General Physiology: An Outline of the Science of Life

It might appear paradoxical that thirty-five years after Rudolf Virchow ('58) expounded, in his Celhdarpathologie, the cell principle as the basis of all organic investigation- — a basis upon which all our medical ideas now rest — physiology is beginning to develop from a science of the organ into that of bhe cell. But we can recognise in this only the normal course of development, which first takes into consideration the gross activities of the organs and then pushes gradually deeper and deeper until it arrives at the cell. At all times anatomy has been the forerunner of physiology ; and it must be so in order to smooth the way. Just as anatomy began with the organs of the body and only in the present century has reached the smallest elements of the organs, the cells, with the delicate morphological investigation of which the brilliant advance of modern anatomy is consummated, so physiology necessarily began with the study of the functions of the large and obvious organs, and not till the present time has it been able to attack the vital phenomena of the cell. We would be guilty of gross ingratitude if we were to underestimate the eminent importance of past physiological research, upon the results of which we more or less constantly build. Its aims and ideas are destined to lead us still farther, and its methods are indispensable. Yet, in judging the course of physiological research, we cannot forget one factor which controls the development of every science, the psychological factor of fashion. The course of every science depends upon the powerful influence of great discoveries. Wherever we look at the history of investigation, we find that imposing discoveries, such as are represented in physiology by the work of Ludwig, Claude Bernard, du Bois-Reymorid, Liebig, Pasteur, Koch, and others, divert interest from other fields and cause many investigators to labour on in the same direction with the same methods, especially when the methods prove so unusually fruitful as in the cases mentioned.

Thus, definite fields of work in connection with epoch-making achievements immediately become the fashion, while interest flags in other fields. In the course of time equalisation takes place, for every field is limited and in time becomes exhausted. We have evidently arrived at such a period in physiology; the science of the physiology of the organ has passed the culminating-point of its development. In the course of time cell-physiology also will become exhausted, and other aims and methods, such as the state of the problem at the time demands, will succeed it in the incessant evolution.

For the present, cell-physiology has before it an unbounded field of labour. There are, of course, investigators who, although convinced of the pressing necessity of a cell-physiology, and realising that the cell as the seat of the vital processes must constitute the object of research, nevertheless doubt whether we are at all able to get at the vital mysteries in the cell. It can, therefore, reasonably be asked that a way and methods be shown by which a cell-physiology may be founded. Doubt of the practicability of this undertaking springs chiefly from a fact which unfortunately has

characterised physiology since the death of Johannes Muller, and to which attention has already been directed, namely, the entire lack of a comparative physiology. The science has not yet entered upon this important heritage from Mtiller, our greatest master. How few objects of research the physiology of to-day possesses — the dog, the rabbit, the guinea-pig, the frog, and a few other higher animals. How little known are the many splendid objects offered to the observant eye by the enormous number of lower animals. And it is precisely among these objects that there are to be found such as are fitted in a surprising degree for the cell-physiological solution of elementary physiological questions.

It is quite true that if one attempts to treat the problems of digestion, resorption, and motion, from the standpoint of cellphysiology on men or on the higher animals solely, he will soon run against more or less serious technical difficulties in the investigation of the living gland-cell, the intestinal epithelium-cell, and the muscle-cell. Nevertheless, the admirable investigations of Heidenhain upon secretion, the formation of lymph and resorption, have shown what result the cell-physiological method has been able to achieve even here. Such systematic histological experiments, in which the living cell, while its connection with the body is still intact, is put under definite conditions, and the final results are then investigated after the sudden death of the animal for the purpose of drawing conclusions regarding the events that take place during life under the corresponding conditions, will still without doubt yield much of value. In the tissue-cells the conditions are relatively favourable for chemical investigation ; at least in many cases chemistry is capable of investigating metabolism in large living cell-complexes, and drawing from them conclusions regarding the life of the individual cells. In fact, we are indebted to this phase of chemistry for very decided light upon animal metabolism. But, naturally, in the animal body little opportunity is afforded for employing pure tissues, i.e., complexes of similar cells, as objects of research, and the uncertainty of the significance of the results increases enormously in proportion to the morphological complication of the object. Moreover, investigations on tissuecells are limited by the fact that frequently, at least in warm-blooded animals, the tissues offer serious obstacles to the employment of methods such, e.g., as that of microscopic experiment during normal life.

