earlier were termed different forces are termed now different forms of energy. Thus, physics now recognises in general the following forms of energy : 1. Chemical energy (chemical affinity, attraction of atoms). 2. Molecular energy (cohesion, adhesion, attraction of molecules). 3. Mechanical energy (pressure, traction, thrust). 4. Energy of gravitation (gravity, attraction of masses). 5. Thermal energy (heat). 6. Photic energy (light). 7. Electrical energy (electricity, galvanism). 8. Magnetic energy (magnetism). We will glance at these individual forms. Modern natural science, as is well known, conceives the physical world to be composed of extremely small particles ; it terms the particles that cannot be divided further without losing their proper- ties, molecules, and those that compose the molecule and are indivis- ible, atoms. Chemical energy is that form of energy by which atoms attract one another in order to form a molecule ; molecular energy that form by which molecules attract one another in order to form masses. If a mass is in motion and strikes against another mov- able body, it puts this likewise into motion if the impact be strong enough. The form of energy that puts in motion the body that is struck is mechanical energy. Further, masses attract one another, p 210 GENERAL PHYSIOLOGY like the atoms in the molecule and the molecules in the mass ; since Newton's immortal discovery it has been known that the paths of the heavenly bodies result from the mutual attractions of their powerful masses. This mass attraction, which binds the earth to the sun, and the moon to the earth, and compels a stone thrown upward to return again to the earth, is gravity or the energy of gravitation. Finally, thermal, photic, electrical, and magnetic energy are the forms of energy that put the atoms of the hypothetical ether, which fills universal space and penetrates all bodies, into those forms of motion termed heat, light, electricity and magnetism ; for in accordance with the researches of modern physics the phenomena of heat, light, electricity and magnetism result merely from the vibrations of very minute particles. But simple reflection shows that these forms of energy are not equivalent and separate. If all matter, including the hypothetical ether, is composed of atoms as its smallest physical particles, and if nothing corporeal exists beyond matter, all forms of energy, since they are associated with matter, must have their seat in atoms. In other words, atoms are the smallest particles endowed with energy, and it is evident that the forms of energy that are assumed for the motions of masses, such as gravity, must have their seat in atoms. Now, a priori, it is in the highest degree improbable that every atom is provided with eight different forms of energy. Scientific experience, which shows that everywhere in nature apparent multiplicity can be traced to unity, suggests that all these different forms of energy may be traced to a single form. As a matter of fact, molecular and mechanical energy and energy of gravitation, upon the one side, have been put into close relations with one another, as well as thermal, photic, electrical and magnetic energy upon the other side ; and very recently electro-chemical re- searches have made it appear that a very close relation exists between chemical and electrical energy. Hence we have a well- founded hope that before very long physics will succeed in demon- strating all forms of energy to be merely the expression of one and the same form, which appears different under different conditions ; just as chemistry hopes to be able sometime to reduce the multi- plicity of the chemical elements to the properties of a single original element, perhaps the universal ether. The probability that the different forms of energy are only different modes of appearance of one and the same energy, amounts almost to a certainty in the light of the fact that one form of energy may be changed into another form, and in nature is con- tinually so changed. As is well known, this all-important fact finds expression in the law of the conservation of energy, which was discovered and founded by Robert Mayer and Helmholtz, and which has become the foundation of our whole modern view of nature. This fact is explicable only in accordance with the idea that energy ELEMENTARY VITAL PHENOMENA 211 itself is always the same, and that the different forms of its appear- ance are merely cloaks, which may be exchanged according to the conditions at the moment. Just as we speak of different forms of energy, we can distinguish in the single form two different modifications, according as the energy actually produces motion or only has potentially the capacity of putting into action under proper conditions. Physicists term these two modifications kinetic energy (also actual energy, or energy of motion) and potential energy (energy of position). The energy of gravitation, e.g., is kinetic when it draws a stone to the earth at the moment when the stone is set free ; it is potential so long as the stone is fixed above the earth's surface. Likewise, chemical energy is kinetic when it brings two atoms to each other ; but it is potential when an atom has no other one in its vicinity that it can attract. Kinetic energy passes over constantly into potential energy and vice versa. The law of the conservation of energy, therefore, controls all that happens in nature; it is the fundamental law of energetics. According to it, as has already been seen, energy in the world never originates or disappears ; the sum of energy in the world is constant, just as the law of the conservation of matter expresses the same constancy in the quantity of matter. Where a certain quantity of energy seems to originate or disappear, in reality it simply goes over into another form or modification. If, e.g., an electric current be passed through a vessel containing water, the electrical energy seems to be lost. But in reality it does not go out of existence, for it has been seen that the molecules of the water are decomposed into their hydrogen and oxygen atoms, and these accumulate in a gaseous state upon the two poles of the electrical conductors. Hence the electric current has performed work and has separated the atoms of the molecules of water from one another. But the atoms of hydrogen and oxygen set free have a chemical affinity for one another ; hence in the experiment the kinetic energy of the electric current has simply been trans- formed into the potential energy of chemical affinity. If, therefore, the separate atoms of hydrogen and oxygen be brought again into union under proper conditions, the chemical potential passes over again into kinetic energy, and a certain quantity of heat is liber- ated thereby. This heat can be transformed again into electricity in a thermo-electric apparatus, and, if the technical difficulties would allow the whole experiment to be carried out with sufficient exactness, it would be found that the same quan- tity of electricity has again been obtained as was consumed previously in the splitting-up of the water. During all trans- formations the original quantity of energy remains the same. In order to have a unit for the measurement of any quantity of energy, physicists have chosen, in accordance with Joule's p 2 212 GENERAL PHYSIOLOGY researches upon the relation of heat to mechanical energy, a certain quantity of heat as the unit of heat or calorie. A calorie is that quantity of heat that is necessary to warm one kilogram of water from 0° to 1° C. Heat was chosen with good reason as that form of energy which may serve as a unit of measure for all others, for it holds a peculiar position in relation to all others ; it is the sole form into which all others can be transformed completely. When, therefore, it is desired to express in numbers a quantity of any desired form of energy, e.g., mechanical or chemical energy, the latter is expressed in measures of heat, that is, in the number of equivalent calories. Thus, one calorie computed in the form of mechanical work corresponds to the quantity of energy that is needed to raise a weight of 424 kilograms one metre high ; in other words, the mechanical equivalent of one calorie is 424 kilogrammetres and, vice versa, one calorie is the heat-equivalent of 424 kilogrammetres. In the same way the quantity of all other forms of energy can be expressed in heat-equivalents. The calorie is the unit of measure for all energy. B. THE INTRODUCTION OF ENERGY INTO THE ORGANISM Life has often been compared with fire, an idea which plays a rdle in the oldest mythological folk-views of nature and, as is well known, first assumed a fixed form in the philosophy of Heraclitus. In many points the comparison is fitting. To extend it somewhat further, the organism is the burning coal which is being constantly consumed, the breath is the smoke, and the food is the freshly added fuel which constantly replaces the old. Just as the burn- ing mass of coal represents a physical system in which a continual transformation of energy is taking place, potential energy being introduced with the fuel and transformed into two forms of kinetic energy manifest outside, namely, heat and, by proper arrangement, as in the steam engine, mechanical work, so an organism is a physical system in which a similar transformation of energy con- tinually takes place. Just as by heaping new coal upon the fire, energy is added in the potential form, so also, at least in the animal organism, by far the greater part of all the energy introduced is potential energy. The introduction of energy is considerably less evident to the eye than the production of energy; the latter results from the transformation of the introduced potential and is expressed in movements and other visible work. 1. The Introduction of Chemical Energy Since cenfused ideas concerning the transformation of energy in chemical processes are wide-spread, it will be advantageous first to glance at the general facts. ELEMENTARY VITAL PHENOMENA 213 By chemical energy is understood, as is well known, the capacity of atoms to attract other atoms ; this property has also been termed chemical affinity. Every atom, regarded as isolated, represents accordingly a small magazine of energy. The chemical energy in it is potential so long as the atom has no opportunity to unite by means of its affinity with another atom. But, as soon as two atoms combine, a part of the potential, corresponding to the strength of their affinities, passes over into kinetic energy and is set free in the form of heat, light, mechanical energy, etc. Since, further, chemical affinity is quantitatively very different in different kinds of atoms, the stronger the combining affinities, the more energy is set free. A chemical compound, must, therefore, contain less potential energy, the stronger the affinities are that have brought together its atoms. Vice versa, if two combined atoms become separated, a certain quantity of kinetic energy is absorbed in the process, and after the separation the same quan- tity appears again in the potential form as the free affinities of the atoms. Thus there is a complete cycle. An example will make this relation more evident. Suppose a strong glass cylinder to be inverted over a mercury trough and to contain in a small space free from mercury a gaseous mixture consisting of two-thirds hydrogen and one-third oxygen ; such a mixture consists of molecules whose atoms contain large quantities of potential energy in the form of chemical affinity for one another. If, now, the conditions be made such that the atoms of oxygen and hydrogen can combine, the atoms rush eagerly toward one another, unite and give off to the outside all their stored potential in the form of heat, light, and mechanical energy. A spark appears, the cylinder becomes heated, and the mercury is forcibly driven down. The latter soon rises again, for the vapour that results from the union of the atoms of oxygen and hydrogen becomes condensed with the increasing cooling into water, which finally occupies only a minute space within the cylinder. Thus, in the synthesis of water from hydrogen and oxygen the potential energy of chemical affinity is transformed into kinetic energy and is set free as heat, light, etc. Hence the molecule of water has lost to its environment this quantity of energy, and this can be exactly determined. Vice versa, the atoms of water can be separated again into atoms of hydrogen and oxygen by introducing from outside the same quantity of energy. Electrical energy serves best for this purpose. If an electric current be passed through water, atoms of hydrogen and oxygen are set free at the poles in the same degree as the electrical energy disappears. Hence energy is absorbed in separating the atoms of the water- molecule ; but this energy appears again as the potential of chemical affinity in the free atoms, for, when the free hydrogen and oxygen are brought into combination, kinetic energy is obtained anew, and so on. 214 ' GENERAL PHYSIOLOGY This consideration is very important, for from it there follows a principle of far-reaching significance which usually is not formu- lated with sufficient clearness, viz. : In the combination of atoms kinetic energy is liberated ; in the separation of atoms kinetic energy is absorbed. This principle, which is a necessary sequence of the law of the conservation of energy, must be considered as a fundamental one for all chemical transformations, and forms the starting-point for an understanding of all the phenomena connected with the trans- formation of energy within the living organism. That as a rule it has not been established and applied with sufficient clearness, is to be ascribed chiefly to the fact that in certain cases at first sight it suffers apparently an exception. To make the relations clear, this must be considered, at least briefly. To express in terms of heat the energy that is transformed in a chemical process, there are recognised processes in which heat is evolved and processes in which heat is absorbed. In accordance with the nomenclature of thermo-chemistry, the heat that is evolved in a chemical process is termed the positive thermo-chemical equiva- lent, the heat that is absorbed, on the other hand, the negative thermo-chemical equivalent. From the above considerations, it would be expected that all synthetic processes, i.e., all processes in which bodies unite, would be accompanied by an evolution of heat, for in every synthesis atoms become united, and in every union of atoms energy is liberated. Vice versa, it would be expected that all decomposition-processes, i.e., all processes in which united atoms become separated, would be accompanied by an absorption of heat. If the conceptions of synthesis and decomposition are employed in their pure significance, this is always the case. Nevertheless, at first sight there appear certain exceptions to the rule. For example, some syntheses are known in chemistry, such as that of hydrogen iodide, which are accompanied by an absorption of heat ; on the other hand, there are many decompositions, especially of the more complex compounds, such as nitroglycerine and other explosives, in which a powerful evolution of energy takes place. These are undeniable facts, but, if the details of these processes be analysed somewhat fully, the apparent paradox becomes at once clear and in reality confirms the law. Since no free atoms are known, but since the similar atoms of every chemical element are united always into molecules, or groups of atoms, it is evident that unless whole mole- cules enter into combination without rearrangement of their atoms or are split off from a combination as preformed groups, then a decomposition of the active molecules into their atoms must precede every synthesis, and a synthesis of the free atoms into new mole- cules must follow every decomposition. Hence, no synthesis occurs without previous decomposition, and no decomposition without subsequent synthesis. Accordingly, it is clear that under certain circumstances heat can be absorbed in a synthesis : for example, ELEMENTARY VITAL PHENOMENA 215 when, as in the iodine molecule, the atoms of iodine or, as in the hydrogen molecule, the atoms of hydrogen have a greater affinity for one another than the iodine atoms have for the hydrogen atoms. In these cases more energy becomes absorbed, in order to separate from one another the atoms of the iodine molecule and the atoms of the hydrogen molecule than becomes free when the atoms of iodine and hydrogen unite into a molecule of hydrogen iodide, and, since in every calorimetric experiment the end-result and not the inter- mediate processes come under observation, it is explained why at the end of the reaction there must be an absorption of heat. The reverse is the case in the decomposition-processes accom- panied by an evolution of heat. It is well known that nitroglycerine (glyceryl tri-nitrate), upon being shaken, explodes with an enormous evolution of energy, being decomposed into water, carbonic acid, oxygen and nitrogen. These products of decomposition are not preformed stereochemically in the molecule of nitroglycerine, but they arise from a synthetic rearrangement of the atoms set free by the decomposition. Since the atoms of water, carbonic acid, oxygen and nitrogen, have greater affinities for each other in this arrange- ment than in their position in the nitroglycerine molecule, a small quantity of energy suffices to cause the decomposition of the latter, while from the resulting syntheses an extraordinary quantity of energy becomes free. Hence as the end-result there is an evolution of heat. Therefore, just as in the synthesis of hydrogen iodide, strictly speaking, the absorption of heat is not to be credited to the synthesis, so in the dynamite explosion the evolution of energy does not come in reality from the decomposition of the nitroglycerine molecule. This fact should be clearly understood. But, since, when a synthesis is spoken of, the preceding decomposition is left out of account, and when a decomposition is spoken of, the subsequent synthesis is similarly treated, it is more exact to express the funda- mental law of the transformation of energy in chemical processes in the following form : If in a chemical process affinities become united rather than separated, energy is liberated ; if affinities become separated rather than united, energy is absorbed. To return from our excursus, it is clear from the discussion that chemical energy can be introduced into the organism only when the food-stuffs contain affinities for the satisfy- ing of which an opportunity is afforded within the organism. Hence substances must be introduced into the body, which undergo among themselves chemical transformations with the evolution of heat. This takes place in two ways, which we have just become acquainted with, viz., first, by the introduction of simple substances possessing strong affinities, and, second, by the intro- duction into or synthesis within the body of complex compounds which are easily decomposed and, like explosive bodies, furnish decomposition-products that combine synthetically into new 216 GENERAL PHYSIOLOGY substances with a rearrangement of their atoms. Free affinities come into the body with oxygen especially ; and it is well known that in the combination of oxygen with other substances, or, in other words, in combustion, a great quantity of energy is liberated. Hence the process of oxidation plays an extremely important role in all life ; and, as has already been seen, the comparison of life with fire is a very happy one. Complex compounds come into the organism, especially in the case of animals, with the organic food ; there they undergo a long series of transformations, which thus far have not been followed, in which decompositions and syntheses proceed together to the construction of the living proteid molecule. Living proteids may be classed with explosive bodies. They tend toward decomposition ; and out of the com- plexes of atoms set free there arise synthetically by rearrangement, partly immediately after the decomposition and partly later in combination with substances newly introduced, chemical com- pounds the origin of which under certain circumstances is again associated with the evolution of energy. In the present condition of our knowledge it is not possible to follow in detail the intricate series of chemical processes, the decompositions and syntheses and the transformations of energy associated with them, from the first cleavage of carbonic acid and the synthesis of the first product of assimilation in the plant to the decomposition of the living proteid in the plant and the animal. It is known, however, that the final products of metabolism, such as carbonic acid, water, urea, etc., are extremely poor in chemical energy. The larger quantity of chemical energy introduced into the body with the food must, therefore, have been transformed into other forms of energy upon its way through metabolism, and thus results the work of the organism. 2. The Introduction of Light and Heat It has been said that the main quantity of all the energy that is introduced comes into the body as chemical energy. For the animal organism this statement holds good without limitation; for the plant, however, it needs a correction. It is true that in the plant the energy at the expense of which its work goes on is likewise pre-eminently chemical ; but a part of this potential is not introduced into the body as free, available energy, i.e., in the form of free affinities, such as oxygen possesses ; another form of energy must first be introduced in order to create free affinities in the former. It is well known that carbonic acid and water are necessary for the synthesis of the first product of assimilation.1 But carbonic acid and water as such are poor in chemical energy 1 Cf. p. 158. ELEMENTARY VITAL PHENOMENA 217 because their atoms are coupled together by very strong affinities. Hence, in order to make them free and serviceable for new labours, they must first be split up, and for this an introduction of energy is necessary. The energy that performs this cleavage is light in combination with the chemical energy of the living plant-sub- stance. Without light no plant-life is possible, and since without plant-life no animal-life can exist, it may be said that without light no life whatever would exist. Hence, although light plays an essential role as a direct source of energy only in the plant, it is as indispensable for the maintenance of life upon the earth's surface as the chemical energy of food. The places in the plant where light effects the cleavage of carbonic acid are the green parts of the plant-body, and hence especially the leaves. This can best be demonstrated by the experiment on assimilation already described.1 This experiment shows that in the part played by the rays of light in the cleavage of carbonic acid in the green plant-cell, two factors are present, the intensity and the wave-length of the rays. The efficiency of the light increases with the intensity, so that in a brighter light, more carbonic acid is split up than in a feebler one. Moreover, with the same intensity the rays of red light (not those of yellow, as botanists formerly supposed) are the most effective. Engelmann ('81, 1 ; '94) in a series of researches placed this beyond all doubt by a microscopic method that depends upon the action on bacteria of the oxygen set free in the cleavage of carbonic acid. At the same time these researches confirmed the view that the cleavage of carbonic acid in the green plant-cell takes place in the chloro- phyll-bodies only, and established the fact that the cleavage begins at once upon the admission of light and ceases immediately upon darkening. Hence the dependence of this property of the chlorophyll-body upon light is extremely close. The heat that comes into the living organism from the outside, partly by radiation and partly by conduction, plays, like light, a role in the chemical transformations within living substance. Since with increasing temperature the power of decomposition increases in all chemical compounds, the heat that is introduced takes part especially in the processes of decomposition in the living substance. The rdle of heat as a source of energy may be recognised especially clearly in the so-called cold-blooded animals. These are better termed animals possessing a changeable tempera- ture (poikilothermal), since in contrast to the so-called warm- blooded animals, or animals possessing a uniform temperature (homothermal), the temperature of their bodies changes continually with that of their environment : with a high external temperature they may have a body-temperature equal to that of the warm- blooded animals. When the temperature of the medium in which 1 Cf. p. 158. 218 GENERAL PHYSIOLOGY they live is high, these animals, such as insects and reptiles, are extremely lively, move about much, and show in general an intense activity. With decreasing temperature the liveliness of their movements decreases, and at 0° in many cases vital activity is hardly to be observed in them, the transformation of energy has almost ceased. " Wherever we look into the realm of living organisms," says Pfliiger (75, 1), "we see how the intensity of vital processes, and hence decomposition, varies proportionately with the temperature. When I observe the lively, moving, nimble lizard in summer, and then see how the same animal, exposed to a temperature below 0°, becomes gradually quiet and sinks into a death-like torpor, and inquire what is the reason why the animal becomes again so active in warmth, appearance tells me that it is because heat has been introduced into the organs ; heat puts the atoms into vibration and promotes dissociation." The heat that is introduced serves in this way directly as a source of energy for the work of the organism. This completes the enumeration of the sources from which the organism receives energy. The other forms of energy have almost no importance in this respect. C. THE PRODUCTION OF ENERGY BY THE ORGANISM At present it is wholly impossible to follow the tortuous paths taken by the energy that is introduced in its changes through the living body. Scarcely a beginning has been made in investi- gating the transformations that this energy undergoes under the various conditions found by it in living substance. There is here needed a long series of exhaustive special researches and especially a detailed knowledge of metabolic processes, before an intelligible conception can be formed of the mechanism of these transforma- tions. The field of physiological energetics offers rich problems full of reward for the future, which thus far have been scarcely noticed. Only the final links of the chain of metamorphoses, the outward achievements of the living organism, are now known with certainty. The evolution of energy outward, especially that of mechanical energy, which expresses itself in the movements of the living body, is undoubtedly the most evident of all vital phenomena ; it is more or less the first criterion of life for the untrained observer, and perhaps this is the reason why physiology from early times has made the phenomena of movement a favourite object of research. Less evident, because either uncommon or difficult to observe, is the production, on the part of living substance, of other forms of energy, such as light, heat and electricity. ELEMENTARY VITAL PHENOMENA 219 1. The Production of Mechanical Energy All living substance moves, i.e., the single points of its material system change their positions in space. There results, according to the special conditions, a shifting of the single particles, the ex- ternal form remaining the same, a change in the external form, a change of place of the whole (locomotion), or several of these changes at the same time. But although motion in itself is a general phenomenon of life, all forms of living substance do not show the same kind of motion. The variety of modes of motion that may be observed in different organisms is very great. Never- theless, all may be classified in accordance with the manner of their occurrence into a few large groups, of which only certain ones, on account of their wide distribution, possess any considerable im- portance. Since the • motion of living substance is the most evident vital phenomenon, and special interest is therefore lent to it, we are justified in considering it somewhat in detail. It is useful first to classify the various modes of motion into : (a) Passive movements. (b) Movements by swelling of the cell-walls. (c) Movements by change of the cell-turgor. (d) Movements by change of the specific gravity of the cell. (*) Movements by secretion on the part of the cell. (f) Movements by growth of the cell. (g) Movements by contraction and expansion of the cell- body : Amoeboid movement. Muscular movement. Ciliary movement. a. Passive Movements In passive movements the cause lies outside the part that is moved. Passive movements in living substance are, therefore, not a vital phenomenon of the elements that are moved, but the ex- pression of vital phenomena in the environment. The movement of the red blood-corpuscles, the streaming of the blood-plasma in the blood-vessels of the human body, are passive movements ; for the blood-corpuscles and the plasma possess no intrinsic power of movement; they are only passively driven by the activity of the heart, which works like a suction- and force-pump in the system of branch- ing tubes filled with blood. This streaming of the blood in the fine capillary vessels can be observed very beautifully under the microscope, if a frog, paralysed by the South American arrow poison, curare, be placed upon a cork plate and the web between the toes of the hind leg be stretched out by needles over an opening 220 GENERAL PHYSIOLOGY in the plate. A picture full of interest for every observer will then be presented (Fig. 86). The much-branched network of the capil- lary system is seen, and in it the blood flows with its apparently yellow corpuscles so slowly that one can easily follow every indi- vidual corpuscle as it winds its way in the clear plasma through the fine canals and sinuosities. Even in the single cell such passive movements are found. The fine granules that lie embedded in the protoplasm of the naked cells of rhizopods show a streaming movement, especially in the long, thread-like pseudopodia of marine species ; this so-called granular streaming presents a spectacle as fascinating as the streaming of the blood in the capillaries, although going on much more slowly. Like pedestrians in the street, or like ants, the granules take their self- established paths, now in a centrifugal, now in a cen- tripetal direction, now standing still, now turning about, and now again pro- ceeding. This granular streaming does not come about by the active pro- gressive movement of the granules themselves ; but by their being passively dragged along by the liquid protoplasmic ground - sub - stance in which they lie embedded, and which has constantly an active flowing motion. Another interesting form of passive movements that occur in the living cell is the so-called Brownian molecular movement. There lives in fresh water a small, unicellular, green alga, Closterium, of a delicate crescent-shape (Fig. 87, 7). In its protoplasm at each end of its body is a vacuole of liquid, in which as a rule lie fine granules which show Brownian motion By strong magnification it may be seen that the granules are continually dancing about each other with a delicate trembling motion, but without moving to any considerable distances. The dancing continues tirelessly and unceasingly. Here the object in which this peculiar motion is seen is living. More frequently, how- ever, it can be observed in dead cells, and it has long been known in the so-called salivary corpuscles in the saliva, which are dead leucocytes (white blood-corpuscles). These leucocytes are swollen into a spherical form by the absorption of water, and possess a nucleus surrounded by granular protoplasm (Fig. 87, 77). FIG. 86. — Capillary circulation in the web of the frog's foot. (After Ranke.) ELEMENTARY VITAL PHENOMENA 221 Upon strong magnification the granules of this swollen proto- plasm show clearly molecular motion. That the strange Brownian molecular movement does not occur in living organisms exclusively, follows from the fact that all light, microscopic granules of what- ever kind, when suspended in water or any other easily moving liquid, show it. Among the most beautiful lifeless objects adapted for this purpose and occurring in the organism are the fine crystals (Fig. 87, ///) in the calcareous sacs that lie in the body-cavity of the frog on each side of the spinal column between the transverse processes of adjacent vertebrae. If some of the white substance be placed in a drop of water and examined under a cover-glass with a high power of the microscope, the wonderful picture of this restless, trembling dance of lifeless crystals is pre- FIG. 87. — Browniau molecular movement. /. Closterium (after Strasburger). In the vacuoles, K> at the two ends of the crescent-shaped body there are numerous granules in active molecular motion. //. A so-called salivary corpuscle, a dead and spherically contracted leucocyte from the human saliva, in the swollen contents of which the granules are in dancing motion. ///. Crystals from the calcareous sacs of the frog ; when put into water they show a restless, dancing motion. sented in its most graceful form, especially in the smaller crystals.1 When the English botanist Brown in the year 1827 discovered such peculiar motions in plant-cells, it was believed that the motion of the fine granules was an active one, resulting from the vibrations of their molecules, and it was accordingly termed " molecular motion." In accordance with more modern ideas this view became untenable, and for a long time the significance of the puzzling phenomenon was not understood. But in the year 1863 Wiener, and soon afterwards Exner, studied very carefully the physical conditions of the motion, and found an explanation that is in entire accord with our present ideas of the molecular con- dition of liquids. In fact, the behaviour of the molecules of a liquid even requires such phenomena of motion of small light par- 1 Cf. P. 4. 222 GENERAL PHYSIOLOGY ticles suspended in it. As is well known, the molecules in a liquid are conceived to be in constant motion, crowding together, bound- ing against one another, pushing away, moving off and again col- liding. This motion of the molecules cannot be seen even with the strongest magnifying powers, for liquids appear homogeneous because their molecules are too small to be perceived even micro- scopically. But the result of the motion can be observed in small, light granules suspended in the liquid; if the molecules possess the given kind of motion, they must strike the particles continually, so that with their delicate mobility the latter are put into a trembling, dancing motion. Hence, the so-called Brownian molecular movement of small granules is a purely passive move- ment caused by the constant slight impulses given to the granules by the dancing molecules of the liquid. An excellent proof of the correctness of this view is afforded by the fact that the Brownian movement gains in intensity with increasing temperature of the liquid. This might have been predicted from the fact that the motion of the molecules of the liquid is greater the higher the temperature ; it finally becomes so great that the individual molecules are driven violently apart, that is, the liquid evaporates. &. Movements ly Swelling of the Cell-walls Movements that are caused by swelling of the cell-walls constitute a variety intermediate between passive movements and all those mentioned below, which latter depend upon the activity of living substance. The phenomenon of swelling, as is well known, is due to the fact that between the molecules of a dry, expansible body, brought into a moist environment, molecules of water become stored, being attracted so strongly by the molecules of the body that they force the latter powerfully apart ; during the process the volume of the body becomes markedly increased. If the swollen body comes again into an environment free from water, e.g., dry warm air, it gradually gives off its water, diminishes its volume proportionately and shrinks; upon being again moistened, it swells again. The organic products of the metabolism of plants, especially the cellulose walls of plant-cells, are peculiarly prone to swell. This is not associated in any way with the life of the plant-cell, but goes on for an indefinite time in the cellulose of dead cells, in the same manner as in that of living cells. In order that a movement in one direction may be brought about by the increase in volume caused by the swelling or by the decrease in volume caused by the drying of an expansible object, such as the stem of a leaf or a membrane, the different sides of the object must be capable of swelling differently, one side strongly, the other feebly or not at all. Were all parts equally capable, there would result a uniform enlargement toward all sides. If, however, ELEMENTARY VITAL PHENOMENA 223 one side of an elongated structure swells more than the opposite, the former becomes lengthened more than the latter, and the result is a bending of the whole structure, which takes place suddenly or gradually as the swelling is rapid or slow. The well-known resurrection-plants (Sdaginella lepidopJiylla), which of late have frequently come to Europe from the American deserts, are characteristic objects for the observation of swelling- movements. During a drought their leaf-stalks are brought together like the fingers in a closed fist, but when moistened they bend out as in the open hand, the leaf-stalks strongly swelling FIG. 88.— Seed of the crane's bill (Erodium cicutarium), a, in the dry, 6, in the swollen state. upon their inner side. The well-known rose of Jericho, which is simply the dry, dead branch of a crucifer (Anastatica) growing in the Arabian deserts, behaves similarly. Its spreading when placed in water has led to the common belief that the rose of Jericho is resurrected to a new life, while in reality the phenomenon depends merely upon the swelling-movements of the dead branch. Selaginella, however, is a real resurrection-plant in so far as it can remain for years completely dry without losing its capacity of life. The seeds of many species of crane's bill likewise show very clearly the phenomena of swelling-movements. Erodium cicutarmm has seeds that are provided with a long stalk 224 GENERAL PHYSIOLOGY beset with hairs ; in a drought this stalk is rolled up like a cork- screw into a beautiful spiral (Fig. 88, a), but when moistened it becomes straightened, one turn after another unrolling itself by swelling and extension of the inner side (Fig. 88, &). The movements of the so-called elaters on the spores of the horse-tail are very interesting and striking because of their rapidity. The ripe spores of the horse-tail are spherical cells surrounded by a cellulose-wall. This wall is split into two bands the elaters (Fig. 89), which run in a spiral from above downward around the whole ball, being fastened to each other and to the spore itself at a certain spot in the equator. If the spores, slightly moistened, be brought under the microscope, the two bands are seen to lie in two parallel spirals and form a closed capsule about the spore (Fig. 89, a). If they be allowed to dry, the two spirals become extended into straight bands (Fig. 89, &} FIG. 89.— Spore of a horse-tail, a. The elaters in the moist state are curled around the cell 6. The elaters in the dry state are rapidly spread apart, through the drying and shortening of their outer sides. If, while observing with the microscope, one breathes upon them in this extended state, they are seen to coil themselves in spirals about the spore with excessive rapidity, their outer surfaces extending by swelling. At the moment when the moisture of the breath disappears, the bands extend again with equal rapidity ; and the experiment can be repeated, like all experiments on swelling, as often as one wishes. Swelling-movements are very common among plants, and some of them play an important role in plant life. The great power that can be developed by swelling can be realised from the fact that huge rocks can be split with wedges of swelling wood. ELEMENTARY VITAL PHENOMENA 225 c. Movements by Change of the Gell-turgor With movements caused by a change of the cell-turgor, we begin the consideration of those phenomena of motion that pre- suppose normal life in the object in which they appear. With the death of their substratum they are extinguished. Turgescence-movements are chiefly found among plants ; and it is necessary, therefore, that certain peculiarities of the plant-cell be recalled. The plant-cell, as is well known, is a cylindrical capsule, the walls of which are formed by an elastic membrane of cellulose. FIG. 90. — Scheme of cell-turgor of a plant-cell ; Ji, cell-membrane ; p, primordial utricle ; k, nucleus ; c, chlorophyll-bodies ; s, cell-sap ; e, infiltrating salt solution. In A, the cell is in complete tur- gescence, the primordial utricle lies close to the cell-membrane. In B the turgor has decreased as a result of the action of a salt solution, the cell has become smaller, but the primordial utricle still lies in contact with the cell-membrane. In C the turgor has become still less, the pri- mordial utricle is beginning to be pulled away from the cell-membrane, which latter has reached its minimum. In D the primordial utricle has contracted completely, because the osmotic effect of the salt solution acting from the outside has reached a very high degree. (After de Vries.) The inner surface of the capsule fs covered by a thin but con- tinuous protoplasmic layer, the so-called primordial utricle, which encloses like a sac or bladder a liquid, the cell-sap, and as a rule sends through the large vacuole strands of protoplasm which branch lengthwise and crosswise (Fig. 90; in this figure the strands are wanting). Various chemical substances, which have been produced by the vital activity of the cell, are dissolved in the sap. In its usual uninjured condition the protoplasm is impermeable to these substances, hence they cannot diffuse from the interior to the outside through the primordial utricle. But the protoplasm is likewise impermeable to many substances that are dissolved in the water outside the cell, and which, therefore, Q 226 GENERAL PHYSIOLOGY cannot diffuse into the cell. Now it is known that the molecules of such soluble substances as salts, sugar, etc., attract water, every molecule taking to itself a number of molecules of water. The molecules of the former are said to act " osmotically." As Van t'Hoff has recently shown by his important researches, the osmotic pressure is proportional to the number of molecules dissolved in the unit of volume. If, therefore, there are stored within the cell-sap strongly osmotic substances, and outside the cell in the water substances that are less osmotic, and if the wall of the primordial utricle is impermeable to these dissolved substances, an equalisation by diffusion cannot take place ; but, since the primordial utricle allows pure water to pass through it unhindered, water must be drawn by the osmotic substances of the sap into the interior and held there permanently. The result of this process is that the pressure in the primordial utricle becomes constantly greater the more osmotic substances are dissolved in the sap, i.e.. the more the concentration of the sap increases. The primordial utricle of the cell, therefore, must be extended from within outward ; and this tension, stretching the elastic cellulose wall, is the turgor of the cell. It is evident that the turgor will become greater, that the cell must be put more upon the stretch, the more osmotic substances accumulate in the sap and the less in the surrounding medium. Prom this brief consideration it is clear that the turgor of the cell can be changed in different ways. First, the quantitative relations of the osmotic substances within and without the cell can change, by the concentration outside or inside becoming increased or decreased. If, e.g., substances in solution be added gradually to the surrounding medium, water will be drawn out constantly from the interior, and the turgor will decrease. This phenomenon has been termed, with little appropriateness, plasmolysis. Further, the turgor can likewise be changed by the wall of the primordial utricle from some cause becoming permeable to the substances in solution in the cell-sap. Then an equalisation by diffusion must take place, and the tension of the cell-wall must disappear. Finally, a change in turgor will take place when the tension of the primordial utricle in- creases or decreases because of active changes in its protoplasm. If, e.g., the protoplasm contracts, the contraction will partially or wholly overcome the osmotic pressure opposing it, and the result will be that a corresponding quantity of water minus the osmotic sub- stances will be pressed out from the sap through the primordial utricle. When the contraction of the primordial utricle ceases, the osmotic substances of the sap will attract more molecules of water, and the turgor will again increase. The result of diminishing the turgor must in all cases be the same. The primordial utricle, which previously was stretched from within outward by the tension, will shrink together, and its ELEMENTARY VITAL PHENOMENA 227 circumference will become smaller (Fig. 90). But what is more important for the present purpose is the diminution in size of the whole cell with decrease of the turgor, for the tension of the elastic cellulose coat will be decreased to the same extent as that of the primordial utricle, and, as a result of its elasticity, the wall will assume finally a circumference corresponding to its decreased tension (Fig. 90, B, C, D). In the movements of plants now under consideration a change of turgor takes place solely by the contraction of the primordial utricle of certain cells for some cause, either spontaneously or as the result of stimulation, in such a manner that water is squeezed out of the cells ; the phenomenon passes away after some time, and the turgor again appears pari passu with the disappearance of the contraction. There thus appears under certain circumstances a sudden diminution of the turgor and with it a diminution in the size of the cell, and only gradually does the previous condition return. In order that upon this principle a microscopic movement may take place in a plant, the cells that undergo the change of turgescence must have a definite arrangement. If in one of two parallel rows of cells the turgor is suddenly diminished, so that the cells become smaller, while in the other it remains unchanged, the first row must shorten. Hence, according to simple mechanical principles, a bending will occur with the concavity upon the shortened side. At the same time the other side will be extended passively. If, later, a gradual increase of turgor and a lengthening of the cells upon the shortened side takes place, the elasticity of the other side will assist the extension. Such a diminution of turgescence appears in many plants, often very suddenly, both spontaneously and after mechanical stimulation, and the result is a sudden movement of certain parts. In most cases both the arrangement and the shape of the cells that cause the movement are very complicated. As a rule, at the base of the motile leaves, or petioles, small enlarge- ments, called pulvini, are developed, the cells of which can diminish their turgor very rapidly. One of the best-known examples of this kind is the movement of the petioles in the sensi- tive Mimosa pudica, which in the " waking " state, i.e., during the day, are upright with the leaflets extended (Fig. 91, /, A, and //, A), while in the " sleeping " state, i.e., at night, they are depressed and the leaflets are folded upward together (Fig. 91,7,5, and //, B). If a Mimosa- in the waking state be vigorously shaken, the night position is suddenly assumed in the daytime. Upon the same principle depend numerous other movements of the sensitive plants, such as those of the leaves of clover, the stamens of barberry, the insect-catching organs of carnivorous plants, and many others. Q 2 228 GENERAL PHYSIOLOGY position). (//. after Detmer.) ELEMENTARY VITAL PHENOMENA 229 d. Movements ~by Change of the Specific G-ravity of the Cell Among the wonderful forms of animals, mostly of glassy trans- parency, that lead a pelagic life in the upper strata of the sea and lately as plankton have become the object of detailed investi- gation, there are many that are endowed with the remarkable capacity of slowly rising or sinking in the water without the use of any locomotor organs. These are especially the Radiolaria, Ctenophora, and Siphonophora. Some unicellular, fresh-water organisms, such as Actinosphceriwn, also possess this power. Since all external causes for this mysterious suspension, such as currents of water, may be excluded, and since the movement of special organs of the body does not share in it, it can depend only upon changes in specific gravity, and this has been demonstrated. As has already been seen,1 protoplasm is heavier than water. Hence a cell that lies upon the bottom can raise itself only when substances that are lighter than water appear and accumulate in the protoplasm. It is well known that certain fresh-water Rhizopoda, especially Arcella and Difflugia, which are provided with delicate capsules, are heavier than water, and usually creep about upon the bottoms of ponds and puddles between particles of mud and decaying leaves, can actively raise themselves by developing a bubble of carbonic acid in their protoplasmic bodies ; when it has become sufficiently large, they rise to the surface like a small balloon. Engelmann ('69) first carefully investigated this fact. At times in a culture-vessel containing Difflugia, when conditions favour the development of carbonic acid in the protoplasm, the movement of individuals from the bottom to the surface becomes epidemic. If the carbonic acid is then given off, the individuals sink again to the bottom. In this manner there may arise in nature a very considerable change of habita- tion, which under certain circumstances, as when the Protista have come under unfavourable conditions, can be of great useful- ness to the species. In an analogous manner take place the rising and sinking of the Radiolaria and, in all probability, those of the Ctenophora and many other pelagic animals. Thalassicolla nucleata, e.g., is a large globular radiolarian of 3-4 mm. in size, which represents a single cell, the nucleus of which, surrounded by protoplasm, lies in a spherical central capsule (Fig. 92). The whole extracapsular protoplasm is filled with innumerable vacuoles, so that it appears like a mass of foam, and it is bordered externally on the side of the sea- water by a solid layer of jelly. This vacuole-layer is the portion of the cell that is lighter than the sea-water, and 1 Cf. p 97. 230 GENERAL PHYSIOLOGY maintains the undisturbed Thalassicolla suspended at the surface of the sea.1 This can be made out readily by removing from the living animal single constituents of the cell, by cutting off the layer of jelly, isolating the vacuole-layer and extirpating the cen- tral capsule with its contents. All constituents, when isolated, sink to the bottom of the water, except the vacuole-mass ; this remains at the surface, and, if submerged, continually returns to it.2 Correspondingly, the whole Thalassicolla begins to sink as soon as the vacuole-layer collapses by the bursting of the vacuoles, which takes place as a result of stimulation, in nature especially from the impact of violent waves. Then the cell falls into more quiet depths, and thus is protected from entire destruction ; the FIG. 92.— Thalassicolla, nucleata, a spherical radiolarian cell in section. In the middle of the central capsule, which is surrounded by black pigment, lies the vesicular nucleus. The central capsule is surrounded by the vacuole-layer, which is enveloped by a zone of jelly and sends through the latter radiating, thread-like pseudopodia. vacuole-layer can regenerate itself, and the Thalassicolla, increasing in volume, in quiet weather rises again from the depths to the sunny surface. The great importance of this manner of move- ment for the life of pelagic organisms is evident. It is a question how the contents of the vacuoles can become lighter than the surrounding sea-water. The cause of the appear- ance of vacuoles, the formation of which can easily be observed in any isolated central capsule, consists in the accumulation through- out the protoplasm of osmotic substances, which cause the water to come in from the outside to them through the protoplasm. The size of the vacuole increases in proportion as the formation and concentration of osmotic substances in the protoplasm increase, for an equalisation of the osmotic pressure in the liquid of the vacuole CJ. Brandt ('85). Cf. Verworn ('93). ELEMENTARY VITAL PHENOMENA 231 and in the surrounding water must always take place, i.e., the liquid of the vacuole must always contain in solution the same number of molecules as the water. But it must be assumed that these are molecules of substances different from those in the water. If, therefore, we imagine some of the substances dissolved in the liquid of the vacuole to possess low specific gravity, we can under- stand how, upon the whole, the contents of the vacuole can be lighter than the water. K. Brandt ('95) has recently made it very probable that it is the carbonic acid produced by the protoplasm that, dissolved in the liquid of the vacuole, lowers the specific gravity of the protoplasm below that of the sea-water. If the vacuole-layer is developed -to a sufficient extent, the specific gravity of the whole cell will be less than that of the sea- water, i.e., the cell will float at the surface. If by the bursting of the vacuoles the volume of the layer becomes diminished, or if in the cold, when the metabolism sinks to a minimum, the production of carbonic acid becomes greatly decreased, the radiolarians will sink again. e. Movements Toy Secretion Movements that come about through secretion by the cell are limited to a few groups of organisms, particularly the Algce, Desmidiacece, and Oscillaricv. The principle of this mode of motion is extremely simple. It consists simply in the cell lying upon the bottom and pressing out at a definite place upon its surface and in a definite direction a mass of secretion, usually of a slimy nature ; this sticks to the bottom, and the motile cell-body thereby thrusts FIG. 93.— Closterium, a desmid, shoving itself along the bottom by a secretion of slime. The non- secreting end swings freely in the water. itself forward in a definite direction, just as a fisherman pushes his boat off the shore with a pole. If the secretion continues, the cell glides slowly along. In this manner the Desmidiacece move themselves. The crescent- shaped Closterium (Fig. 93), which we have already become acquainted with in considering the Brownian molecular movement, secretes a slimy substance at each end of its unicellular body. While it thus clings to the bottom with one end, the other end floats freely in the water, so that the whole body is directed 232 GENERAL PHYSIOLOGY 1 upward obliquely at a certain angle. The Closterium shoves itself slowly forward, as Klebs ('85) and Aderhold ('88) have shown, by the attached end expelling a mass of slimy secretion (Fig. 93), the cell maintaining approximately its angle of inclination to the bottom. But in gliding forward it alternates its two poles, the swinging pole sinking, adhering and secreting, while the previously attached pole rises and swings freely. Thus the alga gradually moves forward upon its support. As regards the movement of the Diatom-zee, the small, brown, boa -shaped or rod-shaped Algce, provided with an extremely delicate silicious shell, which are found in enormous variety in both fresh and salt water, a literature almost too vast for review has appeared. When these unicellular forms are observed in a drop of water upon a slide, they are seen gliding forward upon the bottom in the direction of their long axis in a peculiar hesitating manner, sometimes slowly, sometimes rapidly, and often going backward with the poles reversed in direction. It seems impossible to discover any sort of locomotor organs in the body. The numerous investigators who, like Max Schultze, Engelmann, and others, earlier studied this graceful form of motion, adopted widely different views as to its origin. Afterward, from the researches of Biitschli ('92, 2) and Lauterborn ('94), it appeared as if it depended upon the above principle of the extrusion of a slimy secretion. Biitschli and Lauterborn succeeded in showing that certain forms of JJiatomece are enveloped in a covering of jelly and extrude peculiar threads of secretion, which can be made visible by adherent granules of india ink (Fig. 94). But recently the very detailed investigations of O. Miiller ('93, '94, '96, '97) have shown that these threads have a subordinate significance in the progression of the Diatomece, and that the mode of motion of these small cells is much more complicated, and perhaps more allied to movement by protoplasmic streaming. As to the long, blue-green, thread-like Oscillarise, which consist of many cells arranged one after another in a row and creep slowly through the water like the Diatomece, it is highly probable that they really shove themselves along the bottom by the expulsion of FIG. 94. — Diatom with threads of slime extruded. (After Butschli.) ELEMENTARY VITAL PHENOMENA 233 a secretion. Recently, Schewiakoff has shown the same also for the Gregarince (Fig. 22, I, p. 80), which are parasitic unicellular organisms that likewise perform very slow, gliding movements without special locomotor organs. /. Movements ly Growth Movements that are associated with the growth of cells need only be mentioned briefly; their principle needs no elucidation. All growth is accompanied by movement, for, as a cell increases in volume, it becomes expanded. Hence growth-movements are common to all living substance, but they take place so slowly that they can scarcely be followed with the eye. If, however, growing objects be compared with their earlier stages after considerable spaces of time, if the sprouting seed be first considered and then the plant that has developed from it with all its branches, leaves and flowers, it is evident that extensive movements have taken place, by which the building material has been transported to the places where it is laid down. Growth-movements are recognised also especially clearly in long plant-stalks or tendrils, when the cells grow or multiply more rapidly upon one side than upon the other, so that the part becomes curved. But the most apparent move- ments caused by growth are in those cases in which the mechanical energy developed by growth is not continually set free, but is accumulated in the form of tension, and finally by some stimulus is suddenly transformed into kinetic energy; this appears most beautifully in the seeds and fruits of certain plants, e.g., Impatiens, which, upon being touched, suddenly burst with a jerking motion and throw out their contents. It is not necessary to go further into the mode of growth-movements, since their principle is plain and they are met with at every step in living nature. That the phenomena of growth are powerful sources of energy is clear when it is recalled that trees growing between rocks are able to force apart huge masses of stone by their roots. g. Movements by Contraction and Expansion Finally, movements that are produced by the contraction and expansion of the cell-body, and which are usually termed, in brief, contraction-phenomena, are distinguished from all other organic modes of motion by the fact that they consist of changes in the form of the surface of the living substance itself, which changes are associated with an alternate shifting of position of its particles. All contraction-phenomena comprise two phases of move- ment, that of contraction and that of expansion. The particles of living substance arrange themselves with reference to one another in contraction, so that the mass presents a smaller surface, 234 GENERAL PHYSIOLOGY in expansion, so that the same mass presents a larger surface. Transition from one phase to the other alone renders possible phenomena of motion. It is evident that only bodies of more or less liquid consistency can show such movement ; only a liquid can diminish or increase its surface by rearrangement of its particles, becoming spherical or spread out, according as its surface-tension is equal in all directions, or becomes greater in some places and less in others. A solid, stiff body, even if it is elastic, cannot manifest con- traction-phenomena of this kind, because its particles cannot change their mutual positions. Hence, it is of fundamental im- portance for the occurrence of contraction-phenomena that living substance possess a liquid consistency. As a matter *of fact, all living substance, as has already been found, is more or less liquid, a condition that is imposed upon it by the high percentage of water in its contents, and, therefore, the common view is well founded that all living substance possesses contractility, although many cells are known, such as certain Algce and Bacteria, which in spite of their leading an active life can perform no contraction- phenomena, because they are surrounded by a stiff membrane. Contractility, i.e., the property of executing contraction-move- ments, is, however, a general property of living substance, and hence demands detailed consideration. Among the phenomena of movement brought about by contraction and expansion in accordance with the above principle there can be distinguished, according to the peculiar differentiation of the substratum in which they are observed, three groups, which are termed : Amoeboid movement (protoplasmic streaming) ; Muscular movement (movement of smooth and cross-striated muscle-fibres) ; Ciliary movement (movement of flagella and cilia). Amoeboid movement, the original form of contraction-phen- omena, is found wherever there exist naked protoplasmic masses, that is, cells the protoplasmic bodies of which are not sur- rounded by a cell-membrane, or wherever, as in plant-cells, there is within the membrane a free space for movement. As examples there may be mentioned especially the manifold representatives of the great protistan group Rhizoppda (Figs. 95 and 98); further, in the animal cell-community, leuco- cytes and amoeboid wandering-cells of various kinds (Fig. 96), amoeboid egg-cells of certain animals, such as sponges (Fig. 17, a), pigment-cells of widely different organs1 (Fig. 97), 1 The view often expressed in recent times, that in the movements of pigment- cells there is a change of place of the granules of pigment without a simultaneous change of form of the protoplasmic body, appears to me wholly untenable. ELEMENTARY VITAL PHENOMENA 235 intestinal epithelium-cells (Fig. 45) ; and, finally, various kinds of plant-cells (Fig. 24, a, and Fig. 35). The movement of Amoeba can serve as a type (Fig. 95). This organism is the lowest of all living things, and its formless body holds within itself the whole secret of life. Taken with a pipette in a drop of water from the bottom of a pond and brought under the microscope upon a slide, the amoeba-cell appears as a small grey semi- transparent droplet of a more or less pronounced spherical form ; in the central portion lie the nucleus and usually a contractile vacuole, surrounded by a more or less granular endoplasm, while the peripheral layer consists of a more hyaline exoplasm. If this drop of living substance be observed for some time, it is FIG. 95. — Amoeba in eight successive stages of movement. seen that at some point of its surface the spherical mass bulges out in the form of a lobate projection ; this becomes constantly larger and extends itself farther and farther, more protoplasm flowing into it constantly ; the phenomenon spreads from the peripheral parts toward the centre, so that a continual streaming takes place from the centre toward the periphery in this so-called pseudopodium (Fig. 95). Frequently the whole protoplasmic mass of the amoeba flows over into this one lobate projection, so that the body forms a single extended mass, as can be observed especially in Amoeba Umax. Frequently, however, the centrifugal protoplasmic streaming of the pseudopodium becomes interrupted, while at the same time at another point of the surface a second pseudopodium is formed in the same manner by a centrifugal 236 GENERAL PHYSIOLOGY flowing of the protoplasm into the medium, and a third may follow this, so that the amoeba protrudes its substance in various directions, and thus considerably increases its surface. This extension of pseudopodia, this flowing of substance into the medium, represents the phase of expansion. While a new pseudopodium is being extended, protoplasm usually flows out of another one, from the periphery back to the centre to afford material for the new one, that is, the old pseudopodium is drawn in. This retraction of pseudopodia, this centripetal back-flow of the protoplasm and diminution of the surface associated with it, represents the phase of contraction. If all pseudopodia are drawn FIG. 96.— A leucocyte (white blood-corpuscle) of the frog, in various stages of movement. (After Engelmann.) in, the amoeba-cell again assumes a spherical form. The spherical form is, therefore, the expression of most complete contraction in naked protoplasmic masses. When undisturbed, however, simul- taneous contractions and expansions usually take place in the same amoeba at different points on its surface. Hence the pseudopodia are not preformed. Substance flows out, now here, now there, is mixed continually and flows back again, and this changeable play is the amoeboid movement. In the various amoeboid protoplasmic masses the form of the pseudopodia varies greatly, according to the special consistency and composition of the living substance. As has already been .seen,1 there occur among the numerous forms of rhizopod-cells 1 feebly, ore strongly. immediately after the movement of the preceding cilium has begun arid before it is ended. It thus happens that, considering the row from above downward, the movement of each upper cilium slightly ELEMENTARY VITAL PHENOMENA 249 precedes that of each lower one (Fig. 108). In other words, the uppermost cilium gives the sign to the others ; if the uppermost one is at rest, the others rest ; if it contracts, they also contract in order ; and this is true not only of the cilia of the single cell, but, FIG. 108. — Motion of a row of cilia, in profile. in ciliated epithelium, of the cilia of all the cells in a row. In this manner there occurs an extremely delicate and regular play of the cilia, which has fascinated many observers and gives the impression of regular waves passing over the ciliated row, somewhat as the wind sweeps over a field of grain. When several parallel rows of cilia are present, the cilia standing beside one another in adjacent rows beat synchronously, just as the fibrillse lying beside one another in a muscle-fibre contract at the same time. The phases of movement of the individual cilium can best be studied in the swimming-plates of the Ctenophora.1 The body of these remarkable animals consists of a delicate transparent jelly, and possesses eight stripes or ribs (Fig. 109) extending from one FIG. 109. — Beroe ovata, a ctenophore, natural size. Of the eight ribs or rows of swimming-plates extending from the upper (sense-)pole to the lower (mouth-) pole, only the four rows of one side are to be seen, two from the front, and two from the side. pole to the other ; each rib consists of a row of plates, the swim- ming-plates, that lie upon one another like tiles upon a roof. Each swimming-plate is about 2 mm. long, and consists of a con- siderable number of cilia, cemented together, which belong to the cell-bodies lying beneath. On account of their extraordinary 1 Cf. Verworn ('90, 2). 