CELL-LIFE AND CELL-MULTIPLICATION.

§ 74a. The progress of science is simultaneously towards simplification and towards complication. Analysis simplifies its conceptions by resolving phenomena into their factors, and by then showing how each simple mode of action may be traced under multitudinous forms; while, at the same time, synthesis shows how each factor, by cooperation with various other factors in countless modes and degrees, produces different results innumerable in their amounts and varieties. Of course this truth holds alike of processes and of products. Observation and the grouping into classes make it clear that through multitudinous things superficially unlike there run the same cardinal traits of structure; while, along with these major unities, examination discloses innumerable minor diversities.

A concomitant truth, or the same truth under another aspect, is that Nature everywhere presents us with complexities within complexities, which go on revealing themselves as we investigate smaller and smaller objects. In a preceding chapter (§§54a, 54b) it was pointed out that each primitive organism, in common with each of the units out of which the higher and larger organisms are built, was found a generation ago to consist of nucleus, protoplasm, and cell-wall. This general conception of a cell remained for a time the outcome of inquiry; but with the advance of microscopy it became manifest that within these minute structures processes and products of an astonishing nature are to be seen. These we have now to contemplate.

In the passages just referred to it was said that the external layer or cell-wall is a non-essential, inanimate part produced by the animate contents. Itself a product of protoplasmic action, it takes no part in protoplasmic changes, and may therefore here be ignored.

§ 74b. One of the complexities within complexities was disclosed when it was found that the protoplasm itself has a complicated structure. Different observers have described it as constituted by a network or reticulum, a sponge-work, a foam-work. Of these the first may be rejected; since it implies a structure lying in one plane. If we accept the second we have to conceive the threads of protoplasm, corresponding to the fibres of the sponge, as leaving interstices filled either with liquid or solid. They cannot be filled with a continuous solid, since all motion of the protoplasm would be negatived; and that their content is not liquid seems shown by the fact that its parts move about under the form of granules or microsomes. But the conception of moving granules implies the conception of immersion in a liquid or semi-liquid substance in which they move—not a sponge-work of threads but a foam-work, consisting everywhere of septa interposed among the granules. This is the hypothesis which sundry microscopists espouse, and which seems mechanically the most feasible: the only one which consists with the "streaming" of protoplasm. Ordinarily the name protoplasm is applied to the aggregate mass—the semi-liquid, hyaline substance and the granules or microsomes it contains.

What these granules or microsomes are—whether, as some have contended, they are the essential living elements of the protoplasm, or whether, as is otherwise held, they are nutritive particles, is at present undecided. But the fact, alleged by sundry observers, that the microsomes often form rows, held together by intervening substance, seems to imply that these minute bodies are not inert. Leaving aside unsettled questions, however, one fact of significance is manifest—an immense multiplication of surfaces over which inter-action may take place. Anyone who drops into dilute sulphuric acid a small nail and then drops a pinch of iron filings, will be shown, by the rapid disappearance of the last and the long continuance of the first, how greatly the increasing of surfaces by multiplication of fragments facilitates change. The effect of subdivision in producing a large area in a small space, is shown in the lungs, where the air-cells on the sides of which the blood-vessels ramify, are less than 1/100th of an inch in diameter, while they number 700,000,000. In the composition of every tissue we see the same principle. The living part, or protoplasm, is divided into innumerable protoplasts, among which are distributed the materials and agencies producing changes. And now we find this principle carried still deeper in the structure of the protoplasm itself. Each microscopic portion of it is minutely divided in such ways that its threads or septa have multitudinous contacts with those included portions of matter which take part in its activities.