The free-living cells in the organism, such as the white blood-corpuscles, offer considerably fewer difficulties in this respect ; and thus it has come about that in very recent times we have obtained very detailed knowledge of the vital phenomena of leucocytes, especially through the labours of Metschnikoff. Massart, Leber, Buchner, and many others. If, however, the comparative-physiological standpoint, which Johannes Muller always defended energetically, be adopted, an

unbounded field for cell -physiological investigation is revealed. The comparative method demonstrates one fact of fundamental importance, namely, that the elementary vital phenomena belong to every cell, whether it be from a tissue of the higher animals, the lower animals, the plants, or free-living, an independent unicellular organism. Every one of these cells exhibits in its individual form general vital phenomena. Realising this, it is only necessary for the investigator to select from the variety of species the objects best fitted for each special research, and these obtrude themselves upon him in due form, if he possesses some knowledge of the animal and plant world. It is no longer necessary for him to cling to the tissue-cells of the higher vertebrates alone, which can be employed for microscopic experiments alive and under normal vital conditions only in rare and exceptional cases, and which, as soon as they are separated from the tissue, are under abnormal conditions and rapidly die or give reactions that may lead to false conclusions. Much more favourable in this respect are the tissue-cells of many invertebrates, cold-blooded animals, or plants, which can be investigated more readily under approximately normal conditions, although frequently they also do not endure long-continued study. But the free-living unicellular organisms, the Protista, appear to be the most favourable objects for cell-physiological purposes. They seem to have been created by nature for the physiologists, for, besides their great capacity of resistance, of all living things they have the invaluable advantage of standing nearest to the first and simplest forms of life ; hence they show in the simplest and most primitive form many vital phenomena that by special adaptation have developed to great complexity in the cells of the cell-community.

Naturally it has been maintained that exactly the reverse is true, that those forms of cells that are adapted to very special functions in the cell-community of higher animals afford far more favourable objects for the investigation of the phenomena in question than unicellular organisms. Thus, it has been urged that the cross-striated muscle-cell is decidedly more fitted for the investigation of contraction than the amoeba-cell, because in the latter all the phenomena of life are not separated, but are united with the same substratum. However logical this assertion may appear at first sight, upon careful consideration it proves to be little applicable. In the first place, it is a great error to assume that the various phenomena of life are inseparably united in one cell in unicellular organisms alone. This is equally true of every tissue-cell, whether it is adapted to a specific purpose or exhibits prominently to external observation a single vital phenomenon. Every cell, wherever it is, performs all the elementary functions of life. Without being nourished, without respiring, and without excreting, the muscle-cell can execute its

movements no more than can the amoeba. There is no cell whatever that plays one role alone, for it is inherent in the nature of the vital process to exhibit different phases. Hence it is quite wrong to regard the inauguration of the act of contraction in the muscle-cell as something simpler than that in the amoeba. But further, microscopic study teaches that contraction in the crossstriated muscle-cell is associated with a substratum morphologically much more complex than that in the amoeba. The differentiation of various kinds of elements in the former, regarding the significance of which we have scarcely any idea, is very astonishing in comparison with the naked amoeba with its single cell-body. Moreover, the history of research has shown satisfactorily that in spite of the overwhelming amount of labour that has been employed for centuries upon the investigation of contractile phenomena in muscle, up to the present time we have hardly gone beyond conjecture of the most general kind in the solution of the problem. Hence we are not only justified in employing, but even compelled to employ the simpler forms of contractile substance as an important research-object in the investigation of the problem of contraction, and an analogous requirement is demanded for the investigation of other problems, It is obvious that in the study of an elementary vital phenomenon, even among unicellular organisms, objects must always be chosen in which the phenomenon is exhibited sufficiently clearly. For the investigation of secretion cells must be chosen in which the act of secretion is readily accessible ; just as in the study of contraction only those in which contractile movements are directly visible.