250 GENERAL PHYSIOLOGY size, the unusual simplicity of their arrangement in rows, and the fact of the rhythm of their beat being frequently very slow, these swimming-plates serve as no other object does for experimentation and observation. As was said above, the plates are formed of many cilia cemented together, but each cilium evidently makes exactly the same movement as the whole plate, so that observations made upon the whole plate may be transferred to the conditions in a single cilium. On account of the size of the object observations can be made with the naked eye or with a weak lens. If a single swimming-plate be observed in profile, it is seen that in the resting-position it lies flat against the body, so that it shows two curves, a greater one of smaller radius immediately above the base, and a smaller one of greater radius and in the opposite direction in the upper half (Fig. 110). This FIG. 110. — Swimming-plates of Beroe in profile, a, In the resting-position; b, in the position of extreme contraction. is the position of rest. If now the plate performs a stroke, the lower curve beginning from the base of the cilium extends itself completely, even giving place to a slight curve in the opposite direction. Hence, in the position of extreme swing the plate stands erect with a slight curve toward the opposite side. The progressive phase of the stroke is thereby completed. Now follows the retrogressive phase, in which the plate falls back again into its position of rest, the original curve at the base gradually coming back until the plate again lies against the body. The retrogressive phase proceeds more slowly than the progressive. Because of this fact and by means of the upper curve — into the special significance of which we shall go no further — it is rendered possible that the motor effect of the progressive phase is not balanced by the retrogressive phase; otherwise the animal would remain continually in the same place in the* water. The movement of ELEMENTARY VITAL PHENOMENA 251 individual cilia can be followed in Infusoria under the microscope, if the stroke be slowed by placing the objects in a thickish medium, such as a solution of gelatine. It is then found that the rest ing-position, from which the cilium performs its movements, is changeable. At one time the cilium lies more against the bodyr at another time it stands more vertical ; hence the amplitude of the swing, and thus the amount of the motor effect can be very finely graded (Fig. 111). It follows from the change of form of the individual cilium in carrying out the stroke, that in the progressive phase a contraction, starting from the base of the cilium, takes place on the side toward which the stroke is carried out, for a simple measurement shows that this side is shortened when it passes into the position of extreme swing. At the same time the opposite side is drawn FIG. 111. — Movement of a single cilium of a ciliate infusoriau (Urostyla grandis, border-cilium) from two different resting-positions, / and 11. A. Progressive, B, retrogressive phase of the movement in several successive stages. The arrows indicate the direction toward which the body is driven. over passively, being extended necessarily, according to simple mechanical principles. In the retrogressive phase the contracted side relaxes, and to the same extent the cilium, as a result of the elasticity of the extended side, bends back into the position of rest. The progressive phase, therefore, is the phase of contraction, the retrogressive phase that of expansion of the single stroke of the cilium. The play of the ciliary movement comes about by the rhythmic alternation of the two. But all cilia do not contract in one plane like those of the swimming-plates of the ctenophores. Many, especially certain flagella, describe more complicated paths, funnel-shaped, screw- shaped, and like the path of a whip-lash, and accordingly the earlier physiologists distinguished several forms of ciliary move- ment. But whatever the path of vibration of the different cilia may be, the same principle lies at the basis of all, viz. : that a 252 GENERAL PHYSIOLOGY contractile side contracts from the cell-body outward, and thereby the opposite side is extended; in the phase of expansion the latter, by its elasticity, brings the cilium back into the position of rest. According to the relative positions of the contractile and the passively extended substances there results a movement in a plane or a more complicated form. The work performed in ciliary movement is much less than that of muscular movement. Engelmann, Bowditch and others have calculated the work of ciliated epithelia, and recently Jensen {'93, 2) has measured the force of a single ciliate-infusorian cell, Paramcecium, which is well fitted for a great variety of investiga- tions. Jensen determined that a Paramcecium, which possesses a length of about 0'25 mm., is able to raise a weight of 0*00158 mgr., i.e., about nine times the weight of its own body. The view is sometimes expressed that amoeboid movement has nothing in common with muscular movement, and the latter nothing in common with ciliary movement, that the three are utterly different in kind. The above brief examination is sufficient to show, however, that these three forms of contraction constitute a, single group in contrast to all other modes of motion. It is true that they show among themselves certain differences, and that at first sight they appear quite unlike one another, but it has been seen that they all rest upon the same principle, namely, that of alter- nating diminution of surface (contraction) and increase of surface (expansion) by means of a rearrangement of the particles of the living- substance. That in amoeboid movement this shifting of the particles is wholly without rule, while in muscular and ciliary movements it is orderly, proves only that the two latter represent a higher stage of differentiation than the former. That, however, they stand in the closest genetic connection with amoeboid movement, that they have become evolved from it phylogenetically, is proved by numerous cases of transition, on the one hand between amoeboid and muscular movement, and on the other between amoeboid and ciliary movement. Engelmann ('81, 2) has found rhizopods (Acanthoeystis) possessing straight, filose, unbranched pseudopodia, which are capable of contracting longitudinally with excessive rapidity, and from which a small muscle-fibre is distin- fuishable only by its constant differentiation: Engelmann has ttingly termed these pseudopodia myopodia. Moreover, man} cases have been observed where filose pseudopodia of amoeboid cells carry out pendular vibrations, at first irregularly and slowly, later rhythmically, until they have developed into genuine, constant cilia. In view of such facts no proof is needed to place beyond doubt the genetic connection of the three forms of contraction, even if careful observation of their single factors had not proved sufficiently clearly the identity of the principles upon ELEMENTARY VITAL PHENOMENA 253 which they are based and their relationship in comparison with all other modes of motion. The contraction of living substance follows the same principle everywhere, whether the living substance creeps about as an Amaba upon decaying leaves in a pool of water, whether as a white blood-corpuscle it forces its way through lymph spaces in the tissues of the animal body, whether as a protoplasmic network it circulates in the cellulose-capsule of a plant-cell, whether as a muscle-fibre it performs the contractions of the untiring human heart, or, finally, as a cilium on the oviduct of woman it trans- ports the unfertilised egg-cell to the uterus to undergo fertilisa- tion,— everywhere there is the same phenomenon of alternating contraction and expansion of the living substance by means of the reciprocal rearrangement of its particles. 2. The Production of Light In the movements of living substance, especially in the phenomena of contraction, the transformation into kinetic energy of the potential energy introduced into the body as food, comes out very clearly. This is much less evident in the production of other forms of kinetic energy, such as light, heat, and electricity, for the demonstration of which very complicated methods and sensitive instruments are often required. Next to the mechanical energy of movement, the production of light is most evident to the senses, and has always had a mysterious fascination for the observer. It has a curious charm, when at night the water of a quiet sea breaks into a bright,, yellow glow at every stroke of an oar, or when in southern climates in the spring, the mild night air is filled by innumerable sparks, which silently flash up and circle about, and then disappear. The emission of light by living substance is wide-spread. It is an especially significant fact that, of the wonderful pelagic animals whose delicate transparent bodies occupy the upper strata of the sea and float about as plankton, almost all possess luminous power. Associated with this fact is the presumption that the luminous capacity of living substance is possibly much wider- spread than is realised, that we do not see the light because the organisms are not transparent, or because the production is too feeble to allow the light to be seen through thick body-layers; indeed, it is not impossible that in our own bodies certain cells may be photogenic. In most cases, as in luminous insects, the power of emitting light is a peculiarity specially perfected by selection and possesses its own significance for the life of the animals in question. In pelagic marine animals also such a significance is certainly present ; as a rule, these animals emit light 254 GENERAL PHYSIOLOGY suddenly and only upon stimulation, and hence it may be sup- posed that the light serves as a means of frightening enemies (Fig. 112). The spontaneous emission of light is much less common. It appears especially in certain putrefactive bacteria that live upon decaying sea-fish and flesh (Bacterium phosphor escens), as well as in mushrooms (Agaricus), and certain insects (Mater, Lampyris). Numerous researches have been carried on respecting the nature of the light, e.g., those of Panceri and Secchi on Salpce (Pyrosoma), those of Moseley on deep-sea ccelenterates (Alcyonaria), and more recently, especially those of Langley and Very ('90) upon the lightning-bug (Pyrophorus noctilucus). To obtain a comparison of insect-light and sunlight, Langley and Very super- posed a spectrum of the light of Pyrophorus above the solar spectrum (Fig. 113), and thus determined that with equal luminosity the solar spectrum extends further toward both the violet and the red than the light of Pyrophorus, but that the latter is more intense than sunlight in the green. It is easily understood that the origin of so pe- culiar a phenomenon as organic luminosity has especially attracted the attention of investigators, and it is not surprising that an enormous literature upon the subject has appeared. Pfliiger (75, 1, 2) has collected a series of physiologically interesting accounts. It appears therefrom that very different views have been put forward upon the origin of the light in organisms. The idea early met with great approval, especially among non-specialists, that organic light depends upon the presence of phosphorus, to the mild light of which it has a certain external similarity. But exact investigations have shown that it has nothing whatever to do with phosphorus. This follows from the fact, among others, that the emission of light presupposes life in the cell. It can be observed in the single cell, a free-living bacterium from decaying fish, an infusorian or radiolarian from sea- water, or a tissue-cell of a composite animal- or plant-body : but in every case the photogenic substance is produced only in FIG. 112. — Noctiluca miliaris, a pelagic flagellated cell which becomes luminous upon stimulation. ELEMENTARY VITAL PHENOMENA 255 the cell-metabolism, although R. Dubois ('92) has shown that in certain animals, e.g., the boring mussel Pkolas, the substance can be extruded from the body as a cell-product without immediately losing its luminous power. Phosphorus is an active poison for all living substance ; hence, in the free state, in which it becomes luminous, it is wholly incompatible with the life of the cell. A trace of free phosphorus or luminous compounds of phos- phorus has never been found in luminous animals. Nevertheless, it can be stated with certainty that the luminosity of living substance is associated, as in phosphorus, with very slow oxida- tion-processes. This follows especially from the fact that the light continues only in the presence of oxygen. Moreover, Fabre ('55) has found that the luminous mushroom, Agaricus, produces much more carbonic acid, when emitting light, than at other times. Finally, there belongs here a fact that was observed by O.35 . OAO 0.50 Q.6O O.7O ;Fio. 113. — /, Solar spectrum ; ///.spectrum. Pyropliorus noctilucus. (After Langley and Very.) Max Schultze ('65) in the cells of the photogenic organs of light- ning-bugs, namely, that these photogenic cells stand always in the 'closest connection with the tracheae, which serve as breathing- tubes ; and, if they be placed under the microscope with perosmic acid, they withdraw oxygen from the latter, a fact which may be recognised by the appearance of a black precipitate. The photo- genic cells, therefore, absorb oxygen actively. Pfliiger appropriately says concerning it : " Here, in the wonderful spectacle of animal phosphorescence nature has given us an example that shows where the taper burns that we call life." " It is certainly no rare exception, but only the special expression of the general law that all cells are burning continually, although with our corporeal eyes we do not see the light." As regards the special processes of oxidation with which the luminosity of living organisms is associated, at present, with our very scanty knowledge of metabolism, almost nothing can be said with certainty. The beautiful researches of Radziszewski ('80) 256 GENERAL PHYSIOLOGY more than any others have elucidated this subject. Radziszewski studied in detail the conditions under which chemical substances exhibit phenomena of phosphorescence, and found that a whole series of organic bodies emit light when they are slowly combined with active oxygen in an alkaline solution. Such bodies comprise especially many fats, ethereal oils, hydrocarbons and alcohols. In many the light appears at ordinary temperatures, in others only upon warming. If, e.g., oleic acid be added to an alcoholic solution of potassium hydrate in a test-tube, a light lasting for a short time may be observed in the dark while the acid is being dis- solved. If, after the light has ceased, a drop of a solution of peroxide of hydrogen be added to the liquid, a clear strip of light is seen to pass through the test-tube along with the drop of peroxide of hydrogen as it falls to the bottom. This is due to the fact that the peroxide of hydrogen gives off active oxygen to the oleic acid. The same phenomenon of light is shown still more clearly when oleic acid is dissolved in pure toluol, which likewise is capable of phosphorescence, and the solution is poured over a piece of potassium or sodium hydrate. The intensity of the light can always be increased by shaking, because the free atoms of oxygen are thus brought more into contact with the molecules of the phosphorescent body. If, e.g., into a glass bulb containing a mixture consisting of equal parts of pure toluol and cod-liver oil (which latter always contains in addition to oleic acid free atoms of oxygen), there be thrown a few pieces of potassium or sodium hydrate, and the whole be gently warmed and placed in the dark, no light is seen at first. But, if the contents of the bulb be gently shaken, there is seen " at once a beautiful light streaming through the whole mass like a flash of lightning." It is in the highest degree probable that the luminosity of living substance depends upon analogous processes. Fats, oils, etc., are wide-spread in living substance, and Panceri believes of certain luminous marine fishes that the liquid fat is the luminous body. Substances that give an alkaline reaction are likewise found everywhere in living substance, and the luminosity of organisms is associated with processes of oxidation. Thus the same conditions are present in living substance as in the experiment of Radziszewski. 3. The Production of Heat The production of heat is much less apparent to the senses than that of light. While we can observe the latter readily in the single cell, the amount of heat produced by the single cell, because of the small size of the object, cannot be measured with our crude instruments for the measurement of temperature. Never- theless, it must be assumed that in the interior of every living cell ELEMENTARY VITAL PHENOMENA 257 heat is produced, for chemical processes are there present that are accompanied by the production of kinetic energy, and heat is the form of kinetic energy that is evolved in all such processes with- out exception, either alone or in addition to other forms of energy. In fact, there is even good ground for supposing with Pfliiger that in single molecules of living substance temperatures of several thousand degrees Centigrade become developed suddenly. This may be the case in the production of a molecule of carbonic acid, since the heat yielded by the combustion of carbon amounts to 8,000 calories. But the molecule of carbonic acid is excessively small, and it is surrounded in the cell by an enormous number of other molecules which possess a very low temperature. Hence, the heat that suddenly flashes up is counterbalanced as rapidly as it appears ; and, since all heat-forming molecules are not produced simultaneously, but appear now here and now there between large masses of other molecules, it is evident that the total temperature of the cell resulting from the equalisation of all the various indi- vidual temperatures cannot reach a remarkable height. Further, with our crude methods of heat-measurement, we cannot yet measure the actual heat given off to the outside by a single cell, since the greater part is lost in the process by conduction and radiation. It is, therefore, necessary to employ for the determin- ation of the heat-production, not a single cell, but large cell- complexes, such as considerable masses of tissue or whole organisms. The production of heat is most evident in the bodies of homo- thermal, or so-called warm-blooded, animals. It has already been seen that the earlier division of animals into warm-blooded and cold-blooded has been very fittingly replaced by that into homo- thermal and poikilothermal animals, i.e., those that maintain under all external conditions the same body-temperature and those whose body-temperature rises and falls with the temperature of the environment. Homothermal animals show most clearly the production of body-heat because they have contrivances for storing up heat in themselves to a certain definite degree and maintaining it at this degree by an extremely delicate regulating mechanism. Hence, with an external temperature not too high the body of the homothermal animal is always warmer than the surrounding medium. This may be determined readily by the method of thermometric measurement. Thus, the body of man possesses in its interior a constant temperature of 37° — 39° C., upon its surface a temperature somewhat less, corresponding to the external cooling, in the mouth-cavity about 37° C., and in the axilla about 36'5° C. Birds with their active metabolism have the highest body-temperature, e.g., the swallow more than 44° C. But that poikilothermal animals can attain considerable temperatures when under conditions in which the heat produced by them is stored and s 258 GENERAL PHYSIOLOGY not given off to the medium by conduction or radiation, is proved by the fact that bees in their hives can produce temperatures of from 30° to 40° C. Even plants can raise their temperature above the temperature of the surroundings, as can be determined thermo- metrically, especially in sprouting and in vigorous growth where the metabolic processes are particularly active. Sachs was able to determine with a thermometer a rise of temperature of 1*5° C. in peas which were allowed to sprout in a funnel under a bell-jar (Fig. 114). Very remarkable temperatures have been observed in the spadices of the peculiar Aro'ideae during their development : here not rarely a rise of 15° C. is found. A rise which under favour- able conditions can amount to more than 14° C. is produced also by yeast-cells in the fermentation of sugar solutions. For the determination of delicate changes of temperature, especially in the tissues of poikilothermal animals, the rough method of measurement of temperature by the thermo- meter is not sufficient, and hence the finer method of thermo-electric measurement has been employed. As is well known, in a thermo-electric element, which consists of two pieces of different metals soldered to- gether at one end (the best metals are German silver and iron, or antimony and bismuth), an electric tension is produced by slight warming of the soldered place. If the two free ends of the metals be joined by a wire so that a closed circuit exists, an electric current can be led off from them, the presence of which is shown by the deviation of a mag- netic needle in the vicinity. For the demon- stration of very feeble currents especially sensitive apparatus is needed, such as the multiplier and the galvanometer, the mag- nets of which are moved by very delicate currents. The multiplier consists of a suspended and easily moved astatic system, i.e., two horizontal magnetic needles which are fastened together parallel one above the other, so that the north pole of the one lies above the south pole of the other. In the region of the lower needle the wire of the circuit is wound into a coil consisting of an exceedingly large number of turns, so that when the current goes through it, all the individual turns tend to deviate the needle in the same direction. The upper needle hangs above a disc divided into degrees, so that here the deviation of the needle can be measured (Fig. 115). In the FIG. 114. — Apparatus for demonstrating the rise of temperature in the sprouting of peas. Under a bell-jar is a funnel con- taining sprouting peas, into which projects a thermometer. e( After Sachs.) ELEMENTARY VITAL PHENOMENA 259 galvanometer (Fig. 116) the magnet has the form of a ring which is suspended by a silk fibre in the space within the coil ; a small mirror is connected with the ring and accompanies all the move- ments of the latter (Fig. 116 /3 7). At some distance from the apparatus stands a telescope bearing a scale, the image of which by careful adjustment can be observed through the telescope in the mirror of the galvanometer (Fig. 116 7). The slightest deviation of the ring-magnet is shown in the telescope by a shifting of the image of the scale. According to the extent of this shifting the strength of the electric current can be computed, FIG. 115.— Multiplier. /, Plan. An astatic system, with the north poles N and N', is suspended upon a silk fibre G. Around the lower needle is a coil of wire W ; the upper needle moves above a graduated disc. (After Landois.) //, Multiplier complete. (After Cyon.) and hence empirically the amount of heating of the thermo- electric element, or, better, a whole series of thermo-electric elements. Thus the most delicate changes of temperature that a living tissue undergoes can be determined. By investigations of this kind it has been established that a higher temperature is pro- duced by greater activity of the cells of a tissue, e.g., a gland or a muscle, than by less activity or during rest. This result is in close accord with our ideas concerning the production of heat, for the greater activity of the cells depends upon a greater metabolism in them, and heat results from chemical transformations in the cell. It is an old experience that one can warm himself by vigorous muscular activity. s 2 260 GENERAL PHYSIOLOGY All measurements of temperature, whether by the thermometer or the thermo-electric method, serve only to determine the temperature that prevails in some one place in the organism at some one time. They give no particulars regarding the quantity of heat that the organism or the individual tissue produces. But it is possible to determine the quantity of heat by investing the number of heat-units, or calories, that the living body gives off to the outside in a certain time. Thus calorimetry has developed by the side of thermometry. As is well known, a calorie is that FIG. 116 a.— Mirror galvanometer. Upon a board is an upright, supported by two columns ; the upper portion consists of a glass tube in which hangs a silk fibre suspending a ring-magnet in the lower portion. At the two sides are two coils of wire. (After Cyon.) quantity of heat that is necessary to warm one kilogram of water from 0° C. to 1° C. In order to measure the number of calories that a living body, for example an animal, produces in a definite time, the water-calorimeter has been constructed (Fig. 117). This consists of a box having double walls that may be closed upon all sides. The space between the two walls is filled with water, the animal is placed in the box, and the whole is protected from cooling or warming from the outside by a non-conducting covering. The heat produced by the animal is communicated to the water ELEMENTARY VITAL PHENOMENA 261 and raises its temperature ; the latter can be read off upon a thermometer projecting into the water. Various contrivances serve to reduce the sources of error that depend upon possible loss of heat. From the quantity of water and the warming of it in a FIG. 116/3. — A portion of the galvanometer enlarged. The two columns sustain a compartment within which is the ring-magnet in connection above with a small mirror ; the latter is sus- pended in a case (outlined in dotted lines) by the silk fibre, and accompanies all the movements of the magnet. (After Cyon.) FIG. 116 y.— I. Arrangement of apparatus for thermo-electric measurement ; a, /, thermo-electric needles, which are joined together on one side by the wire b, and on the other by the wire 61 ; b is coiled about the ring-magnet m having the north pole n. The magnet mis suspended by a silk fibre c and fastened to a mirror s. In front of the ring-magnet is a straight magnet M, having the north pole N, at such a distance that the ring-magnet can still point toward the north. An extremely slight current suffices to cause it to deviate from its position. In front of the galvanometer is a telescope F with a scale KK, the image of which the ob- server B can see in the mirror s of the galvanometer ; thus he perceives every movement of the mirror or of the ring-magnet by the shifting of the image of the scale. II and III. Dif- ferent forms of thermo-electric needles, a, German silver ; /, iron. (After Landois.) definite time, the heat-production of the animal can be determined with approximate exactness. In recent times the water- calorimeter has been replaced by the air-calorimeter, in which the cage containing the animal is surrounded by a closed air-chamber ; 262 GENERAL PHYSIOLOGY the air of the chamber is expanded by the heat given off by the animal, and from the amount of the expansion the quantity of heat produced may readily be computed. Partly by one method and partly by another, Dulong, Desprez, Helmholtz, Rosenthal, and Kubner, have determined the quantity of heat produced by the animal body. Since all such heat is derived from the chemical energy of the food introduced into the body, and since all the energy of the body, in case the latter performs no work, is FIG. 117. — Dulong's water-calorimeter. A box with double walls ; the wide space between the two walls contains water, through which a tube runs in spiral coils to the interior of the box for the admission of air from the outside at D to the animal, and for the removal of the used air through D'. At T and T" are thermometers. (After Rosenthal.) transformed finally into heat, the quantity of chemical energy that is introduced into the body with the food, expressed in calories, must according to the law of the conservation of energy be equal to the quantity of heat given off from the body to the outside. As a matter of fact, in the experiments this result has been attained with all desired exactness, and thus the validity of the law of the conservation of energy for the living body has been experimentally confirmed. 4. The Production of Electricity As with heat, so thus far the production of electricity cannot be proved upon the single cell, because even our most delicate apparatus is too gross. Here also masses of cells are required. But the production of electricity can be perceived without special means of aid in far fewer cases than the production of heat, since all homo- ELEMENTARY VITAL PHENOMENA 263 thermal animals show the latter. The former may be observed without further aid only where it occurs in large proportions, i.e., only in the electric fishes, whose powerful shocks were known even to the ancients. The history of the science of animal electricity is associated closely with the discovery of galvanism and with the names of Galvani and Volta. It is certainly a note- worthy fact that the discovery of the physical fact of galvanism required for its starting-point physiological phenomena. In September, 1786, Aloisio Galvani was making investi- gations upon the terrace of his house in the ancient university city of Bologna on the influence of atmospheric electricity upon a frog's leg from which the skin had been removed. Several years before he had carried on similar researches with the aid of his wife, Lucia, since early deceased. In the course of his experiments he stuck a copper hook through the frog's spinal column, which was still in connection with the nerves. When he laid this preparation upon the iron railing of the terrace he noticed to his astonishment that whenever the hook touched the railing, the frog's leg attached to it executed violent contractions. This simple observation is said to have been the starting-point of the discovery of contact electricity, the inconceivable range of which in relation to civilisation is only now appreciated. Alessandro Volta discovered the explanation of this phenomenon by establishing the fact that in the contact of two different metals with a moist conductor an electric tension arises, which is equalised in the form of an electric current as soon as the metals are joined with one another. In Galvani's experiment the nerves and muscles of the frog constituted such a moist conductor between the copper hook and the iron railing ; the current went through the muscles and stimulated them so that they contracted. -This correct interpretation of Volta was opposed by Galvani, who imagined that the twitch of the frog's leg might be caused by electricity originating within the leg itself; but this error is said to have led him fortunately to a new discovery. In labouring to prove to Volta that the contact of metals was not necessary for the production of the twitch, he endeavoured to bring out the twitch without metals ; and he succeeded in this by placing the free end of a freshly prepared nerve of a frog's leg in contact with the flesh. In this experiment, as is now known, the nerve is stimulated by the electric current produced in the muscle itself; and so Galvani became the discoverer of animal electricity, as previously, although unwittingly, he had discovered contact electricity. Pfaff, Humboldt, Ritter, Nobili, Matteucci and others laboured in the further development of the science of animal electricity, but it was reserved for the classic investigations of du Bois- Reymond ('48 — '84) to place this field of physiology, which was then half-mystical and constituted one of the chief supports of the doctrine 264 GENERAL PHYSIOLOGY of vital force, upon a clear, exact foundation by creating for the first time sure and comprehensive methods of research. In the beginning, for evident reasons, only the muscles and nerves of the frog served as objects of experiment; but soon du Bois-Reymond brought into the range of his studies the interesting phenomena of the electrical fishes. And numerous inquirers, such as H. Munk, Hermann, Engelmann, Bernstein, and most recently Biedermann ('95), investigated the electrical phenomena of plants and various animal tissues. We are indebted to the researches of Hermann for the key to an understanding of the electrical U FIG. 118. — A, Simple arrangement for the production of a galvanic current. Zn, Zinc ; Cu, copper ; the two joined below by a moist thread. The arrows indicate the direction of the current. B, Simplest form of a galvanic element. Two metal strips (copper and zinc) dip into a liquid and are joined together by a metal at their free ends. The current goes in the direction of the arrow. phenomena of living substance. But it is due indisputably to the fundamental labours of du Bois-Reymond that the science of animal electricity has become one of the best-known branches of physiology. The simplest method of obtaining a galvanic current, as is well known, is that of soldering together at one end two strips of different metals, e.g., copper and zinc, and bringing their free ends into contact with a moist conductor, e.g., a moist thread (Fig. 118, A). At the moment when the free ends of the metals are joined by the conductor, an electric current begins to flow in the closed circuit, passing from the zinc through the conductor to the copper and from the copper through the ELEMENTARY VITAL PHENOMENA 265 soldered place back to the zinc and circulating as long as the circuit is closed. This arrangement corresponds to Galvani's original experiment in which the nerve represented the moist conductor between the two metals, copper and iron. This principle for the production of a galvanic current has been employed in somewhat more perfect form in galvanic elements (Fig. 118, B}, in which a liquid is employed as the moist conductor, while the two metals, the lower ends of which dip into the vessel containing the liquid, are in contact with one another at their upper ends by a copper wire in place of the soldering ; this has the advantage of allowing the current to be conducted by means of the flexible wire wherever it is needed. Following the views of Clausius upon the phenomena of electricity in liquids, Sohncke ('88) has presented a very clear idea of the origin of the galvanic current. According to Clausius ('57) the molecules in a liquid are in constant motion and con- stantly crowd upon one another, the result being that some split into their constituent atoms while other atoms unite into mole- cules. Hence simultaneously and at all times free atoms and whole molecules are present in the liquid. But while the closed molecule as a whole is electrically indifferent (e.g., water, H2O), its various kinds of constituent atoms, when free, have different kinds of electricity (e.g., hydrogen, H, positive, oxygen, 0, negative). Within the liquid the free atoms retain their charge of electricity. If they come in contact with atoms charged similarly they break away from them ; if they meet those charged dissimilarly, they remain no longer free but unite with the latter chemically into a molecule which is electrically indifferent. But the situation is changed when there is introduced into the liquid a metal plate that exercises upon one kind of the free atoms a chemical attraction. These atoms then accumulate on the surface of the metal, which is non-electric and a conductor, and give off their electric tension to it by conduction. If, therefore, into a vessel containing acidified water a zinc plate be dipped, free atoms of oxygen accumulate upon its surface and give off their negative electricity to it ; in other words, it becomes negatively charged. If at the same time a copper plate be dipped into the liquid, atoms of hydrogen collect upon it and give to it their positive charge. There arises, therefore, an electric tension between the two metals ; if now the free ends of the copper and the zinc plates be joined by a metallic conductor, this tension is able to equalise itself. During this process, however, new atoms become attracted to the place of contact of the metals with the liquid and become chemically united ; thus the tension becomes continually re-established, and in this way a continual galvanic current is produced. As is known from the researches of electro-chemistry, especially 266 GENERAL PHYSIOLOGY since the brilliant work of Arrhenius led to the great de- velopment of this science, in all chemical processes a disturbance of electric equilibrium takes place. In every chemical decom- position positively and negatively electric atoms or groups of atoms appear. If similar chemical processes take place at all points of a physical system and to the same extent, no current can be led off' from it, for no tension exists between the leading- off points, because both positive and negative groups of atoms arise in equal quantity (Fig. 119, I). But if in the system, such as a liquid mass, different kinds of chemical transformations, spatially separated, go on, so that there appear at one point a larger number of groups of atoms positively charged, and at another point a larger number negatively charged, an electric tension develops between these two points ; and, so long as the processes continue, a galvanic current can be led off from the PIG. 119. — Schematic. /. A drop of liquid in which the chemical processes are alike at all points is without a current. //. A drop of liquid in which at two different points chemical pro- cesses of different kinds occur gives a current. The large circle is the drop of liquid, the small one the multiplier with the magnetic needle ; the two are united by wires. points to the outside (Fig. 119, //). The conditions under which a galvanic current can appear may be expressed, therefore, as follows : A current can be led off to the outside from a physical system when chemical processes take place in it that produce differences in the electric charge at the two leading-off points. This proposition is valid for living as well as for lifeless substance. The living substance of a cell is a drop of liquid in which complex chemical transformations continually take place. If these be alike at all points of the cell, no current can be led off (Fig. 120, /); if, however, they be qualitatively or quanti- tatively different at two different poles, so that differences in the electric charge appear, a tension between the two poles results : and if these could be joined together by a conductor, a current would be obtained in the closed circuit. Naturally, this experi- ment cannot be performed upon a single cell on account of the ELEMENTARY VITAL PHENOMENA 267 minuteness of the latter, but the rule must hold good as well for the cell-complex, the tissue. As a matter of fact it may be demonstrated in the latter, and Herman's " differential theory " ('67 — '68), according to which a current may be led off from a tissue (muscle, nerve, mucous membrane, etc.) only when differ- ent processes are taking place at the leading-off points, is merely the expression of the actual relations. In a resting uninjured muscle, e.g., the sartorms of the frog, which is the best object for demonstrating the truth of this, no current is present, because the same internal processes are taking place at every point (Fig. 121). If, however, at two points in the muscle a difference be produced artificially by warming one point, by cutting the muscle across, which is associated with a local decomposition of living substance, or by making a contraction- wave pass over the muscle, an electric current is obtained; the warmed, dying or contracting part becomes negative to all other parts. Tissues FIG. 120.— Schematic. /. A cell in which at all points of the living substance similar chemical processes are taking place is without a current. //. Polarised cells (e.g., cells of mucous mem- brane) in which at one pole chemical processes are present that differ from those at the other give a current. whose cells do not possess polar differentiation never show a current in the undisturbed condition, but relatively strong currents can be led off always from glands and mucous membranes, even when undisturbed ; here the cells are polarised in such a manner that the lower part of the cylindrical cell-body contains different substances and transformations of substances from the upper part (Fig. 120, II). The fact discovered by Mendelssohn is interesting, that an excised nerve, when led off from both cross- sections, shows an axial current which runs in a direction contrary to the nerve-conduction, i.e., in motor nerves centripetally, in sensory nerves centrifugally. All such currents may be demonstrated, like those arising ther- mometrically, by means of the multiplier or the galvanometer (Figs. 115 and 116, p. 259). But a special arrangement of the leading-off electrodes is necessary to avoid false results. If a current be allowed to pass for a time through a wire, the ends of which dip into a moist conductor, electrolytic decomposition- 268 GENERAL PHYSIOLOGY products of the moist conductor appear at the two ends of the wire, the electrodes, and accumulate there. The precipitation of these products at the two poles produces an electric tension that leads to a current, the so-called polarisation-current, flowing in a direction contrary to the original one. It is evident that the stronger the polarisation-current becomes, the more must the intensity of the original current be thereby diminished. If, therefore, a current be led off from a living tissue by means of metallic electrodes, after a short time a polarisation-current •appears that completely obliterates the tissue-current. In order to avoid this inconvenience, so-called non-polarisalle electrodes have been con- structed, which consist of non-metallic conductors. The most convenient of these non-polarisable electrodes are the brush electrodes suggested by Fleischl, which consist of a glass tube closed at one end by a stopper of plastic clay, and filled with a concentrated solution of sulphate of zinc. A short, soft, pointed camel's-hair brush is stuck into the stopper, and into the solution of zinc sulphate there is dipped an amal- 111 gamated zinc rod, to which the wire is fastened (Fig. 122). The brushes of two such electrodes, each of which is attached to a movable stand, are laid upon the FIG. 121.— "-1- — .——...- ?^f Aj^iJd^St^ that In this manner *he disturbing pheno- is without a current. //. when mena of polarisation are avoided. injured (cut across), it shows a T j i i j • i i •• current the injured place being In the electrical phenomena ot most SSon ^KJSSS^ animal- and a11 Plant-tissues the currents the right through the muscle), it are alwavs so feeble that especially sensi- shows a current ; the active place . •/ . r _ , . J . , is negative. tive apparatus is necessary for their de- monstration ; but in the interesting elec- trical fishes there are currents of extraordinary strength, although the well-known tale of Alexander von Humboldt, that the South American electric eel is able to stun horses by its shocks must rest upon an error. In contrast to the currents of other tissues, those of the electric fishes are characterised chiefly by their short duration and great intensity ; they appear as brief, strong electric shocks, which can be given off by the animal several times in succession, either spontaneously or upon stimulation. This is comprehensible when it is considered that the production of electricity in these animals serves as a means of defence, which has become differentiated to this great efficiency during the evolution of the race. In accordance with this fact special ELEMENTARY VITAL PHENOMENA organs are developed in the electric fishes for the production of electricity alone. It is most interesting that these electric FIG. 122. — Non-polarisable electrodes. 1. Two non-polarisable electrodes laid upon an excised gastrocnemius muscle of the frog. //. A non-polarisable electrode in its stand. organs have the same embryonic origin as cross-striated muscles, to which also in their adult state they possess great similarity. FIG. 123. — /. Torpedo marmoratus ; the skin is partially cut away so that the electric organ, a, is visible ; it consists of numerous polygonal columns, which are here seen in cross-section. (After Ranvier.) //. Two electric columns from the torpedo seen en face with the electric nerves branching over them. (After R. Wagner.) The electric organ of the torpedo is composed of numerous long columns, hexagonal in cross-section, which correspond to- 270 GENERAL PHYSIOLOGY muscle-fibres (Fig. 123). Each of these columns is composed of transverse discs lying symmetrically upon one another (Fig. 124, A) ; these are exactly homologous with the cross-striation of the muscle- fibre, but do not possess doubly refracting elements, and do not undergo changes of form during activity. Still greater is the correspondence in structure of the electric columns and cross- striated muscle in the half-electric or pseudo- electric fishes, e.g., Raja clavata (Fig. 124, B). A very interesting and obvious change iftfi nwiwi FIG. 124. — A. Two electric columns of Gymnotus electricus. (After Schultze.) B. I. Columns from the pseudo-electric organs of Raja clavata. II. a and b. Single segments of I, more strongly magnified ; the left half in ordinary light, the right half in polarised light. (After Engel- mann.) of function is here presented, for the electric organs develop out of genuine, contractile, cross-striated muscle-fibres ; and, as contrac- tility is lost, the electric properties come into greater prominence. The similarity with the muscle is also evident during the activity of the completely-developed organ; for just as the muscle in a single twitch gives only a brief current, so in the electric organ the current is momentary, although of incomparably greater strength. ELEMENTARY VITAL PHENOMENA 271 The above picture of the transformation of energy in living substance is as incomplete as was that of metabolism. As in the latter, so in the former, only the beginning- and the end- components of the series are known. Energy enters the living body as chemical energy, light and heat. Light and heat are consumed in providing more chemical energy — light in splitting up in plants carbonic acid, which has in itself very slight value in respect to energy, into atoms of carbon and oxygen possessing free affinities, heat in causing a re-arrangement in the labile compounds of living substance by an increase in intensity of the intramolecular vibrations. Chemical energy is, therefore, the source of all other forms of energy in the organism ; by its transformation there are derived mechanical energy, light, heat, and electricity. In the same proportion in which these are given out by the organism, chemical energy disappears. Hence the end-products of life, carbonic acid, water, ammonia, etc., possess extremely little chemical energy ; into such the introduction of new energy from the outside, in both light and chemical substances, is necessary, in order to make available in the plant new potential energy in the form of free affinities. These are the beginning and the end •of the series. But what in detail are the complex transformations in the living body, what forms of energy in each special case proceed directly from the introduced energy, what intermediate .and retrograde changes the chemical energy passes through, until it leaves the body again in the form of mechanical movement, light, heat and electricity — these are subjects that in great part .are still obscure. More light may be expected here with the advance of knowledge regarding the more special metabolic processes, for the transformation of energy cannot be separated from metabolism. For convenience, in this chapter, the phenomena of changes of substance, of form, and of energy have been considered separately. In reality, these three groups cannot be separated from one another, for the possession of form and energy belongs to the essence of •substance. Every change of substance is at the same time a change of form and energy. This is inherent in the nature of our conception of matter, and applies to living as well as lifeless matter. What has been treated separately under these three heads is one and the same event merely looked at from different points of view. In brief: All vital phenomena of a body are the expression of a .continual change of the substance of which it consists. CHAPTER IV THE GENERAL CONDITIONS OF LIFE THE living substance of organisms forms a part of the mass of matter that composes the earth. As has been seen, the differences between it and lifeless substances are not fundamental in nature, for the elements that constitute the former constitute also the latter. The differences between organic and inorganic substance are no greater than the differences between many inorganic sub- stances, and consist merely in the mode of union of the elements. It is important to familiarise ourselves with the thought of living substance, not as something mystical, which has no connection with and stands in contrast to all other substance, but as a part of the matter that constitutes the earth's crust. It is evident that life is conditioned wholly by the character of the environment, that the evolution of living substance must be inseparably connected with the evolution of the earth. Accordingly, the composition and the form of the living substance that now covers the earth's surface are to be considered from exactly the same point of view as, for example, the composition of the present sea, i.e., as something that has gradually become, and exists in its present state only because the conditions are such as they are at the moment. Just as the sea with its salt could not have existed as it does now before the water had appeared upon the earth in a liquid state, so also living sub- stance could not then exist with its present composition, for it contains upon an average more than fifty per cent, of water. But just as water was obliged to assume its present form when certain conditions in the earth's evolution were fulfilled, so living substance was obliged gradually to take on its present character to the extent to which the present conditions of the earth's surface were per- fected. The separation of living substance out of the mixture of materials of the earth's crust is only one result of the earth's evolution, like the separation of rocks, salts, or water. The same idea is arrived at from another starting-point, when, not the elementary composition, but the, vital phenomena of living substance are considered. It is an error easily conceived and due THE GENERAL CONDITIONS OF LIFE 273 to superficial impressions to consider the organism as a closed system, independent of its environment. The fact of metabolism shows this at once ; for, if the organism lives only so long as it takes in matter from the outside and gives off matter to the outside, it stands in the closest dependence upon the external world ; the latter conditions its life. Thus arises the conception of conditions of life, i.e., conditions that must be fulfilled in order that the life of the organism can exist. It is evident that every change of such conditions must exercise an influence upon the life of the organism. Hence, in order to complete a picture of the mutual relations of the organic world and its conditions, it is necessary not only to investigate the latter as they are now, but, so far as possible, as they were in the earlier periods of the earth's evolution. A few fixed points may thus be obtained for the consideration of the question of the origin, the descent and the evolution of life upon the earth. I. THE PRESENT CONDITIONS OF LIFE UPON THE EARTH'S SURFACE All the conditions of life are not equally necessary for all organisms living at the present time. What is absolutely necessary for the existence of one organism may even endanger the life of another. Marine animals when brought into fresh water soon die, and fresh -water animals placed in sea- water experience the same fate. This principle holds good not only for large groups of organisms but for every individual form as well. Every individual organism requires for its existence definite special conditions, without the fulfilment of which it cannot continue to live. These special conditions of life are as manifold as the innumerable forms of organisms themselves. -To describe them is to describe the natural history of every organism, and their investigation belongs to the field of special physiology. But in contrast to them there are other requirements that must be fulfilled for all organisms if the latter are to live, and these must, therefore, be termed general conditions of life. General physiology deals with the latter. In the following pages we shall be able to glance at the special conditions only momentarily, when they are of particular interest and present peculiar adaptations of living substance to peculiar circumstances. It is usual to consider under conditions of life only external factors, such as food, water, oxygen, temperature, etc. But in contrast to these external conditions there are internal con- ditions, which are inherent in the composition of the organism, and the absence of which, like that of the external factors, is followed by death. T 274 GENERAL PHYSIOLOGY A. THE GENERAL EXTERNAL CONDITIONS OF LIFE 1. Food The presence of food is required by the fact of metabolism. If living substance is continually undergoing spontaneous destruction, then, in order that it may continue to live, a stream of substances must come into it from the outside, which comprise all those chemical elements that are necessary to its construction. Such chemical substances constitute food. Accordingly, water and oxygen belong to the general conception of food ; it is not customary, however, to include them therein. Following the usage, we shall consider them separately, and shall take up, first, food in the more special sense. The twelve organic elements of which all living substance is composed (p. 100) must come into the body of the organism in some form as food. In this lies the general significance of food. But the chemical compounds in which these elements are intro- duced into the body are as manifold for the various forms of organisms as the organisms themselves. A general food for all organisms does not exist; and it has already been seen1 that according to the kind of food-stuffs and the manner in which living substance is constructed from them, organisms may be divided into several large groups, such as green plants, fungi and animals. While the green plants are able to construct their living substance out of inorganic material only, carbonic acid and solutions of various salts, animals without exception require organic food, and cannot live without complex organic^ compounds, such as proteid, carbohydrate, fat, etc. The fungi stand in a certain measure between these two groups, since they can supply their need of nitrogen from inorganic salts, although they require organic compounds for their carbon. An exception to this condition is shown by the interesting nitrogen-bacteria only, which derive both their nitrogen and carbon from ammonium carbonate, and thus like the green plants live exclusively upon inorganic food-stuffs. But, however in individual cases food may be procured, without food of some kind no living body can continue to live. Regarding quantitative conditions of food, the maximum and the minimum of food that the living body requires, which is different for every form of organism, only a few special cases have been investigated thus far, and these are among the higher vertebrates exclusively. These are questions that still require detailed answer, and, if treated from the cell-physiological stand- point, are capable of yielding results equally important theoretic- ally and practically. Thus far individual values for the whole 1 Cf. p. 138. THE GENERAL CONDITIONS OF LIFE 275 organism have been obtained in the case of men only. Voit ('81) has shown that an adult man performing active work can subsist upon a daily food comprising 118 grs. of proteid, 56 grs. of fat and 500 grs. of carbohydrate. With such a diet the man is in metabolic equilibrium, i.e., the quantities of elements excreted in the urine, the sweat, the expired- air, and the faeces are equal to those that are introduced with the food. But, more specifically, these values for the individual elements, such as nitrogen, carbon, etc., introduced with the food must be determined separately, since the body when, e.g., in carbon equilibrium is not necessarily always in nitrogen eqidlibrium. It is thus found that nitrogen equilibrium can be obtained with a quantity of proteid of only 50 grs. (which corresponds to 7*5 grs. of nitrogen), provided only that the quantity of the non-nitrogenous food-stuffs, carbohydrates and fats, is correspondingly increased. 7 '5 grs., therefore, would correspond to the daily minimum of nitrogen with which a man can continue to exist. The minimum of food necessary to the maintenance of meta- bolic equilibrium and life is of great importance. If the income of food rises above the minimum, metabolic equilibrium is disturbed only in a very slight degree, slightly smaller quantities of elements appearing in the excreta than are taken in with the food. These very small quantities remain in the body and serve for the increase of living substance and the storing up of reserve - substances, a phenomenon that in husbandry is termed fattening. But this depends upon many factors, which are as yet known exactly only in part. If, on the other hand, the quantity of food falls below the minimum or becomes zero, the condition of hunger or inanition appears, in which the metabolic equilibrium becomes more and more disturbed. This condition has been investigated more fully. It is worth while to follow somewhat fully the changes experienced by the living organism in the condition of inanition. Every living cell under normal conditions possesses within itself in greater or less quantity substances at whose expense the vital pro- cess continues for a time if the food-supply be cut off. These are its reserve-substances. It is a general fact that during inanition the reserve-substances disappear first. Plant-cells that are filled with starch grains consume these when they are brought into the dark, i.e., when they are forced to hunger, for in the dark no assimilation of starch from carbonic acid and water, in other words, no nutri- tion, takes place. Infusoria, whose cell-bodies in their infusions, where they revel in a superfluity of food, contain all sorts of particles, and hence appear opaque and granular, become clear, transparent and free from granules, when placed in water containing little food-stuff; their cell-bodies become gradually smaller (Fig. 125). The cell, therefore, does not die immediately T 2 276 GENERAL PHYSIOLOGY at the moment of the withdrawal of food, but lives for some time at the expense of the materials of its own cell-body. If these be consumed, it gradually perishes, just as a clock that is not wound up gradually runs down and then stops. The phenomena of inanition have been studied most carefully in compound multi- cellular organisms, especially vertebrates, and an important task in this field is left for cell-physiological investigation. Since it is a characteristic peculiarity of living substance that it is continually undergoing spontaneous decomposition, it is clear that in fasting animals metabolic equilibrium must be disturbed. In the decomposition-products of living substance, nitrogen, carbon, hydrogen, oxygen, etc., are continually being excreted, while there is no new individual cell so in income. The result is that, as in the the multicellular organism, the living- substance is gradually consumed and the organism decreases in weight. The animal lives for some time upon its own tissues. It is, therefore, conceivable that as regards their excreta fasting herbivora are like carnivora. The urine of herbiv- ora, which during normal nutrition is alkaline and . turbid, becomes during inanition acid and clear like that of carnivora ; for during inanition herbivora live upon their own, that is, upon animal tissue, and hence in a certain degree become carnivorous. The living sub- stance gradually consumes itself, until the body- weight has undergone so great a loss that the animal dies. By many experiments Chossat ('43) established this limit of decrease of weight, and found that with widely different animals death appears when the loss of weight has reached approximately O4 of the whole body-weight. This limit is reached by different animals at very different times. Frogs live longer than a year, and Proteus anguineus, a peculiar amphibian of the Adelsberg grotto, lives several years without food. Man dies in a relatively short time. In earlier times opportunities for investigating human beings who were fasting for a long time were rare, and the early results are to be accepted with caution. Thus, in the year 1831 in Toulouse a convict, who would take only water, is said to have died only after sixty-three days. In later times, with the appearance of the professional faster physiologists have had more frequent opportunity for making exact investigations on fasting men. Luciani ('90) has produced a striking monograph upon fasting, based upon investigations of the well-known Succi, who undertook a thirty FIG. 125. — Cotpidium colpoda, a ciliate-infusorian cell, a, In the normal condition ; b, in the con- dition of inanition. The cell- body has become smaller and more transparent, and the gran- ules in the interior have disap- peared. Magnification in both 260. (After observations and drawings by Jensen.) THE GENERAL CONDITIONS OF LIFE 277 days' fast under his charge. By this case it is proved beyond doubt that under favourable conditions a normal man can exist at least thirty days without food. The different tissues partake in the loss of weight of the body in very different degrees. While the cells of many tissues become affected greatly and very rapidly, those of others experience only slight changes. This is shown by the following experiment of Chossat. Two pigeons of the same brood, and of like size, sex, and weight, are employed. One is killed at once, and its individual tissues are weighed. The other is allowed to fast until it dies, and then its tissues are likewise weighed. In this manner what- ever changes of weight that the individual tissues have experienced during inanition are determined. It is thus found that fat-tissue has lost approximately 93 per cent, of its weight, the tissue of the spleen, the pancreas and the liver 71 — 62 per cent., that of the muscles 45 — 34 per cent., that of the skin, the kidneys and the lungs 33 — 22 per cent., that of the bones 17 per cent., and that of the nervous system only about 2 per cent. Fat-tissue is, there- fore, the most affected, the nervous system the least. Of course this difference in the increase in weight of the individual kinds of tissues or cells is not to be regarded as depending solely upon a different rate of decrease on the part of each kind of cell by the cessation of the income of food-stuffs. Luciani, rather, holds rightly the view that another factor in addition plays a role, viz., that among the different tissue-cells a contest over the food takes place, such that some cells seize upon the reserve-substances present in the body more greedily than others, and, after their consumption, appropriate also the material of the other cells in order to maintain their metabolism. This is indicated at least by an interesting observation of Miescher-Rusch ('80). When salmon migrate from the sea up the Rhine they are strong, muscular animals in good nutritive condition. During their stay of six to nine months in the river they fast. Their muscles, especially those of the back, decrease enormously in volume, while the sexual organs develop extraordinarily. Here, therefore, a struggle for existence between the tissue-elements of the sexual organs and those of the muscles takes place, in which the former prove superior and appropriate the substance of the latter for their own needs. Likewise between other tissue-elements in other animals in the condition of inanition, a struggle for existence takes place, although not in so remarkable a manner as in the salmon. The final result of all fasting is always death. The clock finally runs down if it is not wound up. The assertion that death is the ultimate outcome of fasting requires a certain correction. It is true of organisms only so long as they continue in the condition of actual life. Organisms in the state of latent life, such as dried Rotifera, Tardigrada, spores of 278 GENERAL PHYSIOLOGY bacteria, and seed-grains, require no food ; for, as has been seen,1 no metabolism can be found in them even with the most delicate means of investigation. Hence, when food is wanting in their environment, they do not die. Here the clock has merely stopped, it has not run down. In order, finally, to obtain an idea of the far-reaching adapta- tions of individual organisms to special vital conditions of a very unusual kind, so far as they have to do with food, it is necessary only to glance at the peculiar vital relations of certain forms of Bacteria, which have become known recently, especially through the striking work of Winogradsky ('88). The sulphur-bacteria (Beggiatoa) constitute a family of microbes that live in decaying pools and puddles of both fresh and salt water. These remarkable beings, which swarm about in the water in the form of short rods or long threads (Fig. 126), can exist only when considerable quantities of sulphuretted hydrogen are available. Their metabolism requires this gas, since they manufacture from it, by oxidation, free sulphur, which they store up in their tiny cell-bodies in the form of fine, strongly refracting granules (Fig. 126) ; by continued oxidation they transform the sulphur further into sulphuric acid, and in this form excrete it to the outside. If the sulphur-bacteria be brought into spring- water that contains no sul- phuretted hydrogen, they perish after they have oxidised and excreted the sulphur present in their bodies. Sulphuretted hydrogen, a gas that is poisonous to most organisms, belongs, therefore, among their essential conditions of life. Without it they cannot continue to exist. Winogradsky ('88) has pointed out a similar special adapta- tion to peculiar vital conditions in the iron-bacteria. Bog iron- ore moors are very generally known, occurring wide-spread in marshy regions, with an oily, iridescent scum upon the surface of their water and thick, reddish-yellow mud below. These are the abode of the iron-bacteria, and the production of bog-ore is in 1 Of. p. 132. FIG. 126. — Various forms of sulphur- bacteria. The granules in the interior are particles of sulphur. (After are parces o sup Schenk and Warming.) THE GENERAL CONDITIONS OF LIFE 279 part their life-work. They require for their metabolism ferrous carbonate, which is dissolved in the water. They absorb this and oxidise it into ferric carbonate, which they give off to the outside. The excreted ferric carbonate in time passes over into simple ferric oxide, which is insoluble, and forms a yellowish- brown precipitate upon the gelatinous covering excreted by the bacteria, in which their bodies lie. If the iron-bacteria be culti- vated without ferrous carbonate, their vital phenomena become gradually feebler and finally come to a complete standstill. Hence the presence of this substance belongs among the conditions of life of these remarkable microbes. These examples suffice to show how peculiar may be the special conditions of life among different organisms as regards food. This is not the place for their further consideration ; they belong to the province of special physiology. 