Concerning the protoplasm contained in each cell, named by some cytoplasm, it remains to say that it always includes a small body called the centrosome, which appears to have a directive function. Usually the centrosome lies outside the nucleus, but is alleged to be sometimes within it. During what is called the "resting stage," or what might more properly be called the growing stage (for clearly the occasional divisions imply that in the intervals between them there has been increase) the centrosome remains quiescent, save in the respect that it exercises some coercive influence on the protoplasm around. This results in the radially-arranged lines constituting an "aster." What is the nature of the coercion exercised by the centrosome—a body hardly distinguishable in size from the microsomes or granules of protoplasm around—is not known. It can scarcely be a repelling force; since, in a substance of liquid or semi-liquid kind, this could not produce approximately straight lines. That it is an attractive force seems more probable; and the nature of the attraction would be comprehensible did the centrosome augment in bulk with rapidity. For if integration were in progress, the drawing in of materials might well produce converging lines. But this seems scarcely a tenable interpretation; since, during the so-called "resting stage," this star-like structure exists—exists, that is, while no active growth of the centrosome is going on.

Respecting this small body we have further to note that, like the cell as a whole, it multiplies by fission, and that the bisection of it terminates the resting or growing stage and initiates those complicated processes by which two cells are produced out of one: the first step following the fission being the movement of the halves, with their respective completed asters, to the opposite sides of the nucleus.

§ 74c. With the hypothesis, now general, that the nucleus or kernel of a cell is its essential part, there has not unnaturally grown up the dogma that it is always present; but there is reason to think that the evidence is somewhat strained to justify this dogma.

In the first place, beyond the cases in which the nucleus, though ordinarily invisible, is said to have been rendered visible by a re-agent, there are cases, as in the already-named Archerina, where no re-agent makes one visible. In the second place, there is the admitted fact that some nuclei are diffused; as in Trachelocerca and some other Infusoria. In them the numerous scattered granules are supposed to constitute a nucleus: an interpretation obviously biassed by the desire to save the generalization. In the third place, the nucleus is frequently multiple in cells of low types; as in some families of AlgÆ and predominantly among Fungi. Once more, the so-called nucleus is occasionally a branching structure scarcely to be called a "kernel."

The facts as thus grouped suggest that the nucleus has arisen in conformity with the law of evolution—that the primitive protoplast, though not homogeneous in the full sense, was homogeneous in the sense of being a uniformly granular protoplasm; and that the protoplasts with diffused nuclei, together with those which are multi-nucleate, and those which have nuclei of a branching form, represent stages in that process by which the relatively homogeneous protoplast passed into the relatively heterogeneous one now almost universal.

Concerning the structure and composition of the developed nucleus, the primary fact to be named is that, like the surrounding granular cytoplasm, it is formed of two distinct elements. It has a groundwork or matrix not differing much from that of the cytoplasm, and at some periods continuous with it; and immersed in this it has a special matter named chromatin, distinguished from its matrix by becoming dyed more or less deeply when exposed to fit re-agents. During the "resting stage," or period of growth and activity which comes between periods of division, the chromatin is dispersed throughout the ground-substance, either in discrete portions or in such way as to form an irregular network or sponge-work, various in appearance. When the time for fission is approaching this dispersed chromatin begins to gather itself together: reaching its eventual concentration through several stages. By its concentration are produced the chromosomes, constant in number in each species of plant or animal. It is alleged that the substance of the chromosomes is not continuous, but consists of separate elements or granules, which have been named chromomeres; and it is also alleged that, whether in the dispersed or integrated form, each chromosome retains its individuality—that the chromomeres composing it, now spreading out into a network and now uniting into a worm-like body, form a group which never loses its identity. Be this as it may, however, the essential fact is that during the growth-period the chromatin substance is widely distributed, and concentration of it is one of the chief steps towards a division of the nucleus and presently of the cell.

