General Physiology: An Outline of the Science of Life

The old myth of the metamorphoses of the multiform Proteus never found a more beautiful realisation than in the developmental history of the individual. Just as the organic world as a whole has undergone an unbroken change of form in the course of innumerable centuries, so the single individual, especially the multicellular animal, during its development into the adult organism passes through in the briefest time a long series of manifold forms until it becomes like or approximately like its parents. It does not belong to the task of general physiology to follow the cycle of development of individual groups of organisms ; by the great growth of the fundamental ideas of Darwin and Haeckel our knowledge of individual or ontogenetic development has expanded into an independent science, embryology, the great importance of which for the understanding of the present organic world has been demonstrated during the last few decades. To-day no biologist or physician, who has not became a blind specialist, is unequipped with embryological knowledge. But, although the study of the more special facts of the ontogenetic development of form must be left to the embryologist as his well-earned right, physiology has to deal with certain general and elementary vital phenomena, upon which the development of the individual rests. These are the phenomena of reproduction.

As should be the case with all vital processes, these phenomena should be studied in the cell. The success of this method of treatment has already been demonstrated with reproductive phenomena ; morphology has laboured here intelligently and has illumined the whole field solely by means of cellular methods. As a result, we are now oriented as to the minute details of the visible events. Reproduction cannot be separated from growth, for in the widest sense it is only a special case of growth; the earlier embryology was prompted to regard reproduction as growth beyond the measure of the individual. The general process that constitutes growth is an increase of living substance, and the essence of reproduction likewise consists merely in an increase of living substance. The difference between that which is usually termed growth in the narrow sense and the phenomenon of reproduction consists only in the fact that in the former case the newly formed

FIG. 67.— SUntor polymorplms. N, Monilifonn nucleus ; o, mouth-opening, cv, contractile vacuole. /. Young individual extended. II. Older individual in the process of division, contracted. (After Stein.) living substance remains in constant connection with the original organism and helps to increase its volume ; while in the latter case a part of the substance separates itself from the original organism, either, as in most cases, being set entirely free, or, as in the increase of tissue-cells, being separated merely by a partitionwall and remaining in place. Correspondingly, there is a large number of transitions between the growth, in the narrow sense, and the reproduction of the cell. Examples of such are afforded especially by many multinucleated cells, as, e.g., Opalina,the infusoriari living in the intestine of the frog, which at first is uninucleated and in growth becomes multinucleated by the repeated division of its nucleus. There occurs here a reproduction of the nuclei, while the

protoplasm belonging to them remains in one mass ; the final result is a very large but multinucleate cell. Every cell exhibits, if not continually, at least at a certain time of its life, phenomena of growth ; the mass of its living substance increases. This can occur only by taking in material from the outside, or, in other words, by metabolism ; and the conception of growth can be rendered precise by bearing in mind that in meta- Fio. 68. — 7. Formation of eggs in the sea-urchin. A, Piece of a young ovary with the germinal epithelium within ; B, piece of an older ovary, in which the cells of the germinal epithelium are developing into eggs which are being constricted off. (After Ludwig.) //. Egg-tubes of the ovary of an insect. In the tubes lie eggs in different stages of formation. (After Hatschek.)

bolism more living substance is built up than is broken down. But, as has been seen, the size of every cell is limited and does not surpass a certain measure. Particularly the size of every definite cell-form has a limit assigned for that particular form, which varies little. Hence, if the quantity of the living substance increases further by growth, this must lead to a " growth beyond the measure of the individual," the cell-mass must divide, i.e., it reproduces. The cell, therefore, multiplies by division ; and every one of the

parts that arise, every daughter-cell, is correspondingly smaller ; it can then grow in turn until it has reached the limit of its individual measure. But in the reproduction of the cell by division, parts must pass over into the daughter-cells from both the essential cell-constituents, the nucleus and the protoplasm, otherwise the daughter-cells would not represent complete cells, and hence could not continue to live. In another chapter in which we shall consider the mechanical explanation of vital phenomena we shall have to enquire after the deeper-lying causes of growth and of limitation in the size of cells. In this place it is necessary merely to obtain an outlook over the field of vital phenomena. If it be accepted provisionally that reproduction is merely further growth, while the size of the cell is