2. Water Living substance is liquid. It is necessary to remember this fundamental physical property. The liquid jelly-like condition of living substance is due to the water that it contains, which fact can be proved easily by evaporating the water. Only liquid, not solid masses, only substances that contain water can be living, for only with the liquid state is metabolism compatible. Hence in the organism all substances that are solid and hard, such as the con- nective tissues of the teeth and the bones, are not living. Similarly, vital activity is lessened along with the withdrawal of water. In dried Rotifera and Tardigrada, and in dried seeds, no vital phenomena can be perceived. Life begins to manifest itself only when the seeds are made to swell by the addition of water, only when the substance of their cells becomes again liquid. Water, therefore, belongs to the general conditions of life. This conclusion is very simple and clear. But there are cases where, even in places of the greatest drought, organic life continually exists. In spite of their dryness the waste, burning deserts of Arabia and Africa, which present to the traveller most powerfully impressive pictures of eternal lifelessness, and whose sands are moistened scarcely once in a year by showers of rain, harbour manifold varieties of animals and plants. This apparent exception depends upon the fact that all desert-organisms are peculiarly adapted to life in long drought, and they manage ex- tremely frugally and economically with the little water that comes to hand at long intervals of time. One is astonished in the driest desert to come upon green plants that contain abundant juices, plants (Mesembryanthemum crystallinum) beset over and over with cells, which harbour such quantities of clear water that the latter 280 GENERAL PHYSIOLOGY appear like small crystal droplets (Fig. 127). These desert-plants have a remarkable power of retaining water, either by storing up in their cell-sap soluble substances that possess great attraction for water, or by being covered over their whole surface with a fine layer of wax, so that with the stomata closed scarcely a trace of water can pass by evaporation out of the plant-body. Moreover, they possess usually much-branched roots extending very far and superficially in the soil, and these greedily suck up every trace of water that moistens the earth. The desert-animals also, such as the snails, FIG. 127. — Mesembryanthemum crystallinum, a desert-plant from Southern Africa. The whole stem and the under side of the leaves are beset with clear crystal-like water-cells. which are confined to their dry home because of their slight powers of locomotion, protect themselves by limiting their excretion of water to a minimum. The snails close the opening of their shells with a thick, double cover, so that scarcely a trace of water can be lost from the body by evaporation. Hence, in all these cases the dryness of the environment does not extend to the living sub- stance of the organisms. On the contrary, here, as everywhere, the living substance is liquid, and in fact all desert-organisms have an actual, not a latent, life, although their life is depressed to a minimum. They show directly how the intensity of life increases THE GENERAL CONDITIONS OF LIFE 281 and decreases with the rise and fall of the water-contents. If a slight shower of rain comes, activity immediately begins, the plants grow and bloom, and the sluggish animals awake from their summer sleep. In a manner somewhat different from that of the desert-plants and animals, other organisms which at times are obliged to undergo a lack of water are adapted to life in drought, since at such times they assume a quiescent phase and are protected against drying. Such quiescent phases occur especially among unicellular organ- isms, as m the spores of Bacteria (Fig. 128) or the cysts of Rhizopoda and Infusoria (Fig. 84, p. 205), which enclose the living cell-substance in a thick, completely impervious skin. FIG. 128. — Bacillus butyricus, forming spores, a, Beginning of the process ; b, ripe spores still within the bacilli ; c, spores after the dissolution of the membrane of the mother-cells ; d, spores beginning to germinate and to allow the bacilli to come forth. (After Mjgula.) The seeds of plants likewise belong to these permanent conditions of organisms. But in all these cases life is latent ; no trace of vital phenomena can be demonstrated in them by means of the most delicate methods. It would appear that in all such cases life stands still, like a wound-up clock that has been suddenly stopped. From these facts the importance of water for the maintenance of life is evident. Without water life cannot exist. With the increase and decrease of the water- contents of living substance within certain limits the intensity of life rises, falls, and becomes zero. 3. Oxygen It was Priestley, the discoverer of oxygen, who recognised the fundamental importance of this gas for life upon the earth ; by his epoch-making discovery of the gas and its properties he gave a real background to Mayow's ingenious comparison of respiration with combustion. In respiration free oxygen is taken up by the living substance, and in return carbonic acid is given off; hence a combustion, an oxidation of carbon, must take place in the 282 GENERAL PHYSIOLOGY living substance. If, therefore, as has been seen,1 all organisms without exception respire as long as they live, i.e., if the processes of oxidation are an integral link in the chain of metabolic pro- cesses, it necessarily follows that the presence of oxygen belongs to the general vital conditions of living substance. As is well known, the composition of the atmosphere, as regards its essential constituents, is as follows : Nitrogen and argon, 79'02, oxygen 20'95, carbonic acid 0*03 volumes. This composition is essen- tially the same at all times and all places upon the earth's surface. If, therefore, land organisms be considered — and upon them have been made the greater number of the investigations regarding the dependence of living things upon oxygen — it may be said that they live continually in an atmosphere in which in round numbers 21 per cent, of oxygen is present. The striking investigations of W. Mliller and Paul Bert have, however, shown that organisms are not bound exclusively to this percentage and the pressure of one atmosphere, but within certain limits are independent of the partial pressure of oxygen. W. Mtiller ('58) found, for example, that mammals can continue to exist with 14 per cent, of oxygen, they begin to be disturbed at 7 per cent., while at 3 per cent, death by asphyxia takes place ; on the other hand, they thrive in pure oxygen at a pressure of one atmosphere. In like manner a series of experiments published by Paul Bert ('73) shows in animals a far-reaching independence of the partial pressure of oxygen. In atmospheric air animals can still exist with a minimal pressure of about 250 mm. mercury and with a maximal pressure of fifteen atmospheres ; in pure oxygen the minimum of pressure is considerably lower, but a pressure of two atmospheres for plants and of three atmospheres for animals is fatal. In general, it follows from the experiments of Paul Bert that the effects of a too small percentage of oxygen can within certain limits be compensated for by a rise of pressure, and the effects of a too high pressure by a fall of the percentage. The remarkable fact that organisms in pure oxygen with too high partial pressure die, and, as Paul Bert has shown, die of asphyxia, has been made clear by Pflliger ('75, 1), by means of an analogy between living substance and active phos- phorus. As is well known, in atmospheric air phosphorus becomes oxidised actively, gives out light, and evolves fumes of phosphorous acid, while in pure oxygen it is not oxidised at all. So living substance in pure oxygen with a high pressure ceases to oxidise, and hence appears the paradoxical phenomenon of death by asphyxia in pure oxygen. The minima and maxima of the percentage and the partial pres- sure of oxygen are very different for different organisms, and thus far are known only in a few cases. These details are of little 1 Cf. p. 141. THE GENERAL CONDITIONS OF LIFE 283 interest here. It is, however, interesting to glance at the results of complete removal of oxygen. The final results of complete removal of oxygen are evident. If oxygen be a general condition of life, all living substance must perish after its complete withdrawal. This has been shown by experiments that have been performed partly upon single cells, partly upon tissues, and partly upon multicellular organisms. But different kinds of cells perish after different intervals of time, some very rapidly, some gradually, just as do different organisms upon withdrawal of food. The cells of the nervous system are FIG. 129. — /. Engelmann's gas-chamber. An annular space is closed below by a glass plate and above by a metal cover, the latter having in its middle a cover-glass for the examination of a hanging drop ; a,a', are tubes that open into the cavity of the ring and serve to heat the latter by conveying through it warm water ; b,b' are tubes that open into the glass-covered chamber and serve for the passage of the gas ; the drop hanging upon the cover-glass with its living contents is bathed by the gas in the chamber. II. Arrangement of the experiment for in- vestigation in pure hydrogen, a, Kipp's apparatus for the preparation of hydrogen ; b, two wash-bottles for purifying the hydrogen ; c, microscope, upon which is the gas-chamber con- taining the hanging drop. the most sensitive to absence of oxygen. Hence without oxygen the higher vertebrates, in which the movements of respiration, the activity of the heart, etc., are dependent upon the cells of the nerve-centres, perish very soon with violent phenomena of stimu- lation. Other kinds of cells, however, continue to live for a considerable time even in a medium wholly free from oxygen. By the use of hydrogen, a gas absolutely indifferent to the organism, oxygen may be readily and completely excluded with- out introducing into the experiment other harmful factors. Since in a closed space atmospheric air, in which oxygen is the sole 284 GENERAL PHYSIOLOGY effective constituent, at least for animal-cells, can be very easily removed and replaced by hydrogen, it is only necessary to prepare chemically pure hydrogen by means of Kipp's apparatus and con- duct it through a closed gas-chamber. The most convenient gas- chamber for microscopical investigations is that devised by Engelmann (Fig. 129, /). The cells to be investigated are placed in such a chamber and observed in a hanging drop of the liquid in which they live. By a series of experiments Kiihne ('64) has shown that after replacing the air by hydrogen Amoeba gradually suspends its movements after about 24 minutes. From this condition it can be brought back to life by a renewal of atmo- spheric air. But, if it remains for some time longer in the absence of oxygen, it dies. The movements of large plasmodia of Myxomycetes in a medium free from oxygen often cease only after three hours, and later the plasmodia die. For the study of the question how the two phases of contraction- movements, namely, expansion and contraction, are influenced by the withdrawal of oxygen, the most favourable objects are marine Rhizopoda, possessing long pseudopodia, over which the movement of each particle of protoplasm is extended for a very considerable distance. Such a one is Ehizoplasma Kaiseri, a naked rhizopod possessing a nuninucleated, orange-red cell-body , from which radiate out in all directions fine, anastomosing pseudopodia, in which the protoplasmic streaming is uncommonly active (Fig. 130, /). If a Rhizoplasma l be placed in the Engelmann gas-chamber and a current of oxygen be passed through, after one and a half to three hours the effects of the withdrawal of oxygen become noticeable. The centrifugal current in the protoplasm, which before was very active, so that the pseudopodia were extended, becomes feebler and feebler and finally ceases. But the centripetal current con- tinues for a while longer, so that the pseudopodia slowly shorten : gradually, however, the centripetal current also diminishes and soon is scarcely noticeable. The protoplasm has accumulated, at the places where the pseudopodia branch, into tiny masses, which are not spherical and spindle-shaped, as when contracted because of strong stimulation, but are more pointed, angular and toothed. In this form the Rhizoplasma is finally completely motionless (Fig. 130, 77). Specimens possessing shorter pseudopodia finally draw them completely in. Hence, by the withdrawal of oxygen, the phase of expansion (the centrifugal protoplasmic streaming) first comes to a standstill, and then gradually the phase of contraction (the centripetal protoplasmic streaming). If now atmospheric air be introduced, after about five minutes tips of new pseudopodia begin to project from the central cell-body. After about ten minutes, active streaming is again apparent upon the old pseudopodia. A new current from the centre appears upon them, 1 Cf. Verworn ('96, 3). FIG. 130.— Rhizoplasma Kaiseri. I. formal individual, with extended pseudopodia and active proto- plasmic streaming. //. Standstill of the protoplasmic movement after the withdrawal of oxygen ; the protoplasm forms small, angular accumulations at the places where the pseudo- podia branch. 286 GENERAL PHYSIOLOGY and the small accumulations of protoplasm break up, their sub- stance flowing partly centrifugally, partly centripetally. In this manner the pseudopodia again become smooth, their streaming becomes more active, and after a half-hour the same appearance is present as at the beginning of the experiment. Engelman was able also to determine that ciliated cells are capable of maintaining life for several hours without oxygen. Hermann ('67-'68) has shown the same for muscle by placing one of two exactly similar gastrocnemius muscles of the frog in a cylinder containing pure hydrogen, the other in a cylinder filled with air containing oxygen, and testing their irritability by means of electric stimuli, which both muscles received at the same time. The muscle in pure hydrogen lived several hours before becoming inexcitable, while the muscle in oxygen continued to live unchanged. From all these experiments it follows that certain cells and tissues can maintain life for a considerable time in a medium free of oxygen. This fact, especially in regard to muscle, has been variously employed as the basis of an unjustified conclusion. Since Hermann has shown that no free oxygen can be extracted by means of the gas-pump from an excised bloodless muscle, the inference has been drawn that muscle, while able to perform movements for a long time without external oxygen, works solely by means of cleavage-processes. This conclusion is unjustified, since, from the fact that no free oxygen can be pumped out of a muscle, it ought not to be inferred that no oxygen whatever capable of being used for oxidation is longer present in the muscle. On the contrary, it is very probable that in the muscle, perhaps in the sarcoplasm, there exists in combination oxygen that during activity is continually being consumed by the contractile particles for their oxidisation. As a matter of fact, haemoglobin has been found in the muscles of some invertebrates that possess in their blood no hemoglobin whatever. It must hence be supposed that in cells that continue to live for a long time in the absence of oxygen, oxidation-processes still take place, certain complexes of atoms of the living substance withdrawing the oxygen for their own oxidation from others that contain it in loose combination, until finally all the oxygen is con- sumed and combined into the cleavage-products. However this may be, in the absence of oxygen all living organisms perish after a shorter or longer time. Without oxygen no life can exist permanently. There are some apparent exceptions to this principle ; there are organisms that apparently can continue to live without oxygen. At first sight the green plants appear to form such an exception, and at one time they were really believed to do so. In one respect THE GENERAL CONDITIONS OF LIFE 287 these plants are the exact reverse of animals : they take up carbonic acid and give off oxygen. So long as the sunlight acts upon their green leaves, they need no oxygen. A green plant, therefore, can be kept alive in a space free from oxygen, if it be allowed to stand in the light and receive carbonic acid. But this taking-in of carbonic acid and giving-out of oxygen is not the plant's respiration. In reality, as has already been seen,1 the plant like the animal inspires oxygen and expires carbonic acid. This fact is simply disguised by the process of assimilation. During the night, how- ever, when assimilation ceases in the darkness, the plant inspires oxygen and expires carbonic acid ; and, if it be cultivated in a closed space, it lives during the night upon the oxygen that it has set free during the day by the cleavage of the car- bonic acid that it has taken in. The process of assimilation of carbonic acid is, therefore, to be sharply separated from that of respiration. The two phenomena are entirely distinct from one another. But in a peculiar kind of organ- isms, the so-called Anaerobia, the relations are even much less clear than in the plants. The Anaerobia are organisms, belonging chiefly to the Bacteria, that can continue to live with complete absence of oxygen. Many of them even perish when they come in contact with free oxygen. Since Pasteur, the father of Bac- teriology, first asserted the reality of such rare beings, their actual existence has frequently been doubted, but there is no longer any question of the correctness of this claim. Thus, e.g., the bacteria of symptomatic anthrax and of tetanus grow anaerobically (Fig. 131). So, also, the vibrios of cholera are able to live admirably in alkaline nutrient media with absence of air ; under these conditions they increase rapidly in the intestine, where scarcely a trace of pure oxygen exists. This fact is the more remarkable since when brought into contact with air 1 Cf. p. 173. FIG. 131.— A, Culture of the bacteria of symptomatic anthrax. (After Migula.) The spherical colonies lie in the interior of nutrient gelatine excluded from the air. J3, Culture of the bacteria of tetanus. The bacteria have liquefied the lower part of the nutrient gelatine in the test-tube and have formed a bubble of gas, which lies at the upper end of the liquefied mass. They have grown only in the lower parts of the test-tube, separated from the air by a thick layer of gelatine. 288 GENERAL PHYSIOLOGY they show themselves to be unusually greedy for oxygen. Since it cannot be supposed that without oxygen they are capable of increasing so remarkably as they do in the intestine, and since their greed for free oxygen is acknowledged, it must be assumed that they as well as other Anaerobia, such as the bacteria of tetanus and the bacilli of symptomatic anthrax, are capable in the absence of free oxygen of withdrawing oxygen from the salts of the alkalies that occur in their media — in other words, they are able to take oxygen from fixed chemical compounds. This assumption requires experimental proof, and the same may be said also of the other anaerobic parasites of the intestine, which, as, e.g., the thread-worms, according to Bunge's researches ('83), are capable of living in active movement for 4 — 5 days in a medium completely free from oxygen. Finally, organisms in the condition of latent life occupy an exceptional position in respect to oxygen, as to all other vital conditions that bear directly upon metabolism. They require no oxygen, just as they require no food and no water and yet are capable of life. The fact is not unaccountable, for where metabolism cannot be demonstrated, no oxidation-processes are found. 4. Temperature Besides the conditions characterised by the introduction of matter (food, water and oxygen), upon which metabolism directly depends, certain dynamic requirements must be fulfilled, if life is to be maintained. Among them, before all others, is a temperature within certain limits. It is well known that chemical compounds are influenced in a marked degree by temperature. In general, high temperatures lead to the dissociation of compounds that at low temperatures can readily exist unchanged. Living substance is a mixture of numerous chemical substances, among which occur highly complex compounds in an extremely labile condition. It is evident, therefore, that living substance also must be dependent in a marked degree upon temperature, that life can exist only within definite temperature-limits. These limits, the minimum and maxi- mum of temperature, are of course very different for different forms of living substance. Temperatures in which some organisms thrive are fatal for others. It is not necessary here to determine for individual species the higher and the lower limits, but it is important to find out what are the minimum and the maximum at which life in general can exist upon the earth's surface. The observation has frequently been made that poikilothermal animals and plants can be frozen without losing their vital capacity. Thus, in his polar expedition in the year 1820 John Franklin saw THE GENERAL CONDITIONS OF LIFE 289 carps, which, after having been frozen solid, revived and moved about actively upon being warmed before a fire, although in specimens that were killed the intestines were so solid that they could be removed as a single piece. Likewise, by careful warming Dumeril revived frogs that had been frozen solid in water of 4° to 12°; and Preyer ('80), who has collected considerable testimony upon this subject, made the observation that frogs frozen solid could be revived if their internal temperature had not reached 2 '5° C. Romanes made similar observations upon Medusa (Aurelia aurita), whose delicate jelly-like bodies were pierced by abundant, fine ice-crystals. But all these statements are to be accepted with some criticism. The fact is not to be doubted that these animals can be actually frozen solid in ice and yet be revived by careful thawing, but in all the observations it is not certain whether the living sub- stance of the cells themselves possesses a temperature below 0° C. As is well known, all cells produce a certain quantity of heat in their metabolism, and as a result of this when they are frozen their internal temperature is always slightly higher than that of the surrounding ice. It is, therefore, possible that in all the observations the living substance of the cells itself was not cooled to 0° or below 0°. Hence, more exact investigations were needed in order to decide the question whether the living cell itself undergoes without harm cooling of its substance to or below 0° C. Such experiments have been performed by Ktihne, and more recently and in great detail by Kochs. Kiihne ('64) placed upon ice in a watch glass a drop of water containing many amoebae, and found that gradually, in proportion to the cooling, the movements became slower and slower, until finally they ceased altogether and the amoebae lay completely motionless. If the drop were again brought to the usual room- temperature, the movements would begin again ; the amoebae, therefore, were still alive. But the result was different when the drop was frozen. Then, even after warming, the amoebae remained motionless and could not again be revived. More recently, Kochs ('90) performed very detailed experi- ments upon frogs and water-beetles. He froze these animals in glasses containing water. If the temperature was not very low, there remained around the animals, surrounded by ice, a liquid mass of water, the temperature of which was 2° below the zero-point, as was shown by boring through the mass of ice. If, after boring, this last layer of water was frozen, the animals could still be revived by warming, provided that they had not been frozen longer than five to six hours. By sawing through such a preparation it was shown that the animals were not frozen solid internally. But, if the experiment was extended so that the animals were thus frozen, which was the case when they were brought into cold air of 4° C., all attempts at resuscitation were in vain. u 290 GENERAL PHYSIOLOGY In the light of these experiments the assumption that organisms always perish when the living substance of the tissue-cells itself is frozen solid, appeared very highly probable. But in opposition to them recently Raoul Pictet ('93) has established facts in accordance with which our ideas must apparently be wholly changed. This well-known investigator, who has made a number of sur- prising and extraordinarily valuable discoveries concerning the chemical effects of very low temperatures, recently carried out in his laboratory experiments upon the physiological effects of such temperatures. The objects of his experiments were protected by wood from contact with the metal walls of the cold vessel in which they were placed, so that they were exposed to the low temperature of the air only. It was thus shown that different animals behave very differently. Fishes that were cooled down to -15° C. in a block of ice remained living after careful warming, although others in the same experiment could be ground to powder like ice. But upon cooling to -20° C. the fishes died. Frogs endured without dying a temperature of -28° C., myriopods -50° C., snails -120° C., and bacteria even less than -200° C. In view of these surprising experi- ments it can hardly be doubted that in individual cases the living substance of cells can be frozen to ice without losing its capacity of life. These phenomena suggest the question whether in frozen organisms there is really a complete standstill of the vital pro- cesses— a question that Preyer believes must be answered in the affirmative. Theoretically, there is nothing opposed to this idea ; for, when it is seen how with falling temperature the energy of the vital processes constantly decreases, it must be believed that in time a point may be reached where they cease altogether. The possibility that the cell-liquid itself can freeze without abolish- ing the vital capacity of the cell, would support this view ; for, as has been seen, life cannot exist without water in the liquid state. It would be expected therefore, that, as soon as the water in the living substance has passed over into the solid state, the chemical transformations in the cell would be at a standstill. Bub con- clusive experiments for the decision of this question are thus far wanting. If it should be established that living substance in the frozen condition can be maintained for years capable of life, just as certain dried organisms can be so maintained for years, decades, and even centuries, then the probability would approximate to certainty that life in frozen organisms is really at a standstill. At present this is not settled. One fact that is opposed to this idea is the observation made by Pictet, that frozen organisms cannot endure a farther fall of temperature beyond a certain point. Upon thawing they cannot be revived. If life were really at a complete standstill, it would be difficult to understand why THE GENERAL CONDITIONS OF LIFE 291 a farther sinking of the temperature should still be of influence. For the present, therefore, we must forgo a definitive solution of this question. The establishment of the maximum of external temperature meets with difficulties similar to those surrounding that of the minimum. In every case the maximum is represented by the point where the proteids in the living substance of the cell coagulate. The proteids play in the life of the cell the most essential role, and it is conceivable that, when the dissolved albumin passes over into the solid state, metabolism, in other words life, must cease. Accordingly, it might appear very simple to determine the maximum of temperature at which life can still exist. But the temperature of coagulation is very different for different proteids, and, moreover, there are kinds of organisms that still live even at temperatures at which all proteids must long since have coagulated. In a similar manner as with the minimum, Kiihne ('64) per- formed experiments upon Amoeba regarding the maximum of temperature, and found that, when creeping actively at ordinary temperatures, it contracted at 35° C., but still remained capable of life ; after being heated to 40° — 45° C. it could not be revived by cooling. Thus, Kiihne was able to establish that one proteid of the amoeba-cell, which he regarded as contractile substance, coagulated at 40° C., another at 45° C. For plant-cells Max Schultze ('63) found the death-point to be at 47° C. In contrast to these, various other authors have given accounts of remarkable cases in which organisms exist at much higher tem- peratures. The most remarkable testimony was the observation of Ehrenberg ('58), who found living ciliate Infusoria and Rotifera between the threads of Oscillaria in the hot springs of Ischia at a temperature of 81° — 85° C. Hoppe-Seyler ('77), who tested this statement of Ehrenberg at Casamicciola, Ischia, found considerably lower temperatures. Algce, when exposed to hot vapours, were living at 64'7° C., but, when in water, the highest temperature in which they existed was only 53° C. Hence it is certain that organisms are still able to live in water of 53° C. Some time ago very detailed investigations were under- taken in the hot springs of the Yellowstone Park in North America, and living algoe were found at much higher tempera- tures. The older statement of Ehrenberg does not appear therefore, to have been incorrect. Although these statements are surprising, a well-authen- ticated and easily observed fact is known that is much more remarkable. This is the behaviour of the spores of certain bacteria to high temperatures. Koch, Brefeld and others, have shown that the spores of the bacillus of splenic fever (Bacillus anthracis) and the hay-bacillus (Bacillus subtilis) can endure u 2 292 GENERAL PHYSIOLOGY temperatures of more than 100° C. without losing their capacity of life. For the present an explanation of these puzzling facts is want- ing. It can only be assumed that the proteids in these organisms occur in a condition in which they cannot be made to coagulate by high temperatures, even, as in the case of the spores of the hay-bacillus, by a boiling temperature. The two assumptions, that, in spite of the temperature of the surrounding medium, the living substance is not heated to the coagulation-point of the proteid, and that the vital capacity is maintained in spite of the coagulation of the proteids in them, are equally improbable. It is not yet known upon what molecular changes the process of coagulation is based, and by what conditions apart from the known factors its appearance is influenced. When more is known upon these questions, some light will be thrown also upon the puzzling phenomena mentioned above. 5. Pressure Like temperature, the pressure surrounding bodies has an influence upon their chemical constitution. This is especially noticeable in cases where the chemical body exists in a medium with the constituents of which it is in chemical relation. If this condition is fulfilled, if a chemical body exists in a gaseous or liquid medium containing substances that have a chemical affinity for it, then, by an increase of the pressure, a chemical combination between the body and the substances in the medium can take place, and by a subsequent decrease of the pressure a decomposition into the previous constituents can occur. This phenomenon depends upon an antagonism between the vibrations of the atoms and the pressure. With a greater pressure the atoms become crowded together, hence more atoms of the medium are able to come into contact with atoms of the body ; with a less pressure the vibrations become again so great that the atoms are disengaged from the loose combination. Living substance exists in such a condition. It lives in a medium, either air or water, with which it can undergo chemical exchange. It is clear, therefore, that the pressure, either of the air or of the water, will have a great significance for life, and that a pressure within definite limits must belong to the general vital conditions. Unfortunately this condition has been very little investigated thus far, and at present it is possible to state only in part under what pressure of air or water life in general is still possible, and between what limits of pressure it is confined in its present form upon the earth's surface. The experimental investigation of this THE GENERAL CONDITIONS OF LIFE 293 problem will require specialised methods, and the values for the individual constituents of the air and the water, such as oxygen, carbonic acid, etc., must be separately determined manometrically. In discussing oxygen as a general condition of life, we became acquainted with the importance of the partial pressure of this gas,1 and learned that pure oxygen at a pressure of more than three atmospheres is fatal to homothermal animals, while with ordinary air the same result appears at a pressure of 15 — 20 atmospheres. Death likewise follows when the partial pressure of the oxygen falls too low. The venturesome method of balloon-travel has been employed to collect facts regarding the height at which the pressure of the air becomes so small that danger to human life results. The balloon trip that was made out of Paris in the year 1875, by Spinelli, Sivel and Tissandier, has become famous. They rose with considerable rapidity, and without any disturbance reached a height of 7,000 metres. At about 7,500 metres, Tissandier relates, they felt constantly increasing weakness and apathy, which soon increased to complete absence of the power of motion, although their minds still remained clear. They could no longer perform voluntary movements, nor could they even use their tongues for speaking. After Tissandier had made the observa- tion that the balloon had passed a height of 8,000 metres, and after vain efforts to communicate this fact to his two companions, he lost consciousness. When he awoke, they had descended to 7,059 metres. Then Spinelli, who also had awaked, threw out sand in order that they should not fall too rapidly. As a result of this the balloon again rose, and the aeronauts again lost con- sciousness. When Tissandier awoke a second time they had sunk to 6,000 metres, and the barometer showed that the balloon had reached a height of about 8,500 metres. Spinelli and Sivel never regained consciousness. The minimum of air-pressure under which plants and animals can still remain alive can be determined by the air-pump. In such an experiment the most important thing for animals is the partial pressure of oxygen, for plants that of carbonic acid. As regards the water-pressure under which life can exist, far fewer facts are known than as regards the pressure of the air. The interesting deep-sea investigations of the last ten years have shown, in opposition to earlier ideas, that living organisms exist even in the greatest depths of the sea, where darkness always prevails and bodies are subject to a pressure of several hundred atmospheres. This pressure is so great that upon its sudden with- drawal, as when the animals are drawn to the surface, they burst. Fishes come up swollen, with their scales standing out and their intestines protruding from their mouths (Fig. 132) ; this is observed 1 Cf. p. 282. 294 GENERAL PHYSIOLOGY even in the fishes that live in the depths of the Lake of Constance. The height to which the pressure can rise before all life ceases has thus far not been investigated. The diminution of the water- pressure to the pressure of the atmosphere resting upon the water, by means of an air-pump, appears to be without influence upon organisms living in the water. But a great diminution of the FIG. 132.— Ntoscopelus macrolepidotus, brought to the surface from a depth of 1500m. The eye and the intestines are swollen out and the scales are falling off, owing to the great tension of the skin over the body. (After Keller.) water-pressure is not possible without altering the liquid state of the water. Here the question of the minimum of water-pressure passes over into that of the minimum of air-pressure, and the partial pressure of the contained gases, water- vapour, oxygen, etc., and becomes connected with the questions of the importance of moisture in the atmosphere, oxygen, etc., as general conditions of life. B. THE GENERAL INTERNAL CONDITIONS OF LIFE The conditions, thus far spoken of, namely, a supply of food and other substances, a definite degree of temperature, and a certain pressure, comprise all the general conditions of life that must be afforded by the medium. Others, such as light, are likewise external but not general conditions, and pertain only to certain organisms or groups of organisms. But along with the general external conditions there are associated others that must be fulfilled also in order that life can continue. These lie within the organism itself, and constitute the general internal conditions of life. Obviously the chief requisite for the existence of life through THE GENERAL CONDITIONS OF LIFE .295 the fulfilment of all external conditions is the presence of a substance, capable of life, in which vital phenomena can take place. Hence, if a tiny drop of living substance be imagined in a medium in which all the external conditions of life are fulfilled, it must be assumed that it will remain living so long as disturbing influences do not enter from without. But experiments contradict this. A small mass of living substance can be easily obtained by cutting off with a fine scalpel under the microscope a piece of hyaline protoplasm from a living cell, e.g., Amoeba. The piece cut off is living ; this is recognised from the fact that after the opera- PIG. 133. — Stentor roeselii, a ciliate-infusorian cell. The clear, extended, rod-shaped mass in the interior is the nucleus. A, Cut into two nucleated pieces at * ; at B and Cthe nucleated pieces have become regenerated into whole Stentors and continue to live. tion it still performs such movements as the whole Amoeba performs. The external vital conditions, moreover, are all fulfilled, for the part exists in the same medium and has the same external relations as the whole Amasba. Nevertheless, it lasts for a short time only, it soon dies and cannot be restored to life by any agency. Every like experiment without exception upon any other cell yields the same result (Fig. 133). In all such cases a certain mass of living substance exists in a medium in which all external vital conditions are fulfilled, and yet the mass cannot continue living. Hence some factor among the general conditions of life is wanting. 296 GENERAL PHYSIOLOGY Inasmuch as there exists upon the earth at present no living substance that is homogeneous throughout, the absent factor, as shown by the experiment, is the natural coherence and correlation of the essential parts of the organism. This is true equally of the cell-community and the individual cell. But the objection may be raised that in many cases parts and even whole organs can be separated from an organism without endangering its existence. This is true, but in all such cases the parts are such as are not absolutely necessary to the maintenance of the individual, whether it be because they are present in abundance and can be replaced in function by others, or because they are not closely related to the other parts, and, therefore, when separated, represent complete individuals. A polyp can be cut into two parts, both of which continue to live, and from a polyp- stalk a single polyp can be cut off without dying. In the above experiment upon Amoeba the nucleated cell-body continues living even after the separation of a portion of the protoplasm, because it still possesses a quantity of protoplasmic particles of the same kind as were removed. But the piece of protoplasm that is cut off perishes, because its connection and correlation with the nuclear mass have ceased. The living substance that now exists upon the earth's surface is recognised only in the form of cells, either alone or bound together into cell-communities. The cell contains as its essential constituents two different substances, the protoplasm and the nucleus.1 Wherever a little protoplasm and a little nuclear substance exist in union; there is a cell ; and only such is capable of life when the external vital conditions are fulfilled. A large cell can be divided into many pieces capable of life, so long as the requirements are complied with that every piece shall possess some protoplasm and a little nuclear substance, and that the disproportion between the two masses shall not exceed a certain limit.2 With some skill it is not difficult to perform the experiment upon large unicellular organisms. But, if a cell be so divided that the nucleus is separated from the protoplasm, both parts invariably perish. Since the cell is the general elementary constituent of organisms, the individual of the lowest order, the association of nucleus and protoplasm in the cell may be established as a general internal condition of life. Only where these two are united can life continue to exist. A physical phenomenon takes place when, on the one hand, a material substratum is present in which it can take place, and, on the other, certain external conditions are fulfilled. The same holds good of vital phenomena. Vital phenomena appear with 1 Cf. p. 71. 2 Cf. Lillie ('96). THE GENERAL CONDITIONS OF LIFE 297 the same necessity that characterises the appearance of physical phenomena, when matter capable of life is present, and when the external general and special conditions of life are fulfilled. In other words vital phenomena are an expression of the correlation of living substance and the surrounding medium, or, as Claude Bernard ('79) says: "Vital manifestations result from a conflict between two factors — the organised living substance and the medium." In considering this correlation the question comes up : How was it with life at a time when conditions wholly different from present ones prevailed upon the globe ? Was life then able to exist ? When and how did it arise ? II. THE ORIGIN OF LIFE UPON THE EARTH As is well known, the earth was once in a fiery condition, like the sun from which it came. The hard rocks and solid metals that now compose its solidified crust were then in a molten state ; its liquid nucleus was surrounded by an atmosphere of incandescent gases ; its particles were in violent motion, and its temperature measured thousands of degrees. The idea that the earth in its evolution once passed through such a condition is now an accepted generality of all branches of natural science. Astronomy, physics, geology, geogony, mineralogy and chemistry, all agree in this. Moreover, modern science, with the help of the telescope and the spectroscope, has brought the fact directly before us, that even now, everywhere in the universe, the same process of evolution that the earth once passed through is being repeated, and that there exist upon other heavenly bodies conditions analogous to each stage of the earth's evolution. There now exist in space gaseous nebulae, molten spheres, and solid, ice-cold masses, the last representing the present condition of the moon and the future fate of the earth. The fact that the earth was once in a condition in which its temperature was enormous and not a drop of water existed upon it, in short, a condition in which the vital conditions that are^liow regarded as indispensable to the existence of organisms were wanting — this fact will always be an important factor with whiqh all speculations upon the origin of life upon the earth must deal. In the light of this we will consider the various views upon the origin of life that have been founded upon a scientific basis by various men of science, and will endeavour to form some idea respecting it, even though the idea be only a general one. 298 GENERAL PHYSIOLOGY A. THEORIES CONCERNING THE ORIGIN OF LIFE UPON THE EARTH 1. The Doctrine of Spontaneous Generation The modern doctrine of spontaneous generation (archegony, abiogenesis, generatio spontanea or cequivoca, etc.) in its general form is as follows. Since there was a time in the evolution of the earth when the existence of the living substance that now inhabits the cool surface of the latter was absolutely impossible, living substance must have arisen from lifeless substance at some later period. The question accordingly arises, how and under what conditions were the first organisms created ? To the ancients, even to a mind having so comprehensive a knowledge of nature as that of Aristotle, the idea presented no especial difficulties that animals, such as worms, insects and even fishes, could come into existence out of mud. Only at a relatively late time and particularly in connection with the researches of Redi and Svvammerdamm upon the development of insects, were these crude ideas laid aside as incompatible with established scientific knowledge. But the doctrine of spontaneous generation obtained a new point of support, when the invention of the microscope led to the discovery of a world hitherto wholly unknown and excessively rich in forms, when it was found that whenever an aqueous infusion of dead organic substance was prepared, after a short time an abundance of minute living beings developed in it, which even yet are termed Infusoria. It was fully believed that in Infusoria organisms had been found that were produced by spontaneous generation out of the dead substances in the infusion. This view necessarily seemed all the more probable because the Infusoria were the lowest and simplest beings that had been known up to that time. But in this case also it was established later that the organisms did not originate spontaneously, but were developed from germs that were previously contained in the substances or came into the vessel through the air. Milne Edwards, Schwann, Max Schultze, Helmholtz and others showed that if the substances had previously been freed from germs by boiling, and if germs were prevented from entering through the air, the development of Infusoria never took place, however long the infusion was allowed to stand. When, later, the smallest of all micro-organisms, the Bacteria, began to attract strongly the attention of the scientific world, and when it was found by refined methods of investigation that these minute beings or their germs are present everywhere in the air, the earth and the water, the doctrine of spontaneous generation THE GENERAL CONDITIONS OF LIFE 299 seized upon them and claimed that they as the lowest organisms are continually arising at the present time from lifeless matter. But modern bacteriology, with its admirable and delicate methods, for which it is indebted to its founders, especially Pasteur and Robert Koch, has refuted this doctrine again. It has shown that by the exclusion of all germs that can come to the preparation from the outside, even the richest nutrient medium, containing all the substances required for the nutrition of bacteria in the most favourable mixture, remains free from micro-organisms ; and, on the other hand, that a whole world of diverse forms develop in the medium as soon as it is left standing, for a brief time, open to the air. Along with this continual strife over the doctrine of spon- taneous generation, attempts have been made, even down to very recent times, to manufacture living organisms artificially in the laboratory. The latest of these attempts is associated especially with the name of Pouchet, who was the last active adherent of the view that it is possible to produce artificially from lifeless matter unicellular organisms, such as bacteria, yeast, and similar microbes, simply by mixing the necessary constituents and putting them under favourable external conditions. Even when at times these experiments have seemed to lead to positive results, the bacteriologists have always appeared with their critical methods, and have shown that in every case there was a development of germs that had come in from the outside or were already present in the vessels used for the experiment. These attempts are really not different from the undertaking of the famulus Wagner to compound man himself from chemical mixtures in a retort. How can one hope to produce chemically even the simplest organism when the chemical composition of living proteids, the most important substances of which all living sub- stance consists, is at present completely unknown ? To Haeckel ('66) belongs the credit of having removed from the early absurd ideas of spontaneous generation their sound kernel and of having transferred it to a purely scientific soil. For him the question is indifferent, whether at the present day living substance arises anywhere spontaneously or not. To-day, more than thirty years after Haeckel wrote, and after our know- ledge of the lowest organisms and their reproduction has made so enormous a development, the great majority of investigators are inclined to answer this question negatively. Nevertheless, Haeckel was the first to draw sharply the conclusion that because there was a time when the earth was in a condition that excluded all organic life, living substance must have originated at some time in the earth's development from lifeless substances. Accord- ing to him this time cannot be dated earlier than when the water- vapour, suspended throughout the atmosphere, had been precipi- 300 GENERAL PHYSIOLOGY tated in the form of liquid. Further, he justly lays the greatest value upon the principle that the organisms that arose by spontaneous generation must have been, not cells but the lowest and simplest organisms that can be imagined, " completely homo- geneous, structureless, formless lumps of proteid." It is con- ceivable that these living proteid lumps arose from the mutual action of substances dissolved in the primitive sea. But Haeckel expressly refuses to discuss in detail the " how " of their origin : " Every detailed portrayal of autogony is for the present inadmis- sible, for the reason that we can form absolutely no satisfactory idea of the peculiar condition presented by the earth's surface at the time of the first appearance of organisms." From the very simple and low organisms that arose spontaneously, which on account of their simplicity Haeckel termed Monera, there have been derived by continuous descent the cells and all forms of organisms that to-day inhabit the earth's surface. This in its essentials is the doctrine of spontaneous generation in its present form. Notwithstanding the fact that its conclusion is so simple and obvious, it has been contradicted on many sides and has led to the establishment of other theories upon the origin of life upon the earth. 2. The Theory of Cosmozoa The theory of germs of lower organisms capable of life moving about in space, or, as Preyer has termed it in brief, the theory of cosmozoa, was the first to appear in recent times in opposition to the doctrine of spontaneous generation. Its founder was H. E. Richter ('65, 70, and 71). Starting from the idea that small solid particles are moving about everywhere in space and in the rapid flight of the heavenly bodies are continually being stripped off from them, Richter assumes that, at the same time and attached to these solid particles, germs of micro- organisms capable of life are also continually being thrown off from such heavenly bodies as are inhabited and carried to others. If such germs come to other heavenly bodies whose state of develop- ment presents favourable vital conditions, especially moderate heat and moisture, they begin there to develop and become the starting- point of a host of organisms. Somewhere in space, Richter thinks, there have always been heavenly bodies upon which life exists in the form of cells. The existence of living cells in the universe is eternal. " Omne vivum ab ceternitate e cellula" says Richter, modi- fying anew, according to the precedent of Virchow, Harvey's old dictum. Organic life, therefore, has never originated but has always been transferred from one world to another. Thus, according to Richter, the problem of the origin of life upon the earth is not : How has life arisen upon the earth ? but : How has THE GENERAL CONDITIONS OF LIFE 301 it come to the earth from other worlds ? and this question he answers by the theory of cosmozoa. For the possibility that germs capable of life came from space through the atmosphere to the earth's surface, without perishing from the incandescent heat arising from the enormous friction, Richter believes that he finds a support in the assertion of observers that in many meteoric stones traces of coal and even humus and petroleum-like substances occur. If these can come to the earth without undergoing combustion it is possible that germs capable of life also pass through the atmosphere without losing their vital capacity. That organic germs can endure a long journey through space from one heavenly body to another without water and food can- not be doubted, if in apparently dead organisms, such as the spores of micro-organisms, there be recognised substance actually capable of life that can continue in its apparently dead condition for a long time without water and food and yet revive as soon as it comes under the required vital conditions. Independently of Richter, some years later Helmholtz and Sir William Thompson discussed the question whether life may not, perhaps, have been transferred from other heavenly bodies to the earth ; and both termed this view not unscientific. Helmholtz ('84) says : " Meteoric stones sometimes contain hydrocarbon compounds ; the intrinsic light of the heads of comets shows a spectrum that is very similar to that of the incandescent electric light in gases containing hydrocarbons. But carbon is the characteristic element of the organic compounds of which living- bodies are composed. Who can say whether these bodies that swarm everywhere through space do not spread also the germs of life wherever a new world has become capable of affording a dwelling-place to organic creatures ? And this life we might, perhaps, have reason to regard as even allied to our own in germ, however various may be the forms in which it might adapt itself to the conditions of its new dwelling-place." That meteors can be the bearers of such germs Helmholtz holds to be entirely possible, since large meteoric stones in passing through the atmosphere of the earth are greatly heated upon their surface only, while in their interior they remain cool. Helmholtz says, further, regarding the theory of cosmozoa : " I cannot contend against one who would regard this hypothesis as highly or wholly improbable. But it appears to me to be a wholly correct scientific procedure, when all our endeavours to produce organisms out of lifeless substance are thwarted, to question whether after all life has ever arisen, whether it may not be even as old as matter, and whether its germs, passed from one world to another, may not have developed where they found favourable soil." " The true alterna- tive is evident ; organic life has either begun to exist at some one time, or has existed from eternity." 302 GENERAL PHYSIOLOGY 3. Preyer s Theory of the Continuity of Life By considerations of another kind, Preyer ('80) has arrived at a theory regarding the derivation of life which is opposed to the theories both of spontaneous generation and of cosmozoa. Preyer cannot accept the idea of spontaneous generation for the following reasons. If it be assumed that at some one time in the earth's development living substance has arisen spontaneously from lifeless substance, it must be claimed that this is pos- sible even now. But the failure of the innumerable experi- ments directed toward this problem has made it in the highest degree improbable. On the other hand, the supposition that spontaneous generation was possible only once in the primaeval past, but now no longer occurs, is likewise improbable ; " for the same conditions that are essential for the maintenance of life and are now realised, must necessarily have been realised also at the time of the supposed origin of living from inorganic bodies ; otherwise, the product of spontaneous generation would not have been able to continue living." In other words, if spontaneous generation were once possible, it is difficult to see why it is not possible now. Preyer is likewise not able to accept the theory of cosmozoa, because he sees in it not a solution, but only a postponement of the problem, i.e., a shifting of it from the earth to some other world, the problem itself, however, always remaining. Proceeding from the inductive fact that organisms are always derived from other organisms similar to them, that thus far observation has never been able to establish the origin of any organism without a parent, Preyer raises the question whether the problem of spontaneous generation may not rest upon a false conception, when it demands that living substance shall at some time have originated from lifeless substance. Must it not rather be formulated in the reverse order : has lifeless originated from living substance ? Organisms are always derived from other living organisms ; but inorganic, lifeless substance is continually being derived from both lifeless substance and living organisms, either being excreted from the latter as dead matter or remaining after their death. In contrast, therefore, to the doctrine of spontane- ous generation, Preyer puts forward the theory that living substance is the primary thing, and that lifeless substance is derived from it secondarily by excretion.1 He thus demands that continuity in the derivation of living substance has never been broken. " Who- ever interrupts the series of successive generations of organisms by the introduction of a generation without previous parentage ; in other words, whoever denies the continuity of life is arbitrary." 1 Of. p. 121. THE GENERAL CONDITIONS OF LIFE 303 Omne viviim e vivo — this proposition has never experienced an exception. The consequences following from this idea are very interesting. If life upon the earth has never been derived from lifeless, but always from living substance, life must have existed Avhen the earth was still an incandescent body. In fact, Preyer so con- cludes. He is, therefore, obliged to give to the conception of life a considerably wider scope than usual ; and to regard as living not only present living substance, but also the incandescent liquid masses as they existed at one time in place of protoplasmic organisms. " If, however, we free ourselves," says Preyer, " from the wholly voluntary and really improbable thought that only protoplasm of the quality existing at present can live, and from the old prejudice, which is sustained simply by convenience, that at first only the inorganic existed, then we will not shrink from the one great step further, we will lay aside spontaneous generation and recognise that vital motion has had no beginning. Omne vivum e vivo ! " In accordance with these considerations, Preyer sketches some- what as follows the picture of the derivation of life upon the earth. Originally the whole molten mass of the earth's body was a single giant organism. The powerful movement that its sub- stance possessed was its life. When the earth's body began to cool, the substances that could no longer remain in the liquid state at that temperature, as, e.g., the heavy metals, were separated out as solid masses, and, since they no longer had a share in the vital movements of the whole, formed dead, inorganic substance. Thus arose the first inorganic masses. This process continued. It is remembered that at first hot, molten masses represented the life of the earth. " When in the course of time these compounds became solidified upon the surface of the globe, or, in other words, died, compounds of the elements that thus far had remained still gaseous and liquid appeared, and these became gradually more and more like protoplasm, the basis of the living substance of the present day. With the decrease of temperature and the lessened dissociations there must constantly have appeared more complex compounds, chemical substitutions, denser bodies, and more in- volved and correlated movements of the parts which were being massed closer together. Thus, the first forms of plants and animals, resembling one another and made possible by advancing differentiation, were able to exist." " We do not say, therefore, that protoplasm as such existed from the beginning of the earth's formation ; or that without beginning it wandered as such from elsewhere out of space to the cooled earth ; or, still less, that without life it became compounded upon the planets out of inorganic bodies, as spontaneous generation would have it ; but we maintain that the movement that exists in 304 GENERAL PHYSIOLOGY the universe without beginning is life, and that, after the bodies now termed inorganic had been separated out upon the cooling surface of the incandescent planet by its intense vital activity, and were not able to return again into the hot liquids which gradually decreased in quantity because of the progressive decrease in temperature of the earth's crust — we maintain that, after this had occurred, protoplasm must necessarily have remained over. The heavy metals, once organic elements, no longer melted, and did not return into the circulation from which they had been cast out. They are the signs of the rigor mortis of the gigantic, cooling, primaeval organisms, whose breath perchance was luminous iron-vapour, whose blood was liquid metal, and whose food was meteorites." 