During this process of mitosis or karyokinesis, the dispersed chromatin having passed through the coil-stage, reaches presently the star-stage, in which the chromosomes are arranged symmetrically about the equatorial plane of the nucleus. Meanwhile in each of them there has been a preparation for splitting longitudinally in such way that the halves when separated contain (or are assumed to contain) equal numbers of the granules or chromomeres, which some think are the ultimate morphological units of the chromosomes. A simultaneous change has occurred: there has been in course of formation a structure known as the amphiaster. The two centrosomes which, as before said, place themselves on opposite sides of the nucleus, become the terminal poles of a spindle-shaped arrangement of fibres, arising mainly from the groundwork of the nucleus, now continuous with the groundwork of the cytoplasm. A conception of this structure may be formed by supposing that the radiating fibres of the respective asters, meeting one another and uniting in the intermediate space, thereafter exercise a tractive force; since it is clear that, while the central fibres of the bundle will form straight lines, the outer ones, pulling against one another not in straight lines, will form curved lines, becoming more pronounced in their curvatures as the distance from the axis increases. That a tractive force is at work seems inferable from the results. For the separated halves of the split chromosomes, which now form clusters on the two sides of the equatorial plane, gradually part company, and are apparently drawn as clusters towards the opposing centrosomes. As this change progresses the original nucleus loses its individuality. The new chromosomes, halves of the previous chromosomes, concentrate to found two new nuclei; and, by something like a reversal of the stages above described, the chromatin becomes dispersed throughout the substance of each new nucleus. While this is going on the cell itself, undergoing constriction round its equator, divides into two.

Many parts of this complex process are still imperfectly understood, and various opinions concerning them are current. But the essential facts are that this peculiar substance, the chromatin, at other times existing dispersed, is, when division is approaching, gathered together and dealt with in such manner as apparently to insure equal quantities being bequeathed by the mother-cell to the two daughter-cells.

§ 74d. What is the physiological interpretation of these structures and changes? What function does the nucleus discharge; and, more especially, what is the function discharged by the chromatin? There have been to these questions sundry speculative answers.

The theory espoused by some, that the nucleus is the regulative organ of the cell, is met by difficulties. One of them is that, as pointed out in the chapter on "Structure," the nucleus, though morphologically central, is not central geometrically considered; and that its position, often near to some parts of the periphery and remote from others, almost of itself negatives the conclusion that its function is directive in the ordinary sense of the word. It could not well control the cytoplasm in the same ways in all directions and at different distances. A further difficulty is that the cytoplasm when deprived of its nucleus can perform for some time various of its actions, though it eventually dies without reproducing itself.

For the hypothesis that the nucleus is a vehicle for transmitting hereditary characters, the evidence seems strong. When it was shown that the head of a spermatozoon is simply a detached nucleus, and that its fusion with the nucleus of an ovum is the essential process initiating the development of a new organism, the legitimate inference appeared to be that these two nuclei convey respectively the paternal and maternal traits which are mingled in the offspring. And when there came to be discerned the karyokinesis by which the chromatin is, during cell-fission, exactly halved between the nuclei of the daughter-cells, the conclusion was drawn that the chromatin is more especially the agent of inheritance. But though, taken by themselves, the phenomena of fertilization seem to warrant this inference, the inference does not seem congruous with the phenomena of ordinary cell-multiplication—phenomena which have nothing to do with fertilization and the transmission of hereditary characters. No explanation is yielded of the fact that ordinary cell-multiplication exhibits an elaborate process for exact halving of the chromatin. Why should this substance be so carefully portioned out among the cells of tissues which are not even remotely concerned with propagation of the species? If it be said that the end achieved is the conveyance of paternal and maternal qualities in equal degrees to every tissue; then the reply is that they do not seem to be conveyed in equal degrees. In the offspring there is not a uniform diffusion of the two sets of traits throughout all parts, but an irregular mixture of traits of the one with traits of the other.

In presence of these two suggested hypotheses and these respective difficulties, may we not suspect that the action of the chromatin is one which in a way fulfils both functions? Let us consider what action may do this.

§ 74e. The chemical composition of chromatin is highly complex, and its complexity, apart from other traits, implies relative instability. This is further implied by the special natures of its components. Various analyses have shown that it consists of an organic acid (which has been called nucleic acid) rich in phosphorus, combined with an albuminous substance: probably a combination of various proteids. And the evidence, as summarised by Wilson, seems to show that where the proportion of phosphorized acid is high the activity of the substance is great, as in the heads of spermatozoa; while, conversely, where the quantity of phosphorus is relatively small, the substance approximates in character to the cytoplasm. Now (like sulphur, present in the albuminoid base), phosphorus is an element which, besides having several allotropic forms, has a great affinity for oxygen; and an organic compound into which it enters, beyond the instability otherwise caused, has a special instability caused by its presence. The tendency to undergo change will therefore be great when the proportion of the phosphorized component is great. Hence the statement that "the chemical differences between chromatin and cytoplasm, striking and constant as they are, are differences of degree only;" and the conclusion that the activity of the chromatin is specially associated with the phosphorus.^[26]