Further, it will be necessary to treat the vital phenomena in the various kinds of cells comparatively, for comparative cell-physiology alone is able to separate the special and unessential from the general and essential. Hence it would be a mistake to neglect the tissue-cells while studying unicellular organisms. Not rarely opportunities are offered where for one consideration or another the tissue-cells or whole masses of tissue of plants or animals are to be preferred ; where, indeed, as in many special problems of physiology, the tissue-cell becomes the real object of investigation. It would not be in place here to present a one-sided or schematic view, or to lay down general rules. In every individual case the choice of object is to be determined solely by the problem. One thing only should always be kept in view, namely, the investigation of the life of the cell.

Morphology, the forerunner of all physiology, has smoothed the way for physiological research. We know to-day the structure of cells in minute detail, whether they are free-living or united into tissues, and we are indebted directly to histological research for much important information and many valuable suggestions respecting the vital phenomena, especially of tissue-cells, such as the cells of the central nervous system, glands, and muscles.

We need not be embarrassed in the employment of experimental physiological methods upon the cell, for, with the overwhelming variety of forms in existence, more than one can always be found that are equally fitted for the purpose, and upon which widely different, special methods may be advantageously used. To begin with the simplest method, simple microscopic observation may be employed very conveniently with the free-living cell, and under certain circumstances with the tissue-cell also. Observation alone has led to a fair knowledge of the visible vital phenomena of the cell, and has been used in the detailed investigation of some of them. Among the most prominent acquisitions by this simple method may be mentioned the extremely valuable facts concerning the more detailed phenomena of fertilisation, segmentation, and reproduction which Flemming, Biitschli, van Beneden, the brothers Hertwig, Strasburger, Boveri, Heidenhain, and many others have discovered in recent years, partly on living cells, and partly on cells that have been preserved in certain stages.

Vivisection-operations upon the cell may also be performed under the microscope to the same extent and with greater systematic exactness than they are performed macroscopically upon higher animals. Several investigators, such as Gruber, Balbiani, Hofer, and others have already employed this operative method with great success, and a number of researches have shown how fruitful it is for the treatment of general physiological problems. By this method also Roux, Chabry, the brothers Hertwig, Driesch, and others have carried out their striking experimental investigations upon the development of animals.

Further, a great variety of studies can be made upon the effects of different kinds of stimuli upon the vital phenomena of the cell in its various forms ; in this field a comprehensive mass of facts has already been accumulated. A large number of researches upon unicellular organisms have shown that the reactions that appear in the cell upon the employment of chemical, mechanical, thermal, photic, and galvanic stimuli, are of the greatest importance in a knowledge of vital phenomena. By these researches it has been made possible in recent years to recognise more and more clearly the general laws of excitation and depression of vital processes and their results, and also to approach nearer an understanding of the phenomena of inhibition, which hitherto have been so obscure.

Finally, vital phenomena in the cell can be approached chemically, by both macrochemical and microchemical methods. Large masses of unicellular organisms, such as yeast-cells, leucocytes, and spermatozoa, and no less combinations of cells, such as the tissues, form excellent objects for macrochemical investigation. We are indebted to researches upon such objects as these for the most important portion of our knowledge of the chemical composition and metabolism of the cell. A great variety of favourable researchobjects are also found for microchemical investigation, although thus far, since the methods are still little developed, only the very first beginning in this direction has been made. The labours of Miescher, Kossel, Lilienfeld, Loew and Bokorny, Zacharias, Schwarz, Lb'witt, and others, have already proved that the microchemical investigation of the cell has before it a rich future.

It is, however, superfluous to enumerate single methods which can be employed in cell-physiology. All methods that the special research at the moment demands are useful. Physiology must return constantly to the standpoint that made so fruitful the labours of Johannes Miiller. Throughout his whole life, Miiller defended practically and theoretically the view that there is not a single physiological method, but that every method is right that leads to the goal. He always selected the method in accordance with the problem of the moment, never, as often happens to-day, the problem in accordance with the method. The problem, not the method, is indivisible ; for the solution of the problem the physiologist must employ, as the special purpose demands, alike chemical, physical, anatomical, embryological, zoological, botanical, mathematical, and philosophical methods ; but all should lead to one goal, the investigation of life.