4. Pflugers Idea In one of the most suggestive works in physiological literature Pfliiger (75,1) has discussed very fully the question of the origin of life upon the earth, and has defended the idea of spontaneous generation, that living substance originated upon the earth itself out of lifeless substances. Pfliiger's ideas are especially valuable in that in a strictly scientific manner he discusses the problem in intimate connection with the facts of physiological chemistry, and follows it out far into detail. The essential point of Pfliiger's investigation is constituted by the chemical characteristics of proteid as that substance with which life in its essentials is inseparably united. There exists a fundamental difference between dead proteid, as it occurs, e.g., in egg-albumin, and living proteid, as it constitutes living substance ; this difference is the self-decomposition of the latter. All living sub- stance is continually being decomposed, in some degree spontane- ously and more through outside influences, while dead proteid under favourable conditions remains intact for an unlimited time. The chief condition of this decomposition is intramolecular oxygen, i.e., the oxygen that occurs in the living proteid molecule, and is continually being received by it from the outside through respiration. That this oxygen is the essential condition follows from the facts that during the decomposition carbonic acid is con- tinually being formed, and that carbonic acid does not arise from living proteid by direct oxidation of the carbon and a simple splitting-off of the carbonic acid molecule, but by dissociation, i.e., by an internal rearrangement of the atoms and the separation of new atomic groups from one another. Living substance must contain oxygen already in combination in the living molecule, and in the deconiDosition a rearrangement must take place, other- wise it cannot be conceived how, as Pfliiger has shown upon frogs, animals can exist longer than a day without free oxygen in an THE GENERAL CONDITIONS OF LIFE 305 atmosphere of nitrogen and yet constantly expire carbonic acid. Why the addition of oxygen will transform a more stable molecule into a more labile condition becomes clear when it is borne in mind that, as Keklile has shown, in all organic chemistry there is no single molecule that contains enough oxygen to oxidise all the hydrogen-atoms of the molecule to water and all the carbon-atoms to carbonic acid. For this reason molecules are more or less stable and not inclined to dissociation, unless other chemical causes bring in some lability. If, however, suffi- cient oxygen be introduced to ensure the possibility of the oxidation of the atoms of carbon and of hydrogen into the stable molecules, carbonic acid and water, by intramolecular rearrange- ment, the power of decomposition must become increased, for the affinity of carbon and hydrogen for oxygen is very great. Thus, the great inclination of living substance to decomposition is con- ditioned essentially by the intramolecular oxygen. A comparison of the decomposition-products of living proteid and those obtained by the artificial oxidation of dead proteid is of great importance. The significant fact here appears, that the non-nitrogenous products of the latter agree essentially with those of the former, but that " the great majority of the nitrogenous pro- ducts [of the latter] have not even a remote similarity to the majority of those arising in the living body." It follows that, as regards its non-nitrogenous groups of atoms, its hydrocarbon radicals, living proteid cannot be essentially different from dead proteid, but that a fundamental difference must exist as regards the nitrogenous radicals. Here a starting-point for further con- sideration is afforded by the fact that of the nitrogenous decom- position-products of living proteid, such as uric acid, creatin, and, moreover, the nuclein bases, guanin, xanthin, hypoxanthin, and adenin, a part contain cyanogen, CN, as a radical, and a part, like urea, the most important of all the nitrogenous decomposition- products of living proteid, can be produced artificially from cyanogen compounds by a rearrangement of the atoms. This points strongly to the probability that living proteid contains the radical cyanogen, and thus differs fundamentally from dead or food-proteid. Pfliiger thereupon says: "In the formation of cell-substance, i.e., of living proteid, out of food-proteid, a change of the latter takes place, the atoms of nitrogen going into a cyanogen-like relation with the atoms of carbon, probably with the absorption of considerable heat." That considerable heat is absorbed in the formation of cyanogen follows from the fact that, as calorimetric investigations show, cyanogen is a radical possessing a great quantity of internal energy. By the addition of cyanogen to the living molecule, therefore, there is " introduced into the living matter energetic internal motion." Accordingly, the great property of decomposition possessed by 306 GENERAL PHYSIOLOGY living proteid is explained as the result of the absorption of oxygen ; for. since the atoms of cyanogen are in active vibration, the carbon-atom of the cyanogen at the approach of two oxygen- atoms will pass out of the sphere of influence of the nitrogen- atom into that of the oxygen, and will unite with the latter into carbonic acid. Thus the cause of the formation of carbonic acid, i.e., of the decomposition of living substance, lies in the cyanogen, and the condition is the intramolecular introduction of oxygen. The idea that it is the cyanogen especially that confers upon the living proteid molecule its characteristic properties is supported especially by many analogies that exist between living proteid and the compounds of cyanogen. In the first place, a product of the oxidation of cyanogen, cyanic acid, HCNO, possesses great similarity to living proteid. Pfliiger calls attention to the following interesting points of comparison. Both bodies grow by polymerisation, by chemically combining similar molecules like chains into masses ; the growth of living substance takes place thus, and in this way also the polymeric cyamelid, HwCnN?lOn, comes from cyanic acid, HCNO. Further, both bodies in the presence of water are spontaneously decomposed into carbonic acid and ammonia. Both afford urea by dissociation, i.e., by intramolecular rearrangement, not by direct oxidation. Finally, both are liquid and transparent at low temperatures, and coagulate at higher ones, cyanic acid earlier, living proteid later. " This similarity," says Pfliiger, " is so great that I might term cyanic acid a half-living molecule." These points of view yield most important suggestions con- cerning the question how life may have arisen upon the earth. " When we think of the beginning of organic life, we must not think primarily of carbonic acid and ammonia ; for they are the end of life, not the beginning." " The beginning lies rather in cyanogen." Hence the problem of the origin of living substance culminates in the question: How does cyanogen arise? Here, organic chemistry presents the highly significant fact, that cyanogen and its compounds, such as potassium cyanide, ammonium cyanide, hydrocyanic acid, cyanic acid, etc., arise only in an incandescent heat, e.g., when the necessary nitrogenous compounds are brought in contact with burning coal, or when the mass is heated to a white heat. " Accordingly, nothing is clearer than the possibility of the formation of cyanogen-compounds when the earth was wholly or partially in a fiery or heated state." Moreover, chemistry shows how the other essential constituents of proteid, such as the hydrocarbons, the alcohol radicals, etc., can likewise arise synthetically in heat. " It is seen how strongly and remarkably all facts of chemistry point to fire as the force that has produced by synthesis the THE GENERAL CONDITIONS OF LIFE 307 constituents of proteid. In other words, life is derived from fire, and its fundamental conditions were laid down at a time when the earth was still an incandescent ball." " If now we consider the immeasurably long time during which the cooling of the earth's surface dragged itself slowly along, cyanogen and the compounds that contain cyanogen- and hydro- carbon-substances had time and opportunity to indulge extensively their great tendency toward transformation and polymerisation and to pass over with the aid of oxygen, and later of water and salts, into that self-destructive proteid, living matter." Pfluger thereupon summarises his ideas in the following sentences : " Accordingly, I would say that the first proteid to arise was living matter, endowed in all its radicals with the property of vigorously attracting similar constituents, adding them chemically to its molecule, and thus growing ad infinitum. According to this idea, living proteid does not need to have a constant molecular weight ; it is a huge molecule undergoing constant, never-ending formation and constant decomposition, and probably behaves toward the usual chemical molecules as the sun behaves toward small meteors." " In the plant, living proteid simply continues to do what it has always done since its origin, i.e., regenerate or grow ; wherefore I believe that all proteid existing in the world to-day was derived directly from the first proteid. Therefore, I am doubtful about the occurrence of spontaneous generation at the present time. Comparative biology also points unmistakably to the idea that all living substance has taken its origin from a single root only." B. CRITICAL 1. Eternity or Beginning of Living Substance Among the ideas regarding the derivation of life upon the earth that are contained in the theories just presented, two notions stand in sharp contrast to one another. This contrast finds expression in the alternative already set forth by Helmholtz * : " Organic life either has begun to exist at some one time or has existed from eternity" The former notion lies at the foundation of the doctrine of spontaneous generation, the latter at that of the theory of cosmozoa, and in a certain sense at the basis of Preyer's theory also. Evidently the two notions are mutually exclusive. If one is accepted, the other must be rejected. To which of the two shall we adhere ? We will test first the theory of cosmozoa. According to it life has never originated, but has existed in the universe from eternity, and 1 Loc. dt. x 2 308 GENERAL PHYSIOLOGY has simply been transferred from one world to another. In the present condition of our knowledge it is scarcely possible to obtain a direct contradiction of this doctrine and conclusive proof of its- impossibility. This will be true so long as experience does not suffice to enable us to recognise as wholly impossible the transfer of protoplasmic germs capable of life from one world to another. But; although direct contradiction of the doctrine is at present impossible, the thought that living substance has existed from eternity and has never originated from inorganic substance appears in the highest degree improbable. As a comparison of organisms and inorganic bodies has shown,1 organisms originate only from those chemical elements that occur in inorganic matter also, and differ from the latter only in the chemical compounds of which they are composed. The essen- tial compounds of living substance, proteids, do not stand, therefore,. in fundamental contrast to inorganic compounds, and differ from the latter no more than these differ from one another. Hence any general consideration that is formulated regarding the derivation of living substance, especially of proteid, must be equally applic- able in its fundamental points to inorganic compounds, such as minerals, feldspar, quartz, etc. But it is shown more clearly in non-living than in living substance to what untenable consequences the idea that lies at the foundation of the doctrine of cosmozoa leads ; for, if it be assumed that the complex compounds of living substance, especially proteids, have never originated, but have existed from eternity somewhere in space and have come thence to the earth, with the same logic and the same degree of probability it must be assumed that inorganic compounds also, quartz and feldspar, have always been present as such somewhere in space, and have come to the earth through space from another world. And if this line of thought be carried out to all chemical compounds composing the earth, — and it is as probable of them as of the compounds of living substance — it would lead to the absurd conclusion that all of the earth's compounds have wandered already complete as such from outside into our planetary system. Scarcely any man of science would be willing to accept this conclusion ; every geologist is acquainted with examples of minerals that demonstrably have originated as such chemically upon the earth, and every chemist manufactures daily in his laboratory chemical compounds out of simpler substances. No thinking chemist, indeed, now doubts that even the so-called chemical elements did not exist originally as such, but that those elements possessing high atomic weight have been derived by condensation from those having less atomic weight. If the final conclusion be deduced from the cosmozoan ideas, all evolution, not only of living substance but of the whole earth, must be denied ; for, if all compounds have existed as such from eternity 1 Cf. p. USetfolg. THE GENERAL CONDITIONS OF LIFE 309 and have never originated from simple substances, evolution has not taken place. This is the inexorable consequence of a full acceptance of the cosmozoan doctrine. We repeat that one has no right to assume for feldspar a principle of derivation different from that assumed for albumin. Both are compounds of chemical elements. One fundamental fact in plant physiology practically contra- dicts the assumption that life has never originated from inorganic substances ; namely, at the present time living substance is con- tinually being formed in the plant-cell from simple inorganic compounds, carbonic acid, water, sulphates, nitrates, etc. Between the small seed put into the earth in the spring and the huge plant that grows from it during the summer, an enormous quantity of living substance has been formed out of the purely inorganic sub- stances of the environment, and when winter comes, almost the whole quantity of this living substance returns again to simpler inorganic compounds. It is here seen how inseparably related are inorganic and organic nature, how living substance is originating continually from lifeless substance, and is continually being decom- posed again into lifeless substance. Nageli ('84), one of the most talented botanists, says rightly : " One fact — that in organisms inor- ganic substance becomes organic substance, and that the organic re- turns completely to the inorganic — is sufficient to enable us to deduce by means of the law of causation the spontaneous origin of organic nature from inorganic." " If in the physical world all things stand in causal connection with one another, if all phenomena proceed along natural paths, then organisms, which build themselves up from and finally disintegrate into the substances of which inorganic nature consists, must have originated primitively from inorganic compounds. To deny spontaneous generation is to proclaim a miracle." In a sense entirely different from that of the doctrine of cos- mozoa, which has met with little acceptance, Preyer, in his theory, interprets life as without beginning and eternal. He says : The living substance now inhabiting the earth's surface is derived by continuous descent from the substances that once in a melted condition constituted the earth's mass. Not to term the latter substances living would be arbitrary, since no .sharp limit can be established. Since, however, these substances are derived from the sun's mass, and the latter forms simply a portion of the matter of the universe, which is in eternal motion, so life, which itself is only a complex process of motion, is as old as matter. It is evident that the essential difference between Preyer's theory and the doctrine of spontaneous generation consists in a different understanding of the conception of life. Following the usage of language, the doctrine of spontaneous generation terms living only living substance as it is now recognised, in contra- 310 GENERAL PHYSIOLOGY distinction from lifeless substance; while Preyer extends the conception much farther, even to incandescent mixtures, which have not the slightest similarity to present living substance except that they are in energetic motion. If this wide extension of the conception of life be accepted, no objection can be raised against the other consequences of Preyer's theory. It is, however, question- able whether it is judicious or allowable to carry the vital con- ception so far. The conception of living substance, as scientifically established at the present time, has arisen from an exact comparison of existing living organisms and existing inorganic bodies. As has been seen,1 there is but one absolute difference between these two, and this consists in the metabolism of proteids. No inorganic body possesses proteid. On the other hand, proteid is not wanting in any organism ; and that which constitutes the life of an organism, wherein the living differs from the dead organism, is the meta- bolism of the proteid. This difference between living organisms and dead inorganic bodies, although not fundamental or elementary, is, nevertheless, profound and affords the sole means of sharply characterising living substance. If it be nullified by terming " living " bodies that cannot contain proteid, such as the incan- descent masses of the once fiery globe, the advantage afforded by a sharp definition is wholly lost, and the conception of living substance is dissipated. But here, from the standpoint of Preyer's theory, the question may be raised : If the living substance of to-day is derived in uninterrupted descent from molten mixtures, where is the limit- beyond which the substance may be termed living ? This ques- tion assumes a postulate that is wholly unsupported, viz., that there was a gradual, uninterrupted transition between the molten mixtures and the proteids. Hitherto we have laid great stress upon the idea that no fundamental difference exists between lifeless substances and organisms ; but it cannot be proved that an uninterrupted transition between molten substances and organisms existed. It is known, moreover, that when two chem- ical compounds act upon one another, the resulting substances are not necessarily joined with the original substances by transition- stages, however different they may be from them. Regarding the relations that may have prevailed upon the earth's surface when water was precipitated as liquid, we cannot form even an approxi- mate idea. The idea that living proteid originated without transition by the action of bodies wholly different from it chemi- cally, when the proper conditions existed, would be at least as probable as the idea of a gradual descent associated with uninter- rupted transitions. Further, Preyer implies that the incandescent masses to which 1 Cf. p. 136. THE GENERAL CONDITIONS OF LIFE 311 he extends the conception of life have had a metabolism. This cannot be substantiated. It cannot be doubted, indeed, that these masses possessed an extremely energetic internal motion ; and, life is nothing but a complex motion, to which every other molecular motion is allied in principle. Nevertheless, vital mo- tion, metabolism, is a complex motion very sharply characterising the living organism ; it consists in the continual self-decomposition of living substance, the giving-off to the outside of the decom- position-products, and, in return, the taking-in from the outside of certain substances, which give to the organism the material with which to regenerate itself and grow by the formation of similar groups of atoms, i.e., by polymerisation. This is characteristic of all living substance. But that this peculiar complex motion existed in the incandescent mixtures of the earth and has suffered no interruption from that time down to the present living sub- stance, is in a high degree doubtful. Mixtures of this kind, which, as lava, can be observed at the present day in volcanoes, and there are still at so high a temperature that in flowing from a cleft of the crater over a precipice they present the wonderfully fascinating spectacle of an incandescent waterfall — these extremely liquid mixtures, however mobile they may be, show no metabolism in the real sense, and hence should not be termed living. Nor can the original incandescent mass of the earth be so termed deliberately, however impressive and suggestive Preyer's theory is. There then remains as the sole difference between Preyer's doctrine and that of spontaneous generation the point involved in the very unessen- tial question, whether living substance has come from lifeless substance gradually and by imperceptible transitions ; or whether it has been formed more directly, as is the product of two bodies in a chemical reaction in a test-tube, and has taken on its characteristic properties. In neither case will the conclusion be avoided that living substance once came from substances that are customarily termed lifeless. 2. The Descent of Living Substance Upon the basis of the ideas developed by Pfliiger we are now in a position to form in gross outline an approximate idea of the origin of life upon the earth. The beginnings of living substance reach down into the time when the earth's surface was still incandescent. The compounds of cyanogen then present constitute the essential material from which living substance took its origin. With their property of ready decomposition they were forced into correlation with various kinds of compounds of carbon, whose origin was due likewise to the great heat. When water was precipitated in the form of liquid upon the earth's surface, these compounds entered 312 GENERAL PHYSIOLOGY into chemical relations with the water and its dissolved salts and gases, and thus originated living proteids, i.e., extremely labile compounds, which like other compounds containing the cyanogen- radical are distinguished by their tendency toward decomposition and polymerisation, and which form the essential constituents of living substance. This first living substance, which was formed spon- taneously out of lifeless substance, was very simple and showed no differentiations. It is very probable that it did not have the morphological value of cells, i.e., that its mass was not yet separated into different substances, such as nucleus and proto- plasm, but rather was .homogeneous in all its parts, as Haeckel assumes for his Monera. Such an idea of the origin of living substance has at present some degree of probability in its favour. It is quite possible that in the future it will be considerably modified in its details. Yet further speculation at present regarding the details is of little value, since the stage upon which living substance made its first appearance and the conditions then prevailing are known so in- definitely. But with living substance already present upon the earth we are upon firmer ground ; for here is the point where the doctrine of descent, founded by Lamarck and Darwin, and de- veloped especially by Haeckel, Weismann and their pupils, comes in and elucidates the farther history of this substance down to the present day. It would lie outside the purpose of these pages to speak of the whole enormous complex of ideas that led to the founding of the doctrine of descent. It is sufficient to point to the chief factors, the correctness of which no thinking man of science at present doubts. As is well known, the theory of descent teaches that all the multifarious organisms that live to-day and have lived at any time upon the earth's surface are derived in unbroken descent from the first and simplest living substance that originated from lifeless substances, and that, therefore, all organisms stand in true genetic relationship to one another. The continuity of the organic series during historic time needs no special proof; for simple observation shows that every organism is derived from another organism similar to it, that the continuity of descent is never broken. But for the long geological periods elapsing between the appearance of the first organisms and historic time, direct observa- tion is naturally wanting. Here nature has preserved certain records in which are found entered, although more or less incom- pletely, the history of the evolution of the organic race. The first record is deciphered by Palaeontology, or the science of fossils. Fossils are the testimony that nature has laid down in the strata of the earth's crust regarding the existence and character of earlier organisms. By the study of fossils palseon- THE GENERAL CONDITIONS OF LIFE 313 tology reconstructs to a certain degree the organic world that inhabited the earth's surface at the times when the strata were formed. Thus the ancestry of existing animals and plants is learned. It is seen that existing forms are very similar to those that occur in the latest strata ; that the forms become more dissimilar the farther we go toward the earliest strata ; and that large groups of organisms, which are now considered to be widely separated from one another, have in the older strata common ancestors, which combine in themselves the characteristics of several groups. In the very earliest strata are found lower animals and plants only, no vertebrates and no flowering-plants occur. For every one who is not wedded to a blind, supernatural faith concerning creation, and who does not prefer, in accordance with the biblical account, to think of every form of organism as proceeding by itself from the hand of a personal Creator, there is only .a single natural explanation of all palseontological facts ; namely, that the whole world of organisms, living to-day and living in the past, forms a single, great genealogical tree, the germ of which was the first living substance that appeared upon the earth. This germ developed into a mighty growth with innumerable branches .and twigs and leaves ; its last shoots are seen in the organisms of to-day, its older branches lie buried in the earth. Unfortunately, the pala3ontological record is very imperfect ; for, on the one hand, only a very small fraction of the earth's strata is accessible to investigation — the greater portion of the crust is covered by the .sea ; and, on the other hand, the preservation of organisms is very incomplete, since they can be imbedded only under very definite conditions without becoming destroyed by the impact of the waves, by decomposition, etc. In fact, organisms that did not possess protecting skeletal parts have been preserved hardly at all, because their delicate bodies disintegrated immediately after death. It thus comes about that in the investigation of the oldest and simplest organisms, which possessed no protecting skeletal parts, the palseontological record fails. Comparative anatomy deals with the second record, which is presented in the homologies of the individual organs of existing organisms. By the dissection of organisms into their smallest parts and by the comparison of individual organs and systems of organs belonging to different groups of organisms, comparative anatomy establishes the fact that as regards their essential organic systems certain groups of organisms agree with others to a certain extent. This fact can be interpreted rationally only by the assumption of a natural relationship between such organisms ; in general such a relationship is closer, the more homologies occur, and the more remote, the more differences are present ; for the homologies can be due only to the fact that iit some time in the early past the organisms had common 314 GENERAL PHYSIOLOGY ancestors which possessed the features in question. Of course the record of comparative anatomy is also very incomplete, for existing organisms are only the surviving tips of the various twigs of the genealogical tree, between which the other twigs and branches have perished. But here the palseontological record supplements the facts of comparative anatomy up to a certain degree very satisfactorily, by making the dead branches accessible to comparison with the still living ones. An example will illustrate this. Upon comparative - anatomical grounds the conviction was formed that birds stand in very close rela- tionship to reptiles, but forms that might be considered as common ancestors of the two or were close to their ances- tors were not known. There was then dis- covered in the quarries of the lithographic slates of Solenhofen a fossil animal about the size of a pigeon, the now well- known Arcliceopteryx mac- TUTUS, which possessed the characteristics of both bird and reptile ; it had the jaws of a lizard with teeth, the spinal column of a lizard, and a long lizard-like tail ; but its whole body was covered with bird's feathers, which were impressed upon the rock most delicately (Fig. 134). By this and similar palseonto- logical discoveries the kinship of the birds and the reptiles, which was inferred from comparative anatomy, was very brilliantly con- firmed. Similar examples may be cited in great number. Finally, embryology, or individual germinal development (onto- geny), deals with the third important record of descent. As is well known, the germs of plants and of animals from their simplest condition, the egg-cell, pass through a long series of develop- FIG. 134. — ArchcKopteryx macrums, s. lithographicus. d, Clavicle ; co, coracoid ; h, humerus ; r, radius ; u, ulna ; c, carpus ; sc, scapula ; /. — IV. digits. (After Zittel.) THE GENERAL CONDITIONS OF LIFE 315- mental stages before they come to resemble the mother from which they are derived. Since ancestors transmit their characteristics to their de- scendants, these developmental stages become of extraordinary importance in gaining a knowledge of the ancestral series ; forr since they represent, in gross, forms inherited from ancestors, they indicate, although in rude outline only, the developmental forms that have once appeared in succession in the ancestral series. In other words, the forms that appear in the germinal development or ontogeny of an individual recapitulate in gross the series of forms of the ancestors of the organism in question. This fundamental law of biogenesis, which was founded by Haeckel, and which has been discussed in detail elsewhere,1 enables us, by means of a critical examination of the ontogenetic development of an organism, to reconstruct to a certain degree its phylogenetic descent. From all these facts of palaeontology, comparative anatomy,, and embryology — for the full appreciation of which reference must be had to the works of Darwin, Gegenbaur, Haeckel and their pupils, which have laid the foundation for an understanding of them — the conclusion must necessarily be drawn that existing organisms are derived in uninterrupted descent from the first living substance that originated from lifeless substance. Moreover, at the same time the path is indicated that has been taken by living substance in its development upon the earth. The phylogenetic research of modern morphology has succeeded in discovering this path in general, and thus reconstructing in its gross outlines the genealogical tree of organisms. Although much opposition was expressed at first to the provisional scheme of genealogy that Haeckel presented thirty years ago as an induction from the facts then known, there are few morphologists now who do not accept Haeckel's idea in its essential points. There now prevails essential agreement regarding the phylogenetic relations of the large groups of organisms, although, as to the smaller groups and the special relations, many far-reaching differences of opinion still exist j the latter will be set aside only gradually and by new discoveries. In accordance with Haeckel's ideas and upon the basis of the present condition of its knowledge, modern morpho- logy has pictured somewhat as follows the genealogical tree of organisms : 1 Cf. P. 207. 316 GENERAL PHYSIOLOGY Metaphyta (Plants) AngiospermcK ((Plants having covered seeds, common flower- ing-plants) GymnospermcK {Plants having naked seeds, conifers) FilicinecK (Ferns) Muscinece (Mosses) I Algce Fungi (Sea-weeds) (Mushrooms, moulds, etc. ) \, / Protophyta (Unicellular plants) Metazoa (Animals) Vertebrata (Back-boned animals) Echinodermata Arthropoda Tunicata Mollusca (Starfishes, sea- (Crabs, in- (Tunicates) (Clams, urchins, etc. ) sects, etc. ) snails, etc. ) Ccelenterata Vermes (Polyps, jelly-fishes, etc. ) (Worms) Gastrceada Protozoa (Unicellular animals) Protista Momra SCHEME OF THE GENEALOGICAL TREE OF ORGANISMS. From the first living masses, which Haeckei terms Monera, there were developed, by differentiation of the homogeneous substance into nucleus and protoplasm, the first unicellular organisms, Protista. The Protista constitute the group from which, on the one side, plants, and, on the other side, animals have been developed ; they comprise the lowest organisms now living. Even among the Protista a differentiation as to metabolism took place, and they were divided into the Protophyta, i.e., those having plant-metabolism, and the Protozoa, i.e., those having animal-metabolism. The former continued to construct their living substance out of inorganic substances, while the latter simplified their metabolism by employing the organic substance prepared by the former. From the Protophyta are derived all plants (Meta- phyta), from the Protozoa all animals (Metazoa), as follows : — From the Protophyta two branches went off, the sea-weeds (Algce) and the moulds, etc. (Fungi). Of these two the former group developed, and from it arose in direct descent the mosses (Miiscinece), from them the ferns (Filicinece), from the ferns the plants that have naked seeds (Gymnospermce), and from the latter, finally, the plants that have covered seeds (Angiospermce). The last group shows the THE GENERAL CONDITIONS OF LIFE 317 highest differentiation of the plants. From the Protozoa, on the other hand, arose the Gastrceada, very simple animals consisting of only two layers of cells (entoderm and ectoderm). Probably no representative of this group is now living, but their presence in the genealogical series must necessarily be inferred from the very general appearance of the gastrula-stage in the development of all animals. From the Gastrceada developed on the one side polyps, jelly-fishes, etc. (Ccelenterata), and upon the other side worms ( Vermes). The latter gave origin to four groups comprising respectively star-fishes, sea-urchins, etc. (Echinodermata), crabs, insects, etc. (Arthropoda), tunicates (Tunicata), and clams, snails, etc. (Mollusca). Of these the tunicates became the progenitors of the back-boned animals ( Vertebrata), the most widely differentiated representatives of the animal kingdom. The present living organ- isms form merely the last shoots of all the branches of this great genealogical tree. A glance over the racial development of organisms from their first appearance down to the present time shows that living sub- stance has undergone in the course of the earth's development a remarkable change in form and organisation ; in these respects existing organisms are widely differentiated in very different directions. Darwin's theory of selection has afforded a natural explanation of this phenomenon. This theory proceeds from the fact that all individuals of the same species, even descendants from the same pair of parents, differ from one another more or less markedly. This phenomenon is known as individual variability, and is the result partly of sexual intermixture (Weismann's amphimixis) and partly of the action of various external influences upon the germ-plasm of the individual embryos, whether within or without the maternal organism. Of these more or less different individuals of the same generation Darwin shows that in the struggle for existence only those continue to live that are best fitted to the external conditions of life, while those that are less fitted perish as a result of the competition with the former. Thus, only those that are best adapted to the existing external conditions can reproduce and transmit their characteristics to their descend- ants. In this survival, in this selection of the fitter individuals, Lies the natural selection of Darwin; and it is evident that with the continuance of the process organisms must become adapted to existing vital conditions very perfectly. Hence the form, the organisation, and, in general, all the characteristics of living substance are in the closest correlation with the external con- ditions upon the earth's surface ; if these change, the characteristics of organisms must correspondingly change. But it is a question whether, in the course of time, natural selection is the sole factor that causes organisms to change. 318 GENERAL PHYSIOLOGY Adaptation to external conditions as a result of selection pre- supposes a continual inheritance of innate characteristics, and Weismann ('92, 1) holds the view that the inheritance of innate characteristics alone comes into the question of change in the organic world. Since Darwin believed that acquired character- istics also are transmitted, Weismann, as the defender of the one- sided theory of selection, is, in a certain sense, more Darwinian than Darwin himself. Others, such as Haeckel ('66), Eimer ('88), and Herbert Spencer ('93), are also of the opinion that the inheritance of such characteristics as are acquired during the individual life is of great importance in the transformation of organisms. Naturally there always arises here the question whether these characteristics are properly adapted to external conditions or not. If not, they likewise are soon set aside by selection in the struggle for existence. But at the present time the question whether only innate or also acquired characteristics are inherited, constitutes the point of chief interest for those who theorise upon heredity : and, in spite of much discussion, it still waits for a definitive answer.1 If, finally, a brief examination be made of the nature of the changes that living substance has undergone from its origin down to the present, the fact appears that it has developed from simple to constantly more complex forms and organisation. The result is that the most complex organisms occur at the present time, being represented by the flowering-plants and the vertebrates, in which special parts have become widely differentiated for the exercise of very special occupations. It has frequently been said that in the developmental series of organisms from the earliest beginnings down to the present there may be seen a continual advance — a progressive perfecting. This idea embraces an error which it was the whole endeavour of the Darwinian theory to avoid, viz., that of teleology. The conception of advance, of perfecting, involves a goal toward which the advance is directed. Without this it is an empty conception. In reality, however, there does not exist in the development of organisms a predestined goal toward which the development is striving any more than in any chemical reaction. Organisms can only follow, and must follow in a definite direction, when the proper external conditions are present. Changes in them are dependent solely upon changes in their environment. The employment, therefore, of the idea of advance or perfecting is evidence merely of an anthropocentric stand- point ; we introduce ourselves into the development as the goal. For whatever reason this is done, the goal is an artificial thing which does not exist in nature ; the assumption that mankind is more perfect than an amosba is not justified by reality. It is simply a conventionality to call development a perfecting. J Cf. p. 180. THE GENERAL CONDITIONS OF LIFE 319 Nature itself has no goal to strive for, its method is eternal development, i.e., change without end. To draw, now, the final conclusions from the above discussion, the fact stands out clearly and distinctly that life from its beginning on has been dependent upon the external conditions of the earth's surface. In a mathematical sense, life is a function of the earth's development. Living substance could not exist while the earth was a molten sphere without a solid, cool crust ; it was obliged to appear with the same inevitable necessity as a chemical combination, when the necessary conditions were given ; and it was obliged to change its form and its composition in the same measure as the external conditions of life changed in the course of the earth's development. It is only a portion of the earth's matter. The combination of this matter into living sub- stance was as much the necessary product of the earth's develop- ment as was the origin of water. It was an inevitable result of the progressive cooling of the masses that formed the earth's crust. Likewise, the chemical, physical and morphological characteristics of existing living substance are the necessary result of the influence of the external conditions of life upon the internal relations of past living substance. Internal and external vital conditions are inseparably correlated, and the expression of this correlation is life. III. THE HISTORY OF DEATH Our consideration of vital conditions culminated in the fact that vital phenomena not only can exist, but must appear with the same inevitable necessity as every other natural phenomenon, when a certain complex of conditions is fulfilled. If these conditions are wanting, life is wanting. The appearance of life upon the earth was one consequence of this fact. Another consequence, which is now to be considered, was the development of death. A. THE PHENOMENA OF NECROBIOSIS If one or more of the special vital conditions under which an organism exists fail, vital phenomena cease, life comes to a stand- still. Excepting the few cases of apparent death, this standstill is always real death. But, as has already been seen,1 death never appears instantaneously. There is no sharp limit separating life and death, there is rather a gradual transition between them ; in other words, death undergoes development. Normal life upon the one 1 Of. p. 134 320 GENERAL PHYSIOLOGY hand, and death upon the other, are merely the remote end-stages in this development, and are united to one another by an un- interrupted series of intermediate stages. The two end- stages may be easily and sharply distinguished, but it is impossible to draw a sharp line at the place where life ceases and death begins. Hence this transition from life to death is termed necrobiosis, a word that was introduced into pathology by K. H. Schultz and Virchow. Virchow ('71) distinguishes between necrobiosis and necrosis by means of external characters, speaking of necrobiosis when the original form of the part in question is completely destroyed and done away with, and of necrosis when it is still retained in death. But. however practicable this external dif- ference may be in the judgment of gross relations, of whole organs or tissues, it has little importance theoretically, for whether the end-result assumes this or that form frequently depends upon wholly accessory matters. If, e.g., a cell has a solid wall, its form long remains, although the protoplasmic body may long since have perished ; but if its protoplasm is naked, the cell usually disin- tegrates into a formless mass of granules ; nevertheless, the essence of the process that leads to death may be the same in the two cases. Hence it seems advantageous to lay aside this distinction and so to extend the conception of necrobiosis that it may include also the so-called necrotic processes. There is then understood by necrobiosis those processes that, beginning with an incurable lesion of the noi*mal life, leads slowly or rapidly to unavoidable death. The frequent synonymous conception of degeneration has the disadvan- tage that it has more than one significance and is employed for many very different phenomena. The phenomena of necrobiosis introduce a subject which, on account of its enormous practical importance, has been developed as an independent science and has assumed large proportions ;. this is pathology, the science of diseases. The following considera- tions will, therefore, largely pertain to this subject, and an endeavour will be made to analyse the death-process. Since the cell is the proper seat of life, it must be the object, of study in the investigation of necrobiosis as in that of vital phenomena. The death of compound organisms with their widely differentiated organs and tissues depends simply upon the death of the individual cells composing the cell-community. But the phenomena that lead to death are very different in the individual forms of cells. This depends partly upon the condition of the living substance that characterises each form, and partly upon the nature of the causes that lead to the death of the cell. It is, therefore, evident that necrobiotic phenomena must be very manifold. Nevertheless, they can be brought into two great groups, which differ fundamentally from one another. In one group the normal vital processes drop out gradually without under- THE GENERAL CONDITIONS OF LIFE 321 going an essential change ; these phenomena may be termed histolytic processes. In the other group the normal vital processes are turned into a perverse course by the fatal lesion, and degenerate before they come to a complete standstill. These are termed metamorphic processes. 1. Histolytic Processes The simplest forms of the histolytic processes are the atrophies. They are mostly chronic processes, and consist in the gradual constant decrease in extent and final complete cessation of the ascending phase of the metabolism of the cell in question, that is, of the processes that lead to the construction and regeneration of living substance. The result is that the living substance, con- tinually undergoing decomposition in a certain measure, loses in volume constantly ; the cell becomes constantly smaller, until finally the remnant, having come to an extreme, disintegrates —technically speaking, the cell or the tissue " atrophies." Cases of atrophy of an organ or tissue are wide-spread in the organic world, and play a great role both in the normal develop- ment of animals and in pathological conditions. Among those that appear in the development of the normal organism and are especially well known are the phenomena of histolysis or degeneration of embryonic organs, which are particu- larly characteristic of animals that have a pronounced metamorphosis or larval development. These histolytic processes have been care- fully followed recently in the atrophying tail of the tadpole of the frog by Looss ('89). In its essentials histolysis follows a cor- responding course in different forms of cells. There is notice- able first a loosening of the cement- substance that unites the cells together into the tissue, so that the cells adhere to one another less closely. During this a visible change begins in the protoplasm. " The cell-substance gives up its normal characteristic structure. The spongioplasm, present originally in the form of a more or less pronounced spongy framework and usually capable of staining intensely, draws itself together, the individual strands become thicker, and, finally, the whole dis- integrates into a larger or smaller number of spherical droplets, which lie within the hyaloplasm. The latter stains less or not at all, and has likewise come together into a homogeneous mass." The ground-substance in which the globules lie first begins to dissolve, and later the globules themselves become liquefied. Thus, finally, of the whole protoplasm there remain only a few insoluble granules, and these are devoured by the leucocytes which creep about as phagocytes in all tissues. The nucleus of the cell usually resists destruction considerably longer, but finally becomes the victim of a similar process. Its ground-substance disappears very 322 GENERAL PHYSIOLOGY soon ; the chromatic substance and the nuclear membrane gradu- ally shrink together and disintegrate into single fragments, which likewise are finally dissolved. The muscle -fibres, though in other respects very different, behave similarly. The individual fibrillse swell and become cemented to one another. At the same time FIG. 135.— Histolysis of muscle-fibres in the tail of the larva of the -frog. (After Looss.) the isotropic and the anisotropic substances begin to mingle to- gether, so that the cross-striation gradually disappears. The double refraction of the anisotropic disks also fades away. At the same time the fibres disintegrate into small round fragments, which finally undergo solution (Fig. 135). The processes of histolysis go on in a wholly analogous manner in most other cases, e.g., in the degeneration of the larval organs of insects, the muscles of the salmon, and the thymus-glands of human beings. But from the investigations of Metschnikoff ('83), Kowalevsky ('85, '87), and others, it appears that in many insects, especially in the fly-larva, where the degeneration of the larval tissue proceeds uncommonly FIG. 136.— Fragments of muscle-fibres in the metamorphosis of the fly-larva, destroyed by leucocytes. The darker, granular cells are the leucocytes. (After Kowalevsky.) rapidly, the histolysis is performed chiefly by the leucocytes, which as phagocytes devour the tissue-cells that have not yet disintegrated (Fig. 136). It must be supposed that here also the inauguration of histolysis proceeds from the tissue-cells themselves, and that the leucocytes devour the cells that are already beginning to atrophy. THE GENERAL CONDITIONS OF LIFE 323 The whole difference lies in the fact, as has been set forth by Korotneff ('92), that where a very rapid disappearance of the tissue is concerned, the leucocytes exercise greater activity and begin their work earlier. Among the atrophies in normal life belong, further, the phenomena of senile atrophy, which consists in a very slow and constantly progressive degeneration of the various tissues, and is never wanting in extreme old age. Next to the normal atrophies are the pathological ones, which appear in the organism when diseases have created the proper conditions for them. Thus, e.g., in human beings the muscles of the leg atrophy when, as a result of disease, the knee-joint has become ossified and immovable. Such atrophies, which occur as a result of disuse of the organ, are termed, simply, atrophies from disuse. In these pathological atrophies the processes are, in \ ' , A FIG. 137. — Degeneration of leucocytes in acute leukaemia. 7 and //, Normal leucocytes ; the dark mass is the cell-nucleus, the clear border, the protoplasm. /// — VII, Stages of the dis- solution. (After Gumprecht.) general, the same as in normal ones; nevertheless, at times re- markable phenomena appear. Thus, in muscles that have atro- phied because of disease, a very great increase of nuclei is frequently found, while Loosswas able to determine with certainty that in the muscle-atrophy of the histolytic tail of the tadpole the nuclei were neither increased nor diminished. Further, the tissues atrophying because of disease are at first, as a rule, much more solid and compact than those that undergo normal histolysis — a circumstance that is perhaps based upon the considerably longer duration of the pathological atrophy, during which the dissolved masses have more time to be discharged. But these are all special, accessory factors. The degeneration of leucocytes has recently been followed in detail especially by Gumprecht ('96) in acute leukaemia. It is interesting, since the dissolution of the nucleus takes place in a Y 2 324 GENERAL PHYSIOLOGY very simple manner. The nuclear membrane disappears, the contents of the nucleus mix with the protoplasm, the chromatic substance becomes gradually paler, until the whole leucocyte becomes a homogeneous mass, which disintegrates with swelling and formation of vacuoles (Fig. 137). To the atrophies may be added a series of death-processes, which, although they have little similarity to one another, are grouped in pathology under the common name of necroses.1 In general they have a more acute course than atrophies. Among the various necrotic processes several important forms can be distinguished, which are characterised by definite peculi- arities. One of these is mummification or dry gangrene. In this the tissue-cells shrink into solid, leather-like masses on account of a loss of liquid, so that when the process has reached its end the tissues appear dry, hard and friable. Mummification occurs normally in the drying-up of the remnant of the umbilical cord of the new-born child; in patho- logical conditions, as after burning or freezing the ends of the fingers and of the toes ; particularly in old age ; and also in the drying- up of embryos that develop in the abdominal cavity of the animal or the human being instead of in the uterus and, being incapable of birth, die within the body of the mother. Such embryos as- sume gradually a hard, mummy- like consistency, because the liquid contained in them is absorbed by the mother's body. A second important form of necrosis is coagula- tion-necrosis, first investigated in detail by Weigert (75, 77, 78, '80), which consists in the coagulation of the proteids of the tissue-cells in question. With the coagulation-necroses may be classed the usual rigor of dying muscles, which along with gradual contraction transforms the muscles into stiff organs and causes the rigidity of corpses. Weigert himself does not allow this classification, regarding the co-operation of lymph as essential to the occurrence of the coagulation-necrosis. But the process in rigor mortis, although transitory, is the same in principle ; for the myosin, the proteid that is characteristic of and contained in solution in the living muscle, coagulates in dying and thus produces the stiffen- 1 Of. Cohnheim ('77— '80) and Ziegier ('95). FIG. 138.— Waxy degeneration of muscle in typhoid fever, a, Normal cross-striated nective tissue. (After ziegier.) THE GENERAL CONDITIONS OF LIFE 325 ing ; as a result of other transformations in the muscle the rigor passes away, this process being accompanied by muscular relaxation. A typical coagulation-necrosis in Weigert's sense occurs in muscle under pathological conditions, especially in connection with fevers, such as typhoid ; this is the so-called -waxy 'degeneration, which consists in a coagulation of the muscle-substance with loss of its cross-striation and a separation into waxy-appearing flakes (Fig. 138). Similar coagulation-processes occur in other tissue- cells, especially in active inflammations of the mucous membranes, as in pharyngeal diphtheria. Finally, among the coagulation- necroses in the wider sense there can be classed the pheno- mena of cell-death that appear when, for the purpose of FIG. 139. — Liquefaction at the edge of a blister caused by burning, a, Horny layer of the epi- dermis ; b, rete Malpighii of the epidermis ; c, normal papilla; of the dermis ; d, cells swollen and already partly liquefied ; e, partly normal cells ; /, liquefied mass ; g and h, swollen cells with nuclei destroyed ; i, sunken papillae ; £, coagulated exudation. (After Ziegler.) anatomical or histological preservation, living tissue is placed in liquids that cause coagulation, such as mineral acids, alcohol, sublimate, etc. These are the most acute cases of cell-death, and for this reason these liquids are especially well-fitted for killing and preserving. By their application the living cell is killed suddenly ; it thus has not time to undergo extensive change, but in a moment is fixed in a condition very similar to that of life. In a third form of necrosis, liquefaction, the tissue-cells become completely liquefied, their protoplasm disintegrating into a granular detritus and the nuclei and cell-boundaries dissolv- ing until the tissue is changed into a thickish liquid. Such softenings occur especially in the formation of blisters after burn- ing (Fig. 139), and frequently combine with coagulation-pheno- 326 GENERAL PHYSIOLOGY mena. Not rarely, different forms of necrosis occur combined, and they become complicated especially by secondary factors, such as putrefaction. The latter is the case with moist gangrene, decay, etc., all of which are produced by the action of putrefactive bacteria upon necrobiotic tissue, and some of which represent post- mortem phenomena. Further, certain other forms of necrosis have been more or less identified by pathology, but these patho- logical classes are distinguished much more by the macroscopic phenomena of the end-result than by the microscopic events in the cell itself. The former naturally depend upon various kinds of accessory circumstances that are not immediately conditioned by the pure phenomena of cell-death. Finally, one more series of phenomena may be added to the at- rophies and necroses ; these accompany the death of cells living in aqueous media and are wide-spread among organisms ; they are the phenomena of granular disintegration.1 The one thing held in common by all kinds of granular disintegration is that at the end of the process the cell in question forms a more or less loosely coherent mass of individual granules. Granular disintegration can be observed most easily in many In- fusoria, when their protoplasm is especially rich in water. This is the case in the large, cylindrical Spirostomum ambiguum which has a soft, superficial layer of exoplasm. If such Infusoria be wounded by being cut into two pieces under the microscope, it happens very frequently that the pieces disintegrate away regularly from the surface of the wound. Death can be followed by the eye, and its course resembles that of a spark that passes over a fuse and leaves behind it merely a loose mass of ashes. It creeps over the whole body, seizing upon particle after particle, surprising cilium after cilium in normal activity, and forcing them directly from active life into a standstill, until that which a moment before was in active motion is changed into a dead mass of granules (Fig. 140). These very acute cases in infusorian cells, which interest every observer who sees them for the first time, are not well-adapted to a study of the more delicate protoplasmic processes, since, with the protoplasm already very granular, it is difficult to decide how far the granular material of the disintegrating masses consists of the preformed granules, and how far it is formed directly as such by the process of death. In this respect many Rhizopoda, such as the marine Hyalopus Dujardinii (Fig. 141, I), which are completely hyaline and absolutely free from granules, are extraordinarily suitable. If one of the smooth, clear pseudopodia be cut off by a knife under the microscope, it begins gradually to undergo granular disintegration from the place where it was cut (Fig. 141, // and III}. Then, either very soon or in the 1 Of. Verworn ('96, 1). THE GENERAL CONDITIONS OF LIFE 327 course of a few hours, the time varying according to the thickness and size of the piece, there is seen in place of the transparent protoplasmic mass, a collection of small granules and globules, between which lie isolated, larger, round droplets of hyaline proto- plasm (Fig. 141, ///, D, &), and sometimes one or more faint, round, transparent bubbles (Fig. 141, ///, D, a\ all being loosely held together by a very delicate viscous mass. There is no doubt that this collection of granules and globules has arisen by the transformation of a mass of living substance that originally was wholly clear. In the study of this process with stronger magnifying powers an interesting fact appears. In the normal life of the cell a characteristic difference in the behaviour of the protoplasm of the pseudopodia of the Hyalopus during the phase of expansion and that of contraction may be recognised. While during the former, i.e., extension, the protoplasm appears completely homogeneous, during the latter it assumes the typical alveolar struc- ture of Btitschli,1 and, if the con- traction becomes very strong, as after stimulation, the protoplasm becomes uneven and knobbed upon the sur- face (Fig. 141, Fand VI). Exactly the same phenomenon appears in the development of granular disin- tegration. The protoplasm begins to assume the alveolar structure ; then the alveolar walls are gradually drawn together in uneven and lumpy masses ; they burst here and there, and become rounded off into small globules and droplets ; these are held together in a loose, granular heap merely by the viscous liquid of the burst vacuoles, which frequently flows together into a large, viscous drop (Fig. 141, IV). Thus, granular disintegration depends upon a supra- maximal contraction. This fact is of great interest, for, if the histolytic processes be followed comparatively in different cells, it is found to be a common law that all elements, the contractility of which can be clearly expressed, arid hence especially all naked protoplasmic masses, such as Rhizopoda, protoplasmic drops from tissue-cells, contractile fibrillse, muscle-fibres, etc., without exception die in the phase of contraction. Amoeba and leucocytes (Fig. 142) in necrobiosis, as in every contraction, assume a more or less com- pletely spherical form (Fig. 142, B). Khizopoda possessing long 1 Cf. p. 86. FIG. 140.— Granular disintegration. 7, Piece of a Spirostomumdisin from the wounded place. //, Pelomyxa disintegrating as the result of over- stimulation upon one side. FIG. 141. — For description see next page. THE GENERAL CONDITIONS OF LIFE 329 FIG. 141.— Hyalopus (Gromia) Dujardinii, granular disintegration. /, Whole individual ; numerous pseudopodia are extended from the egg-shaped, membranous shell ; at the left they are being drawn in. II and ///, 'Pseudopodia cut off; granular disintegration is developing; the globules and droplets of protoplasm are held together simply by a loose, viscous connecting- mass ; between them lie scattered larger droplets of hyaline protoplasm (///, D, b), and viscous globules (///, D, a). IV, Pseudopodium which has been cut off at a, and from that point on is undergoing granular disintegration, highly magnified ; at a the granular disin- tegration is completed, the globules are separated ; at b disintegration is beginning, being ushered in by the formation of vacuoles ; between these two points occur all transition-stages. V, Opening of the shell of Hyalopus, with extended pseudopodia ; three have been stimulated at the place indicated by the arrow and have assumed an irregular contour. VI, Place of stimulation of a pseudopodium strongly magnified ; vacuoles are shown, the protoplasm of whose walls is irregularly contracted. Comparison with IV shows the agreement of the two. pseudopodia draw in the latter and become lumpy, or the thread- like pseudopodia become varicose and disintegrate into small globules (Fig. 143). Bits of protoplasm from the interior of cells that have a constant form, e.g., plant-cells or tissue-cells, or even from free-living cells, always become rounded into spherical drops (Fig. 34, a, p. 94). Contractile fibrillse and muscle-fibres pass into rigor mortis, i.e., they contract for the last time (p. 133), and only when the rigor has passed away, when death is completed, do FIG. 142.— 7, Amoeba, ; A, normal ; B, in necrobiosis. II, Leucocyte ; A, normal ; B, in iiecrobiosis. they become again passively extended by the action of elastic elements. In brief, it is found everywhere that protoplasm whose contractility can in any way be expressed dies in the condition of contraction. It would be of value to determine, by a comparative investiga- tion of necrobiotic phenomena, still other peculiarities common to histolytic processes. As Israel ('97, 1, 2) has rightly emphasised very recently in his researches upon the death of the cell, especially the kind of death and the duration of necrobiosis should be studied. Only through the comparative history of death can an under- standing of necrobiotic phenomena, which is now largely wanting, be hoped for in time, and with it will come an advance in our knowledge of the vital process itself. 330 GENERAL PHYSIOLOGY 2. Metamorphic Processes In contrast to simple histolytic phenomena, metamorphic processes are very clearly characterised by the fact that the metabolism of the cell does not merely come gradually to a stand- still, but is previously turned into a perverse course, in such a way '*• FIG. 143. — Necrobiosis of a non-nucleated protoplasmic mass of Orbitolites ; a, the protoplasmic mass has put out still normal pseudopodia ; b, the pseudopodia are becoming varicose and partly drawn in ; c, the protoplasm of the pseudopodia that are not drawn in has disintegrated into drops and globules. that substances which in the normal cell are either not manufactured at all or appear only as intermediate stages, are produced in quantity as a result of the disturbed metabolism, and accumulate within the cell until the latter perishes. The forms of metamorphic processes that are most frequent, best known, and for physiology most important, are fatty degeneration, or fat- THE GENERAL CONDITIONS OF LIFE 331 metamorphosis, mucous degeneration, amyloid degeneration, and calci- fication. To consider first the phenomena of fat-metamorphosis, we must avoid confounding these with apparently similar processes, viz., the deposition of fat or fatty infiltration in fattening, obesity, etc. In these latter also there is a great accumulation of fat in the cells in question, but this fat has not arisen by a disturbance of the metabolism of the cells themselves ; on the contrary, it or its con- stituents has entered into the cells from the outside and has there been deposited. If much fat or materials from which fat can be formed be introduced into the body in the food, such fat becomes deposited by preference in certain parts within the cells, as in the cells of the subcutaneous connective tissue, and thus arises corpulency, the panniculus adiposus. Of course it is not impossible that in many cases of corpulency fat arising pathologi- cally within the body also enters into the cells of the subcutaneous connective tissue and is there deposited. But even here there is always a fatty infiltration of the cells from the outside. In contrast to this, in fat-metamorphosis fat is formed within the cell itself at the expense of its living substance, and there accumulates until the cell is permeated with innumerable, large or small proplets and dies. Such fat-metamorphosis, which ends with the death and disintegration of the cell, occurs in certain places in the healthy body as a normal phenomenon ; thus, it is present in the cells of the lacteal glands at a time when they are secreting milk, when a woman is nursing. It is found that at this time in the lobes of the mammary glands microscopic fat-droplets appear in the protoplasm of the older cells (Fig. 144) ; these gradually increase in number, while the protoplasm gradually dies, and the cell finally becomes a round droplet, full of small milk-globules. The dying protoplasm gradually disintegrates, the fat-globules become free, and the whole mass, i.e., the fat-globules in their liquid, becomes secreted as milk, milk being nothing more than an emulsion of the fat of butter in a solution of salts, proteids, sugar, etc. The younger gland-cells succeed the older, fatty- degenerated and disintegrated cells, and pass through the same changes, and thus the process of milk-formation continues long and uninterruptedly. What occurs as a normal process in the cells of the lacteal glands occurs under pathological con- ditions in much greater extent in very various tissues, and leads almost always to incurable and fatal losses, since as a rule no reparation is made by the younger cells. " The production of milk," says Virchow (71), "in the brain instead of in the lacteal glands, constitutes a form of brain-softening. The same process that in one place affords the happiest and sweetest results, in another induces a painful and bitter wound." Such fatty degenerations appear especially in long-continuing, chronic 332 GENERAL PHYSIOLOGY diseases, such as tuberculosis, heart-diseases, kidney-diseases, etc., in the kidney, heart, liver, blood-vessels, etc. (Fig. 145) ; and their causes always lie in disorders of nutrition, especially in a disturbance of the process of taking in oxygen through the blood. If, e.g., insufficient oxygen is carried to the cell, or if for other reasons its capacity of receiving oxygen is diminished, the fat, which probably in most cells appears in traces, is not burned, i.e., oxidised, as happens normally, but is stored up and accumulates in quantity. For this reason also in habitual drinkers and after phosphorus-poisoning, where as a result of the ingested alcohol or phosphorus the income of oxygen is diminished, a considerable fat-metamorphosis of the tissues, especially of the liver-cells, always takes place : and pathology recognises a whole series of cases where fat-metamorphosis can be traced to the same causes. It is highly probable that in all processes of fat- metamorphosis the fat originates from the decomposition of FIG 144. — Fat-metamorphosis in the forma- tion of milk in the lobes of the lacteal glands. (After Virchow.) FIG. 145. — Fat-metamorphosis of cardiac muscle-cells ; the granules in the cells consist of fat. (After Ziegler.) proteid. It is known that in the decomposition of the proteid- molecule both nitrogenous and non-nitrogenous complexes of atoms appear. Moreover, it has been seen,1 that fat can be formed from proteid ; and Leo ('85) has shown in the case of fat-meta- morphosis after phosphorus-poisoning that the fat originates within the body. Since now, thirdly, it has been found that the excretion of urea is considerably increased after phosphorus-poisoning, the conclusion is justified that after phosphorus-poisoning proteid is decomposed in greater degree, and that the non-nitrogenous complex of atoms that arises during the decomposition is the fat deposited in the cells, while the nitrogenous portion is transformed into urea and given off to the outside. The origin of fat, at least in all fat-metamorphoses, must be regarded as wholly analogous. The phenomena of mucous metamorphosis form a complete counterpart to those of fat-metamorphosis. As in the latter fat, so in the former mucus, is formed from, the living substance of the 1 Cf. p. 163. THE GENERAL CONDITIONS OF LIFE 333 cell. In many cases the mucus that appears contains genuine mucin, in others it consists of mucinoid substances, but it is always a compound of proteid with some kind of carbohydrate.1 It is seen, therefore, that in mucous metamorphosis the origin of the mucus lies in the proteid. Mucous metamorphosis occurs also normally in the healthy body, especially in the cells of the mucous membranes of the respiratory and intestinal tracts, as well as of the urogenital system. In the formation of mucus by these mucous cells under normal conditions the whole cell never perishes, but a part only of its protoplasm is transformed into mucus. Almost always mucous cells are cylindrical cells ; their basal part contains the nucleus, and their upper end bounds the free surface of the mucous membrane. It is always the upper, free end of the cell- FIG. 146.— Mucous cells. A, Three isolated mucous cells ; B, seven mucous cells united. The three at the left are full, the four at the right are empty. (After Schiefferdecker.) body, the protoplasm of which is transformed into mucus, swelling up into a transparent mass containing separate protoplasmic granules ; each mass, having no boundary, unites with the mucous masses of the neighbouring cells into a coherent mucous cover- ing. The process is a continual one and is increased by certain external influences. The lower part of the cell-body containing the nucleus continues to live (Fig. 146), and constantly shoves up- ward new masses of mucus-forming substance, or mucigen, which become transformed into mucus in proportion as they move along. A complete transformation of the whole cell-body into mucus, accompanied by the death of the cell, occurs in many lower animals upon strong external stimulation ; the phenomena of this process are very remarkable. They are most remarkable in certain forms of sea-cucumbers, or holothurians, belonging to the Echinodermata,, plump animals, whose bodies are covered by a tough, brown, leather-like skin and resemble a cucumber. If Holothuria Poll, e.g.,. 1 Cf. p. 108. 834 GENERAL PHYSIOLOGY which lives in the Mediterranean Sea, be brought into the air, the thick, hard skin begins gradually to liquefy into a viscous mucus, and after a few hours becomes completely softened. If small pin- holes be bored through an excised piece of the skin this mucous liquefaction, as Semper ('68) showed, can be rapidly induced ; around each hole the cells begin at once to swell up and disintegrate, and the whole piece is changed finally into a thick liquid mass, which, when touched, can be drawn out into glistening threads. Many species of the holothurian genus Stichopus are said to transform their skin in a very short time into a thick mucus. It would be extremely interesting to investigate both chemically and micro- scopically this wholly unique case of a sudden mucous meta- morphosis of so solid and tough a structure as is the holothurian skin. Krukenberg ('82) alone has made a partial study of it. The mucous metamorphosis of epithelium-cells, leucocytes, etc., which occurs in the human body, es- pecially in intense catarrhs, is well known : in these cases the cells in question die with a swelling and transformation of their living sub- stance into mucus (Fig. 147). In the phenomena of amyloid metamorphosis, in contrast to the FIG. i47.-Mucous-metamorpho8ed ceils. /, processes hitherto considered, a Leucocytes ; ii, ciliated cells. (After substance is formed which, so far as is known, does not occur at all in the normal body. This .substance, which glistens like wax or lard — which probably has conferred upon the disease in question the name of waxy or lardaceous degeneration — was first termed by Virchow amyloid substance, because with iodine staining it behaves like plant-amylum .and cellulose, under certain conditions being coloured blue by the iodine. Later it was recognised as a proteid-like body, for it contains nitrogen and gives certain proteid reactions ; hence, for the present it is classed in the comprehensive group of albuminoids. Its behaviour with the aniline colour, methyl violet, is very characteristic; with it it takes on a beautiful ruby-red colour, while healthy tissues are coloured blue. By its character as an .albuminoid, amyloid substance points plainly to its origin. It can be derived only from the proteids of the cell, and, although thus far nothing is known in detail concerning its origin, it may safely be considered as a metamorphosed proteid, which is excreted to the outside by the cell and stored up. It never seems to be stored within the cell itself, it is always found rather in the connective substances cementing the cells, especially in the walls of the small blood-vessels (Fig. 148). But, in proportion as the cells secrete it, they die, whether as the result of perverse metabolism, the THE GENERAL CONDITIONS OF LIFE 335 product of which is the amyloid substance, or because passively they are torn apart, pressed upon, asphyxiated and killed by the substance accumulating in masses. Amyloid metamorphosis is a secondary phenomenon of disease, appearing especially in connection with long-existing, chronic diseases, such as tuberculosis, long- continued suppurations, etc., in the abdominal organs, especially the spleen, liver, kidneys and lymphatic glands. This indicates that nutritional disturbances of the tissues, very gradually developed and profound, cause the cells to be put into the condition where their proteid changes gradually into amyloid substance. Beyond what has been stated, amyloid metamorphosis remains still one of the most enigmatical among the metamorphic processes, al- though it is wide-spread and possesses great importance in pathology. Finally, calcification is in a certain sense a counterpart to amy- loid metamorphosis ; for, as in the latter amyloid substance, so in the former lime-salts are formed by the cells, and are either excreted to the outside or deposited in the dying cell-substance itself. The formation of bone in the normal body is analo- gous to the former. Large skeletal bones develop from a cartilaginous basis; the cartilage-cells excrete into the ground- substance calcareous salts, especially calcareous phosphate and carbonate ; particles of these press gradually upon one another blend FlG.148._Amyloi(;7e^nerationof the together, and thus form the SOlld bony capillaries of the liver ; the cells i • i ,1 T n are forced apart by the amyloid Substance, in Which the bone-Cells masses stored up between them. continue to live as so-called bone- corpuscles. This process, which ap- pears absolutely necessary in the development of the vertebrate organism, occurs also under pathological conditions, especially when in old age or after certain diseases the cartilaginous discs in the joints ossify. In these cases the same phenomena are present, excepting that, as a rule, the cells by which the lime-salts are excreted later die. Besides this ossification, there occurs also under pathological conditions a true calcification of the cells themselves, in which the lime-salts become stored within the dying cell, until finally the living substance has wholly disappeared and its place is taken by a cemented calcareous mass. This happens in the walls of the arteries (Fig. 149, A), so that they become brittle and afford an opportunity for haemorrhages ; if the latter take place in the brain they constitute apoplexies, or so-called paralytic strokes. Further, in certain brain-diseases the ganglion-cells of the brain become calcified, and there are 336 GENERAL PHYSIOLOGY found, e.g., in the brains of idiots, " petrified " ganglion-cells in the true sense of the word (Fig. 149, B). Besides the forms of metamorphic processes here presented, pathology recognises others, such as pigment-atrophy, hyaline degeneration, colloid metamorphosis, etc., at the basis of which there is always the same principle, namely, that the meta- bolism of the cells takes a perverse course, and forms substances that normally are formed either not at all or only in slight quantity, the final result being the death of the cell. But in the cases FIG. 149.