What, now, are the implications? Molecular agitation results from decomposition of each phosphorized molecule: shocks are continually propagated around. From the chromatin, units of which are thus ever falling into stabler states, there are ever being diffused waves of molecular motion, setting up molecular changes in the cytoplasm. The chromatin stands towards the other contents of the cell in the same relation that a nerve-element stands to any element of an organism which it excites: an interpretation congruous with the fact that the chromatin is as near to as, and indeed nearer than, a nerve-ending to any minute structure stimulated by it.

Several confirmatory facts may be named. During the intervals between cell-fissions, when growth and the usual cell-activities are being carried on, the chromatin is dispersed throughout the nucleus into an irregular network: thus greatly increasing the surface of contact between its substance and the substances in which it is imbedded. As has been remarked, this wide distribution furthers metabolism—a metabolism which in this case has, as we infer, the function of generating, not special matters but special motions. Moreover, just as the wave of disturbance a nerve carries produces an effect which is determined, not by anything which is peculiar in itself, but by the peculiar nature of the organ to which it is carried—muscular, glandular or other; so here, the waves diffused from the chromatin do not determine the kinds of changes in the cytoplasm, but simply excite it: its particular activities, whether of movement, absorption, or structural excretion, being determined by its constitution. And then, further, we observe a parallelism between the metabolic changes in the two cases; for, on the one hand, "diminished staining capacity of the chromatin [implying a decreased amount of phosphorus, which gives the staining capacity] occurs during a period of intense constructive activity in the cytoplasm;" and, on the other hand, in high organisms having nervous systems, the intensity of nervous action is measured by the excretion of phosphates—by the using up of the phosphorus contained in nerve-cells.

For thus interpreting the respective functions of chromatin and cytoplasm, yet a further reason may be given. One of the earliest general steps in the evolution of the Metazoa, is the differentiation of parts which act from parts which make them act. The Hydrozoa show us this. In the hydroid stage there are no specialized contractile organs: these are but incipient: individual ectoderm cells have muscular processes. Nor is there any "special aggregation of nerve-cells." If any stimulating units exist they are scattered. But in the Medusa-stage nerve-matter is collected into a ring round the edge of the umbrella. That is to say, in the undeveloped form such motor action as occurs is not effected by a specialized part which excites another part; but in the developed form a differentiation of the two has taken place. All higher types exhibit this differentiation. Be it muscle or gland or other operating organ, the cause of its activity lies not in itself but in a nervous agent, local or central, with which it is connected. Hence, then, there is congruity between the above interpretation and certain general truths displayed by animal organization at large. We may infer that in a way parallel to that just indicated, cell-evolution was, under one of its aspects, a change from a stage in which the exciting substance and the substance excited were mingled with approximate uniformity, to a stage in which the exciting substance was gathered together into the nucleus and finally into the chromosomes: leaving behind the substance excited, now distinguished as cytoplasm.

§ 74f. Some further general aspects of the phenomena appear to be in harmony with this interpretation. Let us glance at them.

In Chapters III and IIIA of the First Part, reasons were given for concluding that in the animal organism nitrogenous substances play the part of decomposing agents to the carbo-hydrates—that the molecular disturbance set up by the collapse of a proteid molecule destroys the equilibrium of sundry adjacent carbo-hydrate molecules, and causes that evolution of energy which accompanies their fall into molecules of simpler compounds. Here, if the foregoing argument is valid, we may conclude that this highly complex phosphorized compound which chromatin contains, plays the same part to the adjacent nitrogenous compounds as these play to the carbo-hydrates. If so, we see arising a stage earlier that "general physiological method" illustrated in §23f. It was there pointed out that in animal organisms the various structures are so arranged that evolution of a small amount of energy in one, sets up evolution of a larger amount of energy in another; and often this multiplied energy undergoes a second multiplication of like kind. If this view is tenable, we may now suspect that this method displayed in the structures of the Metazoa was initiated in the structures of the Protozoa, and consequently characterizes those homologues of them which compose the Metazoa.

