General Physiology: An Outline of the Science of Life

have a charred appearance, and, when brought into water, disintegrate into a clayey pulp. Nevertheless, from several observations 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 difficulties. Our conception of life has been formed from the observation 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 chemical 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 metabolism 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 metabolism, 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

refined and careful methods of research. The majority of investigators 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 objection 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 conditions 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 expression " 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,

it may be said that such organisms exist in the condition of " Scheintod " (apparent 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 phenomena 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 cellcomplexes, such as the cells of the nervous system and of the muscles, no longer show vital phenomena ; but other cells and cellcomplexes 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

blood-current but also wander about actively in all the tissues of the body and play an important role in the organic household, remain 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, especially the activity of the heart, ceases, cannot consistently be regarded as the moment of death, for other cell-complexes continue 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 physiological 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 multicellular 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 nonnucleated protoplasmic masses that have been cut off from a cell do not continue living. If such a separated piece of protoplasm r

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 foodorganisms 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 foodorganisms, 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 movements 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 irreparable 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 characterise 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 endresults of a long series of changes which run their course successively 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

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 characterisation 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 phenomena 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 elementary 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 inorganic 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 consists 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.

WHAT is called life is a series of vital phenomena very unequal in importance. As regards most of the activities that constitute the daily life of mankind, some are composed of elementary phenomena, and some are secondary results of elementary phenomena. 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 foundation, 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.

' Nourishing," in the widest sense, signifies the whole process involved in the taking-in of food-stuffs from the environment. In 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-substances. 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.

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 foodstuffs, 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 exception, 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 : —

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 colourless, 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, however, 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 arranged so that the upper parts of the plant project 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 carbonic 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 consumed. 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 cylinder containing a nutrient solution. N, Nutrient solution ; S, grain of corn ; K, cork. (After Sachs.) animals exist, such as carnivora, which require only animal foodstuffs, 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 chlorophyllbodies. 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-organisms 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 substances. These remarkable nitrogen-bacteria (Nitromonas), therefore, although they possess no chlorophyll, behave exactly like

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 adaptations 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 excretion 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, itfollows that proteids, which alone represent the nitrogenous foodstuffs, are absolutely necessary for the maintenance of animal life.