— Calcification of cells. A, Calcified cells in the wall of a blood-vessel. B, Calcified ganglion-cells from the brain of an idiot. (After Ziegler.) mentioned these substances and their genesis are much less known than in the metamorphic processes that have been discussed ; hence it does not appear necessary in this place to go into them more fully. In general, metamorphic processes, especially the genesis of the substances that arise in them and the disturbances of normal metabolism upon which they rest, need greater elucidation ; naturally this will come in proportion as the knowledge of meta- bolism in general becomes extended. B. THE CAUSES OF DEATH The causes that lead to death are as manifold as are its phenomena. We have already touched here and there upon some of the special causes, but it is impossible to treat these in every individual case. It is necessary, however, to go somewhat more fully into the general causes, because with them is joined the interesting question whether death is for all living organisms the dira necessitas that it is for mankind — in other words, whether there are organisms whose bodies are immortal. THE GENERAL CONDITIONS OF LIFE 337 1. External and Internal Causes of Death If we start from the fact that life can only arise, and, moreover, must arise, as soon as a certain complex of conditions is fulfilled, the causes of death in their general form are evident ; for death must then take place so soon as the general conditions of life disappear. In accordance with the distinction between external and internal conditions of life, a distinction must also be made between external and internal causes of death, according as death is due to the removal of the external or of the internal vital conditions. To examine, first, the external causes of death, the fact does not require detailed consideration that withdrawal of oxygen, water and food-stuffs, and, further, exceeding the necessary limits of tempera- ture and pressure, lead to death, except in the case of organisms that under certain conditions pass into the state of apparent death. But these do not include all the external causes of death. All these conditions may be fulfilled and yet death be brought about by the action of external causes. Hence we must reckon among the external conditions of life the absence of such influences as are destructive to living substance, especially chemical and electrical influences. The chemical influences that produce fatal effects are the poisons, and they are innumerable. All chemical substances that come into chemical relation with any of the essential constituents of living substance so that the mechanism of metabolism thereby suffers disturbance, cause death, sometimes after very brief, some- times after long-continued action, death following very rapidly or constituting the end of long, necrobiotic changes. If, e.g., mineral acids or metallic salts act upon the living substance of a cell, the cell inevitably dies, because all proteid is precipitated or chemically combined by these substances so that metabolism must cease. Other substances that are poisonous to all living substance are the anaesthetics (chloroform, ether, alcohol), the vapours of which by continued action finally bring all vital phenomena to a standstill, whether in plants, animals or unicellular forms.1 To what change of the living substance this peculiar effect of anaesthetics is due is for the present wholly unknown ; and the same must be said of the great majority of poisons that act, some upon all living substance, and some upon certain cells only. Like poisons, electricity in great intensity also acts harmfully to living substance by producing chemical changes in it. It is well known that chemical compounds in solution can be decomposed by a galvanic current. The compounds of living substance are 1 Of. Bernard (78). 338 GENERAL PHYSIOLOGY likewise decomposed by strong galvanic currents, so that the living substance is killed and disintegrates. Thus, external causes of death are superficially clear and distinct, although the details of their actions are still largely unknown. It is entirely different, however, with the internal causes of death. They are still very obscure. Many investigators believe that there are no internal causes of death that are based upon the properties of living substance, and they explain the appearance of death in old age in people who have never been ill by the gradual accumulation of small, imperceptible disturbances during the whole life. This is the most frequent explanation of the phenomenon. But it appears very insufficient. Johannes Mliller ('44) was not satisfied with it. . In the chapter upon the Mortality of Organic Bodies in his handbook, he says : " The question why organic bodies perish, and why organic force passes from the parts producing it into the young, living products of the organic body while the old parts die, is one of the most difficult in all general physiology. We are unable to answer this question, but can merely present the associated phenomena. It is insufficient to answer that inorganic influences gradually wear away life, for then the organic force would be obliged to begin its diminution at the beginning of the individual. Yet it is well known that at the time of puberty organic force is still so complete that it multiplies itself in the formation of germs. There must, hence, be a very different and deeper-lying cause that conditions the death of individuals, while assuring the trans- mission of organic force from one individual to another and in this way its immortality." Many such objections may be made. Were the view correct that death is brought about by the summa- tion of the actions of external injuries, it would be expected that a man who lives very regularly and avoids as much as possible all harmful things would necessarily live much longer than one who lives irregularly and exposes himself to many hardships. But, even if such a difference in the duration of life should occur, in many cases it would always be minute, for the oldest men have not lived much beyond 120 years, and not all of these persons have followed an especially regular course of life. Another circum- stance comes in. In all men, without exception, whether during their life they have been exposed to the greatest or the least dangers, whether they have been often or never ill, or whether they have had this or that disease, the same phenomena of old age finally appear, consisting of atrophic processes of almost all organs. With special reference to the last circumstance Cohnheim (77-'80) rightly indicates another explanation in saying : " The constancy with which, no matter whether many or few, and especially what pathological phenomena have occurred in the life of an individual, a more or less pronounced atrophy appears in all organs of his THE GENERAL CONDITIONS OF LIFE 339 body in old age, in my opinion speaks very evidently for the idea that the conditions of senile atrophy, so to speak, are physio- logical." Minot ('90, '91) also adopts the same standpoint in his researches upon growth and the phenomena of old age. In fact, when man is considered not as something completed and unchangeable ; when, rather, his whole development is observed, and it is seen how, although living always under the same external conditions, he changes gradually after birth ; how even in childhood many organs, such as the thymus glands, normally atrophy, although not the slightest injuries from the outside act upon them ; and how later in all women even in the prime of life the sexual organs degenerate, etc., etc., — it can no longer be doubted that senile atrophy, which leads finally to death from the feebleness of old age, is simply the end of the long developmental series that man, like every animal, must pass through during his individual life. In reality there is no standstill in the life of the organism. As the adult organism develops gradually from the small egg-cell without the slightest change of its external vital conditions, as is the case in many animals living in the water, so it develops also, although at a different rate, gradually farther to a senile, and finally to a dead, organism. The egg-cell is the beginning, death in old age the natural end of an unbroken development, the cause of which lies in the peculiar composition of the living substance of the egg-cell. It would, hence, be more correct, in place of the current view that death is conditioned by the continual summation of external causes, to believe that the causes of so-called natural death exist in the living organism itself. This view is justified at once if the history of death be con- sidered, not simply with reference to mankind, but comparatively. The fact that the idea of death as an end-result of the develop- mental series appears so late in the history of science is closely associated with the prevalent view, that man, when grown, has finished his development and exists for years and decades in a stationary condition. This view is thoroughly false, and is due simply to the fact that man's development takes place much more slowly during his adult life than during his embryonic and youth- ful stages. In reality, development never ceases. Changes are seen clearly enough when the conditions of the adult are com- pared at long intervals of time. Although no new organs are formed in the meantime, the man of thirty years is a different being from the man of forty years, the man of forty from the man of fifty and sixty. A stationary condition is never present ; cell- division, upon which from the egg-cell on all development depends, takes place in adults and even in old men, although it becomes constantly slower and slower. What is difficult to recognise in man is shown at once by a glance at the relations that prevail z 2 340 GENERAL PHYSIOLOGY among insects. While in man adult life is extremely long in comparison with that of the embryo, in most insects the reverse prevails. Many insects die very soon after copulating or deposit- ing the eggs ; the only individuals to live longer are those that do not copulate. The best example is afforded by the day-flies. The completely-developed adult individuals frequently live but a few hours, dying immediately after depositing the eggs. These facts prove most strikingly that the causes of death are not to be found in the summation of many external injuries, but are already established within the organism itself, and death is simply the natural end of development. In other words, the problems of development and death belong inseparably together, the latter is merely a part of the former. We will now summarise the results of these considerations once more and in somewhat different words. The idea expressed regarding the causes of natural death is based upon the impor- tant fact that the organism undergoes uninterrupted change from its individual origin to its death. The various parts of the organism, however, take part in this change in very different degrees and at very different rates. In this manner there comes gradually in the life of every organism a time when the action of its mechanism has experienced such a disturbance through the changes that the individual parts have undergone in its develop- ment, that it passes into death. For the multicellular organism this means that from internal causes the various cells and cell- groups of its organs become gradually so changed in their de- velopment, that with the close dependent relation among all cells, tissues, and organs, the disturbance of their co-operation becomes constantly greater until the organism dies. The immediate causes of death may be very different for the different cells of the multi- cellular organism. Many of the cells and tissues invariably die from causes lying outside of them but within the organism, because the parts upon which they are dependent, which belong to their external conditions of life, as, e.g., the nerve-centres, have undergone disturbances and have died. If the ganglion-cells whose activity controls the movements of respiration have perished, respiration ceases, the heart stands still, blood circulates in the tissues no longer, the tissue-cells are no longer nourished, and all the tissues alike perish sooner or later, because their external con- ditions of life are withdrawn. But, if the individual tissue-cell does not die from external causes, exactly the same is true of it as of the cell-community — the condition of its living substance undergoes uninterrupted change from internal causes, and there gradually develops a point of time when the disturbances in the co-operation of its constituents have become so great that life ceases. These statements do not, indeed, disclose the special events in living substance, the result of which is death, no more THE GENERAL CONDITIONS OF LIFE 341 than they reveal the mechanism of development and life in general ; but they afford a simplification and a sharper formula- tion of the problem, and bring us somewhat nearer to an understanding of it. The problem of development and the problem of death contain the same question, namely : Why does living substance continually change during its individual life ? Deeper penetration into the chemism of the living cell will alone be able to reveal the special causes of this phenomenon. 2 The Question of Physical Immortality If natural death be considered from the standpoint just pre- sented, a question which during the last decade has been actively discussed upon the scientific side constantly obtrudes itself, viz., Are there not organisms for which death is not a necessity ? Evidently an organism can be imagined the development of which is such that a disturbance that makes impossible the co- operation of the individual parts never appears. This would be the case if the uninterrupted changes that appear during the development of the organism in question form a series composed of members recurring periodically. Such a development could perhaps be represented schematically in the form of the solution of a periodic continued fraction, which, transformed into a decimal fraction, would give a periodic series, while the develop- ment of an organism that is destined to die might be compared to the solution of a definite fraction. Theoretically, such a hypo- thetical organism would necessarily be immortal under external conditions that always remained exactly the same. It is, however, a question whether such organisms really exist. Weismann ('82, '84) believes that this question can be answered in the affirmative, and it is interesting to follow his discussion. He finds a fundamental difference between multi- cellular organisms and unicellular Protista. Starting from the thought that the term death can be employed only where a corpse exists afterwards, he considers all multicellular organisms as mortal, and all unicellular organisms as immortal. In multicellular organisms no case is known where sooner or later the body does not die. In unicellular forms, however, this is not true. A unicellular in- fusorian, e.g., never becomes a corpse unless it is the victim of an external catastrophe. It grows and divides into two halves when it has reached a certain size, but each half likewise grows and later divides and so on, and Weismann believes that this continues without end. But since the two halves are wholly alike, and since the species can be maintained only by continued division, a corpse is never found, and a half never dies without external 342 GENERAL PHYSIOLOGY causes. Hence, according to Weismann's idea, unicellular organisms "are immortal. Weismann, therefore, disputes the view that death is a phenomenon grounded in the nature of living substance, and does not believe that it depends upon " purely internal causes inherent in the nature of life itself." He holds death, rather, to be a phenomenon of adaptation which has been evolved in the course of the organic development of the earth as advantageous, and he represents its appearance in the organic series somewhat as follows : In the unicellular Protista all the functions of the body including that of reproduction are localised in a single cell. If, therefore, natural death were a necessity for the unicellular organism, reproduction would terminate with death ; and, since with the equality of the parts resulting from division the same holds good for all, after a short time the species in question would become extinct. Hence in unicellular forms death is impossible, Weismann maintains, because otherwise the species would become extinct. In multicellular organisms, on the other hand, the higher we go in the series, the more a contrast develops between the sexual cells, which serve for reproduction only and hence for the maintenance of the species, and the cells of the rest of the body, which in the higher animals have completely lost the power of reproducing the species. Here, therefore, there is the possibility of death without the maintenance of the species thereby being endangered ; for, if only one reproductive cell really reproduces, if only one egg develops, all the rest of the body can die without the species becoming extinct. Since now, as Weismann says, " the unlimited duration of the individual would be a luxury without any advantage," according to the well-known principles of selection immortality has been lost as disadvantageous and death has been evolved. " In unicellular animals it was impossible to establish normal death because the individual and the reproductive cell were one and the same; in multicellular organisms, however, somatic and reproductive cells were separate, death became possible, and we see that it was established." It cannot be denied that these deductions of Weismann sound very plausible ; nevertheless, they are not invulnerable, and have already called forth much active contradiction. Especially has the claim always been contested that unicellular organisms should be considered immortal for the single reason that their body never becomes a corpse. In defining the concep- tion of death, emphasis has been laid by Weismann's opponents largely upon the cessation of the individual life, and it has been said : If the unicellular organism divides into halves, its individual existence is therewith ended ; but where the individual existence ceases, the term immortality cannot be used, since in reality the individual has perished; death and reproduction here coincide. It is evident that here there is simply a contest over ideas, which THE GENERAL CONDITIONS OF LIFE 343 leaves untouched the phenomena themselves, for in the end it is a matter of taste, whether the appearance of a corpse, or, what is more general, the end of the individual existence, is regarded as the essential factor of death. The fundamental distinction which Weismann makes between unicellular and multicellular organisms respecting immortality may be attacked from another side. As has been seen, Weismann's theory of the immortality of unicellular organisms rests upon the supposition that the reproduction of these forms by division can go on without end, without any remnant, any corpse, being left over. It is a question whether this supposition is correct. A few years ago Maupas ('88) carried out upon Infusoria a series of striking researches, from which it appears that in that group this is not the case. He bred Infusoria in cultures for many generations, and found that after a large number of succes-1 sive divisions the individuals gradually showed changes that led inevitably to death, unless after a long period of dividing, leading often to hundreds of generations, the opportunity was given them to conjugate, i.e., to enter into a correlation that corresponds in unicellular organisms to the process of fertilisation in higher animals.1 Only when a series of divisions was followed by a period of conjugation were the individuals separating after conju- gation in condition to divide again unchanged without passing gradually into death. If, however, the individuals were isolated after every division, after some time they inevitably died. There is here presented, therefore, a real phenomenon of old age, which corresponds completely to the senile atrophy of tissue-cells in man and the higher animals, and Maupas himself was forced to reject Weismann's doctrine of immortality. But at this point, to save the doctrine, Gruber ('89) speaks a word for Weismann and says: "It is true that those individuals that by chance do not conjugate, perish, but the material of the others lives on for ever." Since now, in nature conjugation is the custom — for, otherwise, the Infusoria would long since have become extinct — the members of this group, Gruber thinks, are really immortal. Although the justice of this argument is to be recognised, another fact should be noticed. R. Hertwig (588-'89), who studied very carefully the events of conjugation, found that a part of every cell dies during the process, viz., the macro-nucleus and a part of the daughter- nuclei, derived by continuous division of the micro-nuclei. These constituents of the cell break up into small fragments, which finally become completely dissolved in the protoplasm.2 In other words, portions of the individual actually die. That the material derived from their disintegration is finally consumed again by the cell, like the ingested food, does not banish the fact that these parts really die. The cells that disintegrate in the histolysis of a 1 Of. p. 200. 2 Of. p. 201. 344 GENERAL PHYSIOLOGY tadpole's tail and the death of which no one will deny, are likewise employed again as material for the construction of other organs. But, if in the conjugation of the Infusoria there are realty dying parts, really partial corpses, the fundamental contrast between unicellular and multicellular organisms, maintained by Weismann, disappears, and the whole difference consists simply in the quanti- tative relation of the surviving and the dying substance ; in multicellular organisms only the body-cells die, while the reproductive cells continue to live. In general, it would be wholly incorrect to say that in multicellular organisms an exceedingly large mass, namely, the whole body, dies, and only tiny masses, the ova or spermatozoa, remain living, while in Infusoria the greater part remains living and the smaller part dies. There are examples among animals where the relation does not differ at all from that in Infusoria. A female frog, e.g., produces in the course of her life a mass of eggs that in relation to her body is even con- siderably greater than the mass of cell-substance that in the in- fusorian body in conjugation remains living in contrast to that which dies. If, therefore, the frog and, in general, the multicellular organism are mortal, the unicellular Infusoria are mortal also ; in both cases it is only a part of the living substance of the individual that is transmitted to the descendants. Not only in the life of the Infusoria, but also in that of other unicellular organisms there are periodically recurring events, in which parts of their body perish. Many Protista reproduce by the formation of spores. If this process be followed in a large radio- larian, e.g., Thalassicolla, which has been studied in detail by R. Hertwig and Brandt, it is found that the nucleus in the central capsule breaks up into many small nuclei, which surround themselves each with a protoplasmic mass, and develop into many small swarm- spores ; the large, extracapsular, protoplasmic body and also a part of the intracapsular protoplasm, which is not consumed in the formation of spores, perish completely. Here, likewise and per- haps still more evidently than in the Infusoria, there are really partial corpses. We see, therefore, that with the great majority of unicellular organisms, with all whose course of development has thus far been studied in detail, Weismann's idea does not agree. ^Finally, the possibility is not to be dismissed that there may be, or may once have been in the course of the phylogeny of living substance, Protista, whose cycle of development is so simple that their living substance simply grows constantly without conjugation and without spore-formation, and, when they have reached a certain volume, divides without any remnant, and continues to grow and divide as long as the external conditions allow. According to Weis- mann's idea, such Protista would be really immortal beings. But at this point the weakness of the doctrine of immortality appears per- haps most distinctly. If Weismann's standpoint be accepted, that THE GENERAL CONDITIONS OF LIFE 345 not the cessation of the existence of the individual, but the transform- ation of living substance into a corpse, i.e., into lifeless substance, is the criterion for the conception of death, then the question of the existence of immortal organisms coincides with that of the immortality of living substance in general. But the conception of living substance as immortal will be accepted by scarcely any one who bears in mind the characteristic peculiarity of living substance, viz., that it continually decomposes, or, in other words, dies. There is no living substance that, so long as it is living at all, is not continually decomposing in some parts, while being regenerated in others. No living molecule is spared this decomposition ; the latter, however, does not seize upon all molecules at the same time ; while one is decomposing, another is being constructed, and so on. One living particle affords the conditions for the origin of another or several others, but itself dies. The particles newly formed in turn give origin to others and, likewise, die. In this manner living substance is continually dying, without life itself ever becoming ex- tinct. Hence, there is no immortality of living substance itself, but merely a continuity in its descent. Life as a complex motion has never become extinct from the time of its first appearance upon the earth down to the present, but living substance in the form of bodies is dying continually. Life as a complex motion does not possess true immortality any more than it has existed from eternity. Just as the earth in its development has passed through a time when no life could yet exist, so it will again pass through a time when all life must become extinct. The moon now shows us the fate that hangs over the earth. From the liquid drop which once was cast off from the great, glowing mass of the earth, it has in a briefer time passed through essentially the same development as the earth which gave it its origin. The intense cold that now prevails upon it will sometime take possession of the earth, and annihilate all life upon the latter. So far as the physical world is concerned, immortality and eternity are the properties not of any special material system, such as living substance, or of any special complex motion, such as life, but only of elementary matter and its motion. Heraclitus compared life with fire. As has been shown above, such a comparison is a pertinent one. Our consideration of vital conditions makes this more evident. It has been shown that life like fire is a phenomenon of nature which appears as soon as the complex of its conditions is fulfilled. If these conditions are all realised, life must appear with the same necessity as fire appears when its conditions are realised ; likewise, life must cease as soon as the complex of its conditions has undergone disturbance, and with the same necessity with which fire is extinguished, when the conditions for its maintenance cease. If, therefore, all vital conditions had been investigated in their 346 GENERAL PHYSIOLOGY minutest details, and it were possible artificially to establish them exactly, life could be produced synthetically, just as fire is pro- duced, and the ideal that existed in the imagination of the mediae- val alchemists in their attempted production of the homunculus would be achieved. But, notwithstanding the fact that this theoretical possibility cannot be denied, every attempt at the present time to produce life artificially and to imitate in the laboratory the obscure act of spontaneous generation must appear preposterous. So long as our knowledge of internal vital conditions, i.e., of the composition of living substance, is so imperfect as it is now, the attempt artificially to compound living substance will be like the undertaking of an engineer to put together a machine the most important parts of which are wanting. For the present the task of physiology can consist only in the investigation of life. When physiology shall actually have accomplished this, it may think of testing the completeness and correctness of its achievement by the artificial inauguration of life. CHAPTER V STIMULI AND THEIR ACTIONS WHEN investigating a phenomenon of nature the physicist is not satisfied with determining the conditions under which it exists ; he endeavours to learn also how it is affected when the conditions are altered. Life is a phenomenon of nature. In the preceding pages we have become acquainted with its manifestations and the conditions of its appearance, and we have seen the results of an entire removal of those conditions. It remains for us to learn how vital phenomena are affected when the conditions are altered and new ones are allowed to surround the living substance. Vital phenomena are called spontaneous, when all the external conditions of life continue unchanged, and •phenomena of stimulation, when other influences act upon them. This distinction is a valid one, but it must be borne in mind that spontaneity is not absolute, that as a matter of fact spontaneous vital phenomena depend upon the interaction of living substance and the environment no less than do the phenomena of stimulation. The former represent merely the reaction of living substance to normal, constant external vital con- ditions; the latter, the reaction of living substance to changed external vital conditions. In many cases it is quite impossible to decide whether a given phenomenon is spontaneous or a result of stimulation, since even in nature the external conditions of an organism do not remain constant, but frequently change in a manner that eludes even the most exact methods of investigation. In order, therefore, to study undoubted phenomena of stimulation we have recourse to the experimental method, and produce the phenomena artificially by causing stimuli to act upon living substance. In so doing we secure the incalculable advantage of keeping in hand and controlling exactly the conditions under which the phenomena exist, and thus are able to experiment with vital as with simple physical phenomena. 348 GENERAL PHYSIOLOGY I. THE NATURE OF STIMULATION In accordance with the foregoing statements, a stimulus may be defined as every change of the external agencies that act upon an organism. If a stimulus comes in contact with a body that possesses the property of irritability, i.e., the capability of reacting to stimuli, the result is stimulation. It is necessary to examine somewhat in detail the general characteristics of the process of stimulation. A. THE RELATION OF STIMULI TO VITAL CONDITIONS 1. The Varieties of the Stimulus If every change of the agencies that act upon the organism from without is able to stimulate, it is evident that innumerable kinds of stimuli exist. Not only may every existing condition of life be changed, but new conditions may appear and affect the organism. Notwithstanding this possibility, stimuli may be classified according to their qualities into a few large groups. A natural classification is possible in accordance with the forms of energ}^ which the different stimuli represent ; for the operation of every external agent upon a body depends upon a transformation of energy. In accordance with this principle all influences of a chemical nature may be grouped as chemical stimuli, including not only changes in the income of food, water, and oxygen, but other chemical changes which ordinarily do not come into contact with the organism. Among chemical stimuli belong also the processes by which in the animal cell-community the nervous system influences the tissue-cells dependent upon it ; for every nerve stimulation has at its foundation a chemical transformation of nerve-substance, which is transmitted to the cells of the tissues and acts towards the latter as a chemical stimulus. In accordance with our modern ideas upon the metabolism of living substance, the old conception that nerve stimuli are merely electrical stimuli, and that nerves behave as copper wires, can find credence no longer. All purely mechanical influences that affect the organism may be termed mechanical stimuli, including those that consist in changes of pressure, such as pushing, shaking, pressing, pulling, and sound-vibrations, those that manifest themselves by molecular attractions, such as cohesion or adhesion in the surrounding medium, and those that depend on the action of gravitation. Thermal stimuli comprise changes of the temperature that surrounds the organism. STIMULI AND THEIR ACTIONS 349 Photic stimuli comprise changes of light. Electrical stimuli comprise electrical changes. The above classes include all forms of energy that come into relation with the organism. It is observed that in this enumeration magnetism is wanting. But it is now known with certainty that magnetism exercises no effect whatever upon living substance, and cannot properly be termed a stimulus. To it was ascribed at one time a most far-reaching and remarkable influence over the living organism ; this was when the physician Mesmer popu- larised the so-called "animal magnetism," and when the possibility of magnetising human beings, animals and plants, by means of magnets was believed in. But later research, and especially the discoveries of the Scotch physician, James Braid, showed that the phenomena that were observed in those cases from which gross deception was excluded were phenomena of hypnosis, and had nothing whatever to do with magnetism ; in their production a piece of glass, a polished button, a gas-flame, or any other visible object had the same significance as a magnet. In accordance with the mysterious attraction that all mysticism is wont to exercise over the human mind, there are found even at the present time, not only among the visionary adherents of spiritualism, but even among acute physicians, some who are convinced of the action of strong magnets upon certain individuals, especially upon hys- terical women. But from all observed cases sober investigation has invariably torn away the veil of mystery, and has revealed either fraud on the part of the " mediums " or self-deception on the part of the observers. Careful experiments upon the influence of magnets upon the living organism have always yielded negative results. The recent, extended researches with very strong electro- magnets by Peterson and Kannelly in America demonstrate the utter ineffectiveness of magnetism upon living matter. Stimuli, therefore, comprise chemical, mechanical, thermal, photic, and electrical changes in the environment of the organism, and no others. 2. The Intensity of the Stimulus In order to form a clearer idea of the relation of stimuli to vital conditions, we must turn our attention to the intensity of the former. Every external vital condition can be fulfilled in different degrees : food, oxygen, etc., may be introduced in small or large quantities ; the temperature may be low or high ; in brief, every vital condition can vary gradually within very wide limits without life thereby being endangered. Nevertheless, limits to most vital conditions are known, both an upper and a lower limit, and these are termed respectively maximum and minimum. Continual life 350 GENERAL PHYSIOLOGY is possible only between these. If they are overstepped, death develops. But all points between the two limits are not equally favourable to life. The intensity of the life-process is less when the vital condition is near its maximum or minimum, than when it has an average value. That degree of any vital condition at which life thrives best, at which the intensity of the life-process is greatest, is termed the optimum. But the optimum is not always Optimum, Tod £eb&n. Tod DIAGRAM OF VITAL CONDITIONS. intermediate between the maximum and the minimum, in many cases it lies nearer the former, in others nearer the latter. In accordance with the above diagram of vital conditions the conception of the stimulus may be at once appreciated. If an organism exists at the optimum of any vital condition, e.g., of temperature, then every deviation of the temperature, whether in the direction of the maximum or the minimum, acts as a stimulus. That degree of any vital condition to which the organism is adapted, represents its optimum, it represents the indifferent point of stimulation ; here the stimulus is equal to zero. If the condition changes toward the maximum or the minimum, the intensity of the stimulus simultaneously increases until it reaches the maximum or the minimum. The stimulus, therefore, has a minimum, which coincides with the optimum of the vital condition in question, and two maxima, the one at the minimum, the other at the maximum of the condition. With supra-maximal stimulation death develops. If, therefore, a diagram of stimulation be constructed, the same points must be designated as in the diagram of vital conditions ; but other names must be given them, for the optimum of the conditions becomes the zero-point of JVidlpunkt Tod Leben, Tod' DIAGRAM OF STIMULATION. stimulation, the minimum and the maximum both become maxima. Every change of intensity between the zero-point and either maximum acts as a stimulus. This diagram comprises all varieties of stimulus, even those which, like certain chemical and electrical stimuli, under normal conditions do not come into relation with the organism at all. The intensity of these latter varieties considered as vital conditions STIMULI AND THEIR ACTIONS 351 is zero : in other words, the complete lack of them corresponds to the optimum. They can, therefore, have but one maximum, so that for them only the right-hand portion of the diagram comes into consideration. They are included in the general definition of the stimulus, namely, every change of the external agencies that act upon an organism ; this definition holds good as well for those agencies which, like heat, function in a definite degree as vital conditions, as for those which, like electricity, under usual circumstances are absent from the environment of the organism, and, therefore, do not exist as conditions of life. In considering the intensity of the stimulus, one more point requires mention. Let us imagine an organism or part of an organism, e.g., a muscle, under conditions in which no stimulus affects it, and let us bring to bear upon it a stimulus, e.g., the gal- vanic current, which varies in intensity from zero upward and can be graded easily and delicately. Then we should expect the muscle to exhibit phenomena of stimulation, i.e., to perform a contraction, as soon as the intensity is increased above 0. But this does not happen. The intensity can be increased considerably before the muscle performs even the slightest twitch. Only when the intensity has reached a certain degree does the muscle respond with a contraction ; from here on the contraction is never wanting, and, up to a certain degree, becomes more energetic the more the intensity is increased. The stimulus, therefore, begins to operate only at a certain intensity, and this point is termed the threshold of stimulation. Below the threshold the stimulus is ineffective ; above it the effect increases with increasing intensity of stimulus. For the different forms of living substance the value of the threshold is very different. Thus, nerve-fibres are put into activity by extremely feeble galvanic stimuli, while Amoeba demands very strong currents. The same is true of all other varieties of stimuli in relation to the various forms of living substance. 3. Trophic Stimuli For the sake of convenience our considerations thus far have been based upon the idea that a certain contrast exists between vital condition and stimulus, in so far as the former represents a stable given state, and the latter every change of that state. This sharp distinction cannot be maintained for the reason that vital conditions are not wholly stable and continuous factors, but in nature are constantly undergoing variations. Hence, under certain circumstances certain vital conditions can be considered also as stimuli, or what is the same thing, certain stimuli function as necessary vital conditions. A few concrete cases will make this at once clear. 352 GENERAL PHYSIOLOGY With all those organisms that do not exist in a constantly uniform nutrient medium, that rather must seek their food, food is available only at irregular intervals. Periods of lack and periods of superfluity alternate with one another. If such an organism has had no food for some time, if, e.g., an Amceba, which nourishes itself upon Algce, has been deprived of food for some time and by chance comes to a place where Algae exist, these food-organisms operate as a stimulus upon it and cause it to creep toward and ingest them. Here food acts as a stimulus, although it is a necessary vital condition. Analogous cases exist in the cell- community. The simplest example is afforded by the green plants. Light forms one of their most important vital conditions. Without light no cleavage of carbonic acid, no formation of starch, no assimilation, takes place in the green parts of the plant ; the plant dies. Yet this condition undergoes the widest variations in intensity, for light continually alternates with darkness and, therefore, acts as a stimulus. Not only can the process of assimilation be regarded as a phenomenon of stimulation, but the light-stimulus produces, in addition, a series of other, very evident reactions which express themselves in motion. In the animal cell-community, also, cases in which stimuli are a vital condition are known in great number. The stimulating impulses that are produced in the central nervous system become transmitted to the tissue-cells through the nerve-fibres. A muscle, e.g., moves only when a stimulus is conducted to it from the brain or the spinal cord through its nerve. If the nerve be cut or in any other way be made incapable of transmitting the impulse from the central nervous system, the muscle can no longer move, and after a time atrophies. In less degree a muscle becomes feeble and decreases in mass when it is used little, i.e., when few impulses are sent to it from the central nervous system. This condition is termed atrophy from disuse. This is true not only of muscle- cells, but of all tissues to which, through their nerves, stimulating impulses are no longer conducted. In cases where, by disease, a portion of a nerve has become temporarily impassable to stimuli, medical treatment endeavours, often with success, to hinder the atrophy of the tissue supplied by the nerve by stimulating it arti- ficially by electrical currents, and in this action of the galvanic current lies the sole therapeutic importance of electricity. The strengthening of an organ by use belongs also in this category. By continued use, as every gymnast, fencer, oarsman, and mountain- climber knows, a muscle of moderate strength can be transformed in a short time into one of marked strength and endurance, the mass increasing very considerably. The effect of all exercise depends upon the fact that stimulating impulses are sent continually into the organ in question, putting it into activity. From these examples it is evident that certain stimuli can be STIMULI AND THEIR ACTIONS 353 at the same time very important vital conditions; and these stimuli, which are necessary to the continued maintenance of life, without which the nutrition, the metabolism, of the organs in question cannot continue undisturbed, are termed trophic stimuli. Trophic stimuli do not stand in contrast with other stimuli ; the term " trophic " simply signifies a special peculiarity of the action, and very different stimuli can have a trophic effect. As regards trophic stimuli that in the animal organism are transmitted through the nerves to the tissues, it has been believed that special trophic nerve-fibres and nerve-centres must be assumed in addition to the fibres and centres of known function ; such nerve- fibres are asserted to have nothing whatever to do with the peculiar function of the tissue supplied by them, but merely regulate its nutrition and metabolism. This idea of so-called trophic nerves has produced in physiology and medicine much mischief and confusion, and recently has misled many men of science into the most fantastic ideas and supposed discoveries. But for every critical investigator, who is wont to associate a definite idea with the conceptions with which he deals, the con- fused idea of trophic nerves is simply a piece of the old mysticism of the vitalists. It is seen that the assumption of special trophic nerves and peculiar trophic stimuli, existing in addition to other stimuli, is not needed in order to explain the phenomena, but that the nerves that influence the characteristic function of every tissue regulate thereby the metabolism of the cells in question ; in other words, every nerve serves as a trophic nerve for the tissue that it supplies, since the impulse which it conveys represents a vital condition for the tissue. B. THE IRRITABILITY OF LIVING SUBSTANCE 1. The Conception of Irritability and the Nature of Reactions Every process of stimulation requires two factors : a stimulus, and a body that is irritable. If the two factors come into correlation there results a phenomenon of stimulation, a reaction. We have considered stimuli ; we will now consider irritability. A definition of irritability (excitability) that shall have general application, must be formulated somewhat as follows : The irrita- bility of living substance is its capacity of reacting to changes in its environment by changes in the equilibrium of its matter and its energy. All other factors that might be included in the definition would be applicable to special cases only. Yet, frequently, the general conception, without being exactly defined, has more or less unconsciously been made to include special factors. For example, as regards the quantitative relations of the stimulus and the reaction, that case has been regarded as the type in which an A A 354 GENERAL PHYSIOLOGY enormous quantity of energy, the reaction, is produced by an excessively small quantity acting as the stimulus ; hence the one- sided view of irritability as the capacity of responding to slight stimuli with a disproportionately great evolution of energy. This case, although representing a special condition, is very obvious and wide-spread, and it is worth while to consider its details. If, as an irritable body, a muscle with its nerve be selected, and as a stimulus the mechanical stimulus of pressure, the following arrangement can be made (Fig. 150). The calf-muscle (gas- trocnemius) of a frog, the nerve of which (sciatic) has been freed, is suspended in a muscle- holder, the thigh-bone to which the muscle is attached at its upper end being fastened by a clamp. The lower end of the muscle with the tendon of Achilles is separated from the bone, and in the tendon a slit is made, into which a hook attached to a long thread is fastened. This thread is carried over two easily moving wheels, and, at its other end, is attached to a pan containing a weight of 100 gr. The nerve of the muscle-preparation lies stretched out upon a horizontal stand. Every stimulation of the nerve causes a twitch of the muscle. If, now, a weight of 10 gr. be allowed to fall upon the nerve from a height of about 1 cm., so that the nerve is mechanically stimulated by the pressure, at the moment of stimulation a twitch of the muscle occurs, and the muscle raises the weight of 100 gr. to a height of about 1 cm. Here the quantity of energy that corre- sponds to the work of the muscle is approximately ten times greater than the quantity of energy that has operated as a stimulus upon the muscle; and under favourable conditions the dispro- portion can be even much greater. According to the law of the conservation of energy it is clear that the considerable quantity of energy that is set free externally in the reaction cannot be derived by the transformation of the small quantity that has been intro- duced into the organism in the stimulus. It must, therefore, have come from the organism itself, and must have been stored pre- Fio. 150. — Apparatus for the demonstration of the inequality of the stimulus and the reaction. A nerve-muscle preparation is suspended upon a myograph ; the muscle is loaded with a weight of 100 gr. and its nerve is laid over a glass plate supported by a stand. Upon the nerve rests a small aluminium pan having a sharp keel on the lower side, and into this a weight of 10 gr. falls from a height of about 1 cm. At the moment of stimulation the muscle contracts and raises the 100 gr. about 1 cm. STIMULI AND THEIR ACTIONS 355 viously in the latter as potential energy. Hence in this case the irritability depends upon the fact that great quantities of potential energy are accumulated in the living substance of the muscle, so that the introduction of only a small quantity is needed to trans- form it into actual energy. But such irritability and such a reaction are not limited to living substance solely. Analogous conditions may be established in lifeless bodies. A spring stretched and held by a fine thread that maintains the tension in equilibrium represents a body in which a great quantity of potential energy is stored, although the body is in complete rest. If the thread that holds the spring be touched lightly with the edge of a sharp knife, the spring flies back with great force and performs external work. By a small stimulus, represented by the cutting of the thread, the potential energy of the spring has been transformed into actual energy ; the cutting of the thread has, as is said, "discharged" the energy of the spring. In explosive bodies also there is such a discharge, and since there it is a dis- charge of chemical tension, the similarity of it with the processes of discharge in living substance is still greater, for in the latter also potential energy is stored up in the form of chemical tension. In a quantity of nitroglycerine the size of a pea there is contained such a quantity of potential energy that it needs only a slight impulse to produce a powerfully destructive effect. Like the nitroglycerine molecule, living substance is explosive, although in a manner that does not call forth so injurious effects. But the processes of discharge, as has been said, are only special cases of reactions, and the relation between stimulus and reaction may be wholly different in other cases ; for, on the one hand, there are stimuli, such as fall of temperature, withdrawal of food, and exclu- sion of oxygen, which consist not in the action but in the with- drawal of energy ; and, on the other hand, there are reactions, such as those of narcotics, which are expressed not by an increase, but by a decrease and even a complete suppression of the produc- tion of energy. Accordingly, it is characteristic of the process of stimulation that no definite, generally valid, relation as regards the quantity of energy exists between the stimulus and the reaction. Hence, a conception of irritability that is to be generally valid must be formulated as above. As regards reactions, it must be said : The general action of all stimuli upon living substance consists in a change of spontaneous vital phenomena. With the enormous multiplicity of vital phenomena in accordance with the composition of living substance, and with the great variety of stimuli, it is a priori conceivable that the phenomena of stimu- lation must be very manifold. Moreover, to increase the variety of the reactions still more, not only the different varieties of the stimulus, but also the different intensities, as well as the time and place of the stimulation, can call forth under circumstances very A A 2 356 GENERAL PHYSIOLOGY different phenomena. This great multiplicity in the phenomena of stimulation, in combination with the fact that general reactions have not yet been investigated systematically, make it at present very difficult to deduce from the facts general laws for reactions. Nevertheless, it is possible to establish empirically for groups of stimulation-phenomena common peculiarities. The changes that spontaneous vital phenomena experience under the influence of stimuli are of various kinds. In the first place, the phenomena may continue unchanged in quality and undergo quantitative changes only. This may be expressed either in an augmentation of all, or of single phenomena — the reaction is then termed excitation [Erregung] — or in a diminution of all or single phenomena — the reaction is then termed depression [Ldhmung].1 In the second place, spontaneous vital phenomena may be wholly changed in kind, so that wholly new phenomena appear which otherwise do not occur at all in the life of the cell. Such reactions occur, e.g., in the metamorphic phenomena of necrobiotic processes,2 where under many influences not yet wholly known the cells of the body form substances, such as amyloid substance, which are completely foreign to them in normal life. These reactions have been very little investigated, and, so far as one can now judge, it appears as if they are only secondary results of quantitative changes of normal vital phenomena. Thus, it can be imagined that in metamorphic processes the appearance of foreign substances in the cell depends upon the fact that, as a result of chronic stimulation, one or more processes in the normal metabolism are gradually decreased or have entirely dropped out, so that compounds that normally are formed, but on account of immediate further transformation do not accumulate, are now stored in quantity, because the processes in the metabolism that are necessary to their transformation no longer exist. For the present, however, this must remain an hypothesis. The following consideration will have to do chiefly with the pheno- mena of excitation and depression. It is not superfluous sharply to emphasize our conceptions of stimulus, excitation, and depression, as well as the relations of these to one another, since not rarely in physiology because of the false idea, usually assumed, that a stimulus must always produce excitation, much confusion and difficulty in the judgment of phenomena have arisen. These can be avoided if the following definitions be accepted : 1 [The best English equivalent of the word Erregung seems to me to be "excitation." The translation of the word Lahmung has given some trouble. The customary English equivalent of the word is " paralysis," but it is easy to see that such a rendering would not convey the exact meaning of the author. After considering and rejecting various proposed terms, I have finally decided to adopt as the opposite of excitation the comparatively unobjectionable word < ' depression."— F. S. L.] 2 Cf. p. 330. STIMULI AND THEIR ACTIONS 357 1. Every change in the external vital conditions of an organism constitutes a stimulus. 2. Every augmentation of a vital phenomenon, either of one or of all, constitutes excitation. 3. Every diminution of a vital phenomenon, either of one or of all, constitutes depression. 4. The action of stimuli can consist of excitation or depression. 2. The Duration of Reactions Another question, that of the duration of reactions, which naturally thus far has received much less systematic treatment, is of no less interest, for it is in the closest relation with subjects, such as those of adaptation, immunisation, etc., which are of far-reaching practical importance. It is to be expected that these subjects, which afford very promising problems for experimental cell-physiological research, will soon attract more attention. For the present only a few disconnected discoveries of a very general nature can be specified. In general, it may be said that the duration of the reaction de- pends primarily upon the duration and intensity of the stimulus, and that after the cessation of the latter the reaction passes away the more rapidly, the briefer and feebler the stimulus was. A few special cases demand particular attention. To consider first the relations under prolonged stimulation, usually during the continuance of the stimulation the reaction un- dergoes a change in accordance with the intensity of the stimulus. With feeble stimuli there is, after some time, an abatement and finally a cessation of the reaction : the living substance becomes accustomed, or adapted to the stimulus. Such phenomena may easily be observed in very different objects and with very differ- ent varieties of stimuli. Thus, as Engelmann (79, 1) and others1 have shown, it is possible to accustom many uni- cellular organisms to relatively strong salt solutions which at first call out distinct phenomena of stimulation. If an Actinosphcerium that has extended its pseudopodia in the customary, ray-like manner be placed in a weak solution of sodium bicarbonate, it gradually draws in its pseudopodia from all sides and becomes spherical. But soon minute projections reappear upon the surface, extend and lengthen, until the organism has assumed its original form and become completely normal. By successively increasing the concentration, the same result can be produced many times in succession. Such adaptations may be brought about to weak solutions of poisons, high temperatures, strong light, etc. If the stimuli are strong, no adaptation takes 1 Cf. Verworn ('89, 1). 358 GENERAL PHYSIOLOGY place, but the phenomena of fatigue and exhaustion develop (these will be discussed elsewhere) ; irritability gradually decreases, and death finally results. In contrast to these phenomena both of adaptation and fatigue, in a few cases with prolonged stimulation the reactions continue with equal intensity. An example of such cases is afforded by the muscles of the mammalian body, which ex- ist in a certain state of excitation, or, to use the common term, pos- sess a " tone." Such are especially the muscles that close the urinary bladder and the anus. These muscles are in a constant state of contraction, which is caused by stimuli that come from the cells of the nervous system and act uninterruptedly upon the former. The skeletal muscles also possess a constant, feeble tone, which is maintained by feeble stimuli coming mostly from the periphery and transmitted to them through the nervous system. With brief stimulation the reactions give place, usually soon after its cessation, to the normal condition of the organism, but FIG. 151.— Guinea-pig, lying motionless upon his back, with the muscles of the extremities tonically contracted. The legs stand out stiffly. there are cases in which the extinction does not begin immediately, but a long, under some circumstances a very long, after-effect exist?,. Thus, a single brief stimulus can put into long-continued, tonic ex- citation certain ganglion-cells and the muscles innervated by them. If, e.g., we seize a guinea-pig with the hands firmly but without great pressure, and turn him suddenly upon his back, he makes a few, brief, defensive movements and then lies motionless. It can be seen that the muscles of the extremities, which just before had made the defensive movements, are strongly contracted, so that the limbs stand out stiffly (Fig. 151). When the animal is undisturbed, this condition of tonic excitation may continue for a half-hour. The phenomena of prolonged reflex tone after brief stimulation may be seen still more clearly in frogs that have been deprived of their cerebrum. If such a frog sitting quietly in the customary squatting attitude (Fig. 152, A) be gently stroked by two fingers along the sides of the spinal column, he raises himself upon his STIMULI AND THEIR ACTIONS 359 extremities by contracting their muscles, and stands, sometimes more than an hour, in this grotesque position (Fig. 152, B). By the proper operations it can be determined that by the mechanical stimulation of the skin the ganglion-cells at the base of the mid- FIG. 152.— Frog that has been deprived of his cerebrum. A, In the customary squatting attitude. B, In the attitude of general reflex tone ; the muscles of the limbs and the back are in constant contraction, so that the frog stands immobile upon his raised legs in the attitude of a frightened cat. brain are put into a tonic state of excitation, which is communicated to all the body-muscles that are innervated from that point.1 The after-effects of many chemical stimuli, especially the bacterial poisons, are the most interesting and of most practical importance. It is an old experience that after recovery from certain infectious diseases, such as small-pox, scarlet fever, and measles, the bodies of men and animals are immune to further infection from the same source. It is well known that the modern thera- 1 Cf. Verworn ('96, 5). 360 GENERAL PHYSIOLOGY peutics and prophylaxis of the infectious diseases are based upon this fact, especially the inoculation- and injection-methods of Jenner, Koch, Pasteur, Behring, Roux and others. We know how to produce immunity at will by the artificial introduction of weakened inoculation-substance, of metabolic products of the excit- ant of the disease in question, or of blood-serum from animals that have been exposed to the infection. In all these purely empirical methods of treatment we are totally ignorant of what goes on in the body ; we can only say that the poisoning by the bacterial poisons produces in the cells an after-effect, which can continue in many cases, such as diphtheria, only a relatively short time, but in others, such as small-pox, for many years. A phe- nomenon is here presented, the explanation of which is as yet scarcely hinted at. But it is to be expected that cell-physiological researches, which replace with the simplest relations the complex and abstruse conditions presented by human and animal bodies, will be of the greatest service in assisting toward an understanding. In fact, investigations upon unicellular organisms with various chemical substances have shown that analogous phenomena are to be met with in these forms. Thus, by accustoming Infusoria to weak solutions of corrosive sublimate, Davenport ('96) has made them immune toward solutions of such strength as were at once fatal to non-immunised individuals. Cell-physiological research opens here an uncommonly wide and fruitful field. The system- atic investigation of reactions in the single cell is of fundamental importance not only theoretically, but also for practical medicine.1 3. The Conduction of the Stimulus Inseparably connected with irritability is another property of living substance, viz., the power of conduction of the stimulus. If a mass of living substance be stimulated locally, as can be done very simply by touching it or pricking it with a fine needle, the reaction is not limited to the point stimulated, but spreads from that place more or less over the neighbouring parts. The capacity of conducting the stimulus belongs to all living substance, but in very different degrees. While one kind conducts rapidly and far, another conducts slowly and only to the nearest surroundings. The capacity of conduction is most pronounced in those forms that are developed exclusively for that purpose, viz., the animal nerve-fibres. Nerves conduct with enormous rapidity and to distances measured by meters. Helmholtz has computed that in a frog's nerve the stimulus is transmitted at a rate of 26 m. per second. In man the rate is still greater^ approximately 34 m. in 1 Cf. Verworn ('96, 2). STIMULI AND THEIR ACTIONS 361 a second ; in the lobster, as Leon Fredericq and Van de Velde have shown, it is less and amounts to about 6 m. in a second. Various methods have been devised for determining the rate of transmission in the nerve, an undertaking that with the great rapidity of the process is not easy. The principle of all these methods depends upon the determination of the difference in time between the appearance of a muscle-contraction, when the nerve belonging to it is stimulated very near the muscle, and its appearance upon stimulation of the nerve at a more remote place (Fig. 153). For this purpose the spring-myograph of du Bois- Reymond can be employed, an apparatus that serves for the graphic representation of a muscular movement (Fig. 154). The apparatus consists of a muscle-holder in which the gastrocnemius muscle of a frog, the nerve of which is freed, is fastened by the femur ; the muscle is connected with a lever, which accompanies every contraction and by means of a fine point records it upon a smoked glass plate which is shoved rapidly by. The glass plate moves in a sledge-like frame in a vertical plane in front of the writing-lever, and is put in motion by a spring. Simultaneously with the release of the spring an electrical stimulus is let loose upon the nerve ; moreover, a tuning fork is made to vibrate, and traces its vibrations, likewise by means of a writing-point, upon the blackened glass plate. If the nerve be stimulated once at a distance of about 3 cm. from the muscle, and once immediately at the muscle, the first contraction follows a short time later than the second, because the first stimulus has a longer stretch than the second to pass over before it can act upon the muscle. This difference in time that in both cases elapses between the moment of stimulation and the appearance of the contraction, can be measured with extreme exactness upon the blackened plate, upon which the contraction is traced in the form of a curve, by the number of vibrations of the tuning fork that are traced simul- taneously (Fig. 155). Since the number of vibrations of the tuning fork in one second is known, the duration of a single vibration can easily be computed, and from the number of vibrations that lie between the beginning of the second contraction and that of the first, the time can be calculated that elapsed FIG. 153. — Gastrocnemius muscle of a frog with the sciatic nerve. ^The femur to which the muscle is attached, is clamped in a muscle-holder, and the nerve is stimulated first at 1, then ate. 362 GENERAL PHYSIOLOGY while the stimulus was passing over a piece of nerve 3 cm. in length. It is thus found that the rate of conduction of the FIG. 154. — Du Bois-Reymond's spring-myograph. stimulus in a frog's nerve under normal conditions amounts to approximately 26 m. in the second. Other forms of living substance conduct the reaction considerably more slowly and some to a very short distanee only, the effect being gradually extinguished with the distance. In very slowly conducting objects the rate of conduction can be followed with the FIG. 155. — Ascending limb of the myographic curve taken with the spring-myograph. R, Moment of stimulation ; 1, beginning of the contraction upon stimulation of the nerve at a remote place (Fig. 153) ; 2, beginning of the contraction upon stimulation immediately at the muscle. Below, the curve of the tuning fork. eye. Thus, in Difflugia the rate of conduction of the ex- citation can be very easily recognised under the microscope in the STIMULI AND THEIR ACTIONS 363 long finger-shaped pseudopodia by the fact that drop-like projec- tions form on the surface of the pseudopodial plasma, beginning at the place of stimulation. If such a pseudopodium be stimulated only slightly at the tip by contact with a needle, the reaction extends a short distance only, the surface of the pseudopodium becoming slight!}7" undulating (Fig. 156, a). But if it be stimulated more strongly, the reaction is stronger and is transmit- ted considerably farther (Fig. 156, b). The re- action diminishes in extent as the distance from the place of stimulation in- creases, and finally it is extinguished.1 Very slight conduction is found in many rhizopods that have thread-like pseudopodia, e.g., OrUtolites (Cf. Fig. 98, p. 238). Here even with the strongest stimulation, such as cutting across a pseudopodium, the excita- tion is limited to the im- mediate vicinity of the place stimulated, the pro- toplasm there being drawn together into one or more small globules. These globules glide centripetally for a very considerable dis- tance along the pseudo- podial thread, which thus begins to shorten, while the globules gradually dis- Fio.l^.-Difflugiaurceolata. Three finger-shaped, hyaline Solve and allow their Sub- pseudopodia are projected out of the urn-shaped shell n . , made of sand-grains. At a feebly stimulated locally, Stance tO DOW into the at & somewhat more strongly stimulated. central body (Fig. 157). Their movement is not to be regarded as a conduction of the excitation,2 but only as the expression of the transport of sub- stance by the stimulated protoplasmic mass to the cell-body ; for the protoplasm in the vicinity of the globules exhibits no pheno- mena of excitation, but streams on quietly in a centrifugal direction. 