GALEN, the father of physiology, recognised clearly that an exact knowledge of the anatomical relations of an organ is a pre-requisite to an explanation of its vital phenomena ; and modern physiology down to the present day, to its great advantage, has maintained this position. In every physiological investigation a knowledge of the material substratum, the vital phenomena of which is to be examined, must be considered as the first pre-requisite. This is true no less for general, than for special, physiology. Therefore, a consideration of living substance, i.e., its composition and its differences, in comparison with lifeless substance, must form the starting-point of general physiology.

The attempt to explain the mystery that surrounds living substance, the substance that nourishes itself, breathes, moves, grows, reproduces, and develops, has exerted from the earliest times a peculiar stimulus upon the minds of inquiring thinkers. The ancients naively believed that they were able to explain the substance of living bodies by the intermixture of certain materials. Thus, Hippocrates believed that the normal human body consists of blood, phlegm, and bile, which are mixed together in certain proportions. In the middle ages, when people endeavoured to solve the riddle of nature by the great power of alchemy, they thought that they were upon the track of the secret of living substance. How strong this delusion was is shown by the many attempts of the middle ages to produce living substance artificially. The ardent expectation with which the mediaeval alchemist in the sombre dusk of his laboratory, surrounded by skilled workers and strange apparatus, hoped every moment to see the homunculus arise complete from the retorts or crucibles is a very characteristic feature of the developmental stage of science during these centuries. But, however proud we may be of our modern science, we have no right

to look with scorn upon those attempts of the middle ages, when we realise that from that time even to the most recent period the attempts have been continued to produce artificially not man himself, but the simplest forms of living substance. Yet all these attempts resemble the endeavour of a man to put together a complicated clock-work without knowing its essential parts. However simple the problem of the artificial production of living substance appeared to the middle ages, the progress of sober thought and critical investigation has shown constantly how far we are yet removed from a knowledge of the intimate composition of such substance. How is it possible to produce chemically a substance the chemical composition of which is not at all known ? Modern research has been directed, therefore, more and more toward an examination of the composition of living substance. It has penetrated deeply, and continues to penetrate, into the morphological, physical and chemical relations, and the intimate structure of living matter.

When the organic world inhabiting the surface of the earth is examined, it is found that living substance does not form a single coherent mass, but that it is divided into separate organic individuals. It is not wholly easy to define the conception of the organic individual ; yet many investigators, in recent times particularly Haeckel ('66), have endeavoured to give it a generally valid form. It arose in early times by a process of abstraction from ideas of man and the higher animals, which appear as unitary living beings independent of one another. But, as with all such early conceptions which spring from a limited circle of experiences and later come to cover a larger circle, the conception of the individual in its original form has become too narrow and requires an extension.

The original idea upon which the conception of individuality was based, was that of indivisibility. According to this an individual was a unitary whole, which was incapable of division without losing its characteristic properties. So long as none but men, vertebrates and perhaps insects were in mind this definition held good, for a man, a vertebrate or an insect cannot be divided into several independent individuals. But difficulties appear when we descend lower in the animal series or attempt to apply the conception to plants.

In fresh-water ponds and lakes there exists a peculiar representative of the great group of Cnidaria, the fresh-water polyp Hydra. This small animal, about one centimetre long, with its slender tube-like body bearing several long thread-like tentacles that serve for catching prey (Fig. 2, A\ began to attract the attention of observers soon after the discovery of the microscope. It was found that this remarkable creature could be divided by a cross-cut into two halves, each one of which could transform itself again into a complete, but correspondingly smaller individual. The anterior half, bearing the tentacles, simply closes up the wound and attaches itself again at its posterior end, while from the posterior half new tentacles soon sprout out from the edges of the wound, and in a short time both pieces have become complete Hydras. The halves can be divided still further, and the animal can even be cut into a large number of small pieces, each one of which can transform itself into a complete individual. The unitary individual has thus been divided into two or even several individuals. If, therefore, indivisibility alone be the standard of

FIG. 2. — Hydra fusca, a fresh-water polyp ; A, cut across at * ; .Band C, the two pieces, which have become regenerated into two complete individuals. individuality, Hydra is not an individual, for it can be divided without the loss, by the pieces, of the characteristics of the original animal ; and the same is true of every tree and every shrub. The criterion of the individual is, therefore, not to be found in indivisibility, but rather in undividedness or unity. So long as Hydra was undivided, it was an individual, a whole, a unit. By the division, however, the original individual came to an end and from it two new units arose which, so long as they are not further cut into pieces, represent complete individuals. Hence the fact of unity alone is decisive in defining the conception of individuality, if the latter is to be stated in such general terms that it holds good for all special cases. An organic individual would accordingly be merely a unitary mass of living substance.

