It is certain that the remarkable transformation of the sphere into a ring during amitosis is not of universal, or even of general, occurrence, as shown by the later studies of vom Rath ('95, 3). In leucocytes, for example, the sphere persists in its typical form, and contains a centrosome, during every stage of the division ; but it is an interesting fact that during all these stages the sphere lies on the concave side of the nucleus in the bay which finally cuts through the entire nucleus. Again, in the liver-cells of the isopod Porcellio, the nucleus divides, not by constriction, as in the leucocyte, but by the appearance of a nuclear plate, in the formation of which the attraction-sphere is apparently not The relations of the centrosome and archoplasm in amitosis are, therefore, still in doubt ; but, on the whole, the evidence goes to show that they take no essential part in the process.
3. Biological Significance of Amitosis A survey of the known cases of amitosis brings out the following significant facts. It is of extreme rarity, if indeed it ever occurs in embryonic cells or such as are in the course of rapid and continued multiplication. It is frequent in pathological growths and in cells such as those of the vertebrate decidua, of the embryonic envelopes of insects, or the yolk-nuclei (periblast, etc.), which are on the way towards degeneration. In many cases, moreover, direct nuclear division is not followed by fission of the cell-body, so that multinuclear cells and polymorphic nuclei are thus often formed. These and many similar facts led Flemming in 1891 to express the opinion that so far as the higher plants and animals are concerned amitosis is " a process which does not lead to a new production and multiplication of cells, but wherever it occurs represents either a degeneration or an aberration, or perhaps in many cases (as in the formation of multinucleated cells by fragmentation) is tributary to metabolism through the increase of nuclear surface." In this direction Flemming sought an explanation of the fact that leucocytes may divide either mitotically or amitotically (t. Peremeschko, LOwit, Arnold, Flemming). In the normal lymph-glands, where new leucocytes are continually regenerated, mitosis is the prevalent mode. Elsewhere (wanderingcells) both processes occur. " Like the cells of other tissues the leucocytes find their normal physiological origin (Neubildung) in mitosis ; only those so produced have the power to live on and reproduce their kind through the same process."' Those that divide amitotically are on the road to ruin. Amitosis in the higher forms is thus conceived as a purely secondary process, not a survival of a primitive process of direct division from the Protozoa, as Strasburger ('82) and Waldeyer ('88) had conceived it.
This hypothesis has been carried still further by Ziegler and vom Rath ('91). In a paper on the origin of the blood in fishes, Ziegler ('87) showed that the periblast-nuclei in the eggs of fishes divide amitotically, and he was thus led like Flemming to the view that amitosis is connected with a high specialization of the cell and may be a forerunner of degeneration. In a second paper ('91), published
shortly after Flemming's, he points out the fact that amitotically dividing nuclei are usually of large size and that the cells are in many cases distinguished by a specially intense secretory or assimilative activity. Thus, Ruge ('90) showed that the absorption of degenerate eggs in the amphibia is effected by means of leucocytes which creep into the egg-substance. The nuclei of these cells become enlarged, divide amitotically, and then frequently degenerate. Other observers (Korschelt, Carnoy) have noted the large size and amitotic division of the nuclei in the ovarian folliclecells and nutritive-cells surrounding the ovum in insects and crustacea. Chun found in the entodermic cells of the radial canals of Siphonophores huge cells filled with nests of nuclei amitotically produced, and suggested ('9o) that the multiplication of nuclei was for the purpose of increasing the nuclear surface as an aid to metabolic interchanges between nucleus and cytoplasm. Amitotic division leading to the formation of multinuclear cells is especially common in gland-cells. Thus, Klein has described such divisions in the mucous skin-glands of Amphibia, and more recently vom Rath has carefully described it in the huge gland-cells (probably salivary) of the isopod Anilocra ('95). Many other cases are known. Dogiel ('90) has observed exceedingly significant facts in this field that place the relations between mitosis and amitosis in a clear light. It is a well-known fact that in stratified epithelium, new cells are continually formed in the deeper layers to replace those cast off from the superficial layers. Dogiel finds in the lining of the bladder of the mouse that the nuclei of the superficial cells, which secrete the mucus covering the surface, regularly divide amitotically, giving rise to huge multinuclear cells, which finally degenerate and are cast off. The new cells that take their place are formed in the deeper layers by mitosis alone. Especially significant, again, is the case of the ciliate Infusoria, which possess two kinds of nuclei in the same cell, a macronucleus and a micronucleus. The former is known to be intimately concerned with the processes of metabolism (cf. p. 165). During conjugation the macronucleus degenerates and disappears and a new one is formed from the micronucleus or one of its descendants. The macronucleus is therefore essentially metabolic, the micronucleus generative in function. In view of this contrast it is a significant fact that while both nuclei divide during the ordinary process of fission the mitotic phenomena are as a rule less clearly marked in the macronucleus than in the micronucleus, and in some cases the former appears to divide directly while the latter always goes through a process of mitosis. In view of all these facts and others of like import Ziegler, like Flemming, concludes that amitosis is of a secondary character, and that when it occurs the series of divisions is approaching an end.