1 Cf. Verworn ('89, 1). 2 In the first edition of this book this was so regarded; but later studies upon the Rhizopoda of the Red Sea have convinced me that conduction of excitation and transport of substance are to be separated from one another in naked proto- plasmic masses. Cf. Verworn ('96, 3). 364 GENERAL PHYSIOLOGY But between the very slight power and rate of conduction possessed by Orbitolites, and the very great power and rate possessed by the nerve, there are found in the various living forms the greatest variety of transitions. The cross-striated muscle-fibre f FIG. 157. — Pseudopodium of Orbitolites. a, At * cut across ; b, effect of stimulation (formation of protoplasmic globules) limited to the immediate vicinity of the place stimulated ; c-f, transport of substance. The stimulated masses are transported along the pseudopodium to the central cell-body, and their substance becomes gradually spread out (e, /) ; the unstimu- lated protoplasm exhibits no phenomena of excitation but continues to flow centrif ugally . and the pseudopodium soon lengthens again (e, f). conducts considerably more slowly than the nerve, the smooth muscle-fibre still more slowly than the cross-striated, and so on. Thus, according to the rate of conduction, living substances can be arranged in a long series showing most delicate transitions. II. THE PHENOMENA OF CELL-STIMULATION After this general discussion of the individual elements of the process of stimulation we can pass to the consideration of the phenomena of stimulation themselves. Since the single cell does not allow the various vital phenomena to be recognised with equal readiness, but according to its specific STIMULI AND THEIR ACTIONS 365 work permits one phase to come more to the front, whether it be metabolism, or change of form, or transformation of energy, it is advantageous to select for the study of any vital phenomenon a specific form of cell in which the vital phenomenon in question is expressed especially clearly. By this method the phenomena of changes of substance, of form and of energy may be considered separately in different objects. But this ought never to lead us into considering these different groups of phenomena as mutually independent. They are merely different phases of one and the same process. A. THE ACTIONS OF THE VARIOUS STIMULI 1. The Actions of Chemical Stimuli The number of chemical bodies that when brought into contact with living substance enter into chemical relation with its con- stituents is enormous, but thus far only a few of them have been investigated as regards their stimulating effects. A comprehensive, comparative, cell-physiological investigation of chemical stimuli and their actions, undertaken from a systematic point of view, would require a very long time, but would surely yield very valuable results. For the present, our knowledge of these stimuli and their effects is so full of gaps that a systematic summary of it is not possible. We must, therefore, limit ourselves to the con- sideration of a few typical phenomena. a. The Phenomena of Excitation In general, increase in the quantity of ingested food-stuffs acts as a chemical stimulus to augment metabolism. The best example is afforded by the cells of the various tissues of the human body, the most essential food-stuff of which is proteid. As Voit ('81) has shown, a strong man, working hard, needs 118 grs. of proteid in order to maintain his nitrogenous equilibrium intact, i.e., in order to replace the quantity of nitrogen derived from the destruction of the living substance of his cells arid excreted in the urine. If this quantity of ingested proteid, which is a necessary vital condition, be increased, as is the case with most men living under good conditions, the greater quantity is not employed for the construction of new cells, for the increase of living substance, but is taken up by the tissue-cells from the blood, passed over into living proteid and split up, to leave the body again almost completely in the urine as the products of retrogressive proteid- metamorphosis (urea, uric acid, creatinin, etc.). The increase of the proteid-income beyond a certain measure (118 grs.)accomplishes, 366 GENERAL PHYSIOLOGY therefore, a corresponding increase of both the assimilatory and the dissimilatory phases of the metabolism of the tissue-cells. A similar condition exists among plants. The carbonic acid of the air serves the plant as food and is split up in the chlorophyll- bodies of the living cells. The carbon set free is then employed, together with the water received through the roots, for the synthesis of starch, or assimilation. If more carbonic acid be brought to the plant than is contained in the air as its necessary vital condition, the splitting-up of carbonic acid and the assimila- tion of starch are increased in equal measure up to a certain degree. The increase of the quantity of food, therefore, conditions also an increase of metabolism. But this does not always hold good. Regarding oxygen, we know, at least, that its increase in quantity beyond the amount necessary for life is essentially without influence upon the metabolism of the tissue-cells. The tissue-cells of the human body are within wide limits independent of the percentage and the partial pressure of oxygen in the air, and experience no augmentation of metabolism with increase of the income of oxygen. Whether the same is true of free-living cells and the cells of lower animals still needs investigation. In many cases the increased income of food that is accompanied by an increase of metabolism causes also a clearly recognisable increase in change of form. While in the tissue-cells of the human body, as has been seen, the food that is introduced beyond the necessary quantity is under normal conditions destroyed excepting an ex- tremely small fraction, and is not employed for the increase of living substance, in many unicellular organisms, especially in Bacteria and Infusoria, an increase of the assimilatory processes, and in unequal measure of the dissimilatory processes also, takes place with increase of food. The result of this is an increase of living substance, a " fattening," which is expressed in rapid growth and continued cell-division. If, e.g., putrefactive bacteria (Bac- terium termo, Spirillum und.ula, etc.) be transferred from a liquid in which they are living in small numbers, into a good nutrient solution, such as an infusion of hay, they at once begin to increase enormously, until from the few bacteria with which the nutrient solution was infected many millions may have developed. If there be placed in such a hay-infusion swarming with putrefactive bacteria a Paramcetium, which nourishes itself upon such bacteria, in a few days it may be seen that from this one infusorian thousands have been produced, so that they give to the liquid a milky cloudiness. Thus the assimilatory phase of the metabolism of these micro-organisms becomes enormously increased by superfluity of food. Under pathological conditions also similar phenomena occur in the tissue-cells of the human body, and modern pathology STIMULI AND THEIR ACTIONS 367 recognises a whole series of analogous cases in the various kinds of pathogenic neoplasms or tumours, to which belong also malignant cancers. These tumours (carcinoma, sarcoma, myoma, fibroma, etc.) arise by the rapid division of the cells of a normal tissue, e.g., the epidermis. There thus results in the particular place an enormous increase of cells, a growth, which leads frequently to a very extensive tumour and completely chokes the neigh- bouring tissues in which it grows, so that they become incapable of life and perish. Without doubt, in many cases this rapid cell-increase is due to chemical causes acting upon the cells in question. Although -thus far it is an open question whether or not tumours, especially carcinoma, are a result of infection by certain micro-organisms, the majority of pathologists incline to the view that they are to be traced to a change in the nutrition of the cells. Much more evident than the effects of chemical stimuli upon metabolism and form-changes are the effects upon the transformation of energy, especially upon movement. Regarding the effects upon the amoe- boid movements of naked protoplasmic masses, such as Rhizopoda, Amoeba, Myxomycetes, Polythala- mia, and the protoplasmic bodies of plant-cells, the classic investigations of Max Schultze ('63) and Kiihne ('64). over thirty years ago, have afforded information. The most wide-spread effect here is the calling-out of a contraction, i.e., the retraction of pseudopodia, frequently after a preliminary acceleration of the protoplasmic streaming at the beginning of the action. The greatest variety of chemical substances can produce this reaction. If, e.g., to a drop of water in which many amoebae exist there be added a 1 — 2 per cent, solution of common salt, or a solution of 0*1 per cent, hydrochloric acid, or of 1 per cent, potassium hydrate, or other acids, alkalies and salts in weak solution, the amoebae immediately draw in their pseudopodia and assume a spherical form (Fig. 158). Carbonic acid exerts the same effect, if the amoebae be exposed in a gas chember 1 for some time to the action of the gas. Other naked protoplasmic masses behave similarly toward these chemical stimuli. The delicate Actinosphcerium Eichhornii, which with its straight, ray-like pseudopodia appears like a minute sun, when 1 Cf. p. 283. FIG. 158. — Amoeba. A, With pseudopodia extending in different directions. B, Creeping, with a long pseudo- podium in one direction (form of Amoeba, Umax). C, Contracted to a ball upon chemical stimulation. 368 GENERAL PHYSIOLOGY brought into contact with these stimuli, likewise gradually draws in its pseudopodia, the protoplasm becoming contracted into numerous, small globules and spindles, which slowly flowcentripe tally into the cell-body l (Fig. 159). Upon the effect of chemical stimuli upon ciliary motion, Engelmann ('79, 1) and Rossbach ('71) especially have carried out detailed investigations. Here also the greatest variety of sub- stances, such as acids, alkalies and salts, carbonic acid and various alkaloids, have like effects, which always consist in an augmentation of the activity of the cilia or flagella, the rate of their beat being considerably increased. The result is a considerable augmentation of the motor effect, which can be clearly observed in free-living ciliated cells, such as Infusoria, in a great acceleration of their A B C FIG. 159. — Actinosphcerium under chemical stimulation. A, Unstimulated ; B. at the beginning of the stimulation ; C, after the stimulation has continued for some time (the pseudopodia are almost entirely drawn in). motion. After the addition of chemical reagents the Infusoria by the strokes of their cilia rush madly through the field of view. Numerous chemical stimuli act upon the different forms of muscle-fibres (myoids, smooth muscle-fibres, cross-striated muscle- fibres) in a manner analogous to that upon naked protoplasmic masses, by calling out contractions. If to a drop of water in which many Vorticellce exist, waving their bodies gracefully upon their extended stalk-muscles, chemical substances of the above-mentioned kinds be added, all the Vorticellce immediately draw together, their stalk-muscles suddenly contracting in their elastic sheaths, and coiling up into delicate spirals (Fig. 160, 5). Cross-striated muscles likewise contract suddenly upon chemical stimulation. If, e.g., the sartorius muscle of a frog, which forms a small band of nearly parallel, cross-striated muscle-fibres, be clamped in a muscle-holder 1 Cf. Verworn ('89, 1). STIMULI AND THEIR ACTIONS 369 by means of the attached leg- bones, and a thread, passing over a wheel and attached to a small weight, be drawn through the pelvic bone, to which the muscle is also attached, every movement of ' the muscle can be observed in a signalling-lever, which is fastened to the wheel (Fig. 161). If, now, a dish containing ammonium carbon- ate be brought under the muscle, the latter is chemically stimulated by the vapours of the ammonia, and performs contractions, which can be shown clearly by the lever and can be traced upon a smoked drum. Biedermann ('80) observed a very remarkable phenomenon in the sartorius muscle when he let it hang in a temperature of 3° — 10° C. in a solution of 5 grs. common salt, 2 grs. alkaline sodium phosphate, and 0'5 grs. sodium carbonate in one litre of water (Fig. 162). The muscle then showed rhyth- mic con tractions, a phenomenon that otherwise is never observed in this muscle during life, and suggests constantly the rhyth- mic motion of cardiac muscle- fibres. The chemical effects of stimulation in contractile sub- stances, thus far spoken of, consist of contractions. But certain chemical stimuli pro- duce expansion. Such, e.g., are food-stuffs, and especially oxy- gen. These phenomena have been discussed elsewhere.1 They consist chiefly in the fact that in an atmosphere free of oxygen Amceba and marine Rhizopoda cease the formation of pseudopodia and undergo a diminution of ex- pansory processes, developing the latter again when new oxygen is introduced. Kiihne (I. c.) has observed the same in Myxomycetes, in the reticulate plasmodia of Didymium. which lives upon decaying leaves. When he introduced a dried, and, therefore, completely motion- less, piece of the plasmodium into a vessel filled with water boiled and hence free of oxygen, which was shut off by mercury from the air, it remained in complete rest. But as soon as a few bubbles of oxygen were added to the Didymium, the latter began to extend pseudopodia and to spread itself out in an arborescent FIG. 160.— Vorticella. a, Extended; b, contracted after chemical stimulation (the stalk-muscle is not seen) ; c, a piece of the stalk-sheath containing the muscle-fibre, strongly mag- nified. Cf. p. 284. B B 370 GENERAL PHYSIOLOGY manner on the inner surface of the vessel. From these experiments it is very clear that oxygen acts as a stimulus, giving rise to the expansory phase of protoplasmic movement. The production of other forms of energy besides that of movement is also excited by chemical stimuli. Since it would, however, lead too far to consider all the excitation-effects of such stimuli, only the facts connected with the production of light will be presented. FIG. 161. — Chemical stimulation of the sartorius muscle. of the frog. For the investigation of this the unicellular organisms are best fitted, for in them all conditions are simplest and most easily observed. It is known of many unicellular organisms, Bacteria, Radiolaria, etc., that they develop light as the result of chemical, as of various other stimuli. But light-production has been investigated most frequently and in most detail in the Noctilucce, the peculiar Flagellata which usually produce the light on the surface or the water in our northern seas (Fig. 163). Recently Massart ('93) has studied again in detail the action of chemical stimuli upon them. In a vessel containing sea-water, in which the Noctilucce rested quietly upon the surface without emitting light, he placed carefully with a pipette various substances, such as distilled water, a concentrated solution of common salt, a solution of sugar, etc., and in each case let the drop spread slowly over the surface of the sea- water. The result was that as soon as the liquids introduced came into contact with the Noctilucce, the latter became brilliantly lighted, and the pleasing spectacle was presented of a slowly widening, glowing circle, spreading over the surface of the water. A similar phenomenon can be observed very well in Radiolaria, especially in the large Thalassicolla, which emits light actively upon a change in the concentration of the sea-water in FIG. 162.— Production of rhythmic con- tractions in the sartorius muscle by chemical stimulation. STIMULI AND THEIR ACTIONS 371 which it exists, or upon being transferred to fresh water. The various luminous Bacteria, which produce, e.g., the luminosity of dead sea-fish, behave similarly. Finally, the living substance of nerves and ganglion-cells can be excited by chemical stimuli. The excitation in the nerve-sub- stance itself is not visible without special methods ; but a clear expression of it in motor nerves is exhibited in the contraction of muscles supplied by them. If, e.g., the sciatic nerve of a frog be stimulated by its central end being dipped into gly- cerine, a concentrated solu- tion of common salt, or a solution of a mineral acid, an alkali, a metallic salt or sugar, contractions of the leg-muscles of the frog take place, and prove that the nerve is excited. Excita- tion by chemical stimuli can be observed in the excised , , f> . , FIG. 163. — Noctiluca mihans, a marine flagellate- nerve also by means ot the infusorian ceil, galvanometer through the development of electricity, which influences the current derived from the resting nerve. 1). The Phenomena of Depression In contrast to the exciting effects of the chemical stimuli just mentioned are the effects of certain chemical substances, which depress or wholly suppress vital phenomena. These substances are, hence, termed narcotics or anaesthetics. Among them belong es- pecially those that depress all forms of living substance and all vital phenomena : alcohol, ether, chloroform, and chloral hydrate. With these belong the great group of alkaloids, comprising morphine, quinine, veratrine, digitaline, strychnine, curare, etc., some of which act upon a great variety of living cells, while others affect specific cells only, especially those of the central nervous system. The depressing effects of narcotics upon the phenomena of metabolism have been studied especially by Claude Bernard (78). This well-known Parisian physiologist showed that metabolism is suppressed by chloroform-narcosis in very different forms of cells. If yeast-cells, which, as is well known, in the course of their B B 2 372 GENERAL PHYSIOLOGY metabolism split up grape-sugar into carbonic acid and alcohol, be placed in two fermentation -tubes (Fig. 164), one of which contains a pure solution of grape-sugar, the other some chloroform-water mixed with a similar solution of grape-sugar, there appears at once, under otherwise completely identical conditions, in the first tube a fermentation, as is evident from the carbonic acid rising and accumulating above (Fig. 164, A), but in the second tube an entire absence of fermentation (Fig. 164, B). If the contents of the second tube be left open to the air for a time, so that the chloroform evaporates, fermentation appears there later. The chloroform-water, therefore, only inhibits the metabolism of the yeast-cells without killing them. In plant-cells also the depression of metabolism is very easily brought about, especially the cessation of the cleavage of carbonic FIG. 164. — Fermentation experiment. A, Produc- tion of carbonic acid in a solution of grape- sugar by means of yeast-cells. B, The solution of grape-sugar is not fermenting because the yeast-cells are narcotised by chloroform- water. FIG. 165,—Spiroffyra, a filose Alga. A, Piece of a thread consisting of many cells arranged in a row. B, Single cell with the character- istic spiral band of chlorophyll and the star-shaped protoplasmic body. acid in chlorophyll. Claude Bernard employed for this a filose, aquatic Alga, Spirogyra, the cylindrical cells of which are arranged lengthwise one after another in fine1 threads and possess a delicate, spirally wound band of chlorophyll (Fig. 165). Under two" bell-jars, of which one was filled with water containing carbonic acid, the other with water containing carbonic acid and chloroform, he placed a quantity of Spirogyra threads and exposed the jar to the sunlight. After some time the cells in the first jar had evolved a considerable quantity of oxygen, while in the second the evolu- tion of oxygen and, therefore, the dissociation of carbonic acid, were wholly absent. Corresponding with the cessation of metabolism, the phenomena STIMULI AND THEIR ACTIONS 373 of form-changes are also depressed in narcosis. Growth and cell- division cease. In order to prove the inhibition of growth, Claude Bernard arranged the following experiment (Fig. 166). Two empty, cylindrical flasks were provided, above and below, with openings that were closed by rubber stoppers, each pierced by a glass tube. In each of these flasks there was placed, half-way up, a moist sponge, and upon the latter sprouting plant-seeds were laid. Through the lower opening one flask («') communicated by means of a rubber tube (V) with a glass cylinder (t), which con- tained at its bottom a layer of ether (S) ; through the stopper of the cylinder, beside the tube V, an open glass tube (a) projected FIG. 166. — Apparatus for the comparison of germinating plant-seeds in the normal condition and in narcosis. (After Claude Bernard.) from the outside down to one-half the depth of the cylinder. The lower opening of the other flask (e) communicated through the glass tube (a') directly with the outside air. To the glass tubes that led outside through the stoppers in the necks of the flasks, a forked rubber tube (b) was fastened, which was in connection with an aspiration-apparatus (P). If the water of the water-pipe (R) was let through the aspirator, it sucked the air through the two glass flasks, of which the one received pure air directly from the outside through the tube (a1), while the other took in through the glass cylinder (t) air charged with ether-vapour. In this way a continuous stream of pure air passed through the germinating seeds of the one cylinder and a stream of ether- vapour 374 GENERAL PHYSIOLOGY through the seeds of the other. After some days under this arrangement the seeds that were in pure air had grown out into long seedlings (e), while those bathed by the ether- vapour showed no growth at all, without, however, having lost the capacity of germinating in pure air. The brothers Hertwig ('87) have investigated the depressing action of solutions of chloral hydrate upon cell-division in eggs of the sea-urchin. When they let a 0'2 — 0'5 per cent, solution of chloral act for some time (5 minutes — 3 hours) upon eggs that were about to develop, cell-division did not go on. Both the nucleus and the protoplasm remained in the stage of division in which they already FIG. 107.— Mimosa pudica, in ether-narcosis. (After Claude Bernard.) were, while the formation of rays about the centrosomes was com- pletely absent. Only after the eggs had been washed for a considerable time with pure sea-water did the development and division of the cell proceed again. Finally, the phenomena of transformation of energy are also depressed by narcosis. Both the spontaneous production of energy and the capacity of reacting to stimuli are diminished, and finally wholly cease. Among the phenomena of motion Claude Bernard has shown this for the turgescence-movements of Mimosa pudica.'1 If a pot containing a Mimosa be placed under a bell-jar, under which is a sponge soaked with ether (Fig. 167), the spontaneous move- 1 Cj. p. 227. STIMULI AND THEIR ACTIONS 375 merits cease, and, moreover, after some time it is no longer possible to call forth by stimuli the well-known movements, which consist of a falling of the branches and a folding together of the leaves. The irritability is extinguished, the plant is in narcosis. " What a singular thing," says Claude Bernard, " plants can be anaesthetised like animals, and absolutely the same phenomena can be observed in the two." Like the turgescence-movements,the growth-movements of plants also cease in narcosis, and the secretory movements of the Diatomece, Oscillarice, and Desmidiacece l are wanting. Contraction-movements are also depressed by narcotics ; but, as a rule, at the beginning of the influence a short stage of excitation is noticed, in which the movements are accelerated. The protoplasmic movements of Amceba cease after the cells have con- tracted into a ball. As Binz ('67) found, quinine especially exerts a powerful paralysing action upon the amoeboid movements of leucocytes. Engelmann ('68) carried out extensive investiga- tions upon the depressing action of narcotics upon ciliary motion. When he let the vapour of ether or chloroform act upon the ciliated cells of the pharyngeal mucous membrane of a frog in a gas-chamber, after a rapid preliminary stage of excitation, in which the motion was accelerated, a standstill of the cilia took place. If the duration of the action was not too long, the motion appeared again after the introduction of fresh air. According to the observations of the Hertwigs ('87), similar behaviour was exhibited by the flagella of spermatozoa that had been brought to complete standstill by ether- and chloroform-vapours, as well as by small doses of quinine and chloral hydrate, so that the fertilisation of the ovum was hindered by the absence of their movements. In Infusoria also by the intro- duction of chloroform -water, after a short stage of excitation in which the cells whirl madly through the water, ciliary motion is inhibited. In Stentor, in addition to this fact, the paralysis of the myoids by the chloroform-water can be observed at the same time. In their undisturbed condition the Stentors are extended in the form of delicate trumpets with their aboral pole attached at the bottom (Fig. 168, A). From time to time, partly spontaneously and partly as a result of stimulation, they jerk together into stalked balls (Fig. 168, C) by the contraction of their fine myoid-fibres that extend from the upper to the lower end of the cell-body in the exoplasm. In narcosis, however, after a sudden twitch at the begin- ning of the influence, they assume a stage of moderate contraction (Fig. 168, B\ their cilia cease to beat, and their bodies do not shrink into the customary ball either spontaneously or upon stimulation, until by transference into fresh water the narcosis is ended. Like the smooth myoid-fibres, the irritability of cross-striated skeletal muscles also is completely abolished by narcosis. A frog's muscle 1 Cf. p. 231. 376 GENERAL PHYSIOLOGY that is carefully and slowly bathed with air containing the vapour of ether cannot be made to contract by any kind of stimulus. Never- theless, the vital processes in the muscle are not at a complete stand- still, as is evident from the fact shown by Biedermann ('85) that the narcotised muscle produces electricity when stimulated, just like the contracting muscle in the normal state. The stimulated part, as well as the artificial cross-section, appears by galvanometric investigation electrically negative to the resting part, as in normal conditions. In narcosis, therefore, certain metabolic processes must still remain FIG. 168. Stentor coemleus. A, Wholly extended in rest; B, in the condition of moderate con- traction as in free swimming ; C, completely contracted. undisturbed ; and perhaps this is true not only of muscle but of the narcotic conditions of all living substance. Recently, Massart ('93) has been able to abolish completely the development of light in Noctilucce by alcohol, by laying several sheets of filter-paper wet with alcohol over the vessel containing the sea- water in which the organisms were swimming quietly upon the surface ; the vapours of the alcohol were thus forced into con- tact with the Noctilucce. After a short time the latter could not be induced by any stimulus to emit light. Finally, best known are the depressing effects of narcotics upon the activity of the ganglion-cells of the central nervous system, STIMULI AND THEIR ACTIONS 377 both those that produce motor impulses, and those that are the seat of the sensations, of consciousness. In their anaesthe- tising action upon the cells of the central nervous system lies the extraordinary practical importance of the narcotics. Through the abolition of sensations, especially of pain, they confer enormous benefits upon mankind. But their misuse, especially that of alcohol and morphine, by inflicting irreparable injuries upon the FIG. 169. — Ganglion-cells of a morphinised dog, stained by Golgi' most of the protoplasmic processes have assumed a monilifor s method. In A all, and in B :orm appearance. (After Demoor.) cells, produces most destructive effects and transforms the benefit into a serious evil. Recently a number of investigators, such as Meynert, Lepine, Duval, Solvay and others, have put forward the view that gang- lion-cells possess the power of amoeboid motion, their protoplasmic processes, or dendrites, being able to shorten and lengthen. Hence it is highly interesting to show, as Demoor ('96) has very recently succeeded in doing, that under the influence of morphine in nar- cosis, and also of other stimuli, distinct phenomena of contraction can be observed in the dendrites of the ganglion-cells, or neurons, which correspond exactly to those contractile phenomena that 378 GENERAL PHYSIOLOGY strong stimuli produce upon the branched pseudopodial filaments of Rhizopoda. The two pictures agree completely ( Cf. Fig. 169, A and jB). The dendrites of the neurons, for example in the brain of a dog, like the pseudopodia of the rhizopods, assume a very characteristic moniliform appearance in morphine- or chloral- narcosis, their protoplasm accumulating in numerous small globules and spindles. Evidently this phenomenon, which can be FIG. llO.—Ampkistegina lessonii. Filose pseudopodia project out through the opening of the lenticular, calcareous shell. At Normal ; £, in chloroform-narcosis. produced only by an excitation of contraction, is an effect of the stage of excitation which the narcotics, as we have seen, cause in other forms of living substance before paralysis begins. In this condition the ganglion-cells are gradually paralysed, and during their narcosis preserve this form of pseudopodia. The same is readily observed1 also in the narcosis of Rhizopoda (Fig. 170), e.g., Amphistegina, Orbitolites, Rhizoplasma, etc. 1 Cf. Verworn ('96, 3). STIMULI AND THEIR ACTIONS 379 2. The Actions of Mechanical Stimuli All changes in the pressure-relations of living substance in its environment may be termed mechanical stimuli. The effects of diminution of pressure have not thus far been investigated in detail, hence only the effects of increase of pressure are to be considered here. Increase of pressure can take place in various ways, ranging from a light touch to a vigorous squeezing or complete crushing of the living substance, from a brief shock to a continuous and lasting pressure, or from an irregular shaking to rhythmically in- termittent impacts, such as a tuning-fork produces. a. The Phenomena of Excitation Among the excitation- effects of mechanical stimuli upon the phenomena of metabolism the clearest is that of the production of substance, secretion, in unicellular organisms. Actinosphcerium, e.g., when completely at rest, floats in the water, with many pseudo- podia extended straight in all directions and evolving no secretion. Absence of secretion is evident from the fact that ciliate Infusoria belonging to the Hypotricha, which have cilia on their ventral side only and by means of them run over objects in the water like lice, not rarely walk along quietly upon the extended pseudopodia of the Actinosphcerium without sticking to them. But if one of the Hypotricha is actively swimming and bounds against a pseudo- podium, the mechanical stimulus is sufficient to cause at the place of contact the secretion of a viscous substance, which holds fast the infusorian as prey.1 A single strong shock likewise causes the secretion of slime upon the pseudopodia, so that small particles suspended in the water remain sticking to them. Such secretion as the effect of mechanical stimulation is wide-spread in the naked protoplasmic bodies of Ehizopoda. The slime becomes directly visible in the large marine radiolarian Thalassicolla. It is possible with little trouble to extirpate from the round body of Thalassi- colla, which has the size of a pea, the central capsule, which is pierced with extremely fine pores and contains protoplasm and nucleus. If this be done without injury to it, after a short time the capsule begins to regenerate into a complete radiolarian, i.e., to form new pseudopodia, and gelatinous and vacuolar layers (Cf. Fig. 171). After the pseudopodia have become extended like a circlet of rays from the yellow spherical body, there is noticed between them an extremely delicate, very liquid slime, which is excreted by the pseudopodia and represents the rudiment of the new gelatinous 1 Cf. Verworn ('89X 1). 380 GENERAL PHYSIOLOGY layer. If in this stage the radiolarian be given a strong shock, it may be seen that the liquid mass of slime increases and becomes at the same time thicker and firmer ; this is manifested more dis- tinctly when the shock is repeated.1 The mechanical stimulation promotes visibly the secretion of slime. No excitation-effects of mechanical stimulation upon the pheno- mena of form-changes, upon growth and cell-division, are thus far known. Effects of excitation upon the phenomena of the transforma- tion of energy have been investigated very fully, and a great FIG. 171. — Thalassicolla nucleata, a spherical radiolarian cell. A, Uninjured individual in optical section. In the middle lies the central capsule, containing the nucleus, surrounded by black pigment. B, Central capsule removed. It has already surrounded itself with a new" circlet of pseudopodia. C, The same central capsule after strong stimulation. The pseudopodia are somewhat drawn in, and between them a thick mass of slime has been secreted. B and C strongly magnified. mass of observed facts exists. From these we will select the typical phenomena. Those connected with motion, which are called out by mechanical stimuli, constitute here also the chief point of interest. The pro- duction of turgescence-movements in the so-called sensitive plants, such as the delicate Mimosa pudica, is generally known. Mimosa, which resembles a small Acacia tree, during the day and while 1 Cf. Verworn('91). STIMULI AND THEIR ACTIONS 381 undisturbed holds its primary petioles, which spring from the trunk, directed obliquely upward. The secondary petioles, which bear the rows of leaflets, are spread out wide apart, and the leaflets them- selves stand horizontal and widely extended (Fig. 172, A). But as soon as the pot in which the plant is growing is shaken, the picture changes almost immediately. The primary petioles fall down as a result of the decrease of the turgor of the cells of their pulvini, the secondary petioles turn toward each other, while the leaf- lets are raised and lie with their upper surfaces together (Fig. 172, B). The plant, when left at rest, remains for some time in this position , and then very gradually returns to its original condition, the cell- turgor again increasing at the corresponding portions of the pulvini. In the single leaflet the position of stimulation can be called out FIG. 172. — Mimosa pudica. A, A branch uiistimulated and extended ; £, a branch stimulated and fallen, with its leaves folded. (After Detmer.) also by a very gentle local touch. If the touch be stronger, the leaflets may be seen to move in succession like a row of dominoes, thus affording a very striking demonstration of the transmission of the stimulus. Among the contraction-movements resulting from the mechanical stimuli the contraction-phase only is thus far recognised with certainty, although it is not improbable that in many cases very delicate tactile stimuli may produce expansion. Thus, the contact of an amoeboid protoplasmic mass with a smooth support might influence by cohesion the extension of the pseudopodia. In the naked protoplasmic bodies of Rhizopoda a single shock upon the extended pseudopodia, such as can be produced by a vigorous rap of the slide under the microscope, produces more or less pro- 382 GENERAL PHYSIOLOGY nounced phenomena of contraction, according to the very various grades of irritability of the different species.1 An Amceba or an Adinosphcerium, stimulated in this way, ceases momentarily its centrifugal protoplasmic streaming, i.e., the extension of its pseudopodia; upon stronger stimulation there may be a partial indrawing of the pseudopodia, a transitory centripetal streaming. Other forms, such as Difflugia, react more energetically (Fig. 173). With a gentle shock the pseudopodia become slowly more or less retracted, their previously smooth contour becoming wrinkled FIG. ns.—Difflugia. From the shell of sand-grains project three finger-like pseudopodia. A, Unstimulated ; B, stimulated by a gentle shock. (Fig. 173, B ) ; with a stronger shock the pseudopodia are frequently drawn with such force into the protoplasmic body, that their ends, being fastened to the support by means of a sticky secretion, are torn off. With stronger stimulation the change in the pseudopodia is much more pronounced than with feebler : they become not only wrinkled, but on their whole surface small drop- lets swell out from the smooth contour ; 2 the more the reaction develops, the larger become the droplets ; they flow together into n myelin-like mass, and are distinguished clearly by a strongly refractive strand visible in the axis of the pseudopodium (Fig. 174) ; 1 Of. Verworn ('89, 1). 2 C£ Fig. 156) p> 363- STIMULI AND THEIR ACTIONS 383 finally, the latter is wholly drawn in, and its mass mingles with the rest of the body-protoplasm. Among the marine PolytJialamia also there are many forms that possess very great irritability ; these draw I H FIG. 174.— Contraction of a pseudopodium of Diffliiffia lobostoma after vigorous shaking Seven successive stages of retraction. in their whole richly-branched net- work of pseudopodia upon a single j shock. In the same manner there can be observed upon the slide under the microscope the effects of a shock upon the motion of flagella and cilia. E.g., Peranema, by means of the regular lash- ings of the flagellum at its anterior end, moves through the water quietly and in a straight line (Fig. 175). But, if the slide be given a brief shock, there follows at once an energetic lashing of the whole flagellum, which gives the cell another direction. It then continues its way quietly as before, with only the end of its flagellum vibrating. The mechanical stimulus, therefore, has had the result of intensifying the stroke of the flagel- lum. The same thing can be observed in the ciliary motion of the ciliate Infusoria. If a Paramcecium be observed in quiet and not too rapid locomotion, moving through the water by the play of its cilia as by innumerable small and rapidly moving oars, it is seen that upon being jarred it suddenly accelerates its motion, returning immediately, however, Fl:'•''•'. '•'•" ' O FIG. 215. — Chematoxis of Paramcecium aurelia. A, Chemotactic cover-glass preparation ; a drop of liquid that induces negatively chemotactic properties has been introduced under the cover- glass by means of a capillary pipette. £, Positively chemotactic assemblage. C, The same with too strong a solution ; the Paramacia have congregated in a circle at the optimum-point of concentration. D, A bubble of carbonic acid and one of air are under the cover-glass ; the former (at the left) induces positively chemotactic properties ; the latter is indifferent. £, The same preparation a few minutes later ; the carbonic acid has diffused into the surrounding water and by its too high concentration has driven the Paramcecia to the place where they find their optimum of carbonic acid. (After Jennings.) decrease in concentration must take place on one side. In other words, it is the amount of the difference in concentration at the 440 GENERAL PHYSIOLOGY two ends of the spermatozoid that determines the appearance of the chemotactic effect. Since the spermatozoid possesses only the minute length of 0'015 mm., we can form an approximate idea of how extraordinarily small must be the difference in concentration at its two poles, and therewith the amount of the stimulus that calls out a chemotactic effect. Thus, chemotactic phenomena and, as we shall see, analogous phenomena caused by other stimuli, give us a better idea than all other reactions of how excessively feeble stimuli produce a remarkable effect upon living substance. Living substance responds to extremely delicate influences. When homoeopathy affirms the effectiveness of extremely small quantities of certain medicines, its claim in this respect is fairly justified, however much superstition in other respects may attach to the homoeopathic doctrine. 2. Barotaxis All mechanical stimulation of living substance consists in a change of the pressure- relations under which it exists. Every degree of pressure can act as a stimulus, from crushing or cutting, which destroys the continuity of the substance, down to the slightest touch and the most delicate change in the pressure of the air or the water that surrounds the organism. Under the unilateral action of pressure-stimuli — in other words, in all cases where differences of pressure exist upon two different parts of the body of an organism- phenomena appear that correspond to those of chemotaxis. Since these possess in common the one characteristic of being called forth by pressure (ffdpos) acting unequally on different sides, they may be designated by the term barotaxis. Various kinds of barotaxis can be distinguished according to the kind of pressure ; and it can be positive or negative, according as the organism turns toward the side of the higher or the lower pressure. Under thigmotaxis, all those cases of barotaxis can be grouped in which the phenomena are caused by the more or less strong contact of living substance with more solid bodies. Naked proto- plasmic masses, such as rhizopods and leucocytes, exhibit the simplest form of this. These afford, indeed, striking examples of how feeble contact calls out positive thigmotaxis, strong contact negative, and how, analogously to the case of chemotaxis, differences in the intensity of the stimulus are of essential importance. If, e.g., a marine rhizopod, such as the often -mentioned Orbitolites (Fig. 98, p. 238), be left quiet in a glass vessel contain- ing sea-water, after some time pseudopodia begin to be put out from the small openings in the calcareous shell. Consisting at first of very short fibrils, they float freely in the water. Soon, becoming longer and heavier, their ends sink to the bottom and become fixed there by means of a delicate secretion, and the protoplasm begins STIMULI AND THEIR ACTIONS 441 actively to stream along the bottom without rising again freely into the water. In other words, upon slight contact with the bottom the living substance of the rhizopods behaves positively thigmotac- tically and turns toward the object. Except in the free-swimming Radiolaria, Heliozoa, etc., extension and wide expansion of the pseudopodia take place always in contact with some body, whether it be the bottom, the cover-glass, the surface of the water, or objects in the water. On the other hand, by strong mechanical stimulation of the tip of an extended pseudopodium of Orbitolites, best by press- I FIG. 216. — Pseudopodium of Orbitolites, in a cut across at * ; b, c, reaction. . The protoplasm is flowing away from the place of stimulation. STIMULI AND THEIR ACTIONS 443 their under side with cilia, which the animals, like woodlice, use as legs, with which to creep about upon objects in the water. These Infusoria are always seen creeping about busily and restlessly upon the slide, the cover-glass, or particles of mud lying in the water, without ever of themselves losing contact with the objects. The following episode from the life of an Oxy- tricha illustrates this positive thigmotaxis particularly well. In a flat dish contain- ing river-water and an Oxytricha, there lay some spherical eggs of the river-mussel Anodonta. When the contents were poured into the dish, the Oxytricha in some manner came into contact with one of the eggs. It ran about unremittingly for hours upon the spherical surface with- out being able to leave it, since the egg rested with one point only upon the level bottom (Fig. 219, C). The organism must have travelled an enormous distance. After four hours it was able to forsake its enforced retreat by means of a particle of mud which came to the isolated egg. Experiments which artificially imitated with other Oxytrichae essentially the same conditions give wholly analogous results. Jennings1 has recently discovered in Paramcecium another typical case of posi- tive thigmotaxis. If a piece of filter- paper, or any other substance provided with a rough surface, be placed under a cover-glass under which are numerous Paramcecia distributed uniformly through the water, after some time the piece is beset with a thick coating of the Infusoria, which touch it with their cilia without moving from their place. By employing high powers it is shown that those cilia that are in direct contact with the foreign body stand straight out and perfectly still (Fig. 220, A), and that the activity of the cilia over all the rest of the body is greatly depressed and eventually wholly stopped. There is here a very pronounced thigmotaxis. In connection with this it is noteworthy that the thigmotactic assemblage of Paramcecia con- 1 Loc. dt. FIG. 218.— Positive thigmotaxis of a plant, a, a, Bod ; 6, b, c, d* twining shoot. (After Sachs.) 444 GENERAL PHYSIOLOGY stantly attracts new individuals chemotactically by its production of carbonic acid ; thus all the individuals in the drop accumulate finally about the foreign body (usually in the course of 5 — -10 minutes), although, since it is surrounded by an impenetrable wall of individuals held thigmotactically, most of them cannot come into direct contact with it (Fig. 220, B). Thigmotaxis, which causes the individuals that swim by chance to the foreign body to remain, is merely the first cause of the assemblage ; chemotaxis toward the carbonic acid produced by them completes it. A second form of baro taxis, in which the stimulus is produced, not as in thigmotaxis by contact with a solid body, but by a gentle current of slowly flowing water, is rheotaxis, which was discovered by Schleicher and carefully investigated by Stahl ('84). This is FIG. 219. — Oxytricha, a ciliate infusorian. A, Seen from below ; B, seen from the side ; C, creeping about over the egg of a mussel. the peculiarity belonging to certain organisms, of taking toward flowing water a direction of motion opposed to the direction of the current. Since these organisms thus turn toward a pressure- stimulus, rheotaxis is merely a special form of positive barotaxis. Thus far rheotaxis is known in a few organisms only. Stahl •demonstrated it best in the plasmodia of Myxomycetez in Aethalium septicum, by the following experiment. He suspended a narrow .strip of filter-paper in a beaker filled with water, and somewhat elevated, in such a manner that one end of the strip dipped into the water, while the other end hung far down over the edge of the beaker. In such a strip there is a continuous slow current of water directed toward the end that hangs down, as is proved by placing upon it a coloured mark. Stahl laid this end upon a mass -of tan, in which the plasmodia of Aethalium live. The result was STIMULI AND THEIR ACTIONS 445 that the plasmodia slowly crept from the tan upward in the strip over the edge of the beaker arid downward upon the inner side of the glass, until they spread themselves out upon the surface of the water. By proper control-experiments it was possible to determine with certainty that it was only the streaming water which afforded the stimulus. Unfortunately the rheotactic properties of other organisms have been little investigated. It is, however, very probable that rheotaxis is wide-spread. Among other cases, it is easy to assume that the human spermatozoa are rheotactic and find their way to the egg-cell by means of this property. When the spermatozoa come into the uterus, they meet a current of mucous liquid coming toward them, since the cilia of the epithelium lining the uterine FIG. 220.— Thigmotaxis of Paramcecium. A, An individual in contact with a fibre of filter-paper ; the cilia that touch the fibre directly are still. £, Assemblage of Paramacia about a bit of filter-paper under the cover-glass. (After Jennings.) cavity have a direction of stroke toward the os, and hence produce a current toward the outside. That it is chemotaxis of the spermatozoa toward the ovum which points out the path to them becomes very improbable when it is remembered ^that the sperma- tozoa wander upward in the uterus before the ovum has left the ovarian follicle. As a matter of fact Roth ('93) has succeeded in showing experimentally that spermatozoa and likewise certain Bacteria are rheotactic, by producing under the cover-glass a feeble continuous current and observing that these unicellular organisms move in opposition to it. As a third form of barotaxis we have to consider finally geotaxis, i.e., the phenomenon that certain organisms place themselves and move with their median axis in a very definite direction toward 446 GENERAL PHYSIOLOGY the centre of the earth. In this case the stimulus is afforded by the minimal differences of pressure that exist at points of different height, both in the water and in the air. These phenomena have been known longest in botany, for all plants are geotactic in a pronounced manner. The roots grow toward the centre of the earth and, therefore, are positively geo- tactic ; the branches and the stems grow away from the centre of the earth and, therefore, are negatively geotactic. Further, in the behaviour of the leaves and in many cases the branches, which grow essentially tangential to the earth's surface, a third sort, transverse geotaxis, is seen. In free-living cells geotactic properties have been recognised, especially by Schwarz ('84, 1), Aderhold ('88), Massart ('91), and Jensen ('93, 1), who have found that of Infusoria and Bacteria in closed vessels containing water, some rise upward and collect upon the surface, while others seek the depths and crowd together upon the bottom. If, e.g., water containing numerous Paramcecia be put into a vertical glass tube, the Infusoria, as Jensen found, in a short time rise and collect at the upper end of the tube (Fig. 221), whether the latter be open or closed. Paramcecia are, therefore, negatively geotactic. Many Bacteria, as Massart observed, behave conversely ; with a similar arrangement of the experiment they accumulate at the lower end of the tube. These are, accordingly, positively geotactic. *^M±££V5£ Until very recen% either ver>' mystical as a result of negative ideas or none at all had been formed con- geotaxis have collected at • ,-, . , . , ., ,, the upper end. (After cermng the manner in which gravity calls out geotactic phenomena; but Jensen has now shown that the effects are due to differ- ences in pressure at different heights. As is well known, the hydrostatic pressure in a column of water is considerably less at the top than at the bottom. The higher pressure operates as a stimulus .and causes the organisms to leave the place where it is present and seek the places of lowest pressure. As all consideration at once shows, no other differences exist between the upper and the lower portions of the column of liquid in the vertical glass tube. An unprejudiced observer must, therefore, recognise in geotactic phenomena a pressure- effect. But that they are this actually, Jensen was able to show by experiment upon the disc of a centrifuge. In tubes placed horizontal and hence in the line of the radius of the disc, in which under ordinary circumstances no geotactic ac- STIMULI AND THEIR ACTIONS 447 cumulation of Paramcecia can take place, he increased by rotation the pressure at the peripheral end in comparison with the central end, and thus artificially imitated the conditions which, according to the laws of the earth's gravity, prevail in a vertical tube. The result was that with not too rapid rotation of the disc the Paramcecia collected at the places of lower pressure, i.e., at the central end of the tube, a phenomenon which Jensen puts beside geotaxis as centrotaxis. With a proper rate of rotation they frequently accumulated with greater certainty than in the upright tube. If they were centrifugalised too rapidly, naturally they were thrown out passively toward the periphery like heavy bodies. Accordingly, geotaxis, which has occupied a peculiar position so long in botany, must be regarded as a special case of barotaxis. 3. Phototaxis A ray of light extends through space from a source of light in a straight direction, and diminishes in intensity with the distance. Hence, any two points in the line of the ray possess different in- tensities ; the point that is nearer the source has the greater, that which is farther away has the less intensity. A ray of light, there- fore, fulfils very completely the conditions that are necessary to the appearance of unilateral stimulation — in fact, it is extremely difficult to establish conditions under which an organism is stimulated by light uniformly upon all sides. As a result of this, stimulation by light calls out very pronounced directive effects, which have been termed phenomena of phototaxis1 and form a complete analogy to those of chemotaxis and barotaxis. The phenomena of phototaxis have been known longest in plants ; as a matter of fact, plant physiology, on account of the less complexity of its objects of study, was able to develop in general into systematic completeness much earlier than animal physiology. Every one who cultivates plants in a room has the fact of positive phototaxis daily before his eyes. He sees that the growing parts turn constantly toward the light ; and, in order to make a plant grow straight upward, he must turn the pot about from time to time so that any phototactic curving may be compensated. Many plants are so extremely phototactic that in bright sunshine in a garden they follow the course of the sun in their curving. For example, in a bed of blue gentians, all the plants turn the broad 1 Formerly a distinction was made between heliotropism and phototaxis, the former word signifying the attitude, bending, and turning of fixed organisms, the latter the movement of motile organisms, with reference to the source of the light. This distinction is not only superfluous, but it introduces the false idea that the phenomena in the two cases are dependent upon different causes. A double terminology for processes that are based upon the same principle should be avoided. The processes are now understood better than at first, and the old distinction, which arose from purely external points of view, should be discarded as unscientific. Many authors have already done this. 448 GENERAL PHYSIOLOGY open surface of their gorgeous blossoms to the sun, and in this position follow its slow movement throughout the day ; at evening their blossoms have a direction almost the opposite of that in the morning. In many plants, as Stahl ('85) has shown in the horse- tails, the direction of growth is influenced by light in a very interesting way even in the spore ; in the division of the spore-cell the first division-wall, which divides the cell into two parts, is formed at right angles to the direction of the incident rays of light. A characteristic difference in the kind of phototaxis of the two halves is noticeable, such that the rhizoid-cell, from which the roots develop later, is always turned away from the source of light, and the prothallium-cell, from which the parts above the earth are derived, toward the source (Fig. 222). Among animals the investigations of Loeb ('90) and Driesch ('90) in recent times have likewise demonstrated wide-spread phototactic phenomena. But, although it is not altogether easy to obtain a correct view of these phenomena in the cell-community of the plant, it is much more difficult in the complex community of the animal body, on account of the varied share taken by the sense-organs, the nervous system, the motile organs, etc. Hence it is advantageous here to turn our attention primarily to the simplest relations, such as exist in the free-living cell. The phototactic phenomena of uni- cellular organisms, observed by Priestley and Ehreriberg, were followed out more fully by Nageli, Hofmeister, Baranetzky, Stahl, Klebs, Cohn, and other botan- ists, but the fundamental labours of Strasburger first gave an exact picture of the laws of the phenomena. Strasburger (78) made his investigations chiefly upon swarm- spores of various chlorophyllaceous Algce, and observed their behaviour toward light falling from a window upon one side of a suspended drop. Essentially the same phenomena were shown by flagellated swarm-spores of very different species. The be- haviour of the swarm-spores of Ulothrix may serve as a type. In diffused daylight of slight intensity these small flagellated cells hasten in straight paths to the edge of the drop that is turned toward the light, and collect there in great crowds. If the in- tensity of the light be increased, which Strasburger accomplished by bringing the preparation nearer the window or employing direct sunlight, with a certain intensity the swarm-spores begin to leave the positive side of the drop, i.e., the side that is turned IG. 222. — Division of the spore- cell of a horse-tail under the influence of light. The arrow indicates the direction of the rays. a, Position of the division-wall, b, direction of the mitotic figure. (After Stahl.) STIMULI AND THEIR ACTIONS 449 toward the source of light, and betake themselves to the opposite or negative side ; by further increase of the intensity all collect at the latter side. There exists, therefore, a point in the intensity, toward which the swarm-spores rush, going toward it from both higher and lower intensities — a phenomenon that Strasburger termed photometry. There is here a complete analogy to chemotaxis ; the latter is positive up to a certain concentration of the effective substance, but from there on with increasing con- centration is negative, so that the term chemometry is justified. Quite analogous to the behaviour of the swarm-spores of Ulothrix is that of the swarm-spores of Chcetomorpha, Ulva, Hcematococcus, and some other Algae, as well as the flagellate infusorian Chilo- monas Paramcecium, and the colourless swarm-spores of the Chytridice, all of which are positively phototactic with feeble intensity of light, and negatively phototactic with stronger intensity. There are forms — e.g., the swarm- spores of Botrydium grami- latum — which show positive phototaxis in all intensities. Next to these researches of Strasburger comes a whole series of observations by other investigators, who have been able to find phototactic phenomena in all sorts of micro-organisms. Thus, Stahl ('84) investi- gated the phototaxis of plasmodia of Myxomycetes, previously observed by Hof- meister and Baranetzky, and found that young plasmodia of Aethalium septicum are positively phototactic in half-darkness, and creep upon the surface of tan, but with stronger illumination they become negatively photo- tactic, and flow back again into the interior of the rhass. Further, Engelmann ('81, 3; '83) found mBacterium chlorinum and Bacterium plwtometricum two forms that possess phototactic properties and collect together in the light. Engelmann ('82), Stahl ('80), Aderhold ('88), and others x discovered phototactic phenomena also in the Diatomece and the Oscillarice, which behave exactly as the swarm- spores of Alyce and form very pronounced assemblages (Fig. 223). Finally, Stahl (/.c.), Klebs ('85), and Aderhold (I.e.) demonstrated 1 Cf. Verworn ('89, 1). G G FIG. 223.— Phototaxis of Diatomece. A particle of mud which was thickly surrounded by Diatomece lies in the middle of the drop. The organisms have all crept toward the edge turned toward the sun. 450 GENERAL PHYSIOLOGY phototactic movements in the Desmidiacece, and showed that these alga-cells place themselves with their long axis parallel to the light-rays, and in this position, by the extrusion of their secretion, move along the bottom in their peculiar manner toward the source of light, or with greater intensity away from the source (Fig. 224). In a preparation containing living Closteria l or Pleuro- tcenice all individuals place themselves with their long axis parallel to one another and to the direction of the incident light-rays. Thus, we find that among unicellular organisms, so far as they are irritable at all to light, phototaxis is a wide-spread phenomenon. After phototactic phenomena had been discovered, the question necessarily arose as to whether the different rays of the spectrum are phototactically effective in an equal degree ; this was decided very easily by the introduction of coloured glasses and solutions between the source of light and the object. The media employed were so chosen that they let through only rays of a certain portion of the spectrum, so that only rays of certain wave-lengths were FIG. 224. — Phototaxis of Clvsterium. The light comes from the right side. The arrow indicates the direction of movement of the Closterium. allowed to fall upon the organism (Fig. 225). In this way Colin, and later Strasburger, established the fact that in general the rays possessing a short wave-length, in other words, the blue and the violet especially, are more effective than those having a greater wave-length, viz., the red ; with not too high degrees of intensity the latter act like complete darkness. One point more deserves mention in the discussion of photo- tactic phenomena. From the preceding consideration and by analogy with the directive effects of other stimuli it is evident that only the difference in the intensity of the light upon different parts of the body can produce a directive effect ; where the stimulus acts upon the surface of the body from all sides with equal intensity, the reason for a definite axial position disappears, as is to be observed most clearly in the action of chemical stimuli upon all sides. Although this is obvious, some investigators, such as Sachs and Loeb, have believed that the direction of the rays is more responsible for the manifestation of phototactic phenomena than are differences in intensity. It is difficult to 1 Cf. p. 231. STIMULI AND THEIR ACTIONS 451 conceive this, for, since the assumption of an axial direction is possible only when differences exist at two different points of the surface of the body, it is wholly mystical how the direction of the rays, which is the same upon all sides of the body, can produce such an effect. In nature, under ordinary conditions, the decrease in intensity coincides with the direction of the rays, and hence we always see the phototactic movement take place in this direction. But the decrease in intensity can very easily be experimentally separated from the direction of transmission of the rays. Olt- manns ('92), making use of an idea already employed by Stras- burger, devised a very excellent contrivance for this purpose. He made a wedge of two glass plates, which were inclined toward one FIG. 225. — Spectra of various media ; 1, of a red glass ; 2, of a cobalt glass ; 3, of a green glass ; 4, of a solution of potassium bichromate ; 5, of an ammoniacal solution of a cupric salt. another at an angle of 2°, and filled the space between the plates with gelatine clouded with India ink. This wedge let through nearly all the light at its thin end, while at its thick end, where the gelatine was darkest, it absorbed much light. If, therefore, the light fell perpendicularly upon the surface of the plates, the greatest decrease of intensity for objects within a dark box behind the wedge lay at right angles to the direction of the incident rays. By means of these plates and the employment of the proper intensities of light it may actually be proved experi- mentally that it is not direction of ray, but solely difference in intensity upon different portions of the surface of the body, that produces phototactic phenomena. 4. Thermotaxis Heat, like light, can be employed very easily for unilateral stimulation, since, whether transmitted by conduction or radiation, it always decreases with the distance from its source, and hence G G 2 452 GENERAL PHYSIOLOGY differences of temperature always exist at two different points in the medium in the same direction from the source. The first observation of thermotactic properties was made by Stahl ('84) in plasmodia of Aethalium septicum. He placed two beakers side by side, one of which was filled with water at a temperature of 7°, the other with water at 30°; he then laid over their edges a strip of filter-paper, upon which the plasmodium had spread itself out, in such a manner that one end of the plasmodium dipped into the colder, the other into the warmer water. The pro- toplasm of the plasmodial network at once began to stream out of the former toward the latter, although before the experiment the opposite direction had been followed. The whole protoplasmic FIG. 226.— Negative thermotaxis of Amoeba. I, A drop of water containing many amoebae lies upon a large cover-glass. The cover-glass lies upon a black ground, which has in the middle a sharp, square opening. By shoving the cover-glass an amoeba can be so placed that it creeps over the edge of the hole, //, A. If concentrated sunlight is then let through the opening from the mirror of the microscope, the amoeba creeps back immediately into the cool darkness, //, B. The arrows indicate the direction of the movement. mass finally passed over to the warm water. This is a case of positive thermotaxis. Negative thermotaxis can be observed in Amoeba} when a temperature of at least 35°C. is allowed to act upon one part of the body while the rest of the protoplasm is at a lower temperature. This can hardly be accomplished by means of conducted heat. Radiating heat and the following arrangement should be em- ployed. A large drop of water, containing many individuals of Amoeba Umax, is placed upon a large thin cover-glass and the latter is laid upon a glass plate cemented to black paper and placed upon the stage of the microscope. In the middle of the paper is a small hole with very sharp edges. The concave mirror of the 1 Cf. Verworn ('89, 1). STIMULI AND THEIR ACTIONS 453 microscope is so placed that it receives bright sunlight and reflects it through the diaphragm. After the introduction of an opaque plate between the stage and the mirror, an Amceba is so placed by the aid of direct light that, its direction of motion remaining con- stant, it must creep beyond the edge of the black paper. As soon as the anterior end of the Amoeba has passed over the edge of the opening, the opaque plate between the mirror and the stage is suddenly removed, so that the concentrated rays of the sun fall upon that end, while the posterior end is still in the shade of the paper. The result is that the Amoeba immediately changes its direction and flows back into the shade (Fig. 226). That this is a pure heat-effect of the sun's rays and not a light-effect can be decided at once by excluding either the chemically acting light- rays by the introduction of an absorbing solution of iodine in carbon bi-sulphide, or the heat-rays by the introduction of plates of ice or alum. In the former case the thermotactic effect is as FIG. 227. — Thermotaxis of Paramcecium. In a black ebonite trough, 10 cm. in length, aro numerous Paramceda ; upon unilateral warming of the trough to 24°— 28" C. they move toward the cooler side. (After Mendelssohn.) distinct as in pure sunlight, in the latter it is wanting in spite of the great illumination. Careful tests show that Amoeba is not at all irritable to light. But therm ometric measurement of the temperature in the drop directly over the opening in the black paper shows that at least a temperature of 35° C. must be reached, if the effect is to appear. The thermotactic action of different degrees of temperature may be studied best in cilate Infusoria, like Paramcecium, which can be bred in great numbers. If a small ebonite trough be placed upon a metallic plate, and liquid containing Paramceda be placed in it, by warming or cooling differences in the temperature which can be measured by a thermometer can be obtained at the two ends of the liquid. These differences have a pronounced thermo- tactic effect (Fig. 227). The accompanying apparatus, constructed by Mendelssohn ('95), allows heating or cooling with hot or cold water (Fig. 228). With this it is shown that Paramceda at temperatures of more than 24° C. to 28° C. are negatively thermo- 38' 454 GENERAL PHYSIOLOGY tactic, i.e., swim in crowds away from the warmer side, while with temperatures below this limit they show positive thermotaxis, since they leave the cooler side. There is here a phenomenon com- pletely analogous to chemotaxis and phototaxis, in which the organisms likewise turn from both sides toward a certain degree of intensity of the stimulus. A simple calculation shows how small the difference in temperature can be at the two poles of the body of the Paramcecium, and still produce a thermotactic effect. The length of the surface of the liquid, the smallest just effective FIG. 228. — Apparatus for the investigation of thermotaxis. A flat trough of black ebonite (Fig. 227), in which is liquid containing Paramcecia, rests in a depression upon a metallic plate. The plate has three tubes, through which from ti beaker, by means of a tube, water of a desired temperature can be passed. Above the trough thermometers are attached to a stand, which dip into the liquid containing the Paramcecia and at any moment allow the temperature prevailing in different places to be read off. (After Mendelssohn.) differences in temperature at its two ends, and the length of the body of the Paramcecium must be known. In such a calculation, which, of course, can give only approximate values, Jensen found that Paramcecia are still thermotactic when at the two ends of their body, 0*2 mm. in length, a difference of temperature of 0'01° C. prevails. There is here expressed a delicacy of distinction in the intensity of stimuli, which finds analogies both in the data obtained by Pfeffer for chemotaxis and in the slight differences of stimulus effective in phototaxis, but which leave the differential capacity of the human consciousness far behind. STIMULI AND THEIR ACTIONS 455 5* Galvanotaxis It is characteristic of the galvanic current that it always calls out phenomena of polar excitation. As a result of this, stimulation by the constant current is especially well fitted to exercise directive effects. Since, further, the current can be graduated in intensity very delicately, arid its direction can be readily controlled, it affords a very perfect means of producing experimentally directive reactions in their most exact form, and with the certainty of physical pheno- mena. The galvanotactic phenomena of motile organisms remind one of the effects of the magnet upon iron particles. The galvanotactic phenomena of animals were first discovered by Hermann ('85), in the larvae of frogs and the embryos of fishes. He observed that when a galvanic current was conducted through a vessel containing these animals, upon the making of the current all placed themselves with their long axis parallel with the curved lines of flow of the current, so that their heads were directed toward the anode and their tails toward the kathode. In this position they remained. Analogous effects have been observed more recently and upon various other higher animals by Nagel ('92, '93, '95), Blasius and Schweizer ('93), and latest by Loeb('96, 2, 3, 4; '97,1,2). Galvanotactic phenomena have also been found in plants, especially the root-tips of many plants ; when the constant current is sent through them for a considerable time, the tips bend toward the kathode. But most striking, and theoretically most interesting, are the phenomena, in free-living unicellular organisms, such as Rhizopoda, leuco- cytes, Infusoria, etc.1 In order to investigate the galvanotaxis of these organisms, we can best employ the above- , described slide with non-polarisable clay-electrodes, or non-polaris- able electrodes that are arranged like camel's-hair brush-electrodes but, instead of the brush, have tips made of fired clay which can be- dipped into the liquid through which the current is to be sent (Fig. 229). If a few drops of water containing many Paramcecia be placed on the slide between the parallel pieces of clay that serve as 1 Cf. Verworn ('89, 2, 3 ; j'92, 2 ;i'96, 4) and Ludloff ('95). PIG. 229. — Non-polaris- able electrode, which, instead of the camel's- hair brash has a tip made of fired clay. 456 GENERAL PHYSIOLOGY electrodes (Fig. 230), and a constant current be passed through the liquid from two brush-electrodes laid upon the clay pieces, at the moment of making all the Paramcecia place themselves with the anterior poles of their bodies toward the kathode, and swim freely toward the latter in a dense crowd. In a few seconds the anode is wholly deserted, and at the kathode there is a dense swarm, Fia 230.