limited, it follows that all reproduction depends upon a division of the living substance of the cell. The widely different varieties of reproduction are nothing but cell-division ; and Virchow has rightly extended the old dictum of Harvey, " omne vivum esc ovo, " into that which forms the basis of all modern ideas of reproduction, " omnis cellula e cellula" This is at once evident in unicellular organisms. They reproduce simply by the division of their cell-body, each daughtercell assuming during the division the shape and form of the mothercell ; and if, as in the Infusoria, the cells possess various kinds of

appendages or organoidjs, the elements that are lacking become regenerated after the division of the body (Fig. 67). But in multicellular organisms, both animals and plants, special reproductive organs are developed, the cells of which become constricted off and as eggs develop by repeated cell-division into similar organisms (Fig. 68). In organisms that have separate sexes the sexual cells of the reproductive organs are different in the male and the female individuals. The male sexual cells are the sperm-cells, or spermatozoa, the female the egg-cells, or ova. For the production of a new individual a union of the two sexual cells, called fertilisation, must take place, except in certain cases where parthenogenesis is present, i.e., where individuals capable of life can develop from unfertilised eggs, as with many Crustacea and insects. Finally, in the lower multicellular animals, in addition to sexual repro-

FIG. 69. — Myrianida, a worm in the process of fission. The single individuals are still hanging together like the links of a chain. a, The original animal ; 6, c, d, e, J, g, the buds from the oldest (6) to the youngest ((/). (After Milne-Edwards.) duction, there occurs asexual increase, by fission and gemmation. In both cases whole complexes of cells are separated off. In fission, e.g., in certain worms (Fig. 69), the whole body, after having reached a certain size by cell-division, is constricted into two or more parts which regenerate themselves again into complete individuals. In gemmation, e.g., in many coelenterates (Fig. 70), there is formed in one part of the body by rapid cell-multiplication a bud, which contains cells from the essential bodylayers and likewise becomes constricted off to regenerate into a new individual.

In all cases, therefore, reproduction, whether asexual or sexual, takes place by cell-division alone, and this depends upon growth. We will now follow the different kinds of cell-division somewhat more in detail and consider the remarkable phenomena that take place in the cell. In order that the daughter-cells of a cell-division may be capable of life, both the nucleus and protoplasm, as already remarked, must divide. But while the division of the protoplasm is very simple, the cell-body simply becoming constricted deeper and deeper by a groove until the protoplasm is separated into two halves, in most cases there appear in the nucleus extremely complicated changes, which in most cells, both animal and plant, agree remarkably in essentials. Regarding the more minute phenomena of cell-division a literature so large as to be almost beyond mastery has appeared during the last two decades, since investigators, misled by the very peculiar behaviour of the nucleus in cell-division, adopted the erroneous view that the nucleus is the sole essential cell-constituent and must be studied as exhaustively as possible in its " active " condition. The fundamental investigations of the phenomena of cell-division comprise the admirable ones of Biitschli (76), Flemming ('82), Strasburger, ('80, '88), O. Hertwig (76, 77, 78, '92), van Beneden ('87), Boveri ('87, '88, '90), and others, who have found objects best fitted for this purpose in the cells of young larvaB of salamanders, in the pollen-cells of lilies, and in the transparent eggs of the sea-urchin and the roundworm of the horse.

The simplest form of cell-division is the direct or amitotic celldivision, which, however, is comparatively rare and, beyond certain unicellular organisms and leucocytes, has been met with only in very few forms of cells. The division of Amoeba can serve as a type (Fig. 71). While the Amoeba is creeping, the original spherical nucleus becomes gradually lengthened, then biscuitshaped, then constricted through the middle ; the connectingpiece becomes constantly slenderer and finally breaks ; and thus two new nuclei result, which immediately assume the spherical form. Then the division of the protoplasm begins ; the Amoeba

FIG. 71. — Amoeba polypodia in six successive stages of division The dark body surrounded by a clear area in the interior is the nucleus, the pale body the contractile vacuole. (After F. E. Schulze.) becomes constricted in a similar manner between the two nuclei like a dumb-bell and creeps towards the two sides, until only a thin thread of protoplasm unites the two halves , this finally breaks so that two new Amcebce, each with one nucleus, result from the division. The process requires a long time, usually several hours, and does not always proceed smoothly : the protoplasm often flows together into one mass after a considerable constriction has taken place, and then flows apart again, until, finally, the uniting bridge is torn through.