But iri*this very general form the definition is too broad. Ac- cording to it a small particle of living substance, cut off from the living cell under the microscope, would be an individual. Such a particle, however, cannot be so considered when it is seen how every minute mass of living substance, which has not the value of the cell, sooner or later invariably perishes. The capability of selfpreservation may, therefore, be added to the conception of the individual and the latter may be denned as follows : An organic individual is a unitary mass of living substance which under definite external vital conditions is capable of self-preservation.

This definition applies to all single, free-living organisms which are spatially separated from one another and are not artificially divided, in other words to all organisms in the form in which they occur in nature. But it includes more than single organisms ; it includes groups of organisms, each one of which is separated from the others by space, but which together form a unit. An example FIG. 3. — Eucorallium rubrum, the precious coral, a, A coral stem containing many individuals ; b, a single individual highly magnified. (After Haeckel.)

of this is a community of ants. The community represents a single individual in so far as it is a unitary whole in which the single parts work together like the parts of an organism. But it consists of many single individuals, males, females, workers, and soldiers. It is thus seen that individuality may be of very different grades. It seems advantageous to distinguish the grades of individuality by terming the more comprehensive form an individual of a higher order, and the forms composing it individuals of a lower order. The condition in the coral-stem is like the relation between the ant-community and the individual ants. The coral-stem (Fig. 3, a) is an individual of a higher order, the single coral-polyp (Fig. 3, b) an individual of a lower order. The sole . difference between this

case and that of the community of ants is that here the individuals of the lower order are in physical connection with one another. It will be advantageous to look about the organic world and see what different grades of individuality are to be found. The community, the colony, is evidently the highest grade, for a sum of communities is not a new and higher unit. The next lower stage in the community is the person. The coral-colony can be regarded in a certain sense as a person which consists of single organs ; this relation, however, is clearer in another group of Coelenterata, the Siphonophora. The Siphonophora represent persons which consist

FIG. 4. — Stephalia corona, a Siphonophpre. A, Longitudinal section ; B, external view ; sb, swimbladder ; sgr, swimming-bells ; go, sexual glands ; hi/, gastric tubes ; o, chief gastric tube ; t, tentacles. All the organs are single individuals. (After Haeckel.) of a number of variously developed organs. Some of these organs are for purposes of movement, others for nutrition, others for reproduction, others for protection of the whole body, and all are grouped in regular order about a longitudinal axis (Fig. 4). But all the organs are single individuals, for the embryology of the Siphonophora shows that they all arise from morphologically homologous parts by budding ; and that in certain cases single individuals, as, e.g., the swimming-bells, can separate themselves from the stem and lead an independent existence as medusae. It is seen, therefore, that the person of the Siphonophora can be considered as a colony of single organs, and that the stage of individuality of the person includes the lower stages of individuality of the organs. Careful dissection of an organ, e.g., a human arm,

shows that it is composed of various constituents, which are termed tissues. The arm contains muscle-tissue, nerve-tissue, bone-tissue, etc. ; the characteristic of the organ is its composition out of one or more tissues. The next lower stage of individuality, therefore, is the tissue. Certain organisms consist of but a single tissue, in which all the constituents are alike. Such free-living tissues are widely represented among the Algce. Eudorina elegans, e.g., is a small transparent ball of jelly, in which many spherical particles lie embedded, which upon close examination prove to be bits of living substance separated from one another. These single minute particles of living substance are termed cells. In this particular case each cell has two delicate flagella, by the movement of which the whole mulberry-mass of

jelly is driven about in the water (Fig. 5). Every such flagellate cell is an independent individual, and continues to live when separated from the ball of jelly, which happens, e.g., spontaneously in reproduction. It is seen, therefore, that the tissue contains within itself the single cell. The tissue is a colony of cells. In the cell the lowest stage of individuality has been reached. The cell is, indeed, composed of various constituents, of a soft ground - substance, the protoplasm, and a more solid cell-nucleus