General Physiology: An Outline of the Science of Life

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 decomposition 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-transformation 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 whatever is known which contradicts the idea that nitrogenous cleavageproducts of the proteid molecule can rebuild themselves synthetically 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 metabolism 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 proteid 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 produced by bacteria, such as cholera, dysentery, diphtheria, and

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 disappearing 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 absolutely 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 tissuecells 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 concretions 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

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 compounds. 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 construction 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.

The form of organisms is not unchangeable. Apart from the changes that are associated with motion, and which will be considered elsewhere, organisms show profound changes of form that are termed their development. Two great series of form-changes are recognised in living substance — phylogenetic or racial development, 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 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 decades 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 introduced 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 interesting 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 morphology 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

vertebrates, are the result of manifold and profound transformations, 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 somewhat 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 mechanical 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.

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 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 peculiarities, 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 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 singing 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 development 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 mutilations. 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 generations that come under observation during the life of one man or of

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. 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 generation 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 development 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 minutest details, of which an untrained observer would never think.

Since the conditions upon the earth's surface have slowly and constantly 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 conditions, 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 individual, 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 environment 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 adaptation in manner of life. A relatively slight change in the composition of the water in which aquatic animals live, leads in most cases to death. Marine animals placed in fresh water and freshwater 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 different 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 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 favourable 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 surface 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 assumed. 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

FIG. 65. — A. Branchipus stagnalis, fresh-water form ; B. Artemia salina, saltwater form of the same crustacean. (From Semper.) 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

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 phenomenon 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

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 remarkable 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 selection 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 purposefulness, reaching to the minutest details, of organisms in relation to the conditions under which they live. If the external conditions remain for a time unchanged, adaptation acts in a conservative 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.

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.