By far the great majority of all animal- and plant-cells follow the mode of the so-called indirect or mitotic cell-division, in which the protoplasm is simply constricted, while the nucleus undergoes very remarkable and typical changes of great regularity. Different authors have distinguished different stages and have designated them by different names. Two phases in nuclear division can be FIG. 72.— Scheme of mitotic cell-division. (After Flemming.)

very generally recognised — a progressive one, in which the changes reach their height, and a retrogressive one, in which the two nuclear halves that arise from the division go back to the " resting-stage " of the nucleus, which latter term designates the condition in which the nucleus shows no phenomena of division. A picture will put before oar eyes the important phenomena of nuclear division better than all classifications and descriptions (Fig. 72>

To begin with the resting nucleus about to undergo division, it is seen that the chromatic substance, which, as is well known, consists of nucleins, arranges itself into threads which appear loosely rolled up into a coil (Fig. 72, A). The threads, which have given to this form of nuclear division the name of mitotic division and have approximately equal lengths, split lengthwise so that from each a double thread results. - At the same time the nuclear membrane becomes dissolved, and at the two opposite poles of the nuclear mass the centrosomes, or central bodies (p. 69), surrounded by their protoplasmic radiations, now become visible, the two being united to one another by a fibrous, spindle-shaped figure which is derived from the achromatic substance mixed with the protoplasm. The double threads form loops, and group themselves in the equator of the achromatic nuclear spindle in such a way that their angles are directed towards the centre (Fig. 72, B). Presently the spindle-fibres, streaming out from the centrosomes, by their own contraction divide the double threads in such a way that one half of each is turned toward one pole, the other half toward the other (Fig. 72, G). Thus two groups of threads separate from each other and from the equator of the spindle (Fig. 72, Z>). With this the progressive phase of nuclear division is ended and the retrogressive phase begins. The two groups of chromatic threads proceed further and further toward the two poles, so that the whole equatorial part of the spindle becomes free (Fig. 72, E). FIG. 73.— Centrosomes with Presently the spindle-fibres between the

m the division of the two groups begin to become indistinct, egg-ceii. (After Boveri.) and the threads become twisted again into this process the whole cell-body has become constricted by a circular groove, the plane of which stands at right angles to the axis of the two nuclear poles. The groove becomes deeper and deeper, until finally the whole cell divides into two equal halves, each of which possesses a nucleus ; the latter surrounds itself with a new nuclear membrane, the spindle-fibres completely disappearing, and thus returns to its resting-stage. Thus by the division of the mother-cell two daughter-cells have arisen, and these continue the growth on their own behalf (Fig. 72, F). But during the division a phenomenon has appeared in the protoplasm. Simultaneously with the appearance of the spindle, the poles of which are formed by the centrosomes, two starshaped figures begin to appear in the protoplasm, by the latter arranging itself at each pole like rays around the centrosome as a centre ; the centrosomes thus become surrounded exactly like two suns by a closed circle of rays (Fig. 73). As the spindlefibres become indistinct the protoplasmic rays also disappear.

This mode of mitotic nuclear division is the same in the different forms of cells, almost without exception and even to the finest details. But the division of the cell as a whole does not always proceed in exactly the same manner. Deviations from the type occur in various cases, especially in the division of egg-cells that contain much nutrient material (yolk). With O. Hertwig ('92) FIG. 74. — /. Division of the frog's egg. P, Pigmented surface of the egg ; pr, protoplasmic pole ; d, pole rich in yolk ; sp, nuclear spindle. (After Hertwig.) //. Unequal division of the egg of a worm (Fabricia). A, Protoplasmic pole ; V, pole rich in yolk. (After Haeckel.)