— Galvanotaxis of Paramwcium. The arrow indicates the direction in which the Parama-cia are swimming ; in B all have collected at the kathode, A Microscopic, B, macroscopic picture. which remains as long as the circuit is closed If now the current be reversed, so that what was before the anode becomes the kathode, and vice versa, the whole swarm rushes over in one mass to the opposite side, and collects, as before, at the kathode. This experi- ment, which because of the great exactness of the reaction is very fascinating to the observer, can be repeated as often as desired STIMULI AND THEIR ACTIONS 457 If the current be broken, the assemblage disappears from the kathode, and the Paramcecia scatter themselves again uniformly throughout the liquid. If the Paramcecia be put into a large drop upon a glass plate, and the pointed electrodes be dipped into the drop, upon making the current the infusorians arrange themselves in the direction of the curved lines of flow of the current like iron filings above a magnet, and swim in this direction (Fig. 231) until they have reached the kathode, behind which they collect in a dense swarm. If the kathodic electrode be made movable, so that its position in the drop can be changed at will, it is possible to direct the Paramcecia with the point of the electrode wherever one wishes, just as tin-fishes may be directed in water FIG. 231. — Galvanotactic curves of swimming Paramcecia, pointed electrodes being used in the drop of water. A, Beginning of the effect; B, completed assemblage. with a magnet. Since the motion of the Paramcecia is directed toward the kathode, this case may be termed kathodic galvanotaxis. Like Paramcecium, the majority of the ciliate Infusoria are kathodically galvanotactic. Among other Protista that show the same phenomenon, Amoeba alone may be mentioned. Amoeba Umax, when the current is made, abandons its original direction ; its pseudopodia flow forward toward the kathode, the whole proto- plasmic mass streams after, and the body assumes the typical extended creeping form, in which it flows unerringly to the kathode. Other forms of Amoeba, such as Amoeba proteus (Fig. 232), Amoeba verrucosa, and Amoeba diffluens (Fig. 233), behave in all respects similarly. Many flagellate Infusoria show a behaviour opposite to that of the above-mentioned organisms. If, e.g., a constant current be passed through a drop in which is a large number of individuals of the small egg-shaped species, Polytoma uvellat which move through the water, revolving continually about their axis, by means of their two flagella (Fig. 234), upon making the current all individuals immediately turn their anterior flagellated ends toward the anode, and freely swim in their usual manner straight to this pole, where 458 GENERAL PHYSIOLOGY they collect in dense crowds. After the breaking of the current they scatter again uniformly throughout the drop. Polytoma, therefore, behaves toward the two electrodes exactly the reverse of Paramcecmm ; in contrast to the latter it is anodically galvanotactic. FIG. 232. — Galvanotaxis of Amoeba proteus. At the left unstimulated and possessing numerous pseudopodia. At the right, above, after making the current ; below, after reversal of the current. The arrows indicate the direction in which the animal is creeping. A very fascinating spectacle results from exposing to the influence of the current, at the same time, anodically galvanotactic Infusoria, e.g., a flagellate form, such as Polytoma, and kathodically galvano- tactic forms, e.g., a small ciliate genus, such as Halteria or Pleuronema. The previously inextricable intermingling of the FIG. 233. — Galvanotaxis of Amoeba ditfluens. A, Unstimulated, creeping; B, after making the constant current. The arrow indicates the direction of the motion. two forms ceases at once after the making of the current. The C'diata collect at the kathode, the Flayellata at the anode. After a short time the liquid is entirely deserted in the middle, and the two assemblages are sharply separated from one another. If now STIMULI AND THEIR ACTIONS 459 the current be reversed, so that the previous anode becomes the kathode, and vice versa, the two crowds of Infusoria rush toward one another like two hostile armies, cross and again assemble at the opposite poles. There are few physiological experiments that FIG. 234.— Galvanotaxis of Polytoma uvella. A, Resting quietly ; £, swimming toward the anodu after the making of the constant current. are so pleasing and graceful as the galvanotactic dance of the Infusoria. A third form of galvanotaxis is shown by the ciliate infusorian Spirostomum ambiguum.1 If these elongated Infusoria, which can be perceived even with the naked eye as small white fibres c. 2 mm. in length, be placed in water between parallel clay-electrodes, it is seen that upon the making of the constant current they draw together suddenly by the sudden contraction of their myoid-fibres, but do not, as might perhaps be expected, swim toward one or the other pole. Instead of this, by means of their ciliary motion accompanied by much bending of the body, they gradually turn so FIG. 235. — Galvanotaxis of Spirostomum ambiguum. After the making of the current the Infusoria place themselves with their long axis at right angles to the direction of the current that their long axes are at right angles to the direction of the current, and maintain this position, although constantly bending and twitching their long bodies (Fig. 235). This form of gal- vanotaxis may be termed transverse. In other organisms trans- 1 Cf. Verworn ('92, '96). 460 GENERAL PHYSIOLOGY verse galvanotaxis has not been observed thus far, although it is scarcely doubtful that it will yet be found to occur in other unicellular organisms. C. THE PHENOMENA OF OVER-STIMULATION When the Athenians, under the leadership of Miltiades, had gained the victory of Marathon, one of the soldiers named Eukles, still hot from the struggle, hastened from the battle-field to Athens in order to be the first to bring to his countrymen the news of the victory. Plutarch1 who has given us the anecdote, tells of the dramatic fate of this runner of Marathon. When Eukles entered Athens exhausted by the effort of the long run, he still had power to call out to his countrymen the news of the victory in the words " Xeu/oere, ^aipojmev I " whereupon he fell dead. One of our modern sculptors, Max Kruse, has illustrated this tale by his figure of the runner of Marathon now in the National Gallery at Berlin, and has given striking expression to the physiological phenomena of total exhaustion. The cause of the tragic end of Eukles was his excessive muscular exertion. Under the influence of long duration or great intensity of stimuli, changes gradually appear in the living substance which, when they have reached a certain extent, lead to death. In the following pages we will examine somewhat in detail the phenomena resulting from over-stimulation. 1. Fatigue and Exhaustion If a living object be stimulated by long-continued, oft-repeated, or very strong stimuli, after some time it passes into the condition of fatigue. The general characteristic of fatigue is a gradual decrease of the irritability of the living substance. This is expressed especially in the fact that with increasing fatigue, the intensity of the stimulus remaining the same, the result of the stimulation becomes constantly less. We have already become acquainted with some examples of this fact in considering galvanic stimulation.2 If a constant current of average strength be passed through an Actinosphcerium, at the moment of making there begin to appear at the anode marked phenomena of contraction. The protoplasm of the pseudopodia flows centripetally until the latter are drawn in. Then the walls of the vacuoles break ; and a granular disintegra- tion of the protoplasm results, which proceeds constantly farther from the kathode during the passage of the current. This dis- 1 Cf. bibliography. 2 Cf. pp. 422 and 423. STIMULI AND THEIR ACTIONS 461 integration, beginning with great energy, becomes slower and less extensive the longer the current flows, and after some time is at a complete standstill. This means that the living substance of the ActinospTiccrium becomes fatigued in the course of the continual stimulation, and decreases in irritability; hence the stimulus, which at first induced pronounced phenomena of disintegration, later produces no reaction at all. Pelomyxa is fatigued still more rapidly than Actinosphcerium. Stimula- tion for a few seconds is sufficient to make individuals of this genus wholly non-irritable to currents of equal intensity; a much greater intensity is then required to call out the same reaction. In contrast to these forms of living substance which become fatigued very rapidly, nerves seem to be incapable of fatigue : thus far it has been impossible by continual stimulation to demonstrate in them fatigue phenomena. That nerve is really incapable of fatigue is in the highest degree improbable. Since, like all living substance, it has a metabolism so long as it lives, and since its irritability is extinguished with its life, it must be supposed that its irritability is associated with its metabolism, and that every excitation produces a change in its metabolism. Possibly these changes are so slight that fatigue cannot be demonstrated at all by the methods that have been used hereto- fore. To conclude, therefore, from the apparent incapability of fatigue that the function of nerve is entirely independent of metabolism, and is like the capacity of copper wire to conduct galvanic currents, is quite unjustified. Nevertheless, it would be important to investigate the question, whether in nerves the changes of metabolism produced by stimulation are not perhaps compensated by the metabolism as soon as they appear, so that within a limited time no phenomena of fatigue become noticeable externally. That such a condition is very easily possible is shown by the behaviour of another object — viz., cardiac muscle. Although from long before birth up to death the heart-muscle labours uninterruptedly, under normal conditions it does not become fatigued, because the changes resulting from its activity become compensated in its metabolism. Nevertheless, it is capable of fatigue, when for any reason it is obliged to make excessive efforts. This is the case in certain diseases. The phenomena of fatigue become then apparent, not at once, but in the course of long spaces of time, and even the substance of the muscle changes profoundly, until its movements wholly cease. Then death by paralysis of the heart results. While cardiac muscle is thus capable of fatigue only exception- ally, in the tissue of skeletal muscles fatigue phenomena are very easily induced. Fatigue has been studied most fully and most 462 GENERAL PHYSIOLOGY frequently in the cross-striated skeletal muscles of vertebrates. Since by means of the graphic method muscular movement can be recorded and its individual factors made visible, the progressive fatigue of the muscle can be studied very conveniently in the change undergone by the curve that the contracting muscle records. Mosso ('91) has done this 'in the living man by means of his ergograph, and has presented the results in his excellent and fascinating book entitled " La Fatica" The ergograph is a small apparatus in which the arm of a man is fastened by means of a holder, while one finger is free to move. This finger is connected by a cord with a writing-lever, which records upon a rotating drum all the movements of the finger that take place, either voluntarily or FIG. 236.— Mosso's-ergograph. (After Mosso.) involuntarily as the result of electrical stimulation. A weight can be hung upon the cord, and thus the work performed by the flexor muscles of the finger can be changed at will (Fig. 236). By means of this apparatus it can be shown very clearly that, with the stimulating induction-shocks remaining constant in intensity and following each other at equal intervals, the work performed by the muscles constantly decreases, and finally becomes equal to zero. This is expressed in the curve of contraction, which gives only the extent of the contraction, by a constant decrease in the height of the lift (Fig. 237). After a course of contractions it requires considerably stronger stimulation to produce further con- traction of the fatigued muscles equal in height to that at the beginning. The details of the changes are more readily visible when the successive contraction-curves of a frog's leg are recorded over one another upon a myograph from the beginning of the STIMULI AND THEIR ACTIONS 463 series on, as Marey ('68) did a long time ago. Then it is found that, as Helmholtz discovered, with increasing fatigue not only does the curve decrease in height, but it becomes more extended, its descending limb especially undergoing a lengthening. In other words, the work done by the muscle becomes less while the dura- tion of the contraction increases. The latter phenomenon depends chiefly upon the increasing duration of the stage of expansion. The fatigued muscle needs more time to extend to its complete length. The phenomena of fatigue appear, perhaps, still more clearly upon stimulation by the tetanizing current than by single induc- tion-shocks. If the curve of te- tanus of a frog's gastrocnemius muscle, not too strong and weighted, be recorded upon a rotating drum, it is seen that it continues at its original height for a long time, and follows a straight line (Fig. 238). But after some time it begins slowly to fall, and, not rarely at the same time, small irregularities in its course become visible, which are due to the fact that the muscle begins to tremble. The curve continues to fall gradually. If the stimulation be interrupted, the curve usually does not sink at once to the level of its starting- point, but remains some distance above the latter, and only in the course of a considerable time re- turns to it. Hence there is a considerable contraction-remainder in the fatigued muscle after the end of stimulation, and the muscle assumes its original length only very slowly. It is of great interest that microscopic changes have been observed in fatigued muscle. Of a number of wholly similar blue-bottle flies (Musca vomitoria) H. M. Bernard ('94) kept some in continual motion by constantly exciting them, until they fell to the ground completely exhausted. The fatigued flies were at once killed simultaneously with the others, which, in the meantime, had remained at rest. The two kinds of specimens were then subjected to the same treatment. A marked difference appeared between them. While in the resting flies the muscle- fibrillse showed distinct cross-striation and the various discs of the individual segments showed differences in staining-capacity, in the FIG. 237. — Curve of fatigue ; decrease of the height of the curves with numerous suc- cessive contractions of the flexor muscles of the fingers. (After Mosso.) 464 GENERAL PHYSIOLOGY fatigued specimens only Dobie's line was to be seen clearly, and the whole contents of the segments stained uniformly without any differentiation of the discs being noticeable (Fig. 239). But the granules, or sarcosnmes, lying in the sarcoplasm between the FIG. 238.— Curve of tetanus of a fatigued muscle of a frog. individual fibrillse were enormously enlarged in the fatigued, in comparison with the resting, muscle. It would lead us too far to consider in detail the significance of these changes. Hodge ('92), G. Mann ('94), and Lugaro ('95), have recently made known distinct microscopic phenomena of fatigue in the ganglion-cells of mammals, FIG. 239.— Wing-muscles of a blue-bottle fly (Musca vomitoria). A, At rest; £, fatigued. The division of the muscle-segments into discs has become invisible and the sarcosomes between the fibrillse are enormously enlarged. (After H. M. Bernard.) birds, and insects, especially in their nuclei. Thus, according to Hodge, in the sparrow, in the morning, after resting, the cells of the brachial ganglia, which innervate the wing-muscles, have clear, round, vesicular nuclei (Fig. 241, A), while in the evening, after STIMULI AND THEIR ACTIONS 465 the exertion of the day, they have an indented contour (Fig. 241, B). Likewise in the cat, after stimulation for several hours, the nuclei of the ganglion-cells, which previously were vesicular and round, are shrunken and have an irregular contour, while the arrangement of the contents has changed materially (Fig. 240). According to Mann, and also Lugaro, the change of the ganglion- cell during its activity consists essentially in a turgescence of the protoplasm and the nucleus, while during rest a diminution in volume takes place. During work the nucleus becomes poorer in chromatin, and, as Lugaro found, by fatigue the nucleolus can \<5 lk FIG. 240.— Ganglion-cells of the cat. A, In the normal condition ; £, after five hours' stimulation (After Hodge.) be made completely to disappear. Here belong, also, the fatigue- changes which Heidenhain ('83) observed a long time ago in salivary glands after stimulation, the cell-nuclei of which, in rest, put out pseudopodium-like processes, but after stimulation assume the spherical form (Fig. 242). The fatigued muscles recover as soon as the stimulation ceases, and the more rapidly, the less was the degree of fatigue. In recovery the irritability gradually increases; the various pheno- mena of fatigue, which can be seen in the curve of contraction, gradually pass away, and, finally, the muscles are in the same condition as before. H H 466 GENERAL PHYSIOLOGY That which appears especially interesting is the fact, discovered by Valentin ('47), and Eduard Weber ('46), that excised muscles also are capable of recovery. This, also, can best be seen by the aid of the graphic record of the muscular movement. If an isolated gastrocnemius of a frog be fatigued by being alternately tetanized for perhaps five seconds and allowed to rest for five seconds, after some time, the intensity of the stimulus remaining constant, the curve begins to fall, until, finally, the stimulation no longer produces any contraction, and the muscle remains at rest in a slightly contracted condition, determined by the contraction- remainder. If, then, the stimulation be interrupted and the muscle be left to itself for a considerable time, protected from FIG. 241. — Ganglion-cells of the sparrow. A, Morning ; B, evening. (After Hodge.) drying, contractions nearly equal to those before the fatigue can be induced anew with the same strength of stimulus. The muscle now becomes fatigued more rapidly than before. One factor in the recove'ry, which has recently been established in Richet's laboratory by J. Joteyko ('96), is of interest. This is found in the fact that excised muscle recovers only when oxygen is available ; with the exclusion of oxygen after complete fatigue the muscle cannot be put again into activity. Hence oxygen is absolutely necessary for the restoration of the irritability of muscle. But the fact that after great fatigue excised muscle is able to recover in a medium containing oxygen proves that the muscle- substance, while it can perform contractions for a considerable time independently of the circulating blood, must possess in itself, STIMULI AND THEIR ACTIONS 467 also independently of the blood-current which brings in food-stuffs and takes out excretory matters, the factors which, in union with oxygen, are necessary to the restoration of irritability. If we turn from the phenomena of fatigue that are externally visible in the muscle itself to those that develop secondarily in the body as results of very strong muscular effort, we meet with certain facts which bring us a step farther in the knowledge of fatigue. If we observe the phenomena that develop in our body in the course of strong muscular effort, we notice first a considerable acceleration and deepening of the respiration. At the same time the frequency of the heart-beat becomes increased. The produc- tion of heat which is increased by the muscular activity, is essentially compensated reflexly by the outpouring of per- spiration, the evaporation of which lowers the temperature. If FIG. 242.— Parotid of the rabbit. A, During rest ; the cell-nuclei are indented. B, After stimula- tion through the sympathetic ; the nuclei have become round. (After Heidenhain.) the activity has been very considerable, not rarely a slight fever appears, especially when the body has made no muscular effort for a considerable time previously. The temperature rises, there are attacks of shivering, and a certain increase in irritability of the central nervous system is noticeable. This fact is so well known that there is recognised a " gymnast's fever," which appears in gymnastic work after too strong exertion. This fever of fatigue is also very frequently observed after very exhausting mountain tours and after long riding. Among the subjective symptoms that manifest themselves as a result of very strong muscular exertion, the best known are excitement appearing during the stage of the fever, e.g., in the evening after an exhaustive march, sleeplessness, lack of appetite, and intense muscle pains, which appear usually upon the next day or even later. These phenomena together present an interesting complex of symptoms, which remind the physician very strongly of the H H 2 468 GENERAL PHYSIOLOGY picture of events in acute infectious diseases. The conjecture is strongly suggested that all these symptoms that appear as a result of muscular fatigue appear also as the characteristic complex of symptoms of infectious diseases. Concerning the latter, it is known from the later bacteriological investigations that they are the result of poisoning by certain poisonous metabolic products, the so-called toxines,1 which are excreted by invading bacteria. But, like bacteria, a great variety of other forms of living substance excrete poisonous substances in their metabolism, and hence the assumption is not unjustified that the muscles also produce such toxines, which in the quantity usually present produce no effects, but which, as soon as they accumulate in the body in greater quantity as the result of excessive muscular activity, give rise to phenomena of genuine poisoning. Various experiments have proved directly that this conjecture is correct. The first important experiments were those of Eanke ('65), who found that he could make a fatigued muscle again capable of performing work by washing it out with a dilute solution of common salt which, as is well known, is completely indifferent to living tissue. Hence there must have arisen and accumulated in the muscle as the result of activity certain fatigue-substances, which act to paralyse the muscle-substance itself, but after the removal of which the muscle regains its capacity for work. Ranke was able actually to confirm this by the following experiment. He made a watery extract of muscles that had been strongly fatigued, and injected it through the blood-vessels into a fresh muscle. The result was that the muscle immediately lost its working capacity and behaved exactly like a fatigued muscle. It is proved by this experiment that phenomena of fatigue are caused by the accumulation of certain metabolic products in the muscle, and can be set aside by the washing-out of the latter. More recently Mosso ('91) performed upon a dog an experiment an- alogous to Ranke's. When he injected into a narcotized dog blood from a normal dog, the former continued completely normal. But if, instead of this, he used for injection blood from a fatigued dog, whose muscles had been kept in violent contraction by tetanization with the electric current for only two minutes, characteristic phenomena of fatigue immediately appeared : the respiration became accelerated and even dyspnceic, and the heart began to beat strongly. Hence the fatigue-substances that are produced in the muscle do not remain there, but are taken up by the blood and thus go to the organs of the whole body. Hence it comes about that after an exhaustive march not only do the muscles of the legs, but also those of the arms, show phenomena of fatigue. The poisonous substances going with the blood to the brain-centres that control respiration and the movement of the heart, there first 1 Of. p. 175. STIMULI AND THEIR ACTIONS 469 produce an excitation, which results in a powerful increase of the respiration and the activity of the heart, but finally with too great exertion cause a depression, which leads to standstill of the heart and death. The history of the runner of Marathon is a classic example of this course of phenomena. But in seeking the origin of muscle-fatigue, we ought not to attach too much importance to the appearance and accumulation of fatigue-substances in the muscle, as is not rarely done. Al- though it is beyond doubt that the phenomena of fatigue can be produced by the accumulation of fatigue-substances, this is not the sole cause. The chief factor in the production of fatigue is the progressive consumption of substances that are necessary to activity. Accordingly, in muscle and probably in all living sub- stance, two different causes of fatigue may be present. Phenomena of fatigue are observed, on the one hand, when certain substances that are necessary to life are consumed during exhaustive activity more rapidly than they are introduced or reformed ; and, on the other, when certain substances that arise as decomposition-pro- ducts during activity accumulate in such quantity that they produce a depressing effect. On account of this fundamental difference in the genesis of the phenomena in question, it seems advantageous to distinguish between the two causes by the use of different terms, and to call the phenomena of depression that result from the consumption of the necessary substances, exhaus- tion, and those that result from the accumulation of and poisoning by decomposition-products, fatigue. The end-result of the two series of phenomena arising from such different causes is the same. Both are characterised by depression of the irritability and the activity of living substance. 2. Excitation and Depression Let us first bear in mind that excitation and depression are merely quantitative opposites. The two are merely different degrees of one and the same phenomenon, namely, life, excitation being an increase, depression a decrease of the normal intensity of vital phenomena. It has been seen in a previous section that phenomena of depression can be called out by over-stimulation. This fact is important, for it shows that the same stimuli which with slight intensity or short duration produce excitation, with increased intensity or long duration can produce precisely the opposite effect, namely, depression. This relation between excitation and depression is very wide- spread. The phenomena of fatigue are a single example of it. In this respect the effects of anaesthetics form a complete analogy to the phenomena of fatigue. It appears to be a general pro- 470 GENERAL PHYSIOLOGY perty of these substances that in very small doses or with very brief administration they produce phenomena of excitation, while with increasing action phenomena of depression become more and more noticeable, and apparently are able to lead to a com- plete standstill of life.1 This fact is well known in pharmacology. Morphine in small doses and at the beginning of its action produces always a stage of excitation, in which the patients are restless and excited, are not able to sleep, and are haunted by all sorts of illusions. But if the dose given be greater, and the stage of excitation appearing at the beginning of its action be passed, deep sleep comes with total absence of motion and sensation. The same result is seen also with other narcotics and with single cells. In ciliate Infusoria the ciliary motion is increased to furious rapidity under the influence of the vapour of ether or chloroform in small quantity or with brief duration. The excitation of the cilia is so great that the organisms shoot through the water like arrows. But if the dose or the duration of the influence of the narcotic become only slightly increased, the motion becomes slower and slower until, finally, complete paralysis results, and the cells remain motionless. The same phenomena have been observed with the many different kinds of anesthetics, and in all sorts of living substance. Another example of the fact that with increasing intensity of the stimulus excitation is first increased and then after a certain point gives place to depression, is afforded by stimulation by heat.2 With increasing temperature up to a certain degree, which is very different for different forms of living substance and for different vital phenomena in the same form, all vital phenomena undergo an augmentation to a maximum. But if this degree be overstepped, excitation decreases rapidly, and gives place to complete paralysis in the form of heat-rigor. The fermentative activity of yeast-cells, the growth and development of ova, and the protoplasmic and ciliary motions of unicellular organisms, afford distinct examples of this. Other varieties of stimuli illustrate the same general principle. But this relation of excitation and depression holds good only for those stimuli which consist in an increase of the factors that under normal circumstances act upon the organism as vital con- ditions, as, e.g., increase of the surrounding temperature, or those which consist in an incoming of foreign factors, as, e.g., poison- stimulations. Those stimuli, however, which depend upon the diminution of vital conditions, as, e.g., decrease of the surround- ing temperature, appear in general with increasing intensity to depress vital phenomena without previous excitation. With the present condition of our knowledge a law covering these facts cannot be formulated with certainty, for a cautious critic requires 1 Cf. p. 379. * Cf. p. 396. STIMULI AND THEIR ACTIONS 471 a larger number of phenomena before generalising. Nevertheless, large number of discoveries speak directly in favour of the idea here expressed. E.g., with increasing cold the energy of vital phenomena sinks, until at certain low degrees of temperature, which likewise are very different for different objects, apparently complete paralysis results. The experiments of Kuhne ('64) on Amoeba, in which the protoplasmic motion was at a complete standstill in cold- rigor at 0° C., as well as a number of other phenomena previously spoken of, afford examples of this. Further, with decrease of moisture the intensity of vital phenomena sinks, until the latter come to a complete standstill. The behaviour of dried, apparently dead, organisms illustrates this. Finally, with decrease of food and of oxygen vital phenomena are depressed, and, as is instanced by the protoplasmic movement of Amoeba in Kiihne's experiments, cease in an atmosphere of pure hydrogen. The fact cannot be overlooked that there are cases in which with falling temperature, as in the regulation of heat by warm- blooded animals, or with decrease of the water-contents, as in drying nerve and muscle, or with decrease of oxygen, as in the asphyxiation of warm-blooded animals in a space free from oxygen, phenomena of excitation are apparent. But the mode of occurrence of these phenomena, which can be investigated in the cell-com- munity only with difficulty on account of the complexity of the conditions, is in large part still obscure, and many investigations directed toward this point alone, especially in single cells or simple tissues, are needed, before it shall be known clearly whether the principle observed in so many cases, that with decrease of the various vital conditions a gradual depression of vital phenomena comes in without previous excitation, really has general applica- tion. The question whether within the two extreme limits of vital conditions living substance possesses but one maximum of excitation is surely interesting. There are doubtless many cases in which both augmentation and diminution of the vital condi- tions produce depression, and in which between these two points excitation rises to a single maximum. 3. Death ~by Over-stimulation The inevitable end-result of continual or strong over-stimula- tion is death, but the manner in which it develops differs in individual cases according to circumstances. With continued, not too strong stimulation death develops fairly gradually, and here the stages of the reaction can be followed best. The effect of narcotics may serve as an example. If, e.g., an infusorian cell, such as the ciliate Spirostomum, be exposed to the influence of the vapour of chloroform or ether, there is seen first a 472 GENERAL PHYSIOLOGY stage of excitation, in which the ciliary motion becomes strongly accelerated. Gradually with continued action the excitation gives way, and there begins a stage of depression resulting in a complete standstill of the cilia. From this stage by interruption of the stimulus and the re-establishment of the normal vital conditions the organism can be revived. If, however, the action continues still further, this is no longer possible ; narcosis passes directly into death. The same thing is seen in human ganglion-cells in morphine poisoning. At the beginning of the action there is a stage of excitation, which soon gives way to a complete paralysis of the ganglion-cells. With too strong a dose the death of the cells results ; this is seen in a standstill of the functions dependent upon them (movement of the heart, respiration, etc.). The same sequence of actions is produced by the thermal stimulus with continual increase of its intensity. The protoplasmic motion of Amoeba increases with increasing warmth up to nearly 35° C. Here the motion suddenly diminishes ; the organism continues in FIG. 243.— Pelomyxa palustrls. A, Creeping ; B, contracted as a result of feeble chemical Simula- tion ; C, undergoing granular disintegration with long stimulation. the stage of contraction and performs at most very feeble motions. With a slightly higher temperature the latter wholly cease. This is the point of heat-rigor. Upon cooling from this point motion returns. But, if the temperature rises above 40° C., the heat- depression passes over into death. With thermal stimulation the whole sequence of reactions from the minimum of temperature up to the maximum is presented with the greatest clearness : stand- still of vital phenomena in cold-rigor, increasing excitation, depression in heat-rigor, and finally death. The complete series does not always appear. Very frequently one or the other stage is wanting. This depends partly upon the special qualities of the living substance, and partly upon the kind of stimulation. Often under the influence of stimuli of very high intensities all stages are omitted, and death results at once. Sometimes there is a brief stage of excitation, but intense excita- tion is followed immediately by death. If, while Pel.omyxa is creeping quietly, it be stimulated only feebly by acids, alkalies. STIMULI AND THEIR ACTIONS 473 chloroform, or other chemical substances, in a few seconds it draws itself together into a ball (Fig. 243, JB), and thus gives the im- pression of intense excitation of contraction. In the course of a longer, constant action of the stimulus the protoplasmic body begins to undergo granular disintegration from the periphery (Fig. 243, C). If, however, the chemical stimulus be allowed to act in greater intensity upon the resting, extended body, the stage of excitation has no time for its development. The body begins immediately, without first contracting into a ball, to undergo granular disintegration in the form which it had at the moment of stimulation (Fig. 244, B). Here death appears immediately as a result of stimulation, while the other stages of the reaction have not time to develop externally. The same is seen in galvanic stimulation. If Actinosph cerium be stimulated by feeble galvanic currents, the typical phenomena of excitation of contraction appear at the anode. The protoplasm of the pseudopodia forms small globules and spindles, and flows centripetally, until the pseudopodia FIG. 244. — Pelomyxa palustris. A, Creeping; B, undergoing granular disintegration as a result of strong chemical stimulation. are wholly retracted. If, however, a strong galvanic current be applied suddenly, the protoplasm has not time to contract, but immediately undergoes disintegration at the anode. Granular disintegration of protoplasm as a result of supramaximal stimulation is a valuable aid when, as e.g., in stimulation by galvanic currents, the localisation of the excitation is to be determined in objects in which there is no other distinctly visible expression of it. In such cases it is only necessary to employ supramaximal currents, and the place of excitation is recognised at once in the granular disintegration of the protoplasm. Of course this is possible only in forms of living substance which, at the moment of death, show granular disintegration. There are many forms of cells, especially those that are provided with a solid wall, which in dying do not pass into granular disintegration at all. Yeast-cells, e.g., can be killed in various ways by over-stimulation without any disintegra- tion of the body. Their death is indicated only indirectly, by loss of the power of splitting grape-sugar into carbonic acid and alcohol. But we need not here go more in detail into the different forms in 474 GENERAL PHYSIOLOGY which death appears, since we have previously l become acquainted with them. Over-stimulation, in its most general significance, is nothing but that which has been termed elsewhere external causes of death. The fact does not require special mention that over- stimulation, when it consists either in an increase or a decrease of the factors that act as vital conditions, always results finally in death. It has already been seen that overstepping either the minimum or the maximum of vital conditions leads to a fatal outcome. In a previous chapter we came to regard life as a phenomenon of nature that, like all other phenomena of nature, comes into exis- tence when a certain complex of conditions is fulfilled. If the con- ditions become changed, the phenomena also change ; if the former wholly disappear, the latter also cease. In stimuli we have become acquainted with sach changes of vital conditions. Under the in- fluence of stimuli vital phenomena change, and they wholly cease, when the stimuli overstep a certain limit. If we except the small number of cases, thus far largely un- explained, such as the metamorphic processes of necrobiosis, where vital phenomena are forced into a perverted path and are qualita- tively changed under the influence of stimuli, we observe that within certain limits stimuli cause only a single kind of effect, namely, a gradual, quantitative change of the vital phenomena, either increas- ing or decreasing the intensity of the latter. Hence in the vast majority of cases stimuli do not call out new phenomena, but pro- duce merely an excitation or depression of those general vital phenomena already existing. It is here especially to be noticed that the different varieties of stimuli produce in the same object wholly similar reactions. An Amoeba may be made to retract its pseudopodia and assume a spherical form by chemical, mechanical, thermal, and galvanic stimuli ; the cells of a ciliated epithelium respond by an accelera- tion of their ciliary motion to chemical, mechanical, thermal and galvanic stimulation ; and by all of these agencies the production of light can be induced in Noctiluca. This important fact shows that in every form of living substance there must exist an extraordinary inclination toward a specific sequence of processes. This sequence is continually present in slight degree and finds its expression in the spontaneous vital phenomena; but the slightest stimuli of all kinds augment the discharge of the processes always in the same characteristic sequence for each specific variety of living substance, just as the nitroglycerine molecule can always be made explosively to dis- integrate into the same constituents by mechanical, galvanic, or thermal influences. 1 Cf. p. 319. STIMULI AND THEIR ACTIONS 475 The principle of the specific energy of sense-substances in animals provided with sense-organs, as discovered by Johannes Miiller,1 has, therefore, general application. All living substance possesses specific energy in Miiller's sense; within certain limits wholly different stimuli call forth in the same form of living substance the same phenomena, while, conversely, the same stimulus in different forms produces an effect wholly different and characteristic for every form.2 1 Of. pp. 21 and 45. 2 Of. Hering ('84). CHAPTER VI THE MECHANISM OF L1F,E THE principle which the early civilised races with their mythical ideas poetically personified and represented as the cause of all life in the world, lies at the foundation of all vital phenomena according to the scientific knowledge of to-day. Among most people this principle has found expression in its original form in the allegory of the shifting contest between two hostile forces. These forces are life and death, which the ancient Egyptian personified in the forms of Horus and Typhon ; bloom and decay, which the German clothed in the legends of Baldur and Loki ; Ahriman struggling with Ormuzd, by which the Persian represented the interchange of the good and the evil in life ; God striving with the Devil, in which the Christian of the middle ages perceived the all-creating positive element in its opposition to the all-destroying, " ever-deny- ing spirit " ; and, finally, they are recognised in the ever-alternating processes of becoming and passing away, of building up and breaking down, which control every living being and every vital event. We have already recognised in the continual construction and destruction of living substance or, in brief, in unbroken meta- bolism, the real vital process, upon which the physical phenomena of life are based. We have become acquainted with these phenomena, have investigated the conditions under which they make their appearance, and have determined the changes that they experience under external influences. We must now endeavour to construct a bridge between the vital phenomena and the vital process, and, so far as the present condition of our know- ledge allows, derive the former mechanically from the latter ; the investigation of the mechanism of life forms the nucleus of the science that deals with the physical phenomena of life. THE MECHANISM OF LIFE 477 I. THE VITAL PROCESS As previous treatment of this subject has shown,1 our knowledge of the individual events in the metabolism of living substance is unfortunately thus far very meagre. Investigation of the mechanism of the physical phenomena of life is necessarily still far from complete, and progress can be made only slowly. An essential advance in this direction can be expected only from the detailed study of the processes in the cell, for the cell is the place where the vital process itself has its seat, and where all vital phenomena occur in their simplest form. Not until the physiology of organs, which is able to explain only the gross performances of the complex cell -community, develops into cell-physiology, can we hope essentially to enlarge our knowledge of the more delicate mechanism of life. Thus far only the first steps have been taken in this direction. If, therefore, we attempt to form, so far as possible upon the basis of oar present knowledge, a picture of the vital process in living substance, it can be only a sketch in which the most general elements are indicated in gross outline. Notwithstanding this, some kind of a picture of the vital process is necessary for further systematic investigation. A. THE METABOLISM OF BIOGENS 1. Bio gens It has been seen in a previous chapter that, in general, the characteristic of living organisms in comparison with those dead or apparently dead consists in their metabolism, the expression of which constitutes the vital phenomena. It is necessary to go a step beyond this general fact. It will be recalled that in the determination of the chemical compounds that constitute living substance investigation deals exclusively with the dead cell. For the completion of a picture of living substance two questions now remain to be answered, viz. : first, do the chemical compounds which are found in the dead cell occur as such in the living cell ? and, second, are there in the living cell still other compounds which are not present in the dead cell, which, in other words, are bound up inseparably with the life of the cell ? The first of these questions is relatively easy of answer. A careful comparison especially of the solid bodies that may be found as reserve-substances for a time unchanged in the living cell, with the corresponding substances of the dead cell shows that there 1 Cf. p. 157. 478 GENERAL PHYSIOLOGY occur in the living cell proteids, carbohydrates and fats, in other words, the three chief groups of organic compounds, and likewise the products of their decomposition ; in brief, there occur all the essential substances that are found in the dead cell. There remains only the question whether, in addition, com- pounds exist in the living substance which are destroyed at death and hence are not to be found in the dead cell. A comparison of the chemical behaviour of living and dead cell-substance forces us to as- sume the existence of such compounds. Physiological chemistry has shown that between the two kinds of substance very essential chemical differences exist, which prove that living substance ex- periences in dying pronounced chemical changes. A wide-spread difference between the two consists in their reaction. The re- action of living substance is almost without exception alkaline or neutral and with death changes usually to acid. Further, certain proteids that are in solution in living cell-substance, as, e.g., the myosin of muscle, experience very remarkable changes. In death they coagulate and pass into the solid state, which is very unfit for further chemical transformations. Physiological chemistry has shown similar changes in death in great number. All these facts prove that in the death of living cell-substance certain chemical compounds undergo transformations ; hence substances exist in it which are not to be found in dead cell-substance. The fact that these chemical compounds are only present in the living substance and are decomposed with death necessitates the conclusion that the vital process is associated very closely with their existence. At all events an important property belonging to them is their great inclination toward transformation, which is for life an indispensable element. When it is borne in mind how few causes are able to produce death, how almost all chemical sub- stances that are at all soluble in water enter into chemical relations with living cell-substance, while dead cell-substance usually be- haves wholly indifferently to the same influences, it must be said that the substances that distinguish living from dead cell-substance possess a very loose constitution. This conclusion is still more obvious when the fact of metabolism is considered. Metabolism shows that the living cell-substance is being continually broken down and reformed, this process being made possible by the continual giving-off and taking-in of material. In contrast to this, under favourable conditions, dead cell-substance is capable of preservation for an extraordinarily long time without its excreting more than a trace of the material that living cell-substance gives off continually. Hence, in contrast to the former, the latter must be distinguished by the possession of complexes of atoms that have very great tendency toward chemical transformations and are continually undergoing self-decomposition. The great lability of these complexes depends upon the fact that THE MECHANISM OF LIFE 479 their transformation can be considerably augmented by slight in- fluences from the outside, as the excitation of metabolism by stimuli clearly shows. Since, however, metabolism constitutes the real vital process, it is seen at once that life depends directly upon the existence of these labile complexes of atoms. We are, there- fore, justified in examining these significant substances more in detail and investigating their nature somewhat further. In searching after them we can best start from the decomposition- products excreted in metabolism. It is here found that among other substances, such as carbonic acid, water, and lactic acid, which contain only the elements carbon, hydrogen and oxygen, com- pounds also occur that contain nitrogen. The non-nitrogenous decomposition-products may possibly be derived from the decom- position of carbohydrates, fats, etc. ; but those containing nitrogen can come only from the transformation of proteids or their derivatives, for these are the sole bodies containing nitrogen that are present in all living substance. This important fact directs attention first to the proteids. That this is the right path becomes at once clear when the facts concerning the proteids are recalled that have been mentioned in the course of the previous considerations. These facts show with- out doubt that the proteids stand at the centre of all organic life. It is an important fact that in all cases where large quantities of reserve-substances, such as fat, starch, and glycogen, are not ac- cumulated in cells, the proteids constitute by far the largest part of the organic compounds of living substance. This proves that they must play a significant role in the life of the cell. The dom- inant position of the proteids among the chemical compounds of living substance, however, is at once attested by the fact that they are the only substances that can be found in every cell without ex- ception. It is a further fact that of all the more important sub- stances in the cell the proteids and their compounds present the highest complexity in chemical composition, they comprise the largest number and variety of atoms in their molecules. The known chemical relations of the non-nitrogenous organic sub- stances, especially the carbohydrates and fats, to the proteids are in harmony with this dominant position of the latter in living substance ; for, so far as their history is known, those substances either are consumed in building up the proteid molecule, or are derived from the transformations of the latter. The former is, of course, shown most clearly by plants, in which all organic com- pounds are manufactured synthetically out of simpler inorganic substances. In the cells of the green plant occurs the synthesis of the first organic product, starch, out of carbonic acid and water. This carbohydrate constitutes the organic basis from which the proteid molecule is developed synthetically in a complex and still partly unknown manner with the help of nitrogenous and sulphur- 480 GENERAL PHYSIOLOGY containing salts taken from the earth. Regarding fat, it is known that it can serve for the construction of carbohydrate by transformations in the plant ; the carbohydrate then gives off in turn the material for the formation of proteid, for in the seeds of Pceonia, which are filled with fatty oils, all oil disappears, e.g., after long exposure to the air, and starch appears in its place. It is thus seen most clearly in the plant how different substances serve for the construction of the proteid molecule; but the animal demonstrates best the fact that the most important non -nitro- genous groups of atoms in living substance, especially carbohydrates and fats, can be derived from the decomposition of the proteid molecule.1 Thus, the fact that fat can be derived from proteid has been demonstrated by Leo in his experiments on phosphorus poisoning in frogs, and by Franz Hofmann in his experiments on the nutrition of the larvae of flies with blood freed from fat. Further, Claude Bernard and recently Mering have proved upon dogs whose bodies were freed from glycogen by fasting, that after the feeding of proteid glycogen is again manufactured in great quantity, in other words, that this carbohydrate rfan be derived from the transformation of proteid. Finally, Gaglio has established the fact that the lactic acid in the body is derived from the transformation of the proteid molecule, since the quantity of it in the blood is dependent solely upon the quantity of proteid that is eaten. Regarding the nitrogenous excretory products of the body, it is evident that they can be derived only from the transformation of proteids and their compounds, since no other nitrogenous bodies are present among the essential organic compounds of living sub- stance. But the most striking proof of the fact that all substances, both non-nitrogenous and nitrogenous, that are essential to the life of the cell, can be derived by chemical transformation from proteids, is afforded by one of the most significant facts of physio- logy, namely, the possibility that carnivora are capable of main- taining their life upon pure proteid and, as Pfliiger ('91) has recently shown, possess great capacity for doing work. Nothing demonstrates better than this fact the controlling position of the proteid molecule in the vital process. Hence, not only does it follow from the fact of metabolism that very labile complexes of atoms exist in living substance, with the presence of which life is inseparably associated, but it is the pro- teids whose presence constitutes the general, essential condition and focus of life. If we endeavour to harmonize these two facts, the unavoidable necessity arises of assuming in living cell-substance, be- sides the known proteids that occur also in dead substance, certain other proteids or compounds of proteids, that are present in life only and terminate life with their decomposition. Dead proteid, as it is found in the dead egg of the fowl, or as it 1 Cf. p. 163. THE MECHANISM OF LIFE 481 is stored in quantity in living egg-cells in the form of vitellins, is able to exist for an extraordinarily long time without undergoing the slightest decomposition, if protected from bacteria. Certain proteids or proteid compounds of living substance, however, are continually undergoing spontaneous decomposition, even when the living substance is under wholly normal conditions, and, as is shown by the products that are given off, the slightest action of stimuli increases the decomposition. A long time ago Pfliiger (75,1), as has been seen elsewhere,1 called attention to this important difference between the proteid in dead and that in living cell- substance in his valuable work upon oxidation in living substance, and distinguished clearly between living proteid and dead proteid. The fundamental difference between the two consists in the fact that the atoms of the dead proteid molecule are in a condition of stable equilibrium, while the living proteid molecule possesses a very labile constitution. Pfltiger's assumption of living proteid, which distinguishes living cell-substance from dead and in the loose constitution of which lies the essence of life, is necessitated. But this substance must be of essentially different composition from dead proteid, although, as follows from the character of its decomposition-products, certain characteristic atomic groups of the proteids are contained in it. The great lability that distinguishes it from other proteids, can be conditioned only by an essentially different constitution. Further, critics will rightly object to the terming of this hypothetical compound a " living proteid molecule, " for there is a certain contradiction in calling a molecule living. The word " living " can be applied only to something that exhibits vital phenomena. Hence, the expression " living substance " is well justified, for vital phenomena may be observed in living substance as a whole. But a molecule cannot exhibit vital phenomena, at least as long as it exists as such ; for if any changes appear in it it is no longer the original molecule ; and, if it continues unchanged, vital phenomena are not present in it. The latter, which are based upon chemical processes, can be associated only with the construction or the destruction of the molecule in question ; and thus the application of another name to the compound that is at the focus of life is doubly justified. In order to distinguish this body, therefore, from dead proteid and to indicate its high significance in the occurrence of vital phenomena, it appears fitting to replace the term " living proteid" with that of liogen. The expressions "plasma molecule," "plasson molecule," " plastidule," etc., which Elsberg ('74) and Haeckel (76) have employed, and the conceptions of which are comprised approximately in the expression " biogen molecule," are less fitting in so far as they easily give the impression that protoplasm is a chemically unitary body, which consists of 1 Cf. p. 304. I I 482 GENERAL PHYSIOLOGY wholly similar molecules ; such a view must be expressly rejected. Protoplasm is a morphological, not a chemical conception.1 Extremely little is known concerning biogens, and this facb should not be concealed. Since the constitution of the proteids themselves, i.e., substances that can be investigated chemically at any moment, is not at all known, it is readily understood that we possess much less knowledge concerning the biogens, the com- position of which can only be inferred from their decomposition- products. It can be maintained of them only that they are extra- ordinarily labile, and this property gives to them a certain simi- larity to explosive bodies. Pfliiger ("75, 1) has employed certain facts in a most ingenious manner for the purpose of obtaining conclusions regarding certain characteristics of biogens, which make intelligible the great lability of the biogen molecule in comparison with the molecule of dead proteid. The starting-point of Pflliger's discussion is a comparison of the decomposition-products that arise spontaneously and continually in the oxidation of living proteid, such as in respiration, with those that are obtained by the artificial oxidation of dead proteid. This demonstrates the important fact that the non-nitrogenous decomposition-products in the two cases agree essentially, while the nitrogenous products possess not the slightest similarity. " It follows from this that, as regards its hydrocarbon radicals, living proteid is not essentially different from the proteid of food." The important difference between the two consists rather in the arrangement of the nitrogenous groups of atoms. If, however, the nitrogenous decomposition-products of living proteid be examined, such as urea, uric acid, creatin, etc., as well as the nuclein bases, adenin, hypoxanthin, guanin and xanthin. it is found that, in contrast to the nitrogenous products that appear in the oxidation of dead proteid, some can be artificially prepared from cyanogen compounds, while others contain cyanogen (CN) as a radical. Hence it is highly probable that the carbon and the nitrogen are combined in the biogen molecule into cyanogen, a radical that is wanting in dead proteids. Thus there is presented a very fundamental difference in the constitution of biogens and that of dead proteids ; this explains also the great lability of the biogen molecule, for cyanogen is a radical that contains a great quantity of internal energy, all its compounds possessing strong inclination toward decomposition. This fact enables us to understand the process of respiration, for when in the biogen molecule two atoms of oxygen come into the vicinity of the very labile cyanogen radical, by reason of the active intramolecular vibrations of the carbon and nitrogen atoms in cyanogen the carbon atom will unite with the oxygen to form the very stable molecule of carbonic acid. In fact, cyanogen is very 1 Cf. p. 80. THE MECHANISM OF LIFE 483 easily combustible, and in its combustion yields carbonic acid. Thus, Pfiiiger believes that the continual taking-in of oxygen and giving-out of carbonic acid on the part of living substance depends upon the presence of the cyanogen radical, and that the intramo- lecular oxygen is the essential condition of the tendency of living substance to decompose. In these considerations we find a basis for an idea of the manner in which the formation of a biogen molecule takes place in an animal cell out of the ingested food. By the co-operation of the biogens already present, the atoms of the dead proteid molecule introduced in the food undergo in the cell a rearrangement, in such a manner that an atom of nitrogen always unites with an atom of carbon to form the cyanogen radical with the loss of water. The changes that necessarily appear at the same time in the other groups of the proteid molecule are for the present wholly unknown, but, if we may judge from the essential agreement in the non-nitrogenous decomposition-products of the living and of the dead proteid, they do not appear to be of fundamental importance. By the intramolecular addition of inspired oxygen the biogen molecule finally arrives at the maximum of its power of decomposition, so that only very slight impulses are required to bring about the union of the atoms of oxygen with the carbon in the cyanogen. The material of the non-nitrogenous groups of atoms afforded by the explosive decomposition of the biogen molecule can easily be regenerated by the residue of the biogen molecule from the carbohydrates and fats that are present in the living substance and contain such groups ; in fact, it has been seen that these substances are consumed in the building-up of proteid. " Probably this is the essential significance of these satellites of the proteid molecule, " as Pfliiger very fittingly terms the carbohydrates and fats. If, finally, the living substance dies, the labile cyanogen-like compound of nitrogen passes over again into the more stable condition of the ammonia radical with the absorption of water, the nitrogen uniting with the hydrogen of the water. Thus we have again the stable compounds of dead proteid, such as serve for food. These are, in brief, some of the essential features of the abbreviated path followed by the food in the construction of the biogen molecule in the animal cell. The much longer path, which in the plant cell leads from the ingestion of the simplest inorganic compounds through the synthesis of the first carbohydrate and on to the construction of the biogens, is for the present much more obscure. Notwithstanding the facts that the views here developed have been confirmed by experiment only in part, and that they contain many large gaps, which can be filled only slowly, they afford at least a basis for an understanding of the fundamental processes in living substance. The metabolism of living substance, upon which all I I 2 484 GENERAL PHYSIOLOGY life is based, is conditioned by the existence of certain very labile compounds, which stand next to the proteids and on account of their elementary significance in life are best termed biogens. To a certain degree the biogens are continually undergoing spon- taneous decomposition, just as is the case with other organic bodies, e.g., prussic acid. But this decomposition is much more extensive, if even slight external stimuli act upon the living substance. We must imagine that by reason of the extremely active intramolecu- lar vibration of the atoms, which is the cause of the labile con- dition, certain atoms, partly spontaneously and partly as a result of external commotions, come under the influence of others for which they possess greater affinity than for their original neigh- bours, and in this manner more stable groupings of atoms arise as independent compounds. In this respect the biogens can be com- pared to explosive substances, the atoms of which possess likewise very labile equilibrium and which upon receiving violent shocks explode, i.e., rearrange their atoms into more stable compounds ; e.g., nitroglycerine or trinitrate of glyceryl, which is employed for making dynamite, is decomposed by mechanical impulses or electric shocks into water, carbonic acid, nitrogen and oxygen : 2C3H5(O NO^a = 5H2O + 6C02 + 6N + O. But, in contrast to other ex- plosive bodies, we must evidently ascribe to the biogens the peculiarity that in decomposition the whole molecule is not de- stroyed, but that certain groups of atoms, which are formed by rearrangement, are split off, while the residue is again built up into a complete biogen molecule at the expense of the materials found in its vicinity, just as in the manufacture of con- centrated sulphuric acid l the nitrous acid formed from nitric acid by the withdrawal of oxygen is rebuilt into nitric acid with the aid of the oxygen of the air. The substances still pre- sent in the living substance in addition to the biogens are merely " satellites " of the biogen molecule, and either serve for its con- struction or are derived from its transformations. Thus far no substances have been made known in living matter, which can stand in any nearer or more remote relations to the biogens. Nevertheless, from the variety in the decomposition-products that are excreted by different kinds of cells in metabolism, it must be concluded with great probability that biogen molecules have not in all cells exactly the same chemical composition, but that there are various biogen bodies, and even that the biogens not only of different cells, but of the various differentiations of the same cell, such as exoplasm, myoids or contractile fibres, muscle- fibril^, cilia, etc., have different constitutions, although they agree in essential structure. The biogens, therefore, are the real bearers of life. Their continual decomposition and reformation constitutes the life-process, which is expressed in the manifold vital phenomena. 