The Mechanism of Mitosis

Butschli, Carnoy, Platner, and others have sought an explanation in a totally different direction from any of the foregoing, regarding the formation of the amphiaster as due essentially to streaming or osmotic movements of the fluid constituents of the protoplasm, and the movements of the chromosomes as being in a measure mechanically caused by the same agency. Oscar Hertwig adopts a somewhat vague dynamical view, regarding the formation of the mitotic figure as due to an interaction between nucleus and cytoplasm, which he compares to that taking place in a magnetic field between a magnet and a mass of iron filings : " The interaction between nucleus and protoplasm in the cell finds its visible expression in the formation of the polar centres and astral figures ; the result of the interaction is that the nucleus always seeks the middle of its sphere of action." He gives, however, no hint of his view regarding the nature of the action or the causes of the chromosomal movements. Ziegler ('95) accepts a somewhat similar view ; and he has shown that surprisingly close simulacra of the mitotic figure in many of its different phases may be produced by placing bent wires (representing the chromosomes) in the field of a horseshoe magnet strewn with iron filings.

My own studies on the eggs of echinoderms ('95, 2) and annelids have convinced me that no adequate hypothesis of the mitotic mechanism has yet been advanced. In these, as in many other forms, the spindle-fibres show no differentiation into central spindle and peripheral mantle-fibres ; and the chromosomes extend entirely through the substance of the spindle in its equatorial plane. If there be supporting, as opposed to contractile, fibres, they must be intermingled with the latter ; and both forms must have the same origin. The ,4. Metaphase; daughter-chromosomes drawing apart but still united at one end. B. Daugh separating. C. Late anaphase ; daughter-chromosomes lying at the spindlepoles. D. Final anaphase ; daughter-chromosomes converted into vesicles. E. Immediately after division, the asters undivided ; the spindle has disappeared. F. Resting 3-cell stage. the asters divided into two in anticipation of the next division.

In Figs. .4 to D. the centrosphere appears as a large reticulated mass from which the rays proceed. It is probable that a minute centrosome, or pair of centrosomes, lies near the centre of the centrosphere, but this is not shown.

daughter-chromosomes appear to move towards the poles through the substance of the spindle, and do not travel along its periphery as described by Hermann and Driiner in amphibia and by Strasburger ('93, 2) in the plants. No shortening or thickening of the rays can be observed, and the chromosomes proceed to the extreme limit of the spindle-poles and appear actually to pass into the interior of the huge reticulated centrosphere. I cannot see how this behaviour of the chromosomes is to be explained as the result solely of a contraction of fibres stretching between them and the centrosphere. It is certain, moreover, that another factor is at work. Throughout the anaphases, the centrosphere steadily grows until, at the close, it attains an enormous size (Fig. 37), and its substance differs chemically from that of the rays, for after double staining with Congo red (an acid aniline) and hmmatoxylin it becomes bright red while the rays are blue. It seems probable, therefore, that the movements of the chromosomes are affected by definite chemical changes occurring in the centrosphere, as Butschlii and have maintained ; and it is possible that the substance of the spindle-fibres may be actually taken up into the centrosphere, and the chromosomes thus drawn towards it. Strasburger has made the interesting suggestion, which seems well worthy of consideration, that the movements of the chromosomes may be of a chemotactic character. In any case, I believe that no satisfactory hypothesis can be framed that does not reckon with the chemical and physical changes going on in the centrosphere, and take into account also the probability of a dynamic action radiating from it into the surrounding structures. Van Beneden's hypothesis is probably, in principle, correct ; but, as Boveri himself admits in his latest paper ('95), it seems certain that other factors are involved besides the contractility of the achromatic fibres, and the mechanism of mitosis still awaits adequate physiological analysis.

2.

Division of the Chromosomes In developing his theory of fibrillar contractility Van Beneden expressed the view — only, however, as a possibility — that the splitting of the chromosomes might be passively caused by the contractions of the two sets of opposing spindle-fibres to which each is Later observations have demonstrated that this suggestion cannot be sustained ; for in many cases the chromatin-thread splits before division of the centrosome and the formation of the achromatic figure, — sometimes during the spireme-stage, or even in the reticulum, while the nuclear membrane is still intact. Boveri

showed this to be the case in Ascaris, and a similar fact has been observed by many observers since, both in plants and in animals.

The

splitting of the chromosomes is therefore, in Boveri's words, "an independent vital manifestation, an act of reproduction on the part of the chromosomes." I All of the recent researches in this field point to the conclusion that this act of division must be referred to the fission of the chromatin-granules or chromomeres of which the chromatin-thread is built. These granules were first clearly described by Balbiani ('76) in the chromatin-network of epithelial cells in the insectovary, and he found that the spireme-thread arose by the linear arrangement of these granules in a single row like a chain of bacte Six years later Pfitzner ('82) added the interesting discovery, that during the mitosis of various tissue-cells of the salamander, the granules of the spireme-thread divide by fission and thus determine the A. From the endosperm of the lily, showing true nucleoli. [FLEst B. Spermatocyte of salamander. Segmented double spireme-thread composed of chromomeres and completely split. Two centrosomes and central spindle at J. [HERMANN.] C. Spireme-thread completely split, with six nucleoli. Endosperm of Fritillaria. [FLEMMING.] longitudinal splitting of the entire chromosome. This discovery was confirmed by Flemming in the following year ('82, p. 219), and a similar result has been reached by many other observers (Fig. 38). The division of the chromatin-granules may take place at a very early period. Flemming observed as long ago as 1881 that the chromatinthread might split in the spireme-stage (epithelial cells of the salamander), and this has since been shown to occur in many other cases; for instance, by Guignard in the mother-cells of the pollen in the lily ('91). Brauer's recent work on the spermatogenesis of Ascaris shows that the fission of the chromatin-granules here takes place even before the spireme-stage, when the chromatin is still in the form of a reticulum, and long before the division of the centrosome (Fig. 39). He therefore concludes : " With Boveri I regard the splitting as an independent reproductive act of the chromatin. The reconstruction of the nucleus, and in particular the breaking up of the chromosomes after division into small granules and their uniform distribution through the nuclear cavity, is, in the first place, for the purpose of A. Very early prophase ; granules of the nuclear reticulum already divided. B. Spireme ; the continuous chromatin-thread split throughout. C. Later spireme. D. Shortening of the thread. E. Spireme-thread divided into two parts. F. Spireme-thread segmented into four split chromosomes.

allowing a uniform growth to take place ; and in the second place, after the granules have grown to their normal size, to admit of their precisely equal quantitative and qualitative division. I hold that all the succeeding phenomena, such as the grouping of the granules in threads, their union to form larger granules, the division of the thread into segments and finally into chromosomes, are of secondary importance ; all these are only for the purpose of bringing about in the simplest and most certain manner, the transmission of the daughter-granules (Spalthalf ten) to the daughter-cells."' " In my opinion the chromosomes are not independent individuals, but only groups of numberless minute chromatin-granules, which alone have the value of individuals." 2 These observations certainly lend strong support to the view that the chromatin is to be regarded as a morphological aggregate — as a congeries or colony of self-propagating elementary organisms capable of assimilation, growth, and division. They prove, moreover, that mitosis involves two distinct though closely related factors, one of which is the fission of the chromatic nuclear substance, while the other is the distribution of that substance to the daughter-cells. In the first of these it is the chromatin that takes the active part ; in the second it would seem that the main role is played by the archoplasm, or in the last analysis, the centrosome.