When contemplated from the suggested point of view, karyokinesis appears to be not wholly incomprehensible. For if the chromatin yields the energy which initiates changes throughout the rest of the cell, we may see why there eventually arises a process for exact halving of the chromatin in a mother-cell between two daughter-cells. To make clear the reason, let us suppose the portioning out of the chromatin leaves one of the two with a sensibly smaller amount than the other. What must result? Its source of activity being relatively less, its rate of growth and its energy of action will be less. If a protozoon, the weaker progeny arising by division of it will originate an inferior stirp, unable to compete successfully with that arising from the sister-cell endowed with a larger portion of chromatin. By continual elimination of the varieties which produce unequal halving, necessarily at a disadvantage if a moiety of their members tend continually to disappear, there will be established a variety in which the halving is exact: the character of this variety being such that all its members aid the permanent multiplication of the species. If, again, the case is that of a metazoon, there will be the same eventual result. An animal or plant in which the chromatin is unequally divided among the cells, must have tissues of uncertain formation. Assume that an organ has, by survival of the fittest, been adjusted in the proportions and qualities of its parts to a given function. If the multiplying protoplasts, instead of taking equal portions of chromatin, have some of them smaller portions, the parts of the organ formed of these, developing less rapidly and having inferior energies, will throw the organ out of adjustment, and the individual will suffer in the struggle for life. That is to say, irregular division of the chromatin will introduce a deranging factor and natural selection will weed out individuals in which it occurs. Of course no interpretation is thus yielded of the special process known as karyokinesis. Probably other modes of equal division might have arisen. Here the argument implies merely that the tendency of evolution is to establish some mode. In verification of the view that equal division arises from the cause named, it is pointed out to me that amitosis, which is a negation of mitosis or karyokinesis, occurs in transitory tissues or diseased tissues or where degeneracy is going on.

But how does all this consist with the conclusion that the chromatin conveys hereditary traits—that it is the vehicle in which the constitutional structure, primarily of the species and secondarily of recent ancestors and parents, is represented? To this question there seems to be no definite answer. We may say only that this second function is not necessarily in conflict with the first. While the unstable units of chromatin, ever undergoing changes, diffuse energy around, they may also be units which, under the conditions furnished by fertilization, gravitate towards the organization of the species. Possibly it may be that the complex combination of proteids, common to chromatin and cytoplasm, is that part in which the constitutional characters inhere; while the phosphorized component, falling from its unstable union and decomposing, evolves the energy which, ordinarily the cause of changes, now excites the more active changes following fertilization. This suggestion harmonizes with the fact that the fertilizing substance which in animals constitutes the head of the spermatozoon, and in plants that of the spermatozoid or antherozoid, is distinguished from the other agents concerned by having the highest proportion of the phosphorized element; and it also harmonizes with the fact that the extremely active changes set up by fertilization are accompanied by decrease of this phosphorized element. Speculation aside, however, we may say that the two functions of the chromatin do not exclude one another, but that the general activity which originates from it may be but a lower phase of that special activity caused by fertilization.^[27]

§ 74g. Here we come unawares to the remaining topic embraced under the title Cell-Life and Cell-Multiplication. We pass naturally from asexual multiplication of cells to sexual multiplication—from cell-reproduction to cell-generation. The phenomena are so numerous and so varied that a large part of them must be passed over. Conjugation among the Protophyta and Protozoa, beginning with cases in which there is a mingling of the contents of two cells in no visible respect different from one another, and developing into a great variety of processes in which they differ, must be left aside, and attention limited to the terminal process of fertilization as displayed in higher types of organisms.