all known forms of cell-division can be conveniently classified under four types — a. Equal division, ft. Unequal division. c. Gemmation. II. Partial division. In total division, the protoplasm of the daughter-cells is completely divided by a partition, so that complete cells always result from the division. But certain differences are here noticeable. In one case, that of equal division, the daughter-cells are entirely equal, as in the type described above (Fig. 72, F). In another case, that of unequal division (Fig. 74), the two daughter-cells are

unequal in size and their contents differ ; the larger one contains the chief mass of the passive yolk, while the smaller one consists principally of active protoplasm. In this way differences arise which have an important bearing upon the subsequent divisions, and become constantly greater. In the third case, that of gemmation, only a very small portion of the egg-cell becomes divided off; this FIG. 75.— Formation of the polar bodies in the starfish ; sp, nuclear spindle ; rfc1, first polar body ; rib2, second polar body ; ek, egg-nucleus.

occurs especially during the maturation of the egg in the formation of the so-called polar bodies or direction-corpuscles, where the process occurs twice in succession (Fig. 75). In partial division the groove that separates the two daughterhalves extends not through the whole cell, but through a part FIG. 76.— Discoidal cleavage of the egg of a cephalopod. (After Watase.) only, so that in subsequent divisions the daughter-halves remain united on their under side by a common protoplasmic mass (Fig. 76). This form is termed discoidal cleavage.

In multiple division, no division whatever of the protoplasm appears at first, but the nuclei alone multiply in the eggcell ; later, however, they wander to the surface and there surround themselves with a separate protoplasmic covering. Thus there exists upon the whole surface an indifferent yolk-mass surrounded by a single layer of separate cells (Figs. 77 and 78) — a phenomenon that has been termed superficial cleavage. A special kind of multiple division is spore-formation, which is especially common in the Protista. The characteristic of this

FIG. 77. — Superficial cleavage of the egg of an insect in three successive stages. (After Bobretzky.) form of cell-multiplication is that the nucleus breaks up into a very large number of tiny granules. Each of these small nuclei surrounds itself with a certain quantity of protoplasm, so that tiny cell-territories appear, which become free as amoebae or flagellated cells, while the rest of the protoplasmic body perishes. The swarm-spore, set free, represents a very small cell containing a nucleus, and slowly develops into the form of the protistan cell from which it was derived.

Finally, in reducing division, as Weismann has termed certain processes that lead to the formation of the ova and the sperm-cells in the ovary and the testis, a slight deviation in the behaviour of the chromatic fibres of the nucleus appears during division. The sperm-cells arise by repeated division of other cells, the sperm mother-cells. The first division of the sperm mother-cells proceeds according to the type described above, but before the nuclei have returned to the resting-stage a second division takes places, each centrosome dividing into two halves which diverge from one another and attract to themselves on both sides the chromatic fibres that arise from the first division, without the latter being able to split lengthwise as in the normal division. Thus, one half of the chromatin-loops wander toward one pole,

FIG. 78.— Multiple, division in the cleavage of the egg of an insect in two successive stages. (After Balbiani.) the other half toward the other pole, so that by this second division each nucleus obtains only one-half as many chromatin-fibres. as in a normal division (Fig. 79). FIG. 79.— Reducing division in the origin of the sperm-cell from the sperm mother-cell of the threadworm of the horse. (After O. Hertwig.) These comprise the various forms of cell-division which have become known thus far. The only element common to them all is the transfer of both nuclear substance and protoplasm to the daughter-cells.

The act of fertilisation is intimately associated with that profound mystery with which mankind is wont to invest its most sacred feelings. The biologist recognises that fact that the unconscious aim of normal sexual love, one of the most powerful factors that control organic life, is the microscopic act of fertilisation of the female egg-cell by the male sperm-cell. At first sight it might seem strange that so powerful motives, as are those of love in human life, culminate in so tiny a phenomenon, which cannot be perceived by the naked eye ; but when it is borne in mind what the result of this act is, what an endless chain of complex processes and changes associated with the development of the new organism from the egg is caused by fertilisation, and what is the end-result of this long series of developmental processes — namely, the highly complex animal, man, with the immeasurable richness of his life — then this fact loses its strangeness, and we come to attribute to the tiny act of fertilisation an extraordinary significance, which it contains in potentia. It is no wonder, therefore, that since early times physicians and men of science have made sexual reproduction the subject of deep research. Yet it was not till after Leeuwenhoek had constructed the microscope that his pupil, Ludwig van Hammen, discovered the sperm-cells, which because of their active intrinsic movements were called " spermanimalcules " or " spermatozoa." And only the unlooked-for perfection of the microscope in the present time has made possible the brilliant work of Butschli, Fol, Hertwig, van Beneden, Boveri,