1 Of. p. 125. THE MECHANISM OF LIFE 485 2. Biotonus Now that we have become acquainted with the simplest schem- atic expression of the elementary vital process in the construction and destruction of biogens, we must consider more in detail certain metabolic relations that result from these, and we must define certain conceptions which are important in clarifying our ideas upon metabolism. It will be recalled that two phases are distinguished in meta- bolism, assimilation and dissimilation. By assimilation is understood the capacity of living substance to construct its like continually from the ingested food-stuffs ; by dissimilation, the capacity to decompose continually into the products excreted by it. In ac- cordance with the above considerations, this conception can be formulated more exactly as follows : assimilation comprises all those transformations that lead up to the construction of biogens, dis- similation all those that extend from the decomposition of biogens down to the complete formation of the excretion-products. Such an exact definition of these two fundamental conceptions of the theory of metabolism is necessary, for, when we glance at the history of the theory, we find that they have been employed with very different meanings. Assimilation, which originally signified in a very general sense the formation of living substance in the organism out of non-living food, has been employed by botanists in a very special way. Plant physiology in large part still means by assimilation exclusively the synthesis of starch from water and carbonic acid in the chlorophyll-bodies of the green plant-cell. This narrow conception has gradually been widened in animal phy- siology, and the term has been employed not only for the synthesis of the first organic product, but also for the construction out of the ingested food-stuffs of the more complex compounds of living sub- stance, especially those that are characteristic of every form of cell, the proteids. In contrast to this latter use, Ewald Hering ('88) has conceived the word in a narrow sense, and in a small but sug- gestive work has sharply separated assimilation from growth. By the former he understands only the qualitative chemical change of particles already present ; in other words, the completion of the particles up to the maximum of their constitution ; under growth, on the other hand, he includes not qualitative changes, but only a quantitative increase of the particles present. In addition to this Hering has created the conception of dissimilation and placed it beside that of assimilation, finding between dissimilation and atrophy a difference corresponding to that between assimilation and growth ; the qualitative change associated with the separation of certain substances from the particles present he terms dissimila- tion, and the quantitative diminution of the particles, atrophy 486 GENERAL PHYSIOLOGY But this sharp separation of assimilation and dissimilation on the one side, and growth and atrophy on the other, can scarcely be main- tained, at least in so far as the former are conceived to be based upon purely qualitative, the latter upon purely quantitative changes of living substance. The formation of living substance takes place only with the help of living substance already present. Only where such substance already exists can new masses of it be formed. This is true even of the plant-cell, in which the living substance is produced in great measure from purely inorganic materials. It must be concluded from this that in growth the biogen molecule attracts to itself from the food the elements necessary for the formation of living substance and combines them chemically, and, therefore, it is changed qualitatively in growth. The general tendency of proteids, and likewise of the cyanogen-containing groups of atoms hypothetically present in the biogeri molecule, to polymerisation, as Pfliiger has already emphasised, allows us to understand this growth by chemical union. On the other hand, atrophy is only conceivable as taking place by means of chemical decomposition, that is, by a qualitative change of the living particles. But even if we can, and must, dis- tinguish the regeneration of certain parts of the biogen molecule from the reformation of whole biogen molecules, and, likewise, the separation of single groups of atoms from the complete decomposi- tion of the molecule, chemical changes are always present, which are directed to either the construction or the destruction of complete biogen molecules. Regeneration is only a part of the process of the formation of a new biogen molecule, and, likewise, the splitting- off of certain groups of atoms is only a part of the phenomenon of decomposition. In an hypothesis upon the nature of assimilation, Hatschek ('94) has also established a relation between this process and growth. He assumes that in growth the simple molecule of living proteid continually attracts elements to itself from the food until it has become a polymeric molecule ; it then breaks down into simple molecules, and the latter gradually develop chemically anew into a polymeric molecule by the union of the necessary atoms and the groups of atoms, and so on. In other words, Hatschek likewise sees in growth a chemical process, which does not differ fundamentally from regeneration. After all these considerations it appears advantageous to employ the conceptions of assimila- tion and dissimilation in the more general sense, including therein the formation of new and the disappearance of old molecules, and to give to them the above exact wording : Assimilation comprises all those transformations that lead up to the construction of bio gens, dissimilation all those that extend from the decomposition of biogens down to the complete formation of the excretion-products. It is, however important to examine somewhat more in detail THE MECHANISM OF LIFE 487 the relation of these two processes. Living substance is continually performing both. Hering believes that these processes, which constitute the metabolism of living substance, " take place simultaneously in all the most minute parts of the latter." Hatschek has expressed a view differing from this, and emphasises the difficulty of the idea " that the proteid molecule simultaneously receives and gives off carbon." When only a single particle is considered, it is very difficult to conceive this process, for the split- ting-off and the regeneration of any groups of atoms by a molecule exclude each other chronologically, and, when considered strictly, although instantaneous, they are only able to take place in succession, unless it is assumed that corresponding groups of atoms, separated from the molecule at one place, are added to it at another place. This latter idea Hering himself rejects, since he emphasises the following : " We ought not to be misled into picturing living substance as a mass that is at rest internally, while being consumed upon one side and built up upon the other." If we are unable to conceive the dissimilation and assimilation of the minutest individual particle or biogen molecule as absolutely simultaneous, within a larger quantity of living substance these two processes can take place at the same time. In this latter case there are always different molecules that are destroyed and rebuilt at the same moment, for only the residue of the biogens already present is capable of regeneration, and, vice versa, only the complete biogen molecules already present are capable of decomposition. If we consider the quantitative relation of assimilation to dissimi- lation in a considerable mass of living substance, for example such as is contained in a cell, we find it very variable, and even without the influence of stimuli it changes within wide limits. This relation of the two processes in the unit of time, which can be A. expressed by the fraction — and will be termed, in brief, Hot onus, is of fundamental importance for the various phenomena of life. The variations in the value of the fraction effect all changes in the vital manifestations of every organism. The fraction — is merely a general form of the expression of biotonus. In reality, assimilation and dissimilation are not simple processes; on the contrary, the events that lead to the construction of the biogen molecule and the formation of the decomposition-products are very complex and consist of many pro- cesses closely interwoven. Hence, if we would express biotonus in a specialised way, we must give the fraction the form a -j- «, -f «„ 4- #Q + • . • 1-1 17777 •j — -~ — ~ — — — - in which, a, av a2, a3, etc., and a, av a2, a3, etc., a -\- d^ -\- &2 -f- a3 -j- . . . represent the partial processes that combine to form the whole. 488 GENERAL PHYSIOLOGY With our extremely slight knowledge of the more special trans- formations that take place in living substance, it is at present impossible even approximately to review the manifold possi- bilities resulting from changes of the individual components of the biotonous quotient. Therefore, we shall here refer only to some of the more important of the known cases. If the sum of all the members of series A is equal to the sum of series D, i.e., if assimilation and dissimilation are equal in the unit A of time, the fraction yj=l- This case is realised in the condition termed metabolic equilibrium. That is, in the unit of time the sum of the excreted substances of every kind is equal to the sum of the ingested substances. If the individual members of series A increase in a constant re- lation to one another, while the members of series D remain equal or decrease, so that in the unit of time the sum of the members of A is greater than that of the members of D, then the metabolic quo- tient ->l- This case is realised in growth, where the form- ation of living substance surpasses its destruction. If, vice versa, the members of series D grow proportionately to one another, while those of series A remain unchanged or become A smaller, biotonus ^ of the differentiation of ^C^~ ji the cells in the forma- * munity are evidently the same in their most essential features in FlG- Z'n.—Prototpongia H tion of every cell-corn- / Y \^ V f \ \ 576 GENERAL PHYSIOLOGY arising from the continued division of the egg-cell are in harmony with the special conditions under which they appear. All in which this is not the case must perish in the struggle for existence through the action of selection. But the most complete harmony is reached when the individual labours of the different cells so fit into one another that, although every cell or cell-group has de- veloped a different labour for its own specialty, this labour is for the good of all the other cells, is, indeed, necessary to all the others. Thus, the extraordinarily far-reaching differentiation and surprisingly detailed division of labour of the individual cells and tissues in the cell-community become comprehensible. As a result of the division of labour, every kind of cell, every tissue, every organ in the inulticellular community undertakes a special task, and since early times physiology has termed this task the " physiological function " of the cell-complex in question. All elementary vital phenomena which, in the lowest organisms, take place in the individual cell, in multicellular organisms are developed in a special degree as specific functions of definite cell-groups and become adapted very perfectly to specific purposes. Thus, in the higher animals, by the special development of contractility, movement becomes the specific function of the muscle-cells. The capacity of appreciating stimuli is developed in an especially high degree as the function of the sense-organs. The capacity of conducting stimuli is augmented to a surprising extent as the function of nerves. Secretion undergoes its greatest per- fection in the function of gland-cells. Every kind of cell retains all the elementary vital phenomena, but the one becomes pre- eminently developed as its specialty. The more the specialties of the individual cells and cell-groups come to act for the good of all cells and assist their vital processes, the more highly evolved does the cell-community become. It represents a mechanism in which, in spite of its extraordinary extent and its excessive complication, as exhibited especially in the bodies of the higher animals, all its parts co-operate as a unit. C. CENTRALISATION OF ADMINISTRATION If the last point, namely, the development of a unity in the co- operation of the cells and tissues of the cell-community be de- veloped more in detail, it is found that in addition to the principles of dependence and cell-differentiation, a third principle comes into consideration, namely, that of centralisation of administration. This principle is connected very closely with the two others ; con- sidered from the point of view of natural selection, it is in a certain sense a necessary result of those, and it is developed pari passu with them. The farther the differentiation of the cells goes and the closer THE MECHANISM OF LIFE 577 becomes the dependence of the cells upon one another, the stronger is the necessity of bringing into relation with one another the more outlying cells, tissues and organs of the cell-community, in order that unified co-operation may take place ; selection must make this relation constantly more intimate, the more complex the structure of the cell-community becomes. Along with this there arises in the community a tendency toward centralisation. The first step in the direction of cen- tralisation is really taken by means of the division of labour, when certain cell- groups or organs undertake a definite function for the whole community. Thus the function in question becomes cen- tralised for the whole body in one place, and as many centres arise as there are organs differentiated for definite func- tions. This first step toward centralisa- tion of administration is met with in the cell-community of the plant. Here the synthesis of starch, upon which the nutrition of the whole plant depends, is centralised in the green cells of the leaf. Further, the function of taking up water, without which life cannot continue to exist, is localised in the roots alone. Corresponding localisations are present in the animal cell- comm unity. Thus, in the higher animals the nutrition and respiration of the individual tissue-cells are centralised in the heart, which drives the blood, rich in food and oxygen, to all the cells of the various tissues and organs (Fig. 278). In the animal cell-community the second important step toward centralisa- tion is taken, namely, the union of all individual centres or organs of function with one another by the appearance of a central nervous system with its paths of conduction. This principle, in greater and greater perfection, leads finally in the animal series to a far-reaching centralisation, such as is met with in the complex cell-community of the vertebrates, and especially of man. We have in the central nervous system a central organ which alone has the function of uniting cells, tissues, and organs with one another, so that an advantageous co-operation of them becomes possible ; and the farther we ascend in the animal series, p P FIG. 278.— Scheme of the circula- tion of blood in man. Centralisa- tion of the nutrition of all cells in the blood -current. The darker half is the venous, the lighter the arterial system. The two are united by the capillary network of the lungs (above) and of the other tissues (below). In the capillaries the blood - current bathes all the tissues, the cells of which take food from it and give off to it their useless sub- stances. (FromRanke.) 578 GENERAL PHYSIOLOGY the more we find the tendency of the central nervous system to extend its authority toward a unified control of all cells and cell- complexes of the animal body. In order to make graphic the principle upon which the mechanics of the central nervous system is based, it will be advantageous to consider the simplest form in which the function of the latter is expressed, namely, the reflex action. The essence of the reflex action consists in the fact that an element that appreciates stimuli and an element that reacts to stimuli are so put into relation with one another by a central bond, that every stimulus acting upon the appreciating element is conducted first to the centre, and thence, as an impulse to a reaction, to the reacting element. Such a mechanism, in which every stimulus acting upon the sensory end calls out with machine-like certainty a reaction at the other end, is a reflex arc. The most primitive Fia. 279. — Primitive reflex arc in a single cell. /, Poteriodendron , a flagellated cell fixed in a cup-shaped sheath upon a myoid-fibre. //, Neuro-muscular cells from an actinian. (//, after Hertwig.) form of a reflex arc exists in unicellular organisms, the cell-body of which possesses both the sensory and the motor elements, and even functions also as the central bond for the two. A single Poteriodendron represents a reflex arc of the simplest kind (Fig. 279, /). The cell-body, fixed upon a myoid-fibre at the bottom of a delicate, cup-shaped sheath, bears a flagellum which is extremely sensitive. The slightest stimulus which acts upon the latter is conducted centripetally to the cell-body, and from there centrifugally to the myoid-fibre, and the action of the stimulus upon the flagellum is followed at once by the contraction of the fibre. Wholly analogous to this is the behaviour of Vorticella, except that in the latter the sensory elements are present chiefly in the form of the cilia of the peristome. The same relations, further, exist in the so-called neuro-muscular cells of the Ccelen- THE MECHANISM OF LIFE 579 terata (Fig. 279, II). Here, likewise, a cell possesses, upon the one side, a sensory element, and, upon the other, a contractile fibre, which contracts as soon as the sensory end-organoid is stimu- lated. What in all these cases is differentiated within a single cell, is in the nervous system of animals distributed to several cells. In the simplest case of the latter, three different cells are concerned. One cell, the sensory cell, receives the stimulus ; from this a centripetal nerve-path conducts to a central cell, the ganglion- cell, and from here a centrifugal nerve-path conducts to a cell that performs the reaction, the motor end-cell (Fig. 280, A). But this form of reflex arc is realised perhaps only in the invertebrates. In vertebrates, so far as the conditions are known, a fourth cell at least is interpolated in the arc, since in place of one ganglion-cell at least two are present, one of which receives the stimulus from the sensory-cell and conducts it to the other, while the other transfers the impulse to the motor end-cell (Fig. 280, B). In a given case the end-cell of the centri- fugal path may be either motor or secretory, or may produce light or electricity. Thus reflexly by the gang- lion-cells parts of the cell- community, wholly differ- ent and far removed from one another, are put into union and activity by im- pulses from the central nervous system. If we start from the scheme of the reflex arc, the further factors that come into consideration in the mechanism of the central ner- vous system are very simple. They consist only in the facts that, upon the one hand, between the sensory and the motor end- organ more than two ganglion-cells possessing different functions are interpolated, and, upon the other hand, certain ganglion- cells are innervated not simply from one side, by a single other ganglion-cell, but by several, and under certain circumstances by many others. Thus, by means of their nerve-fibres very complex arid intricate connections are formed between the ganglion-cells and the individual systems of ganglion-cells, which latter are the centres of definite vital processes and hence the seat of definite im- pulses. A network of ganglion-cells and uniting nerve-fibres results, which is apparently inextricable, but in reality insures a very definite and unified co-operation of the various parts of the organism that it binds together. By the proper innervation of all p p 2 FIG. 280.— Schemes of the reflex arc. A, Simple scheme of reflex arc. At the left, below, a sensory cell ; in the middle, above, a central ganglion-cell ; at the right, below, a muscle-cell. B, Scheme of a reflex arc in vertebrates. At the left, below, a sensory cell, at the left, above, a sensory ganglion- cell. At the right, above, a motor ganglion-cell, at the right, below, a muscle-cell. (After Gegen- baur.) 580 GENERAL PHYSIOLOGY kinds of cells, tissues and organs of the cell-community by the central nervous system, the cells of which form in vertebrates the brain and the spinal cord together with the sympathetic nervous system, a central system of administration for the whole cell- community is inaugurated, which from the brain and spinal cord by means of their long paths of conduction brings even most distant parts of the community under a unified control (Fig. 281). Hence the nervous system has been compared very graphically to a telegraphic network, the wires of which put the most distant regions of a country into connection with a central place of govern- ment. The comparison of a central nervous system to a great telegraph station and the nerve-fibres to the telegraph wires is very fit- ting with respect to the principle of centralisation upon which the two are based. But, as has some- times happened, such a comparison ought not to be carried too far ; for example, the nerves should not be regarded simply as conduct- ing-wires for electricity. In reality, nerves are extensions of ganglion-cells, and, like these, consist of living sub- stance, i.e., they have a metabolism with which their life and, therefore, their function are inseparably connected. This follows directly from the fact that the nerve invariably perishes, Fm.281.-Ner.vous system of man. The nerve-trunks, ^ any non-nucleated pro- which contain centrifugal and centripetal paths of tOplasmiC maSS, alter being conduction, pass from the brain and spinal cord to ~, - , ^l," all parts of the body, and thus unite the latter Cllt Ott irom tne ganglion- * Cel1 t0 THE MECHANISM OF LIFE 581 The manner in which the elements of the nervous system are united with one another anatomically and functionally deserves special attention, since the later researches upon the finer structure of the central nervous system, which have been made possible by the extraordinary development of the microscopic technique, especially by Golgi, Weigert, Ehrlich, and others, have led to the discovery of very peculiar but fixed relations. The element of the central nervous system is the ganglion-cell, but the ganglion- cell with its characteristic differentiations. From the body of the cell there extend processes, more or less numerous according to the function of the cell, among which two kinds may be distinguished sharply from one another. Some form a more or less richly branched structure, and are, therefore, appropriately termed dendrites. The older histologists termed these protoplasmic processes. The others are the nerve-processes. So far as we now know, as regards the number of the latter there are only two varieties of ganglion-cells: unipolar (previously called multipolar on account of the numerous dendrites), provided with only one nerve-process, and bipolar, with two nerve-processes. These nerve- processes are simply the beginning of the nerve-fibres, which not rarely reach a length of one metre and more. The conducting nerve puts even the most distant cells of the animal body into physical connection with the ganglion-cells, and transmits the impulses that go out from the bodies of the ganglion-cells to the tissue-cells, or in specific cases to other ganglion-cells. In its course from the body of the ganglion-cell to the cell that it inner- vates, the nerve-process appears different at different points. It sends off here and there collateral branches, and a little beyond its origin is surrounded by a sheath consisting of my elm, the medullary sheath. The latter is divided into segments by the so-called nodes of Eanvier, and disappears shortly before the cell which the nerve supplies is reached. The medullary sheath, in which the nerve-fibre runs as the axis-cylinder, is itself usually surrounded by a membranous sheath, the neurilemma. The end of the nerve shows very characteristic differentiations according to the kind of cell which it innervates. Such a complete cell, i.e., a ganglion-cell with all its appendages, represents the elementary constituent of the nervous system, and can fittingly be termed with Waldeyer a neuron (Fig. 282). The combination of the innumerable neurons with one another constitutes the nervous system of the animal. According to the later researches of Golgi, Kb'lliker, His, Ramon y Cajal, and others, the connection of the neurons with one another appears to be everywhere of such a kind that the dendrites of the ganglion-cells receive the stimulating impulses, while the nerve-process transmits them from one ganglion-cell to the den- drites of another. The bipolar ganglion-cells, which are contained chiefly in the spinal ganglia lying at the two sides of the spinal 582 GENERAL PHYSIOLOGY Cell-body. Terminal branches. Fio. 282. — Scheme of a neuron ; a, free axis-cylinder ; 6, axis-cylinder surrounded by iieurilemma alone ; c, axis-cylinder surrounded by the medullary sheath alone ; d, axis-cylinder surrounded by the medullary sheath and the neurilemma, and divided intokegments by the nodes of Ranvier. (From Stohr.) THE MECHANISM OF LIFE 583 cord, alone possess in their one nerve-process a sensory path, which receives impulses from the periphery in the form of external stimuli and transmits them to the cell-bodies ; thence the impulses are continued through the other nerve-process to other neurons. Hence, as regards the body of the ganglion-cell to which they belong, the dendrites conduct always centripetally, the nerve- processes in the unipolar ganglion-cells always centrifugally. The greater or smaller number of the dendrites of a ganglion-cell Dendrites. ' ' Cell-body. Nerve-process. FIG. 283.— Cell of Purkiiije from the grey cortical layer of the brain. (From Stohr.) appears to depend upon the question, with how many other neurons the ganglion-cell is in connection. Thus, the cells of Purkinje in the grey cortical layer of the brain, in which the most complex psychic processes are believed to be localised, have an extraordin- arily richly developed system of dendrites (Figs. 283 and 284). The nerve-fibres of one ganglion-cell pass to the dendrites of another ganglion-cell. It is here a noteworthy fact, that, according to the later investigations, the connection between the two takes place not by direct continuity of their substance, or, as 584 GENERAL PHYSIOLOGY is said "per continuitatem" but through simple contact, "per contigui- tatem" The end of a nerve-fibre and the end of a dendrite join at their tips, but a piece that does not consist of nerve-substance is intercalated between them. It must be assumed that this inter- calated piece, which is to be seen only with very strong magnifying powers, consists also of living substance, else it would be difficult to understand how it is able to conduct the excitation from the nerve- process to the dendrites. While there is great unanimity in the mode of union of the neurons with one another, the kind of transition of the nerve- fibres into the end-cells, which they innervate, or from which they FIG. 284. — Section through the cortex of the cerebellum of a calf. The large, branched cells are Purkinje's cells. (After Schiefferdecker.) spring, is very various. The nerves (sensory) that conduct centri- petally from the periphery of the body, as well as those (motor, secretory, electric, etc.) that conduct centrifugally to the periphery vary according to the organ in which they end. Among the former there are some that end free in the skin in the form of an end-bulb, without being in connection with a sense-cell (Fig. 285, 12). The others appear to go out directly from a sense-cell, which is specially developed for the reception of the stimulus, as, e.g., the rods and cones of the eye, the hair-cells of the ear, the olfactory cells of the nose (Fig. 285, 7), etc. Among the endings THE MECHANISM OF LIFE 585 of centrifugal nerves those of the motor nerves in cross-striated muscles are most characteristic. Here the transition of the nerve- fibre into the muscle-substance is mediated by a specially differ- entiated end-organ, the motor end-plate, a flat or branched extension of the axis-cylinder in the sarcoplasm. The latter, which in this place is very granular and is characterised by many nuclei, is covered by the sarcolemma of the muscle-fibre ; the sarcolemma here passes over directly into the neurilemma of the nerve (Fig. 285, III). The manner of ending of the centrifugal nerves in other organs, such as smooth muscle-cells, gland-cells, photo- FIG. 285.— Nerve-endings. /, Olfactory cells ; A, from the frog, ^,from man. The slender, spindle- shaped cells are the olfactory cells ; to these the nerve goes ; the broad cells, branched below, are epithelial supporting-cells. (After Frey.) //, Nerve end-plate from the conjunctiva of a calf. (After Schiefferdecker.) ///, Motor end-plate in cross-striated muscle, seen from the side. (From Lang.) genie cells, etc., appears to be much less complicated ; but these relations need more careful investigation. Only through the central control of all functions of the whole organism by the nervous system is it possible for the cell- community of the animal body to be differentiated so extensively as it is. Only when at the proper moment this or that organ is put into activity or remains at rest, only when this or that organ reacts appropriately to an influence in this or that part of the body, only when the cells, tissues and organs work together in the most perfect harmony, can so complicated a mechanism be developed, as exists in the cell-community of the vertebrates and especially of man. 586 GENERAL PHYSIOLOGY Here general physiology passes into the special physiology of the animal or plant cell-community and its various forms. It is the task of special physiology to investigate individually the special mechanisms that result from the associated life of the cells in the community, and their co-operation. The sphere of general physiology extends only to those vital phenomena that are common to all organisms. The cell is the element of living substance. All living substance exists in cells, and all the functions of living substance originate in the elementary vital phenomena of the cells. Hence, if the task of physiology lies in the explanation of vital phenomena, general physiology can be only cell-physiology. BIBLIOGRAPHY BIBLIOGRAPHY Throughout the text references to the literature are indicated by placing the abbreviated year of publication after the author's name. If more than one article published during the year is referred to, a numeral is added to indicate the number of the article. In the following biblio- graphical list each reference is similarly headed. The heading is then followed successively by the title of the article, the title of the journal, the year, the volume, and the page. In the case of books, the title, and the place and date of publication are given. F. S. L. ADERHOLD, R. , '88 : Beitrag zur Kenntniss richtender Krafte bei der Bewegung niederer Organismen. Jen. Zeitsch. f. Naturwiss. , 1888, N. F. 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In this book all the literature is reviewed, and the whole subject is systematically summarised from the later points of view. BINZ, C. , '67 : Ueber die Einwirkung des Chinin auf die Protoplasma-Bewegungen. Arch. f. mik. Anat., 1867, III, p. 383. BLASIUS, E. , and SCHWEIZER, F. , '93 : Electrotropismus und verwandte Erschemungen. Arch. f. d. ges. Physiol., 1893, LIII, p. 493. DU BOIS-REYMOND, E. , '48-'84 : Untersuchungen iiber thierische Elektricitat. Berlin, 1848, 1849, 1860, 1884; Id., '59: Gedachtnissrede auf Johannes Miiller. Abhandl. d. kais. Akad. d. Wiss. zu*Berlin, 1859 ; also reprinted, Berlin, 1860; Id., '84: Ueber die Grenzen des Naturerkennens. Leipzig, 1884, also in Reden, erste Folge, Leipzig, 1886. BOVERI, TH., '87, '88, '90: Zellenstudien. Jen. Zeitsch. f. Naturwiss., 1887, N. F. XIV, p. 423 ; 1888, N. F. XV, p. 685 ; 1890, N. F. XVII, p. 314 ; Id., '89: Ein geschlechtlich erzeugter Organismus ohne miitterliche Eigen- schaften. Sitzungsber. d. Ges. f. Morphol. u. 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Sencken- berg. naturforsch. Ges., 1876, X; Id., '90: Ueber den Bau der Bakterien und verwandter Organismen. Leipzig, 1890 ; Id., '92, 1 : Untersuchungen iiber mikroskopische Schiiume und das Protoplasma. Leipzig, 1892 ; author- ised Eng. trans, by E. A. Minchin : Investigations on microscopic foams and on protoplasm. London, 1894. The bibliography of the subject is also given here. Id., '92, 2 : DieBewegung der Diatomeen. Verhandl. d. naturhist.-med. Ver. zu Heidelberg, 1892, N. F. IV, Heft 5 ; Id. '92, 3 : Ueber die kiinst- liche Nachahmung der karyokinetschen Figuren. Ibid., 1892, N. F. V. BUNGE, G., '83 : Ueber das Sauerstoffbediirfniss der Darmparasiten. Zeitschr. f. physiol. Chem., 1883, VIII, p. 48 ; Id., '94 : Lehrbuch der physiologischen und pathologischen Chemie. 3te Aufl., Leipzig, 1894. •CHOSSAT, C., '43 : Recherches experimentales sur I'manition. 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Cunningham : Organic evo!ution as the result of the inheritance of acquired characters according to the laws of organic growth. London, 1890. ELSBERG, '74 : Proceedings of the American Association for the Advancement of Science, Hartford, 1874. ENGELMANN, TH. W., '68 : Ueber die Flimmerbewegung. Jen. Zeitschr. f. Naturw. , 1868, IV, p. 321 ; Id. , '69 : Bertrage zur Physiologic des Protoplasma. Arch. f. d. ges. Physiol., 1869, II, p. 307 ; Id., '70 : Beitrage zur allgemeinen Muskel- und Nervenphysiologie. Ibid., 1870, III, p. 247 ; Id., '73 : Mikros- kopische Untersuchungen itber die quergestreifte Muskelsubstanz. I. II. Ibid., 1873, VII, pp. 33, 155 ; Id., '75 ? Contractilitat und Doppelbrechung. Ibid., 1875, XI, p. 432; Id., '78: Neue Untersuchungen iiber die mikros- kopischen Vorgange bei der Muskelcontraction. Ibid. , 1878, XVIII, p. 1. ; Id. , '79, 1 : Physiologic der Protoplasma- und Flimmerbewegung. Hermann's Handbuch der Physiologic. I, Leipzig, 1879, p. 341; Id., '79, 2: Ueber Reizung contractilen Protoplasmas durch plotzliche Beleuchtung. Arch. f. d. ges. Physiol., 1879, XIX, p. 1 ; Id., '81, 1 : Neue Methode zur Untersuchung der Sauerstoffausscheidung pflanzlicher und thierischer Organismen. Ibid. , 1881, XXV, p. 285 ; Id., '81, 2 : Ueber den fasigeren Bau der contractilen Substanzen, mit besonderer Beriicksichtigung der glatten und doppelt schraggestreiften Muskelfasern. Ibid., 1881, XXV, p. 538 ; Id. '81, 3: Zur Biologic der Schyzomyceten. Ibid., 1881, XXVI, p. 537; Id., '82: Ueber Licht- und Farbenperception niederster Organismen. Ibid., 1882, XXIX, p. 387 ; Id., '83 : Bacterium photometricum. Ein Beitrag zur vergleichenden Physiologic des Licht- und Farbensinns. Ibid., 1883, XXX, p. 95 : Id., '93 : 592 . BIBLIOGRAPHY Ueber den Ursprung der Muskelkraft. 2te Aufl. Leipzig, 1893; Id., '94 : Die Erscheinungsweise der Sauerstoffausscheidung chromophyllhaltiger Zellen im Licht bei Anwendimg der Bacterienmethode. Verhandl. d. kon. Akad. van Wetenseh., Amsterdam, 1894, 2 Sect., III. ; also Onderz. Phypiol. Lab., Utrecht, 1895, IV Reeks, III Deel. The other works of Engelmann upon this subject are here cited. FABRE, '55 : Recherches sur la cavise de la phosphorescence de 1'agaric de 1'olivier Compt. rend, de 1'acad. de sciences, 1855, XLI, p. 1245. FICK, A., '82: Mechanische Arbeit und Warmeentwickelung bei der Muskeltha- tigkeit. Internat. wiss. Bibliothek, LI, Leipzig, 1882; Id., '93, 1 : Einige Bemerkungen zu Engelmann's Abhandlung iiber den Ursprung der Muskel- kraft. Arch. f. d. ges. Physiol., 1893, LIII, p. 606; Id., '93, 2: Noch einige Bemerkungen zu Engelmann's Schrift iiber den Ursprung der Muskelkraft. Ibid., 1893, LIV, p. 313. FICK and WISLICENUS, '65 : Ueber die Entstehung der Muskelkraft. Viertel- jahrsschr. d. Ziiricher naturforsch. Ges., 1865, X, p. 317. FICK, R., '97: Bemerkungen zu M. Heidenhain's Spannungsgesetz. Arch. f. Anat. u. Physiol., Anat. Abth., 1897, p. 97. FLEMMING, W., '82 : Zellsubstanz, Kern und Zelltheilung. Leipzig, 1882. FOL, H. , '91 : Le quadrille des centres. Un episode nouveau dans 1'histoire de la fecondation. Arch, de sci. phys. et nat., 1891, XXV. GAD, J., '78: Zur Lehre von der Fettresorption. Arch. f. Anat. u. Physiol., Physiol. Abth., 1878, p. 157. GAGLIO, G., '86 : Die Milchsaure des Blutes und ihre Ursprungsstatten. Arch, f. Anat. u. Physiol., Physiol. Abth., 1886, p. 400. GERASSIMOFF, '92 : Ueber die kernlosen Zellen bei einigen Conjugaten. Bull, de la soc. imper. des naturalistes de Moscou, 1892 ; Id., '97 : Ueber ein Ver- fahren kernlose Zellen zu erhalten. Ibid., 1897. GOLUBEW, A., '68 : Ueber die Erscheinungen welche elektrische Schlage an den sogenannten farblosen Bestandtheilen des Blutes hervorbringen. Sitzungsber. d. kais. Akad. d. Wiss. Wien., Math.-naturw. Cl., 1868, LVII, II Abth., p. 555. GRAHAM, T., '61 : Liquid diffusion applied to analysis. Phil. Trans, of the Roy. Soc. of London, 1861, CLI, Part I, p. 183. GREENWOOD, M., '86, '87 : On the digestive process in some Rhizopods. I. Journ. of Physiol., 1886, VII, p. 253 ; II. Ibid., 1887, VIII, p. 263 ; Id., '94 : On the constitution and mode of formation of "food vacuoles" in Infusoria, as illus- trated by the history of the processes of digestion in Carchesium polypinum. Phil. Trans, of the Roy. Soc. of London, B., 1894, CLXXXV, Part I, p. 355 ; Id. , '96 : On structural change in the resting nuclei of Protozoa. Part I. The macronucleus of Carchesium polypinum. Journ. of Physiol., 1896, XX, p. 427. GRUBER, A. , '85 : Ueber kiinstliche Theilung der Infusorien. Biol. Centralb., 1885, IV, p. 717 ; V, p. 137 ; Id., '86, 1 : Beitrage zur Kenntniss der Physiologic und Biologic der Protozoen. Ber. d. naturf. Ges. zu Freiburg i. B., 1886, I; Id., '86, 2: Der ConjugationsprocessbeiParamseciumaurelia. Ibid., 1887, II ; Id., '88 : Ueber einige Rhizopoden aus dem Genueser Hafen. Ibid., 1888, IV ; Id., '89 : Biologische Studien an Protozoen. Biol. Centralb., 1889, IX, p. 14. GRUBLER, G., '81 : Ueber ein krystallinisches Eiweiss der Kitrbissamen. Journ. f. prakt, Chemie., 1881, N. F. XXIII, p. 97. GUMPRECHT, '96 : Leukocytenzerfall im Blute bei Leukamie und bei schweren Anamien. Deutsch. Arch. f. klin. Med., 1896, LVII, p. 523. HABERLANDT, G., '87 : Ueber die Beziehungen zwischen Function und Lage des Zellkernes bei den Pflanzen. Jena, 1887 ; Id., '89 : Ueber Einkapselung des Protoplasmas mit Riicksicht auf die Function des Zellkerns. Sitzungsber. d. kais. Akad. d. Wiss. Wien., Math.-naturw. Cl., 1889, XCVIII, Abth. I., p. 190. HAECKEL, E., '62 : Die Radiolarien. Berlin, 1862 ; Id., '66 : Generelle Morpho- logic der Organismen. Berlin, 1866 ; Id., '70 : Biologische Studien. I. Studien iiber Moneren und andere Protisten, Leipzig, 1870 ; Id., '75 : Ziele und Wege der heutigen Entwickelungsgeschichte. Jena, 1875; Id., '76: BIBLIOGRAPHY 593 Die Perigenesis der Plastidule oder die Wellenzeugung der Lebenstheilchen. Berlin, 1876; Id., '91: Anthropogenic oder Entwickelungsgeschichte des Menscheri. 4te Aufl. Leipzig, 1891. v. HALLER, A., 1762: Elementa physiologiae corporis humani. IV. Lausanne, 1762. v. HANSTEIN, J., '80 : Das Protoplasma als Trager der thierischen und pflanz- lichen Lebensverrichtungen. Heidelberg, 1880. HATSCHEK, B., '94 : Hypothese iiberdas Wesen der Assimilation, eine vorlaufige Mittheilung. Lotos, 1894, N. F. XIV. HEIDENHAIN, M., '94 : Neue Untersuchungen iiber die Centralkorper und ihre Beziehungen zum Kern- und Zellenprotoplasma. Arch. f. mik. Anat., 1894, XLIII, p. 423 ; Id., '95 : Cytomechanische Studien. Arch. f. Entwicklungs- mech., 1895, I, p. 473 ; Id., '96 : Ein neues Modell zum Spannungsgesetz der centrirten Systeme. Verhandl. d. anat. Ges. zu Berlin, 1896, p. 67 ; Anat. Anz., 1896, XII. HEIDENHAIN, R. , '83: Physiologic der Absonderungsvorgange. 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Ver. d. preuss. Rheinlande. Bonn, 1884; Id., '86: Ueber die Theilbarkeit der lebendigen Materie. I. Mittheilung. Die spontane und kiinstliche Theilung der Infusorien. Arch. f. mik. Anat., 1886, XXVI, p. 485. OLTMANNS, F., '92 : Ueber die photometrischen Bewegungen der Pflanzen. Flora, 1892, p. 183. PFEFFEB, W., '84 : Locomotorische Richtungsbewegungen durch chemische Reize. Unters. aus d. bot. Inst. zu Tubingen, 1884, I, p. 363; Id., '88: Ueber chemotactische Bewegungen von Bakterien, Flagellaten und Volvocineen ; Ibid., 1888, II, p. 582; Id., '93: Studien zur Energetik der Pflanze. Abhandl. d. math.-phys. Cl. d. sachs. Ges. d. wiss. Leipzig, 1893, XVIII, p. 149. PFLUGER, E., '59 : Untersuchungen iiber die Physiologic des Electrotonus. Berlin, 1859 ; Id., '75, 1 : Ueber die physiologische Verbrennung in den lebendigen Organismen. Arch. f. d. ges. Physiol., 1875, X, p. 251 ; Id., '75, 2 : Ueber die Phosphorescenz verwesender Organismen. Ibid., 1875, XI, p. 222 ; Id., '78 : Ueber Warme und Oxydation der lebendigen Materie. Ibid., 1878, XVIII, p. 247 ; Id., '83, '84: Ueber den Einfluss der Schwerkraft auf die Theilung der Zellen. Ibid., 1883, XXXI, p. 311 ; 1883, XXXII, p. 1 ; 1884, XXXIV, p. 607 ; Id., '91 : Die Quelle-der Muskelkraft. Ibid., 1891, L, p. 98 ; Id., '92 : Ueber Fleisch- und Fettmastung. Ibid., 1892, LII, p. 1 ; Id., '93 : Ueber einige Gesetze des Eiweissstoffwechsels. Ibid., 1893, LIV, p. 333. PICTET, RAOUL, '93 : La vie et les basses temperatures. Rev. scient., 1893, LIIt p. 577. PLUTARCH : Opera moralia. Ed. Didot. I. p. 425. Paris, 1885. PREYER, W., '66 : De hsemoglobino observationes et experimenta, (Dissertation). Bonn, 1866 ; Id., '80 : Die Hypothesen iiber den Ursprung des Lebens. Natur- wissenschaftliche Thatsachen und Probleme. Berlin, 1880; Id., '91, 1 : Die organischen Elemente und ihre Stellung im System. Wiesbaden, 1891; Id., '91, 2 ; '92 : Das genetische System der chemischen Elemente. Naturwiss. Woch- enschr., 1891, VI, No. 52; 1892, VII, Nos. 1,2, 3; also reprint, Berlin, 1893. PREYER, W., and WENDT, G., '91 : Ueber den Chemismus im lebendigen Proto- plasma. I. Mittheilung. Himmel und Erde : Illustrirte Monatsschr. herausg. v. d. Ges. Urania., 1891, IV, p. 15. QTINCKE, G., '88 : Ueber periodische Ausbreitung an Fliissigkeits-Obernacheii und dadurch hervorgerufene Bewegungserscheinungen. Sitzungsber. d. kgl. preuss. Akad. d. wiss. zu Berlin, 1888, p. 791. RADZISZEWSKI, B. , '80 : Ueber die Phosphorescenz der organischen und organisirten Korper. Liebig's Annalen d. Chemie, 1880, CCIII, p. 305. RANKE, J., '65: Tetanus: Eine physiologische Studie. Leipzig, 1865. REINKE, J., '80: Ueber den Einfluss mechanischer Erschiitterung auf die Ent- wicklung der Spaltpilze. Arch. f. d. ges. Physiol., 1880, XXIII, p. 434. REMAK, R., '44 : Neurologische Erlauterungen. Arch. f. Anat., Physiol. u. wiss. Med., 1844, p. 463. RHUMBLER, L., '88: Die verschiedenen Cystenbildungen und die Entwicklungs- geschichte der holotrichen Infusoriengattung Colpoda. Zeitschr. f. wiss. Zool., 1888, XLVI, p. 549 ; Id., '96 : Versuch einer mechanischen Erklarung BIBLIOGRAPHY 597 der indirecten Zell- und Kerntheilung. I. Theil : Die Cytokinese. Arch. f. Entwickelungsmech. , 1896, III, p. 527 ; Id., '97 : Stemmen die Strahlen der Astrophare oder ziehen sie? Ibid., 1897, IV, p. 659. RICHTER, H. E. , '65 : Zur Darwin'schen Lehre. Schmidt's Jahrb. d. ges. Med. , 1865, CXXVI, p. 243 ; Id., '70 : Bericht iiber medicinische Meteorologie und Klimatologie. Ibid., 1870, CXLVIII, p. 57 ;Id., '71 ; Die neuern Kenntnisse von den krankmachenden Schmarotzerpilzen. Ibid., 1871, CLI, p. 313. v. RINDFLEISCH, E.,'88: Aerztliche Philosophic. Festrede zurFeierjdesdreihundert und sechsten Stiftungstages der konigl. Julius-Maximilians-Universitat. Wiirzburg, 1888 ; Id., '95 ; Neovitalismus. Verhandl. d. Ges. deutsch Nat. u. 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INDEX INDEX Acanthocystis, myopodia of, 252 Accessory disc, 243 Achromatic nuclear substance, 91 Actinosphcerium, adaptation of, to stimulus, 357 chemical stimulation of, 367 double refraction of, 99, 560 fatigue of, 460 galvanic stimulation of, 420, 473 mechanical stimulation of, 379, 382, 386 polar excitation of, 420, 473 Adaptation, 179, 182, 208 individual, 183 phyletic, 185 to stimulus, 357 Adenin, 108, 109, 162, 175, 305, 482 jEthalium septicum, chemotaxis of, 430 phototaxis of, 449 plasmodium of, 72 rheotaxis of, 444 thermotaxis of, 452 Agaricus, luminosity of, 255 Albuminoids, 108 Albumins, 107 Albumoses, 152 Alchemy, 55 Aleurone-grains, 83, 105, 108, 172 Algv, 316 Amblytstoma, polar excitation of, 418 Amoeba, action of cold upon, 289, 394 action of heat upon, 291 action of solutions upon, 184 artificial division of, 295, 508 as organism without organs, 119 axial orientation of, 498 behaviour of non-nucleated pieces of, 508, 512 chemical stimulation of, 367 development of, 204 effect of withdrawal of oxygen from, 284, 561 electrical stimulation of, 419, 423, 493 excretion by, 169 food-vacuoles of, 144, 169 galvanotaxis of, 457 Amoeba, ingestion of food by, 143 inheritance in, 544 mechanical stimulation of, 382, 386 movements of, 235, 561 narcosis of, 375 polar excitation of, 419, 493 reproduction of, 192 spherical form of, in death, 327 thermal stimulation of, 392, 472 thermotaxis of, 452 Amoeboid movement, 234, 284, 560 Amphimixis, 317 Amphipyrenin, 92 Amyloid metamorphosis, 491 Amyloid substance, 334 Anabiosis, 130 Anaerobia, 287 Ansesthetics, action of, 337, 371, 469 Anastatica, swelling movements of, 223 Anatomy, comparative, 313 Anax inlander, 8 Angiospermce, 316 Anima, 12, 16 Animals, assimilation in, 160 cold-blooded, 217, 257, 288 genealogical tree of, 316 metabolism of, 164, 173 nutrition of, 138, 274 warm-blooded, 217, 257 Animistic system of Stahl, 16 Anisotropic substance, 243, 245 Anode, 405 Anophrys, chemotaxis of, 436 Apoplexy, 335 Apposition, growth by, 122, 168 Arcella, specific gravity of, 98, 229 Archceopteryx, 314 Archeus, van Helmont's doctrine concerning, 13 Aretaeus, 9 Argentieri, 12 Aristotle, 9 Aroidece, production of heat by, 258 Artemia Milhausenii, 183 salina, 183 Arthropoda, 317 604 INDEX Axcaris, centrosome of spermatozoa of, 70 fertilisation in, 202 Asp, 496 Asphyxia, 282 Assimilation, 157, 485 in animals, 160 in plants, 158, 287 Astronomical knowledge, 33 Atavism, 180 Athenteus, 9 Atmosphere, composition of, 282 Atom, 33, 209 Atrophy, 321, 488 and dissimilation, 485 from disuse, 323, 352 normal, 321 pathological, 323 pigment, 336 senile, 323, 338 Avicenna, 11 Axial orientation, 496 Bacillus butyric us, 112 Bacon, 13 Bacteria, action of temperature upon growth of, 391 anaerobic, 287 chemotaxis of, 432 geotaxis of, 446 iron-, 278 mechanical stimulation of, 388 multiplication of, 366 nitrogen-, 140, 274 nucleus of, 67 nutrition of, 140 of cholera, 287 of symptomatic anthrax, 287 of tetanus, 287 phototaxis of, 449 resistance of, to high temperatures, 291 rheotaxis of, 445 spore-formation of, 281 structure of, 67 sulphur-, 278 Bacterium lacticum, 112 photometricum, 400 Bffityli, 7 Ballooning, effects of, 293 Barotaxis, 440 Barthez, 18 Bear-animalcules, desiccation of, 129 Bees, production of heat by, 258 Bell, Charles, 19 Bell's law, 19 Bernard, Claude, 23 Bioblasts, 63 Biogens, 481 decomposition of, 484 formation of, 483 growth of, 529 polymerism of, 486, 529 Biogenesis, law of, 30, 207, 208, 315, 575 Biotonus, 487 action of general stimuli upon, 489 action of local stimuli upon, 496 Blisters, 325 Blood, circulation of, 577 discovery of circulation of, 11, 12, 13 streaming of, in capillaries, 219 Bcerhaave, 16 du Bois-Reymond, 23, 263 Bone, 168 Bordeu, 18 Borelli, 14 Brain, 580 Branchipus stagnalis, 183 Brown, John, 18 Brownian movement, 4, 220 Butyric acid as decomposition-product of carbohydrate, 113 CALCIFICATION, 335 Calcium guanin, 83, 109, 176 Calcium oxalate in plant-cells, 83 Calorie, 212, 260 Calorimeter, 260 Calorimetry, 44, 260, 549 Cane-sugar, 112 Carbohydrates, 110 as product of proteid- decomposition, 164 as source of muscle energy, 554 combinations of, 108, 113 fate of ingested, 161 localisation of, in cell, 116 origin of, from fat, 480 Carbon-equilibrium, 275 Carbonic acid as constituent of living substance, 115 as excretion, 173 as product of carbohydrate-decompo- sition, 113 as product of proteid-decomposi- tion, 110,164 cleavage of, in plant-cell, 158, 217, 366, 399 Carchesiwm as cell-republic, 568 digestion in, 152 Carnivora, 140, 141, 276 Cartilage, 168 Casein, 108 Catalytic action, 155 Catderpa, 72 Causality, craving for, 5, 32, 35 Cell, amoeboid, 75 artificial, 167 as constituent of organism, 27, 60 as elementary organism, 56 as object of physiological study, 48 chemical compounds of, 102 ciliated, 77, 247 definition of, 68 development of, 204, 530 INDEX 605 Cell, flagellated, 247 form of, 74 growth of, 529 multinucleate, 71, 89 reproduction of, 531 size of, 78 specific gravity of, 97, 229 turgor of, 226 Cell- community, centralisation in, 576 constitutional relations of, 567 differentiation in, 573 division of labour in, 573 Cell-constituents, general and special, 64 Cell-differentiation, 573 Cell-division, action of narcotics upon, 374 direct, 191 equal, 195 forms of, 191 indirect, 193 mechanics of, 531, 533 multiple, 196 partial, 196 reducing, 197 total, 195 unequal, 195 Cell-life, mechanics of, 504 Cell-membrane, 65 growth of, 168 movement by swelling of, 222 Cell-metabolism, mechanics of, 518 scheme of, 522 Cell-republics, 568 Cell-sap, 225 Cell-theory, 27, 65 Cell-turgor, 226 Cellulose, 112 as secretion, 173 Cenogeny, 207 Centralisation in cell-community, 576 Central nervous system, 577 Centrosome, 69 in cell-division, 194 quadrille of, 203 Centrotaxis, 447 Cesalpino, 12 Chaussier, 18 Chemical energy, introduction of, into organism, 212 Chemometry, 449 Chemotaxis, 429 Chemotropism, 429 Chitin, 173 Chlorophyll-bodies, 81 cleavage of carbonic acid in, 217 Cholera, vibrios of, 287 Cholesterins, 110 Chondrin, 173 Chromatic nuclear substance, 91 Chymosin, 171 Cilia, chemical stimulation of, 368 electrical stimulation of, 41 8, 423, 428 Cilia, mechanical stimulation of, 387, 570 narcosis of, 375 optical properties of, 99 polar excitation of, 418 thermal stimulation of ,393 work of, 252 Ciliary movement, 247 in absence of oxygen, 286 metachronism of, 247, 570 Ciliata, galvanotaxis of, 458 Ciliated cells, 77, 247 Circulation of blood, 577 of energy, 546 of protoplasm, 239 Cleavage, discoidal, 196 superficial, 197 Climbing-plants, thigmotaxis of, 442 Ctosterium, Brownian movement in,, 220 locomotion of, 231 phototaxis of, 450 Coagulation of proteids, 106 of silicic acid, 106 -necrosis, 324 Cockroach, thigmotaxis of spermatozoa of, 442 Ccelenterata, 317 Cold, physiological effect of, 288 Cold-blooded animals, 217, 257, 288 Cold-centre, 391 Cold-rigour, 394 Coleps, food-ingestion by, 146 Collagen, 109 Colloids, 105 Colombo, 12 Colony, 59 Colour-vision, Hermg's theory of, 493 Community, 59 Conchiolin, 109 Condensations, 43 Conduction, 360 Conjugation, 92, 200, 517 of Infusoria, 343 Connective substances, 173 Consciousness, 33 Contact-action, 155 Contraction, 233, 244, 558 Engelmann's theory of, 558 relation of varieties of, 252 Cornein, 109 Corpulency, 331 Correlation of parts in organism, 181 Cosmology of Ionic philosophers, 7 Cosmozoa, theory of, 300, 302, 307 Creatin, 109, 162, 163, 175, 305, 482 Creatinin, 109, 163 Crystalloids, 105 Ctenophora, ciliary motion in, 249,. 570 Cyanic acid, 306 Cyanogen, 305, 311, 482 Cytode, 68 600 INDEX DAY-FLIES, life of, 340 Death and life, 133 apparent, 126, 133 as adaptation, 342 by over-stimulation, 471 causes of, 336 development of, 134, 319, 471 external causes of, 337 history of, 134, 319 internal causes of, 338 moment of, 134 natural, 339 of man, 133 of cell, 134 -stiffening, 133, 324, 329 Decay, 326 Degeneration, hyaline, 336 waxy, 325 Dendrites, 581 Depression, 356, 357, 469, 490 and inhibition, 494 by chemical stimuli, 371 by electrical stimuli, 427 by mechanical stimuli, 388 by photic stimuli, 403 by thermal stimuli, 394 Descartes, 13 Descent, theory of, 8, 28, 178, 312 Desert-organisms, 279 Desmids, movement of, 231 phototaxis of, 450 Desiccation of organisms, 129 Development, 178, 204 as perfecting process, 318 germinal, 178, 187, 204, 207, 314, 575 mechanics of, 533 of Amoeba, 204 of Colpoda, 205 of the cell, 204, 530 of the multicellular organism, 206 of the unicellular organism, 204 racial, 178, 207, 313, 575 Dextrose, 110, 112 Diabetes mellituft, 164 Dialyzer, 104, 524 Diastase, 154 Diatoms, locomotion of, 232 mechanical stimulation of, 389 photic stimulation of, 402 phototaxis of, 449 Didymium, action of oxygen upon, 369 Differential theory, Hermann's, 267 Differentiation of cells in cell-com- munity, 573 Difflngia, behaviour of non-nucleated pieces of, 513 capsule of, 148 conduction in, 362 conjugation of, 92, 200 mechanical stimulation of, 382 necrobiosis of, 564 specific gravity of, 98, 229 Digestion, 150 Diphtheria, bacilli of, 176 Direction-corpuscles, 196, 199, 202 Disaccharids, 112 Discharge, conception of, 355 Disintegration, granular, 326 Dissimilation, 161, 485 Division of labour, 573 Dobie's line, 243 Dobereiner's lamp, 43 Drosera, changes in nuclei of cells of, 516 peptonising ferment of, 171 Dualism of body and mind, 7, 14, 16, 38, 40 Dumas, 18 Dytiscus, nuclei in eggs of, 514 Echinodermata, 317 Ectoderm, 317 Egg-albumin, 107 Elastin, 109 Elaters of spores of horse-tail, 224 Electric fishes, 268 organs, 269 Electrical induction, 410 resistance, 407 Electricity, animal, 263 as cause of death, 337 origin of, 265 production of, 262 therapeutic use of, 352 Electrodes, non-polari sable, 268, 406, 455, Electromotive force, 407 Electrotonus, 414, 421 Elements, chemical, 99 galvanic, 265, 404 organic, 99 thermo-electric, 258 Empedocles, 8 Endoplasm, 235 Energy, action of stimuli upon trans- formation of, 551 chemical, 547 circulation of, 546 forms of, 209 introduction of, into organism, 212 kinetic, 26, 211, 355 law of conservation of, 26, 210, 211 mechanics of transformation of, 546 modifications of, 211 potential, 26, 211, 355 theory of specific, 21, 45, 475 transformation of, in chemical proces- ses, 213 Entoderm, 317 Enzymes, 109, 151, 156, 171 Epigenesis, 17, 535, 538 Equilibrium, carbon-, 275 dynamical, 44, 123 metabolic, 275, 488 nitrogen-, 275, 365 INDEX 607 Erasistratus, 8 Ergograph, 462 Esters, 113 Eudorina, 60 as cell-republic, 568 Enylena, axial orientation of, 499 Excitability, 18 Excitation, 356, 357, 469, 490 by chemical stimuli, 365 by electrical stimuli, 412 by mechanical stimuli, 379 by photic stimuli, 399 by thermal stimuli, 389 polar, 414 Excretion by A mceba, 169 of dissolved substances, 166 of gaseous substances, 166 of solid substances, 166 Excretions, 166, 173 gaseous, 173 liquid, 174 solid, 176 Exhaustion, 469 Exoplasm, 235 Expansion, 233 of muscle, 246 Experimentum mirabile, 496 Extra current, 410 FAKIRS, Indian, 126 Fat, 113 decrease of, in hunger, 277 digestion of, 155 fate of ingested, 161 localisation of, in cell, 117 origin of, from carbohydrate, 159 origin of, from proteid, 110, 163, 332, 480 Fat-droplets, 83, 95, 172 ingestion of, 144 Fat-metamorphosis, 331 Fatigue, 460, 469 causes of, 469 Fatigue-curve of muscle, 463 Fatigue-substances, 468 Fattening, 275, 331 Fatty acids, 113, 155 Fatty infiltration, 331 Fermentation, alcoholic, 111, 157 butyric acid, 112 lactic acid, 112 Fermentation-tube, 111, 372 Ferment-organisms, 156 Ferments, 155 van Helmont's doctrine of, 13, 15 organised, 156 unorganised, 109, 151, 156, 171 Fernelius, 12 Ferns, chemotaxis of spermatozoids of, 435 Fertilisation, 190, 198 Fibrin, 107 Fibrinogen, 107 FilicinetK, 316 Fish embryos, galvanotaxis of, 455 Fission, 191 Flayellata, galvanotaxis of, 458 Flagellated cell, 247 Fly-larvae, histolysis of tissue in, 322 origin of fat from proteid in, 164 Food as general vital condition, 274 compensatory, 141, 161, 555 ingestion of, 142 primitive, 141, 555 selection of, 146, 527 Food-bodies in cells, 82 Food-stuffs, 138 Food-vacuoles 144, 146, 169, 527 Force, 209 Force hypermechaniqtie 18, 45 Form, changes of, 177 Fowl, experimentum mirabile, 496 Frog, reflex tone of, 358 Fruit-sugar, 110 Function, change of, 270 physiological, 576 Functions, physical (natural), 11 psychical (animal), 11 sphygmical (vital), 11 Fungi, 316 nutrition of, 140, 274 GALEN, 9 Galvani, 19, 263 Galvanic current, 264, 404 polar excitation by, 414 Galvanic element, 265, 404 • Galvanic key, 406 Galvanism, 263 Galvanometer, 259 Galvanotaxis, 455 Ganglion-cell, 581 action of narcotics upon, 376 calcification of, 335 changes in, during activity, 464, 516 depression of, 494 excitation of, 494 fatigue of, 464 inhibition of, 494 Gangrene, dry, 324 moist, 326 Gas-charnber, Engelmann's, 284, 519 Gases as constituents of living sub- stance, 115 Gas-flame, comparison of vital pheno- mena with, 540 Gastrwada, 317 Gastrula, 317 Gelatine foams, radiation-phenomena in, 531 Gemmation, 191, 196 Genealogical tree of organisms, 178, 316 Geotaxis, 445 Germ-regions, organ-forming, 534 Girtanner, 19 Glisson, 15, 17 (508 INDEX Globulins, 107 Glucose, 110 Glutin, 108, 173 Glycerine, 113, 155 Glycogen, 83, 112, 116 as product of proteid-decomposition, 110, 164, 480 transformation of grape-sugar into, 161 Glyco-proteids, 108 Granular disintegration, 473 Granular streaming, 94, 220, 237 Granules, Altmann's hypothesis con- cerning, 63, 88 in protoplasm, 83 Grape-sugar, 110 as product of proteid-decomposition, 110, 164 transformation of, into glycogen, 161 Graphic method, 23 Gregarince, locomotion of, 233 Growth, action of narcotics upon, 373 action of temperature upon, 391 and assimilation, 485 and reproduction, 188, 488, 531 by apposition, 122, 168 by intussusception, 122, 168 mechanics of, 529 movements by, 233 Guanin, 108, 109, 162, 175, 176, 305, 482 Guinea pig, tonic excitation of, 358 Gymnast's fever, 467 Gymnospermce, 316 HEMOGLOBIN, 103, 105, 108 in muscle, 286 Haller, 16 Harvey, 13 Heart-muscle, work of, 246 Heat, introduction of, into organism, 217 physiological effect of, 291 production of, 256 Heat-centre, 391 Heat-equivalent, 212 Heat-rigour, 396 Heliotropism, 429, 447 van Helmont, 13 Henson's disc, 243 Heraclitus, 8 HerUvora, 140, 276 Hereditary substance, 505, 545 Heredity, see Inheritance Herophilus, 8 Hibernation, 128 Hippocrates, 8 Hippuric acid, 109, 163, 175 Histolysis, 321 Hoffmann, 16 Holothurians, mucous metamorphosis of, 170, 333 Homothermal animals, 217, 257 heat-regulation in, 390 Horse-tails, elaters of spores of, 224 phototaxis of spores of, 448 von Humboldt, 19 Hunger, 275 Hyalopus, graular disintegration of, 326 Hydra, regeneration of, 57 Hydrotaxis, 430 Hypnosis, 349, 496 Hypoxanthin, 108, 109, 162, 175, 305, 482 IATROCHEMICAL school, 15 latromathematical school, 15 latromechanical school, 15 latrophysical school, 15 Igiwrabimus, du Bois-Reymond's, 34, 47 Immortality, physical, 341 Immunity, 359 Impatiens, movements of seeds of, 233 Inanition, 275 Incasement, theory of, 17, 535 Individuals, conception of organic, 56 definition of organic, 58 real and virtual, 62 varieties of, 62 Individuality as idea, 37 Induced current, 410 Infusoria, chemical stimulation of, 368 conjugation of, 92, 200, 343, 517 death of, 343 digestion in, 152 discovery of, 15, 298 granular disintegration of, 326 myoids of, 241 narcosis of, 375 old age of, 343 thermal stimulation of, 394 Ingenhouss, 19 Ingestion of food, 142 Inheritance, 179, 207, 318 and metabolism, 545 mechanics of, 544 nucleus as medium of, 505 of acquired characteristics, 180, 318 Inhibition, 494 Inorganic constituents of living sub- stance, 114 Inotagmata, 559 Intestinal epithelium, resorption through, 144, 527 Intussusception, growth by, 122, 168 Inversion of disaccharids, 112 Invertin, 157 Investigation, conception of, 5 goal of, 40 Ionic philosophers, cosmology of, 7 Iron-bacteria, 278 Irritability, 124, 348, 353 theory of, 15, 17, 18 Isotropic substance, 243, 245 INDEX (309 KATHODE, 405 Keratin, 109, 141 Kidney, excretion by cells of, 166 Knowledge, astronomical, 33 conception of, 31, 34 Knowledge of nature, du Bois-Rey- mond's definition of, 31 limits of, 31 Kiihne, 23 Kymograph, invention of, 23 Lacrymaria, movement of non-nucle- ated pieces of, 509 Lactic acid as excretion, 174 as product of carbohydrate-decompo- sition, 112,113 as product of proteid-decomposition, 110, 164 in synthesis of uric acid, 175 Lactose, 112 Lrevulose, 110, 112 Lavoisier, 19 Law, biogenetic, 30, 207, 208, 315, 575 of conservation of energy, 26, 210, 211 of conservation of matter, 26 of polar excitation, 414 Ohm's, 407 Lecithins, 109 Leeuwenhoek, 15 Leucocytes, action of quinine upon, 375 behaviour of nucleus in narcosis of, 521 chemotaxis of, 430 degeneration of, 323 food-ingestion by, 144 food-selection by, 148 in necrobiosis, 327 role of, in histolysis, 322, 432 Lieberkithnia, ingestion and digestion of food by, 152 Liebig, 23 Life, actual, 132 and apparent death, 126 and death, 133 as proteid-metabolism, 136, 310 conception of, 2, 303, 309 external conditions of, 273, 274 general and special conditions of, 273 internal conditions of, 273, 294 latent, 132 origin of, 297, 307, 311 Pfliiger's idea of origin of, 304 potential, 132 primitive ideas concerning, 3, 7 theory of continuity of, 121, 302, 309 Light, action of, in plant-cell, 158, 217, 547 introduction of, into organism, 217 nature of organic, 254 production of, 253 Lightning-bug, luminosity of, 254, 255 Limn, 92 Liquefaction, 325 Living and lifeless, 4, 118, 481 Living substance, chemical properties of, 99 composition of, 55 formation of, 483 galvanic current of, 266 inorganic constituents of , 114 optical properties of, 98 organisation of , 93, 119 physical properties of, 93 specific gravity of, 97 Ludwig, 23 Luminosity of chemical substances, 256 organic, 253 MACRON UCLEUS, 92, 201, 343, 517 Magendie, 25 Magnetism, animal, 349 Magospficera as cell-republic, 568 Malpighi, 15 Man, fasting of, 276 development of, 339 Marey, 23 Mass- effect, 43 Matter and mind, 34 Matter, law of conservation of, 26 nature of, 33, 35 Maturation of ovum, 199, 202 Maximum of excitation, 471 of stimulus, 350 of temperature, 288, 291, 396 of vital conditions, 349 Mayow, 15 Mechanico-dynamical system of Hoff- man, 16 Mechanical energy, production of, 219 Mechanical equivalent, 212 Mexembryanthemum, water in, 279 Metabolism, 137. 483 action of heat vipon, 390 action of stimuli upon, 489 and oxygen, 366 as characteristic of living organism, 125, 131, 311, 477 curve of, 177 in manufacture of sulphuric acid, 1 25 in tetanus, 388 of animals, 164, 173 of plants, 164, 173 scheme of, in cell, 522 self -regulation of, 489 without nucleus, 518 Metachronism of ciliary motion, 247, 570 Metamorphosis, 330, 491 amyloid, 334, 491 colloid, 336 fat, 331 mucous, 332 Metaphysics and natural science, 39 Metaphyta, 316 Metazoa, 316 Micronucleus, 92, 201, 343, 517 R R 610 INDEX Microscope, invention of, 15 Milk, formation of, 331 Milk-sugar, 112 Mimosa, electrical stimulation of, 426 mechanical stimulation of, 380 movement of, 227 narcosis of, 374 Mind and matter, 34 Egyptian doctrine of, 7 Minimum of stimulus, 350 of temperature, 288, 395 of vital conditions, 349 Mitosis, 193 Molecule, 209 Mollusca, 317 Monera, 66, 300, 312, 316 Monism, 34, 38, 40, 41 Monosaccharids, 110 Movement, amoeboid, 234, 284, 560 as characteristic of life, 4, 7 Brown ian, 4, 220 by change of cell-turgor, 225 by change of specific gravity, 229 by contraction and expansion, 233 by growth, 233 by secretion, 231 by swelling of cell-wall, 222 ciliary, 247, 570 kinds of, 219 muscular, 240 passive, 219 Moulds, adaptation of, to salt solutions, 184 Mucigen,l70, 333 Mucin, 108, 113, 171, 333 Mucous cells, 170, 333 metamorphosis, 332 Mucus, 171, 332 secretion of, 169 Midler, Johannes, 20 Multiplier, 258 Mummification, 324 Mummy wheat, 130 Musca, muscle fatigue of, 463 origin of fat in larvae of, 164 Muscinece, 316 Muscle, action current of, 427 chemical stimulation of, 368 contraction of, 244, 558, 565 contraction of, in absence of oxygen, 286 electrical stimulation of, 413, 415, 420, 427 expansion of, 246 fatigue of, 461 galvanic current of, 267 haemoglobin in, 286 irritability of, 15, 17 mechanical stimulation of, 384, 388 metabolism of, 427 metabolism of tetanised, 388 narcosis of, 375 photic stimulation of, 402 Muscle, polar excitation of, 415, 420 production of heat by, 427 recovery of fatigued, 465 rigor mortis of, 133 secondary results of fatigue of, 467 source of energy of, 553 thermal stimulation of, 394 work of, 246 Muscle-albumin, 107 -fibre, 240 histolysis of, 322 optical properties of, 98, 243, 245, 559 structure of cross-striated, 242 structure of smooth, 241 Muscle-fibrilla, 241 Muscle-segment, 243 Myograph, 424 Myoid, 241 Myopodia, 252 Myosin, 107, 324 Myxomycetes, 72 action of oxygen upon, 369 chemotaxis of, 430 development of, 74 movement of, in absence of oxygen, 284 phototaxis of, 449 protoplasmic streaming in, 239 rheotaxis of, 444 thermotaxis of, 452 NARCOTICS, 337, 371, 469 Natural science and metaphysics, 39 purpose of, 1 Nature, philosophy of, 20, 140 Necrobiosis, 135, 319 Necrosis, 320, 324, 398 Neef's hammer, 411 Neovitalism, 31, 44, 45, 46 Nerve, centripetal and centrifugal, 579, 584 chemical stimulation of, 371 conduction in, 360 electrical stimulation of, 415 fatigue of, 461 galvanic current of, 267 polar excitation of, 415, 421 pressure-paralysis of, 389 sensibility of, 18 Nerve-endings, 584 Nerve-fibre, 581 Neuro-muscular cell, 578 Neuron, 581 Nistisformativvs, 19 Nitetta, action of temperature upon, 393 Nitrogen, excretion of, in urine, 175 Nitrogen-bacteria, 140, 274 Nitrogen-equilibrium, 275, 365 Nitroglycerine, decomposition of, 124, 215, 484 Nitromonas, 140 INDEX 611 Xoctiluca, chemical stimulation of, 370 electrical stimulation of, 427 mechanical stimulation of, 388 narcosis of, 376 Nuclear membrane, 91 Nuclear sap, 91 Nucleic acid, 108 Nuclein bases, 108, 109, 162, 163, 175, 305, 482 Nucleins, 92, 108 in secretion, 516 localisation of, in cell, 116 Nucleo-albumins, 108 Nucleolus, 91 Nucleo-proteids, 108 Nucleus, 88 achromatic substance of, 91 and protoplasm, 296, 511 and respiration, 519 chromatic substance of, 91 direct division of, 192 discovery of, 27, 66 form of, 88 function of, 504, 511 in Bacteria, 67 indirect or mitotic division of, 193 in fatigue, 465 in growth, 514 in Monera, 66 in secretion, 515 mechanics of division of, 531 position of, in cell, 514 resting-stage of, 193 structure of, 92 substance of, 90 theory of dominance of, 504 Nutrient solution for plants, 138 Nutrition of animals and plants, 138, 274 of Bacteria, 140 of Fungi, 140, 274 OHM'S law, 407 Oil-drops, amoeboid processes of, 528, 562 Oil-foams, structure of, 86 Ontogeny, 178, 187, 204, 207, 314, 575 Opalina, 72, 188 Optimum of vital conditions, 350 Orbitolites, conduction in, 363 mechanical stimulation of, 386, 441 necrobiosis of non-nucleated pieces of, 135 protoplasmic streaming in, 239 thigmotaxis of, 440 Organ, 59 Organisation of living substance, 93, 119 Organisms and inorganic bodies, 118 Organisms, form-changes in, 177 genealogical tree of, 178, 316 fa, locomotion of, 232 mechanical stimulation of, 389 phototaxis of, 449 Over- stimulation, 460, 471 Ovum, 190 fertilisation of pieces of, 506 maturation of, 196, 199, 202 types of segmentation of, 195 Oxalic acid as decomposition-product of proteid, 110 Oxygen as excretion, 173 as general vital condition, 141, 281 discovery of, 11, 19, 281 in atmosphere, 282 ingestion of, 142, 174 intramolecular, 483 partial pressure of, 282 results of removal of, 283 Oxytricha, thigmotaxis of, 442 PALAEONTOLOGY, 312 Palingeny, 207 Paracelsus, 12 Paralinin, 92 Paramcecium, axial orientation of, 501 chemotaxis of, 437 conjugation of, 92, 200, 517 galvanic stimulation of, 419 galvanotaxis of, 455 geotaxis of, 446 mechanical stimulation of, 383 multiplication of, 366 polar excitation of, 419 specific gravity of, 97 thermotaxis of, 453 thigmotaxis of, 443 s work of, 252 Paranuclein, 92 Parthenogenesis, 190, 204 Pathology, 320 cellular, 25 Peas, production of heat in growth of, 258 Pelomyxa, chemical stimulation of , 472 fatigue of, 461 nuclei of, 89 photic stimulation of, 399 polar excitation of, 418 Pepsin, 109, 151, 171 Peptone, 105, 152 fate of, 160 Peranema, electrical stimulation of, 423 mechanical stimulation of, 383 Periplaneta, thigmotaxis of spermatozoa of, 442 Perpetual motion, problem of, 38 Person, 59 Phagocytes, 143, 144, 148, 322, 430, 432 Philosophy, Bacon's monistic, 14 Descartes's, 14 012 INDE± Phosphorescence, animal and plant, 254 of chemical substances, 256 Phosphorus poisoning, 163, 332 Photometry, 449 Phototaxis, 447 . CO I