Before fertilization there occurs in the ovum an incidental process of a strange kind—"strange" because it is a collateral change taking no part in subsequent changes. I refer to the production and extrusion of the "polar bodies." It is recognized that the formation of each is analogous to cell-formation in general; though process and product are both dwarfed. Apart from any ascribed meaning, the fact itself is clear. There is an abortive cell-formation. Abortiveness is seen firstly in the diminutive size of the separated body or cell, and secondly in the deficient number of its chromosomes: a corresponding deficiency being displayed in the group of chromosomes remaining in the egg—remaining, that is (on the hypothesis here to be suggested), in the sister-cell, supposing the polar body to be an aborted cell. It is currently assumed that the end to be achieved by thus extruding part of the chromosomes, is to reduce the remainder to half the number characterizing the species; so that when, to this group in the germ-cell, the sperm-cell brings a similarly-reduced group, union of the two shall bring the chromosomes to the normal number. I venture to suggest another interpretation. In doing this, however, I must forestall a conclusion contained in the next chapter; namely, the conclusion that gamogenesis begins when agamogenesis is being arrested by unfavourable conditions, and that the failing agamogenesis initiates the gamogenesis. Of numerous illustrations to be presently given I will, to make clear the conception, name only one—the formation of fructifying organs in plants at times when, and in places where, shoots are falling off in vigour and leaves in size. Here the successive foliar organs, decreasingly fitted alike in quality and dimensions for carrying on their normal lives, show us an approaching cessation of asexual multiplication, ending in the aborted individuals we call stamens; and the fact that sudden increase of nutrition while gamogenesis is being thus initiated, causes resumption of agamogenesis, shows that the gamogenesis is consequent upon the failing agamogenesis. See then the parallel. On going back from multicellular organisms to unicellular organisms (or those homologues of them which form the reproductive agents in multicellular organisms), we find the same law hold. The polar bodies are aborted cells, indicating that asexual multiplication can no longer go on, and that the conditions leading to sexual multiplication have arisen. If this be so, decrease in the chromatin becomes an initial cause of the change instead of an accompanying incident; and we need no longer assume that a quantity of precious matter is lost, not by passive incapacity, but by active expulsion. Another anomaly disappears. If from the germ-cell there takes place this extrusion of superfluous chromatin, the implication would seem to be that a parallel extrusion takes place from the sperm-cell. But this is not true. In the sperm-cell there occurs just that failure in the production of chromatin which, according to the hypothesis above sketched out, is to be expected; for, in the process of cell-multiplication, the cells which become spermatozoa are left with half the number of chromosomes possessed by preceding cells: there is actually that impoverishment and declining vigour here suggested as the antecedent of fertilization. It needs only to imagine the ovum and the polar body to be alike in size, to see the parallelism; and to see that obscuration of it arises from the accumulation of cytoplasm in the ovum.

A test fact remains. Sometimes the first polar body extruded undergoes fission while the second is being formed. This can have nothing to do with reducing the number of chromosomes in the ovum. Unquestionably, however, this change is included with the preceding changes in one transaction, effected by one influence. If, then, it is irrelevant to the decrease of chromosomes, so must the preceding changes be irrelevant: the hypothesis lapses. Contrariwise this fact supports the view suggested above. That extrusion of a polar body is a process of cell-fission is congruous with the fact that another fission occurs after extrusion. And that this occurs irregularly shows that the vital activities, seen in cell-growth and cell-multiplication, now succeed in producing further fission of the dwarfed cell and now fail: the energies causing asexual multiplication are exhausted and there arises the state which initiates sexual multiplication.

Maturation of the ovum having been completed, entrance of the spermatozoon, sometimes through the limiting membrane and sometimes through a micropyle or opening in it, takes place. This instantly initiates a series of complicated changes: not many seconds passing before there begins the formation of an aster around one end of the spermatozoon-head. The growth of this aster, apparently by linear rangings of the granules composing the reticulum of the germ-cell, progresses rapidly; while the whole structure hence arising moves inward. Soon there takes place the fusion of this sperm-nucleus with the germ-nucleus to form the cleavage-nucleus, which, after a pause, begins to divide and subdivide in the same manner as cells at large: so presently forming a cluster of cells out of which arise the layers originating the embyro. The details of this process do not concern us. It suffices to indicate thus briefly its general nature.

And now ending thus the account of genesis under its histological aspect, we pass to the account of genesis under its wider and more significant aspects.