and others, who have thrown light upon the minute details of the phenomena of fertilisation. In the human being and the higher animals the process of fertilisation cannot be observed, because it is concealed in the interior of the female body, and it is not possible to keep the eggcells alive outside of the body and there fertilise them with sperm. This latter method, however, succeeds with certain lower animals, and hence in eggs that are particularly large and transparent, such as those of the sea-urchin and the round-worm of the horse, the whole course of this interesting process has been carefully studied.

As has already been seen, the male and the female germ-cells are differentiated very differently. While the ova usually are large, spherical or amoeboid cells consisting of a vesicular nucleus and much protoplasm, the latter containing the building-materials for the future development (Fig. 80), the spermatozoa are ex- FIG. 80.— Ova. /. Spherical ovum of a sea-urchin. (After Hertwig.) II. Amreboid ovum of a calcareous sponge. (After Haeckel.) tremely tiny in comparison with them. The spermatozoa consist chiefly of nuclear substance, and have only a thin protoplasmic covering; in most cases the latter is extended into a motile flagellum, the tail, which is distinguished from the rest of the body, the head, and serves for the movement of the spermatozoon in seeking the ovum. The finer structure of the sperm-cell, as the detailed investigations of Ballowitz ('90) have recently shown, is very complicated, and very various differentiations occur among different animals. The accompanying illustrations present some examples of this (Fig. 81). But both the spermatozoa and the ova are always complete cells, and contain both the essential cell-constituents, protoplasm and nucleus — a fact upon which special emphasis should be laid.

Before fertilisation takes place, in some cases also during the beginning of fertilisation, there occurs the maturation of the ovum, which consists in the formation, by means of two successive divisions of the nucleus, of two buds, the polar bodies or directioncorpuscles, and their subsequent extrusion (Fig. 75, p. 196). Fertilisation, therefore, consists in the union of a mature egg-cell with a sperm-cell, in which process the latter seeks the former by its own locomotion. We shall become acquainted with the mode of locomotion later in considering the phenomena of movement.

The process of the union of two cells is a phenomenon that occurs not only in sexual reproduction but is constantly met with among unicellular organisms, where sexual differentiation cannot be said to exist. There, in the Protista, it is known by the name of conjugation. Conjugation occurs even among the unicellular shell-bearing Ehizopoda, e.g., in Difflugia, which is provided with a delicate capsule. In this genus two, and sometimes three, four,

FIG. 81. — Various forms of spermatozoa, a, From a bat ( J esperugo nocturna) (after Ballowitz) ; b and c, from the frog ; d, from the finch ; e, from the sheep ; / and 0, from the pig. (After Schweigger-Seidel.) h, From a medusa ; i, from a monkey (Cercopithecus) ', I, from a crustacean. (After Claus.) k, From the round-worm (after Boveri). or even more, of the sluggish protoplasmic forms creep closely together; their protoplasmic bodies lie in contact with one another, then coalesce into a common mass, and finally separate after the protoplasm of the various bodies has mixed and certain changes in the nuclei have taken place.1 The phenomena of conjugation in ciliate Infusoria have been studied very thoroughly by Butschli (76), Balbiani ('61), Maupas ('88), A. Gruber ('86, 2), and R Hertwig ('88 — '89). Paramoewum is an oblong infusorian, completely ciliated upon the outside, and constitutes an extraordinarily favourable object for cell-physiological investigations of the greatest variety. Paramcecia, visible to the naked eye, may be cultivated in great quantity in decomposing hayinfusions and may be kept in stock. It is frequently observed that an epidemic of conjugation suddenly appears throughout the whole culture, so that almost none but conjugating individuals are found. The phenomena of conjugation are as follows : — Two indi- 1 Cf. Verworn ('90, 1).