General Physiology: An Outline of the Science of Life

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 depositing 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 important 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 development, that it passes into death. For the multicellular organism this means that from internal causes the various cells and cellgroups of its organs become gradually so changed in their development, 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 multicellular 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 conditions 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

than they reveal the mechanism of development and life in general ; but they afford a simplification and a sharper formulation 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.

If natural death be considered from the standpoint just presented, 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 cooperation 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 development of an organism that is destined to die might be compared to the solution of a definite fraction. Theoretically, such a hypothetical 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 multicellular 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 infusorian, 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

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 conception 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

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 conjugation 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 daughternuclei, 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. 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 quantitative 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 considerably greater than the mass of cell-substance that in the infusorian 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 radiolarian, 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 swarmspores ; 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 perhaps 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 Weismann's idea, such Protista would be really immortal beings. But at this point the weakness of the doctrine of immortality appears perhaps most distinctly. If Weismann's standpoint be accepted, that

not the cessation of the existence of the individual, but the transformation 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 extinct. 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 minutest details, and it were possible artificially to establish them exactly, life could be produced synthetically, just as fire is produced, and the ideal that existed in the imagination of the mediaeval 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.

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 conditions; 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.

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.

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 popularised 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 hysterical 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 electromagnets 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. 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

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

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

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 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 galvanic 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.

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.